Dr.

Mahmud Kaddura, Department of forensic medicine and toxicology,Faculty of medicine

University of Benghazi-Libya
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TOXICOLOGY
INTRODUCTION

Toxicology is the science of poisons that studies toxic substances with respect to their
sources, properties, and mechanism of toxicity, detection, clinical manifestations, and
management.
A poison can be defined as any substance that causes a harmful effect when
administered to a living organism. Any substance can be toxic if it was introduced in a
dose capable of disturbing the normal physiological homeostasis of the exposed body.
The sources of poisons include:
A) Chemical Source: the commonest source e.g. drugs, corrosives
B) Plant Source: e.g. hashish, cocaine
C) Animal Source: the least but most serious source. Poisons of animal are known
as venoms e.g. scorpions, spiders, snakes, wasps.
Sites of Toxic Actions:
1- Local :
Wherever the poison contacts the biological system it starts its harmful effects. It does
not require specific or receptor to elicit its effects. Example: toxicity by acids or alkalis.
2- Remote (systemic):
The poison affects a system far from its portal of entry.
3- Local & Remote:
The poison has the capacity of acting locally and systematically. Oxalic acid is an
example of these poisons.
Types of Toxic Mechanisms:
A. Direct: the poison itself can cause toxic effects as in corrosives.
B. Indirect: toxicity results from the interaction of the poison with the biological
activity within biological system as in CO. This type can take many forms:
a. Binding to cell membrane making changes in their function or structure
thus affecting their normality.
b. Interference with enzymatic actions.
c. Formation of metabolites which are more toxic than the parent poison.
d. Effects on DNA
Factors Affecting Action of Poison
A) Factors related to the poison:
1- Dose: a basic principle in toxicology. Dose is the amount of chemical that comes
into contact with the body or gets inside the body. The increase of dose will
increase the severity of toxicity.
2- Physical status: gaseous state is more toxic than liquid state than the solid
state.
3- Purity: this depends on the impurity of the poison; if the impurities are more toxic

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University of Benghazi-Libya
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than the poison, the toxicity will be more and vice versa.
B) Factors related to the individual:
1- Age
2- Health
3- Sensitivity
4- Sex
C) Factors related to mode of exposure:
Inhalation > IV > IM > ingestion > Skin contact
D) Factors related to eniviroment:
Temperature, pressure, humidity, radiation can cause alterations on poisons status.

PRINCIPLES OF MANAGEMENT OF POISONING

Management of toxic emergency is similar in adults and children and follows regular
steps:
1. Initial assessment and stabilization of the vital functions.
2. Definitive care of poisoning cases:
i. Measures to identify the toxic agent.
ii. Prevention of further absorption.
iii. Antidote therapy (if available).
iv. Enhance elimination of the toxic substance.
3. A secondary survey for infection, trauma, and metabolic derangements.
4.
I- INITIAL ASSESSMENT & STABILIZATION

Supportive measures (ABCD) should be applied before all other considerations in the
management of a poisoned patient, when there is a life-threatening condition. Many
toxic substances can lead to significant defects in respiratory, cardiovascular, and/or
neurological functions. These potentially life-threatening changes should be identified
and treated quickly. Many poisoned patients require only supportive therapy alone in
order to recover. These supportive measures would include:
Airway: should be kept patent and any obstructing material must be removed:

Breathing: Assisted ventilation should be done according to the situation:

Circulation: IV line must be inserted with collection of samples for lab studies.
Immediately after establishing IV line, a "coma cocktail" of dextrose, thiamine,
naloxone and O2 should be given to all patients with altered mental status of unknown
cause. Flumazenil is rarely given emergently. It should not be given as a part of the
coma cocktail as it can worsen cases of TCA overdose, seizures, or habituated to
BZDs.
Disability (Neurological): includes all changes in normal neurological functioning i.e.
perception, cognitive functions, and responses.

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University of Benghazi-Libya
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II- DEFINITIVE CARE WITH THE POISONING

A- IDENTIFICATION OF THE TOXIC SUBSTANCE

Once initial stabilization is completed, we should try to identify the poison. It is important
to take history from sources other than the patient who is often giving an unreliable
history. These sources include family, friends, pharmacists, and the pill bottles at the
scene. Attempt to establish the time and amount of the ingestion.
A careful physical exam, based on knowledge of pharmacology and the effects of drugs
on autonomic nervous system, will allow us to establish the most likely causative agent.
The vital signs should be monitored accurately. The exam should include evaluation for
head trauma, focal neurological findings, needle track marks, and presence of unusual
breath odors.
TOXIDROMES:
A constellation of clinical signs and symptoms that will help identify the specific
toxin ingested.
Physical exam should focus on identifying a "Toxidrome" or toxic syndrome. There are
many exceptions to the toxidromes.
Important Toxidromes:

1. Cholinergic syndrome.
2. Anticholinergic syndrome.
3. Narcotic syndrome.
4. Extra pyramidal syndrome.
5. Sedative / hypnotic syndrome.
6. Sympathomimetic syndrome.
7. Serotonin syndrome.

Narcotic Toxidrome: Triad of respiratory depression, pinpoint pupils, decreased level of

consciousness
Cholinergic Toxidrome: SLUDGE (Salivation, Lacrimation, Urination, Defecation,
Gastric cramping, Emesis) and Pinpoint pupils.

INVESTIGATIONS
1-General Routine Investigations
2- Toxin-specific investigations
A) Toxicology Screening:
Quantitative serum levels of Acetaminophen, Salicylates, Digoxin, Iron, Lithium,
Methanol, Theophylline, Phenobarbitone, Ethylene glycol may influence therapy.
Toxicology screening provides direct evidence of ingestion, but must not affect the initial
management (first 6-8 hrs) and should not await results because:
a) The time factor for reading the screening is very long concerning the emergency
situation.

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University of Benghazi-Libya
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b) A large number of substances including most antihypertensives and new

antidepressants, mushrooms, fentanyl, cyanide, and household products have no
screening.
c) If the initial urine screen is done too soon after ingestion, the concentration of
substance in the urine may be too low for detection.
d) The drugs found on the screen may not be responsible for the symptoms,
especially if not quantitated. Cocaine metabolites may be detected for days and
marijuana metabolites for weeks post-exposure.

B- PREVENTION OF FURTHER ABSORPTION

A- Dermal Exposure: clothes should be removed, and skin to be washed gently.

B- Eye Exposure: Washing conjunctiva with running water or normal saline for 20
minutes. If there are solid corrosives they should be removed by forceps.

C- GIT Exposure:

Gastrointestinal Decontamination Intestinal Decontamination

Induction of emesis Activated charcoal

Gastric lavage Cathartics

Activated Charcoal Whole bowel irrigation

1- INDUCTION OF EMESIS

Chemically induced emesis is the first line procedure in the management of poisoning
and this method is effective when used in prehospital areas. Finger stimulation or
apomorphine is unsafe.

Syrup of Ipecac: It is the practical method to be used. It is derived from the root of the
plant Cephalus Ipecachuana, which contains active alkaloids emetine and cephaline. It
acts through 2 phases:

Early phase: within 30 minutes by direct GIT stimulation.

Late phase: after 30 minutes through its action on chemoreceptor trigger zone.

Contraindication

Absolute: Convulsions. Corrosives. Hydrocarbons.

Relative: Coma or impending coma, Decreased gag reflex. Severe CVS disease or respiratory
distress or emphysema. Recent surgical intervention or hemorrhagic tendencies (varices,
thrombocytopenia). Previous significant vomiting (spontaneously). Less than 6 months of age (not

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University of Benghazi-Libya
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well developed gag reflex).

2- GASTRIC LAVAGE

This method is used in hospitals when emesis was failed or there was contraindication
for it. Gastric lavage is effective in the first 4-6 hrs after ingestion.

Contraindications

Absolute contraindications: 1- Corrosives because of risk of perforation of the esophagus or stomach

(except carbolic acid). 2- Froth producing substances as shampoo or liquid soap.

Relative contraindications: 1- Coma. 2- Convulsions. 3- Petroleum distillates.

3- ACTIVATED CHARCOAL

Activated charcoal exerts its effects by adsorption of a wide variety of drugs and
chemicals. Toxins that are poorly adsorbed by AC include Iron, Lithium, Metals, Alcohol,
Glycols, Corrosives and Hydrocarbons.
Contraindications: Intestinal obstruction. 2- Corrosives. 3- If an oral antidote to a
specific type of drug poisoning is given. 4- Hydrocarbons because of the risk of vomiting
and aspiration.

4- CATHARTICS (Laxatives)
They enhance the passage of material through GIT and decrease the time of contact
between the poison and the absorptive surfaces of the stomach and intestine. Types
are:
a) Osmotic cathartics: increase osmotic pressure in the lumen, as Mg sulfate.
b) Irritant cathartics: act by increasing motility, such as caster oil.

5- WHOLE BOWEL IRRIGATION

Whole bowel iirigation cleans GIT from nonabsorbed ingested toxins.

C- ANTIDOTES
These are substances that abolish or counteract the poison and its toxic effects.
Classification:

I- According to the mode of action:

Physical Chemical Physiological (Pharmacological)

1- Adsorption. 1- Oxidizing. 1- Antagonism.

2- Dilution (milk & water). 2- Reducing. 2- Chelating.

3- Coating. 3- Precipitating. 3- Competitive.

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University of Benghazi-Libya
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4- Dissolving.

II- According to the site of action

1- Interacts with the poison to form a nontoxic complex that can be excreted e.g.
chelators

2- Accelerate detoxification of the poison: N-acetylcysteine, thiosulfate.

3- Decrease rate of conversion of poison into its toxic metabolites: Ethanol, Fomepizole.

4- Compete the poison for certain receptors: Naloxone.

5- Block the receptors through which the toxic effects of the poison are mediated:
atropine

6- Bypass the effect of the poison: O2 treatment in CO and cyanide toxicity.

7- Antibodies to the poison: digiband, antivenoms.

Physiological (Pharmacological) Antidotes

A) Antagonism

1- Competitive Antagonists

Naloxone: it is used in opiate toxicity and replaces them at target tissues.

Naltrexone: used for opiate dependence, it has long action with affinity for mu
receptors.

Flumazenil: antagonist for benzodiazepines but should be used only if necessary.

Atropine: antagonizes acetylcholine effects. It is used in organophosphate, carbamate,

and other parasympathomimetic (pilocarpine, muscarine) toxicities.

Oxygen 100%: used in CO, cyanide toxicities, and methemoglobinemia.

Ethanol: competes with ethylene glycol and methanol for alcohol dehydrogenase.

Fomepizole (4-methyl pyrazole): a new antidote for methanol and ethylene glycol.

2) Non-Competitive Antagonism

Pralidoxime (2-PAM): it is a ChE activator by breaking the alkylphosphate-ChE bond,

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University of Benghazi-Libya
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used in organophosphate toxicity.

Physostigmine: a parasympathomimetic used (in certain situations) to counteract the

anticholinergic effects such as in atropine or TCA toxicities.

B) Chelating Agents:

These compounds unite metallic poisons to form soluble, nonionizable, less toxic, and
easily excreted chelates. The word is derived from the Greek term for claw.
C) Increase Detoxification

N-Acetyl Cysteine (NAC): is the antidote in acetaminiophen toxicity; it is a precursor

for glutathione the main detoxifying system of paracetamol toxic metabolites.

D) Antibodies (Immunology-based Antidotes)

1- Digoxin Specific Antibody Fragment (FAB fragments, Digiband): FAB fragments

are extremely effective for severe acute digitalis toxicity.

2- Polyvalent Antivenom: It neutralizes the venom but do not adverse the local injury.
3- Antibotulism Serum: It binds the toxin and stops disease progression.
4) Other Antidotes
a) Vitamins
1- Vitamin K: for synthesis of factors II, VII, IX, X. Deficiency leads to prolongation of
CT.
2- Vitamin B12 (Hydroxycobalamin): it contains cobalt ion, which is able to bind to
cyanide to form nontoxic cyanocobalamin that is excreted in urine.
b) Glucagon: is used in β-blocker poisoning to stimulate the β-adrenergic nerves on a
receptor different from that occupied by the β-blocker.

D- ENHANCEMENT OF EXCRETION OF ABSORBED POISONS

1- Forced Diuresis

It is a simple method for enhancing excretion of some poisons. It is effect is increase in

some substances with manipulation of urine pH. The types of forced dieresis are:

a- Fluid Diuresis: by using dextrose or dextrose-saline solutions.

b- Osmotic Diuresis: mannitol 10% (excreted by renal tubules to increase their osmotic
pressure).

2- Manipulation of Urine pH. (Ion Trapping)

Definition: changing urine PH in order to make drugs secreted in urine in their ionized

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Dr. Mahmud Kaddura, Department of forensic medicine and toxicology,Faculty of medicine
University of Benghazi-Libya
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form so that preventing there reabsorption. Manipulation of urine is accompanied with

forced diuresis.

- Criteria of drugs that respond to urinary PH manipulation:

1- Excreted mainly in kidney. 4- Low lipid solubility.

2- Week electrolytes. 5- Low plasma protein binding.

3- Low volume of distribution.

a- Forced alkaline diuresis: for week acids as salicylate & phenobarbitone.

- Method: by repeated IV administration of fluid in the following sequence:

1- 0.5L dextrose 5%. 3- 0.5L manitol.

2- 0.5L sodium bicarbonate 1.26%. 4- 3gm KCl over the 1.5L.

- Precautions: 1-Keep urine PH at 7.5 or higher.

2-Keep urine output at 300-500ml/h.

3-Ascertain normal renal function.

4-PH & electrolyte should be monitored in the blood.

5-Auscultate lung bases for possibility of pulmonary edema

- Contraindications: 1- Renal failure. 3- Heart failure.

2- Pulmonary edema. 4- Old age.

- Complications: 1- Electrolyte imbalance. 3- Alkalosis.

2- Fluid overload with pulmonary and cerebral edema.

b- Acid diuresis: it is used for week bases as amphetamine.

- Acidification of urine is no longer used to enhance elimination because of possible

precipitation of myoglobin in renal tubules

- Aim: keep urine pH at 4.5-6.

- Method: - Ammonium chloride 75 mg/Kg/day orally.

- 500 c.c. dextrose 5%. - 0.9% saline.

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Dr. Mahmud Kaddura, Department of forensic medicine and toxicology,Faculty of medicine
University of Benghazi-Libya
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3- Dialysis

Principle: is to allow blood to circulate beside semi permeable membrane to remove

substances from the blood according to concentration gradient.

Dialyzable drugs should have: (Criteria of Dialyzable Toxins)

1-Small volume of distribution. 3-Low molecular weight.

2-Low protein binding capacity. 4-Low lipid solubility.

Examples of dialyzable drugs:

1- Alcohols: ethanol, methanol. 3- Sedatives: phenobarbitone.

2- Analgesics: salicylate, paracetamol. 4- Miscellaneous: theophyllin, Li.

Example of not dialyzable drugs: Opiate, digitalis, antidepressants.

a) Peritoneal dialysis acts by considering peritoneum as semipermeable

membrane.

b) Hemodialysis: in this method the semipermeable membrane is a cellulose bag

(artificial kidney). It is indicated when the condition of the patient is deteriorating despite
proper treatment, or in toxicities with potentially lethal blood levels. Complications
include hypotension, bleeding tendency (due to heparin), electrolyte imbalance, cross
infections, and air embolism.

4- Hemoperfusion

This method is nearly similar to hemodialysis but the blood is allowed to pass
through specific membranes coated with activated charcoal to adsorb the toxins
from the blood. Complications include: Thrombocytopenia. 2- Hypocalcemia. 3-
Hypoglycemia. 4- Hypotension. 5- Adsorption of therapeutic drugs.

4- Hemoperfusion:

- It is the parenteral analogue of oral activated charcoal.

- Blood is passed through a filter containing adsorptive material such as activated

charcoal. It is more superior to hemodialysis.

5- Plasma pheresis & plasma exchange:

- Volume of blood is removed from the body, and then all blood elements are returned
to circulation except plasma.

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Dr. Mahmud Kaddura, Department of forensic medicine and toxicology,Faculty of medicine
University of Benghazi-Libya
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- In plasma pheresis, the extracted plasma is replaced with crystalloid solution while in
plasma exchange, plasma is replaced by a protein solution.

- It is indicated for toxins with high plasma protein binding capacity.

IV- Symptomatic treatment of poisoning:

1- Treatment of Respiratory failure (R.F; care of respiration):

R.F. is defined as a state of PaO2 < 60mmHg with/without PaCO2 > 45mmHg

a- Airway clearance:

1- Aspiration of secretions & vomit and removal of foreign bodies from the mouth

2- Oropharyngeal tube to prevent falling of the tongue backward.

3- Endotracheal intubation better using inflatable cuff.

4- In laryngeal obstruction, use tracheaostomy.

b- Improve ventilation:

1- Before reaching the hospital: patient is put on his back with the neck tilted backward
and the chin pulled foreword then mouth to mouth breathing is done

2- After reaching the hospital: O2 is given, or intubation with mechanical ventilation if

there is apnea.

2- Cardiovascular resuscitation:

1- Patient is placed on his back with mouth to mouth breathing established.

2- External chest compression is done to maintain circulation in a rate of 80 beats/min

with 2 respiration /15 beats.

3- Adrenalin is given if resuscitation is prolonged.

4- In hyperkalemia and Hypocalcaemia calcium chloride is given.

5- In ventricular arrhythmia; Xylocaine l00mg IV or DC shock are given.

3- Care of comatose patient:

1- Regular careful examination of the following hourly: pulse, blood pressure,

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University of Benghazi-Libya
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respiratory rate, temperature, pupil, color of skin, reflexes and respond to painful stimuli.

2- Catheterization to collect urine.

3- Elevate patient head to reduce cerebral venous pressure and possibility of brain
edema.

4- Maintain pharyngeal suction and regular endotracheal suction.

5- Turn patient and massage every 2h to prevent bed sores.

6- Caloric feeding infusion ryle tube. If renal function is adequate, we give 40 ml/kg
fluids daily to maintain output 15-30 ml/kg daily.

7- Regular bowel evacuation.

8- Maintain fluid intake and output chart.

9- Prophylactic antibiotics to guard against pneumonia.

N.B. coma cocktail: 50 ml Glucose (50%), Thiamine, Naloxone & O 2 are given to every
case of coma of unknown etiology.

4- Control of convulsions:

1- Anticonvulsant drugs: as diazepam (6-l0mg IV), short acting barbiturates.

2- In refractory cases, general anesthesia is mandatory.

3- Oxygen is given.

4- Prevent biting tongue by butting soft bad between teeth.

5 - Treatment of pulmonary edema.

1- Relieve anxiety if present by benzodiazepines & Semi- setting position.

2- Use PEEP (positive end expiratory pressure) for short periods.

3- Diuretics such as Lasix.

4- Aminophylline I.V to relieve associated bronchospasm.

5- If H.F is present, digitalize the patient.

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Dr. Mahmud Kaddura, Department of forensic medicine and toxicology,Faculty of medicine
University of Benghazi-Libya
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TOXICITY OF THERAPEUTIC AGENTS

SALICYLATE TOXICITY
Salicylates are widely used for their analgesic and anti-inflammatory actions. Salicylate
ingestion is one of the most common causes of drug toxicity. The incidence of salicylate
toxicity in children has declined due to usage of alternative antipyretics, their
association with Reye syndrome, and the repackaging systems; using child resistant
containers.
Pathophysiology:
In toxicity salicylates cause a variety of metabolic abnormalities:
1. Salicylates uncouple oxidative phosphorylation resulting in hyperthermia,
increased metabolic rate and hyperpnea. The increased energy demand will lead
to increased tissue glycolysis and gluconeogenesis that may result in
hyperglycemia.
2. Salicylates directly inhibit certain enzymes in Kreb's cycle leading to increased
amounts of organic acids (lactate and pyruvate) that contribute to metabolic
acidosis
3. Salicylates stimulate lipid metabolism leading to increased levels of ketones
4. Salicylates inhibit aminotransferase resulting in increased levels of aminoacids
and amnoiaciduria
5. Salicylates may cause renal tubular damage leading to proteinuria.
Clinical Manifestations
GIT Toxicity: gastric pain, nausea and vomiting due to local irritation and centrally
mediated mechanism, gastric erosion, ulceration and bleeding may occur

Ototoxicity: tinnitus, vertigo, and reversible deafness

Neurotoxicity: agitation, hallucinations and convulsions may occur.

Respiratory and acid base abnormalities: salicylates Increase O2 consumption and CO2
production due to increased metabolic demands leading to stimulation rate and depth of
respiration. Tachypnea increases CO2 wash to maintain blood pH. Excessive wash of
CO2 leads to respiratory alkalosis which is compensated by renal excretion of HCO3
leading to compensated respiratory alkalosis. In severe toxicity, CNS and respiratory
depression occur leading to CO2 retention and respiratory acidosis. Metabolic acidosis
occurs due to:

1- Uncoupling of oxidative-phosphorylation  accumulation of lactic and pyruvic

acids
2- Increased levels of circulating amino acids due to inhibition of A.A metabolism
3- Increased levels of ketones due to stimulation of lipid metabolism
4- Renal excretion of HCO3
Non-cardiogenic pulmonary edema: May appear in some patients. The exact etiology is
unknown.
Fluid and Electrolytes: Salicylate poisoning may result in dehydration due to vomiting
and increased insensible fluid losses. Hypokalemia and hypocalcemia can occur due to

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University of Benghazi-Libya
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primary respiratory alkalosis. Hypokalemia results from the shifting of K + into the cells in
exchange for H+ in the presence of alkalemia (from K loss in the urine and from
vomiting with subsequent metabolic alkalosis and bicarbonaturia).
Hematological Toxicity: bleeding tendency is due to:

1- In small doses inhibition of platelet aggregation occurs  increased bleeding time.

This lasts for 4-7 days till new platelets are formed
2- In large doses salicylates are changed in intestine into a dicumarol like
substance, which decreases vitamin K and prothrombin synthesis that leads to
increased PT
Renal Toxicity: Salicylates may cause renal failure through direct renal tubular damage

Metabolic: Hyperglycemia initially due to increased hepatic glycogenolysis then

hypoglycemia due to depletion of glucose stores. Hypoglycemia may appear later on.

Hyperthermia due to uncoupling of oxidative phosphorylation

Skin: Flushing and sweating

Treatment
A- Stabilization of the patient
B- GIT decontamination: Initial treatment should include AC, some authors recommend
gastric lavage in all symptomatic patients regardless of time of ingestion. Repeated
doses of charcoal may enhance salicylate elimination and shorten the serum half-life. A
potential indication for repeated doses of AC is plateau appearance in serum salicylate
concentrations, which may suggest a continued absorption due to salicylate bolus.
Whole bowel irrigation is more effective in reducing absorption of aspirin enteric-coated
tablets.
C- Enhancement of Elimination
1- Urinary alkalization: Renal excretion of salicylates depends on urinary pH. When the
urine pH increases to 8 from 5, the renal clearance of salicylate increases 10-20 times.
Hypokalemia and dehydration limit the effectiveness of urine alkalization. Adequate
serum K+ is essential for successful urinary alkalinization. Symptomatic patients
typically have low or low-normal serum k+. Treatment with NaHCO3 alone may produce
further intracellular shift of K ions, which impairs the ability to excrete alkaline urine.
Repletion of potassium is often necessary even when the serum potassium is in the low
normal range. Urinary alkalization should be continued at least until serum salicylate
levels decline into therapeutic range (<30 mg/dL). Acetazolamide forms bicarbonate-
rich alkaline urine, but it leads to metabolic acidosis that can worsen the toxicity.
2- Haemodialysis: Indicated in salicylate levels >90-100 mg/dL after acute overdose or
>40-50 mg/dL in chronic toxicity, severe fluid or electrolyte disturbances, or inability to
eliminate the salicylate. Hemoperfusion has a slightly higher clearance, but dialysis is
recommended because of its ability to correct for fluid and electrolyte disturbance.
Peritoneal dialysis is only 10-25% as efficient as hemoperfusion or hemodialysis.
D- Supportive treatment
 Correction of hypoglycemia in severe cases
 Correction of dehydration and electrolyte disturbances

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University of Benghazi-Libya
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 Vitamin K1 may be needed

Postmortem Appearance
• Hemorrhagic gastritis
• Subpleural and subpericardial hemorrhages
• Pulmonary and cerebral edema
• Comgestion of viscera

ACETAMINOPHEN TOXICITY

Paracetamol is a widely used analgesic in adults and the most commonly used drug in
pediatrics. The chemical structure of acetaminophen is N-acetyl-p-aminophenol
(APAP). It has an excellent safety profile in therapeutic doses, but hepatotoxicity can
develop with overdoses. Maximum daily dose of acetaminophen is 4 g in adults & 90
mg/kg in children. A single ingestion of 7.5 g (adult) or more than 150 mg/kg in a child is
potentially toxic.
Pathophysiology
Acetaminophen is rapidly absorbed in therapeutic doses, with peak levels in 1-2 hours
and 2-4 hours in the overdose setting. Therapeutic levels range from 10-20 μg/mL.
Metabolism is primarily hepatic; the half-life is 2-4 hours. Acetaminophen is nontoxic,
but hepatic metabolism leads to formation of a toxic metabolite, N-acetyl-
benzoquinoneimine (NABQI). The liver metabolizes more than 90% of acetaminophen
to glucuronide and sulfate conjugates, which are eliminated in the urine. In children,
sulfation is the primary pathway until age 10-12 years; glucuronidation predominates in
adolescents and adults. Hepatotoxicity is the result of formation of the reactive and toxic
metabolite NABQI by the cytochrome P-450. Glutathione can bind NABQI and lead to
excretion of nontoxic mercapturate conjugates. As glutathione stores are diminished,
NABQI is not detoxified and covalently binds to the lipid bilayer of hepatocytes causing
centrilobular necrosis. Glutathione must be replaced by sulfhydryl compounds from the
diet or medication such as NAC. Glutathione stores are affected by age, diet, liver
disease, and medical conditions such as fasting, gastroenteritis, chronic alcoholism, or
HIV disease. Inducers of cytochrome P-450 2E1 such as ethanol, rifampin, phenytoin,
barbiturates, and carbamazepine can lead to increased production of NABQI.
Clinical Manifestations:
Phase 1 (up to 24 hours). Patients typically experience anorexia, nausea, and vomiting.
Some patients may have no initial symptoms, but they have the potential to develop
significant clinical toxicity. The presence of neurologic, respiratory, and cardiac
symptoms is rare in this phase.
Phase 2 (24-48 hours) right upper quadrant pain that coincides with transaminase
elevation.
Phase 3 (3-4 days) patients have symptoms of hepatic failure with jaundice, bleeding,
or encephalopathy. Only about 3.5% of patients who develop hepatotoxicity eventually
develop fulminant hepatic failure. Death may occur due to cerebral edema or sepsis.
Phase 4: occurs after 4-14 days, patients may have complete recovery of liver function
or death.

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University of Benghazi-Libya
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Investigations:
1- Acetaminophen serum concentration: indicated in
A. A history of potentially toxic ingestion
B. An unknown amount of APAP
C. Altered mental status
D. Active suicidal intent.
2- Liver function tests: Hepatotoxicity was defined by elevation of the plasma
transaminase above 1,000 U/L. Typically, transaminase starts to rise within 24 hours
postingestion and peaks at 48-72 hours postingestion.
Treatment
1- Gastric lavage: should be done to patients with recent (within 1h) and life-
threatening toxicity.
2- Activated charcoal adsorbs APAP, but its use has been controversial since oral
NAC also is adsorbed by AC.
3- Antidote is N-Acetyl Cysteine.

DIGITALIS TOXICITY
Digitalis is a purified cardiac glycoside derived from the plant Digitalis lanata & D.
purpurea. They are used in the treatment of heart failure and supraventricular
arrhythmias.
Pathophysiology:
1- They bind to a site on the cell membrane, producing reversible inhibition of Na-K
ATPase pump, which causes increased intracellular Na + & decreased intracellular K.
Elevated intracellular Na concentrations increases intracellular Ca concentrations,
which results in enhanced cardiac contractions that are delayed after depolarizations
and manifest clinically as after contractions, such as premature ventricular contractions.
2- Digitalis increase reduces conduction velocity with increased automaticity and
ectopic activity. Improved inotropy is obtained through an increased concentration of
cytosolic Ca ions during systole. It also has a negative chronotropic action that is partly
a vagal effect and partly a direct effect on the sinoatrial node.
3- Digitalis also has vagotonic effects, resulting in bradycardia and heart blocks.
4- Inhibition of Na-K-ATPase in skeletal muscle results in hyperkalemia.

Clinical Manifestations
The principal manifestations are vomiting and irregular pulse.
1- Cardiovascular Manifestations: Sinus bradycardia and 1st. or 2nd.-degree
atrioventricular blocks are more common in pediatric populations. Ventricular ectopy is
more common in adults. Nonparoxysmal atrial tachycardia with block and bidirectional
ventricular tachycardia are characteristic of severe toxicity. If automaticity is increased
and conduction is depressed, we must think about digitalis toxicity.
2- CNS Manifestation: Lethargy or drowsiness, or confusion. Headaches.
Hallucinations.
3- Visual changes: aberrations of color vision (chromatopsia) and yellow halos around
lights (xanthopsia), transient amblyopia or scotomata, and decreased visual acuity.
Usually observed with chronic toxicity.
4- Gastrointestinal Manifestations: nausea, vomiting, diarrhea, abdominal pain

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Treatment
1- General supportive care including correction of fluids and electrolytes.
2- Digoxin-specific antibodies are effective for severe acute digitalis toxicity & indicated
in:
 Life-threatening arrhythmias (severe bradycardia, 2 nd/3rd.-degree HB, VT
/fibrillation)
 Initial potassium level >5 mEq/l
 Digoxin serum levels >10 ng/mL at 6-8 h post ingestion
 Ingestion >10 mg in healthy adults or >4 mg in children.
3- Decontamination: AC is the preferred method. Multiple charcoal doses may be
beneficial. Induced emesis is not recommended because of increased vagal effect.
Gastric lavage may be useful early but also can increase vagal effects. Whole bowel
irrigation may be useful, but clinical data are lacking. Cholestyramine can interrupt
enterohepatic circulation especially in patients with renal insufficiency.
4- Dysrhythmia control: Fab fragment is considered first line treatment for dysrhythmias.
 Phenytoin is the drug of choice for digoxin-induced arrhythmia. It is effective
against SV ectopics as well as ventricular arrhythmias. Lidocaine is alternative
but is not effective against SV arrhythmias.
 Quinidine and procainamide are not used as they intensify the AV block.
 IV calcium is contraindicated absolutely due to increased intracellular Ca in
digoxin-toxic patients.

IRON TOXICITY

Iron poisoning is one of the most common poisoning emergencies in young children.
The potential severity of iron poisoning is based on the amount of elemental iron
ingested, which can be calculated on the basis of the number of tablets ingested and
the percentage of elemental iron in the salt. Iron exerts both local and systemic effects.
Iron is corrosive to the GI mucosa and affects the lungs and liver. Excess free iron is a
mitochondrial toxin leading to disturbances in energy metabolism. Serum iron levels are
useful in predicting clinical course of the patient.
Pathophysiology
Toxicity is manifested as local and systemic effects. Systemic effects are mainly due to
metabolic acidosis.
Clinical Manifestations
Typically, iron poisoning has been described in 4 sequential phases.
Phase I: GIT effects: occurs during the first 6hrs as hemorrhagic vomiting, diarrhea,
and abdominal pain. it results from local corrosive effects of iron on the GI mucosa.
Phase 2: usually occurring after 6-12 hrs, may be associated with a period of "apparent
recovery" that may be confusing. In mild cases, the recovery may represent true
recovery. In serious ingestions, this phase may not occur at all. This phase may
represent the time of iron distribution throughout the body to cause systemic injury.
Phase 3: begins after 12-24 hrs when ferrous iron is converted to ferric iron and an

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unbuffered H+ ion is liberated. Iron is concentrated in mitochondria and disturbs

oxidative phosphorylation, resulting in lipid peroxidation and production of free radicals,
which increases metabolic acidosis and cell death. Systemic toxicity includes GIT fluid
losses that may lead to hypovolemic shock and acidosis. Cardiovascular symptoms
include decreased heart rate, myocardial activity, and cardiac output, and increased
pulmonary vascular resistance. Phase 3 is associated with a high anion-gap metabolic
acidosis, which results from: (1) the rise of H + during conversion of free plasma iron to
ferric hydroxide, (2) free radical damage to mitochondrial membranes with the
subsequent development of lactic acidosis, (3) hypovolemia and hypoperfusion.
Coagulopathy is observed and may be due to inhibitory effect of free iron on the
formation of thrombin and to reduced levels of clotting due to hepatic failure.
Phase 4: occurs after 2-6 weeks: scarring of the GI tract causing pyloric obstruction or
hepatic cirrhosis.
Investigations
 Serum iron levels.
 Abdominal x-ray: may show radiopaque tablets.
 Deferoxamine challenge test: single dose of deferoxamine will bind free iron to be
excreted in the urine as ferrioxamine complex, changing the urine to reddish (vin rosé)
color, indicating the need for chelation.
Treatment
1- Appropriate supportive care.
2- Deferoxamine is the iron-chelating agent, it excretes iron-deferoxamine complex in
the urine. It does not bind iron in hemoglobin, myoglobin, or other iron carrying proteins.

BARBITURATE TOXICITY
Barbiturates are commonly used drugs. Majority of barbiturate poisonings in adults are
suicidal attempts. In children, the poisoning is usually accidental. Barbiturate abuse is a
common problem and the commonly abused barbiturates include Phenobarbital,
Amobarbital, Secobarbital, and Butabarbital.
They are rapidly absorbed from GIT. They remain largely unionized in acidic contents
as well as in small intestine, where their maximal absorption occurs. Highest
concentration occurs in adipose tissue, followed by brain, liver, and kidney. They cross
the placenta and can be excreted in breast milk. The distribution of barbiturates
depends on lipid solubility, protein binding, and the pKa (extent of ionization). Short-
and intermediate-acting barbiturates are more lipid-soluble than the long-acting
barbiturates, so, they cross more readily cell membranes, and possess high affinity for
tissue and plasma proteins. Lipid solubility also enhances metabolic degradation by
enhancing drug binding to hepatic enzymes. Short-acting barbiturates are more widely
distributed in body tissues and have a very rapid onset of action but exhibit a shorter
duration of action. Long acting barbiturates have a delayed onset but longer duration of
action. The degree of ionization is important for membrane permeability; the nonionized
drug is more membrane permeable. Phenobarb ionization increases and permeability
decreases in alkaline medium.
Barbiturates are metabolized primarily by hepatic enzymes to inactive metabolites,
except. mephobarbital, and methabarbital, which are converted to phenobarbital and
barbital. Urinary excretion of short- and intermediate-acting barbiturates is negligible,

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because even the filtered minimal amount is almost completely reabsorbed in the renal
tubule. Long-acting barbiturates are more dependent on renal excretion.
Barbiturates are general depressants of nerve and muscle tissues, their major site of
action is the synapse. In the CNS, they act on GABA (γ-amino butyric acid) receptors.
Peripherally, they inhibit the excitatory response of acetylcholine at the NM junctions
and the autonomic neuroeffector junctions. Barbiturates influence all levels of the CNS,
reticular formation, brainstem, cerebellum, and cerebral cortex are the most sensitive.
Clinical Presentation
Acute Intoxication:
Grade I: Mild Intoxication
1) The patient is drowsy. Impaired judgment, slurred speech, incoordination, ataxia.
2) Reflex activity and vital signs are not affected.
3) This condition resembles alcohol intoxication without flushed face, and no smell.
Grade II: Moderate Intoxication
1. Depression of consciousness level. Superficial and deep reflexes are depressed.
2. Pupils may be normal, or small and reactive. Severe hypoxia may produce
mydriasis.
3. Respiration is slow but not shallow.
Grade III. Severe Intoxication
1) There is severe impairment of consciousness level.
2) Respiratory depression.
3) Pulmonary edema.
4) Hypotension.
5) Shock.
6) Hypothermia is a frequent finding.
7) Paralytic ileus.
8) Renal failure (hypotension, anoxia, hypothermia, direct toxicity on renal tubules.)
9) Barbiturate blisters: helpful in the diagnosis of comatose patient. The lesions are
clear vesicles and bullae on an erythematous base, located over skin areas at other
pressure sites. They occur in about 5% of cases of acute barbiturate intoxication, and
50% of patients dying from this toxicity.
Management
1- Stabilization of vital functions
2- Prevention of absorption: activated charcoal and gastric lavage with respect to the
level of consciousness.
3- Enhancing elimination:
a) Forced alkaline diuresis. Effective for long-acting barbiturates.
b) Hemodialysis: long-acting & some intermediate-acting barbiturates are dialyzed.

TRICYCLIC ANTIDEPRESSANT TOXICITY

Tricyclic antidepressants (TCA) are well absorbed from the GIT, rapidly distributed, and
quickly bound to body tissue. In overdose, they are absorbed slowly because they are
ionized in the acid stomach and they slow the peristalsis dramatically; the drug may
remain in the stomach for 12 hours or more. Gastric dilatation had been reported. They
act through removing the effects of cathecolamine and serotonin deficiencies, which are

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thought to play a significant role in the pathogenesis of depressive disorders.

Clinical Manifestations
The symptoms and signs of TCA toxicity depend on the amount of the received dose. At
the beginning there will be anticholinergic signs. If the dose is more CNS signs will
appear, and at more severe poisonings the cardiac toxicity signs will be clearer.
1. Anticholinergic effects: tachycardia, hypertension, fever mydriasis. Dry red skin,
dry mouth. Decreased bowel sounds. Urinary retention. Respiratory depression.
2. CNS effects: Disorientation. Agitation. Hallucinations. Pyramidal signs: clonus,
positive Babinski sign, hyperreflexia. Myoclonic jerks. Seizures. Coma.
3. Effects on cardiac conduction and contractility: Hypotension. Bradychardia. AV
block. Cardiac arrest. ECG typical change is prolongation of QRS
Management
The mainstays of treatment in TCA overdose are prevention of absorbtion of the drug
and good respiratory support. Once absorbed, the drug is highly tissue bound with a
very large volume distribution. Thus, even efficient methods of removal, such as
hemoperfusion, will not help too much.
1- Any patient with H/O of TCA ingestion must be placed immediately on cardiac
monitor.
2- Stomach emptying: Putting charcoal down the lavage tube before lavage may
further limit the amount of drug absorbed. AC effectively binds TCA and can decrease
plasma levels. Late gastric lavage should be performed.
3- Ventilatory support and careful monitoring of acid-base status is important, because
many of cardiovascular complications are pH dependent and increase by acidosis.
4- ECG should be obtained to detect changes as tachycardia and QRS prolongation.
5- Hemoperfusion with AC helps to remove the drug from the bloodstream.
Treatment of Specific Complications
1- Coma in about 35% of admitted cases; it needs supportive care. Physostigmine is
sometimes recommended to awaken patients from coma. It is a nonspecific analeptic,
and causes generalized CNS arousal. It has the potential of seizure induction.
2- Seizures and Myoclonic Jerks are seen in 10% of TCA overdoses, they may trigger
dysrhythmias. Seizures had been treated with diazepam. Phenytoin can be used to
treat the seizures and conduction problems but not myoclonic jerks. If given rapidly, it
causes bradycardia. Alkalinization in any patient who is in seizure to minimize CV
toxicity.
3- Cardiovascular Toxicity: Sinus tachycardia is universal in TCA overdose. There is
no reason to treat it unless patient is hypotensive or complicated by HF. Alkalinization of
the blood to a pH of 7.5 is probably the best treatment available for cardiotoxicity.
4- Conduction Blocks: it is dose dependent, and QRS prolongation becomes greater
with more doses. RBBB is also common. QT interval may be prolonged. Alkalinization is
the first choice treatment, and QRS will narrow and conduction improves with this
therapy.
5- Hypotension is present in 14% of patients, usually accompanied by ventricular
blocks and cardiac dysrhythmias. Alkalinization and IV fluid loading are effective.

LITHIUM TOXICITY

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Lithium is commonly used in the treatment of depressive and bipolar affective disorders.
Lithium intoxication may occur because of its narrow therapeutic index. Poisoning may
be intentional or unintentional or may occur as a result of certain factors that elevate its
serum evels. Lithium toxicity can be classified into:

 Acute poisoning: voluntary or accidental ingestion in a previously untreated patient

 Acute-on-chronic: voluntary or accidental ingestion in a patient currently using
lithium
 Chronic poisoning: progressive lithium toxicity in a patient on lithium therapy
Pathophysiology
The CNS is the major organ system affected, although the renal, gastrointestinal,
endocrine, and CVS also may be involved. Lithium is available only for oral
administration. It is almost completely absorbed from the GI tract. Peak levels occur 2-4
hours after ingestion, although absorption can be much slower in massive overdose or
with ingestion of sustained-release preparations. Lithium has low protein binding and
has good volume of distribution. Lithium clearance is predominantly through the
kidneys.
Clinical Manifestations
1- Mild-to-moderate toxicity: Generalized weakness - Fine resting tremor - Mild
confusion
2- Moderate-to-severe toxicity: Severe tremor - Muscle fasciculations –
Choreoathetosis – Hyperreflexia – Clonus – Opisthotonos – Stupor – Seizures –
Coma - Signs of cardiovascular collapse.
Investigations
 Serum lithium concentration if any degree of toxicity is suspected; suspicion of
toxicity should be high in any patient with known lithium use because early toxic
symptoms are very vague and nonspecific.
 Consider toxicology screens in intentional overdoses. Co-ingestions are common in
cases of intentional lithium overdose.
 Lithium toxicity is one of the few clinical entities that may be associated with low
anion gap.
 BUN and creatinine measurements are important for determining the patient's ability
to excrete lithium.
 Electrocardiogram
 Chronic lithium toxicity is frequently associated with depressed ST segments
and T wave inversion.
 Lithium intoxication may result in dysrhythmias, including complete heart block.
Treatment
 Assess airway and breathing and control the airway with endotracheal
intubation, as needed. Initiate volume resuscitation in volume-depleted patients.
 Gastric decontamination
1. Gastric lavage. Activated charcoal does not bind lithium effectively.
2. Consider whole bowel irrigation in ingestions of sustained-release preparations.
 Enhanced elimination .
o Hemodialysis has been the mainstay of therapy in severe toxicity.

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HEAVY METALS
Introduction:
- Over 40 substances are classified as metals; all have local & systemic actions.
- They were used in the past as medicinal (mercurial diuretics, sugar of lead for bruises,
arsenical compounds for worms….).
- Toxicity occurs by any route, the most important is industrial inhalation of fumes, but
ingestion & dermal absorption occur.

General characters of heavy metals

1. Human exposure to heavy metals may occur through ingestion, inhalation or dermal
exposure
2. Toxicity from heavy metals is either acute or chronic
3. Metals have metallic taste if ingested except arsenic which is known to be tasteless
4. They can cause both local and systemic effects.
5. they are general protoplasmic toxins taking the sulphydral (-SH) group of tissue
enzymes, with some organ selectivity e.g:.
a. - .
b. - .
c. - .
d. - .
e. - .
f. - .
g. -These symptoms appear after some latent period during which absorption
takes place.
6. Most metals cause diarrhea except lead which causes constipation.
7. Cumulation: they have cumulative effect: (accumulate in the body tissues).
8. The antidotes are called Chelators

I- LEAD TOXICITY
Lead is the most common metallic poison. It occurs in organic and inorganic forms. Its
toxic effects on humans are well documented in history. Absorption of ingested lead in
children is much more than in adults; about 50% of the ingested dose is absorbed in
children while only 10% in adults.
Lead poisoning is probably the most important chronic environmental illness affecting
children. In children, probably no organ system is immune to the effects of lead
poisoning. Developing brain is the most risky organ to be affected.
Methods of Exposure
1- Occupational: lead workers, glassmakers, and scrap metal workers. Parents
employed in any of these occupations may bring lead dust on their persons or clothing
into the home.
2- Some cosmetics and folk remedies contain lead pigments or salts.

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3- Water & Food contamination: drinking water from lead pipes or storage tanks, and
eating contaminated food grown near factories may lead to poisoning.
4- Foreign body ingestion: several reports have documented cases of childhood lead
poisoning resulting from the ingestion of lead-based foreign bodies. Lead dissolves
reasonably quickly in acid solutions such as in the stomach; thus, significant amounts of
lead may be absorbed.
5- Retained bullet: lead poisoning may develop from absorption of lead of a retained
bullet. Incidental X-ray finding must prompt consideration of possible elevated lead
levels.
6- Illegally manufactured alcohols: home-made alcohol ingestion may cause lead
poisoning.
7- Inhalation of lead from motor vehicle exhaust when leaded gasoline is used.

Pathophysiology
Lead disturbs multiple enzyme systems. As in most heavy metals, any ligand with
sulfhydryl (-SH) groups is a target. Perhaps the best-known effect is that on the
production of heme.
A-Hematological Effects
Lead-induced anemia: hypochromic microcytic anemia occurs more in children in
comparison with adults. The mechanisms included to cause anemia are:
1- Inhibition of heme synthesis as follows:
a) Lead inhibits conversion of δ aminolevulinic acid (DALA) to porphobilinogen.
b) Lead inhibits conversion of coproporphyrinogen III to protoporphyrin.
DALA and coproporphyrin accumulate in urine and are used as toxicity markers.
c) Lead blocks incorporation of iron into protoporphyrin to form heme. Protoporphyrin
accumulates in RBCs and chelate zinc. Erythrocyte protoporphyrin (EP) reflects chronic
lead exposure.
2- Increase of RBC fragility: Lead interferes with Na-K ATPase pump and attacks RBC
membrane causing increased fragility and decreased RBC survival. Bone marrow
responses by reticulocytosis.
3- Erythropoietin deficiency: This results from the toxic effects of lead on renal tubules.
4- Inhibition of 5-pyrimidine nucleotidase: this decreases the ability to rid off RNA
degradation products followed by aggregation of ribosomes, appearing as
basophilic stippling of RBCs.
B- Renal Effects
1. Acute toxicity may cause renal colic.
2. Acute toxicity may cause direct tubular damage (Fanconi-like syndrome,
especially in children).
3. Lead alters rennin-angiotensin system and may cause hypertension.
4. Lead alters uric acid excretion resulting in hyperuricemia and gout.
C- Nervous Effects

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1- Lead has direct effect on CNS causing lead encephalopathy especially in children.
2- DALA is thought to be neurotoxic by interfering with GABA.
3- Chronic lead exposure affects peripheral motor nerves leading to wrist and foot
drops.
D- Reproductive System Effects
1- Lead crosses placenta and may cause abortion, and stillbirth.
2- Lead may cause decreased sperm count, and increased number of abnormal
sperms.
E- Bone Effects
1- Lead triggers hypermineralization, which is reflected in metaphyseal and growth plate
densities, the classic lead lines are observed on radiographs. They reflect bone growth
arrest and not deposition. Their width is related to the duration of exposure.
2- Lead inhibits the conversion of vitamin D into its active form.
Clinical Manifestations
Acute Toxicity
Uncommon and results from exposure to big lead amount or more commonly on top of
chronic exposure.
1- GIT: anorexia, abdominal pain, constipation, vomiting.
2- CNS: lead encephalopathy, behavioral changes, lethargy, fatigue, seizures, and
coma.
Chronic Toxicity (PLUMBISM)
1. Nonspecific: vague body aches, anorexia, constipation and abdominal colic.
2. Blue lines on the gums and around anal margins and are caused by bacterial
action on blood lead at these sites precipitating lead sulfide.
3. Neuropathy: presenting as wrist drop and foot drop. Optic neuropathy may
occur.
4. CNS: cognitive disturbances, headache and encephalopathy
5. Anemia, reticulocytosis and hemolysis.
6. Renal impairment.
7. Bony aches and gouty arthritis.
8. Myocarditis

Investigations
1- Blood Levels of Lead & Erythrocyte Protoporphyrin: Blood levels more than 30 µg/dl
is abnormal. Erythrocyte protoporphyrin (EP) level more than 50 µg/dl is abnorma
3- Urinary DALA can be used as screening test for those exposed to lead.

Treatment

General management: ABC management.

Treatment of encephalopathy by dehydrating measures e.g. mannitol 20%
Treatment of colic by calcium gluconate

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University of Benghazi-Libya
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Specific management: chelators.

Antidotal therapy:
1- British anti-lewisite ( BAL; dimercaprol 2,3 dimercaptopropranolol):
- It gives 2-SH groups for metal  chelator-metal complex which is excreted in urine.
While SH groups of tissues are spared.
- It is chelator of choice in renal compromise.
- Contraindications: liver failure, G6PD deficiency and concurrent use of BAL and iron
(high toxic complex).
- Side effects: - Anorexia, vomiting. - Hyperthermia
- Convulsion. - Rhinorhea, lacrimations.
- Tingling of hands. - Peripheral sterile abscess.
- Dose: 10% oily solution, 2.5mg/kg/dose/4-6h for 2 days then every 12h for 7 days by
deep 1M injection.
2- Cal Na2 EDTA (calcium disodium ethylene diamine tetracetic acid):
- It should not be given without calcium for fear of hypocalcaemia.
- It unites with the metal which takes place of calcium in EDTA.
- Both Ca Na2 EDTA and BAL should be given concurrently, as EDTA mobilizes lead
from the storage sites to the blood, while BAL combine with lead in blood to be excreted
in urine.
- Side effects:
• Hydrobic degeneration of the kidney due to large amount of chelated metal.
• Hypokalemia.
• Hypotension.
• Thrombophelibitis.
• Febrile reaction, dermatitis, anemia.
- Dose: 1 gm in 250 ml saline by IV infusion /12 hours for 5 days.
N.B. In the past, it was thought that BAL-ETDA is toxic in the management of lead
toxicity but it is proved to be non toxic.
3- Penicillamine:
- It is hydrolytic degradation of penicillin.
- It is less effective than BAL & Ca Na 2 EDTA.
- Side effects:
• Hypersensitivity.
• prolonged therapy complications (nausea, vomiting, loss of taste for salts, sweat and
systemic lupus erythromatoses like syndrome)
- Dose: it is given orally 50mg/kg/12h on empty stomach.

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University of Benghazi-Libya
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II- MERCURY TOXICITY

Mercury is the only metal that is liquid at room temperature. Its elemental symbol is Hg,
which is derived from the Greek word hydrargyrias “water silver.” Mercury is found in
many forms but all are toxic:
1- Organic forms: found in long (insecticides) and short (food contaminants) alkyl and
aryl compounds.
2- Inorganic forms. The inorganic form can be further divided into:
a. Elemental mercury (thermometers, barometers, dental
amalgam).
b. Mercuric salts: the most toxic.
Methods of Exposure
1- Elemental mercury: barometers, batteries, calibration instruments, dental
amalgams, electroplating, fingerprinting products, fluorescent and mercury lamps,
infrared detectors, jewelry industry, manometers, neon lamps, paints, photography,
silver and gold production, and thermometers.
2- Inorganic mercury: antisyphilitic agents, acetaldehyde production, chemical
laboratory work, cosmetics, disinfectants, explosives, ink manufacturing, mercury vapor
lamps, mirror silvering, perfume industry, photography, spermicidal jellies, tattooing
inks, and wood preservation.
3- Organic mercury: antiseptics, bactericidals, fungicides, insecticidal products,
laundry products, diaper products, paper manufacturing, seed preservation, and wood
preservatives.
Pharmacokinetics
1- Elemental mercury: found as liquid & easily vaporizes at room temperature. It is well
absorbed (80%) through inhalation but poorly absorbed from GIT. Its lipid-soluble
property allows easy passage through alveoli into bloodstream and red blood cells.
Once inhaled, it is mostly converted to an inorganic divalent (mercuric) form by catalase
in RBC. This inorganic form has similar properties to inorganic Hg (poor lipid solubility,
limited permeability to BBB, and excretion in feces). Small amounts of elemental Hg
continue to persist and account for CNS toxicity.
2- Inorganic mercury: found mostly in the mercuric salt form (eg, batteries). It is highly
toxic and corrosive. It gains access to the body orally (10% rate of absorption) or
dermally. Its poor lipid solubility causes kidney accumulation, causing renal damage.
Although poor lipid solubility characteristics limit CNS penetration, slow elimination and
chronic exposure allow for significant CNS accumulation of mercuric ions and
subsequent toxicity. Excretion of inorganic mercury, as with organic mercury, is mostly
through feces. Renal excretion of mercury is insufficient and leads to chronic exposure
and accumulation within brain, causing CNS effects.
3- Organic mercury can be absorbed more completely from the GI tract than inorganic
salts are. After absorption, the aryl and long chain alkyl compounds are converted to
their inorganic forms.
Pathophysiology
1- Mercury has a high affinity for SH groups, which attributes to its effect on enzyme
dysfunction. Choline acetyl transferase is one of inhibited enzymes, which is involved in
acetylcholine production. This inhibition may lead to ACh deficiency, contributing to the
signs and symptoms of motor dysfunction.

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2- An immune mechanism is attributed to membranous glomerulonephritis and

acrodynia.
Clinical Manifestations
The clinical presentation of mercury toxicity can manifest in a variety of ways,
depending on the nature of the exposure, the intensity of the exposure, and the
chemical form.
1- Acute inhalation elemental mercury: can lead to pulmonary symptoms. Initial signs
and symptoms, such as fever, chills, shortness of breath, metallic taste, and pleuritic
chest pain, may be confused with metal fume fever. Other possible symptoms could
include stomatitis, lethargy, confusion, and vomiting. Recovery is usually without
sequela, but pulmonary complications of inhaled toxicity may include interstitial
emphysema, pneumatocele, pneumothorax, pneumomediastinum, and interstitial
fibrosis. Fatal ARDS has been reported following elemental mercury inhalation.
2- Acute ingestion of inorganic mercury & mercuric salts: Inorganic mercury or
mercuric salt exposure mainly occurs through the oral and GI tract. Its corrosive
properties account for most of the acute signs and symptoms of inorganic mercury or
mercuric salt toxicity. The presentation can include
a) Ashen-gray mucous membranes secondary to precipitation of mercuric salts.
b) Vomiting, severe abdominal pain, hematemesis, and hypovolemic shock.
c) Systemic effects usually begin several hours postingestion and may last several
days. These effects include metallic taste, stomatitis, gingival irritation, foul breath,
loosening of teeth, and renal tubular necrosis leading to oliguria or anuria.
3- Acute ingestion of organic mercury (Methyl mercury): Organic mercury poisoning
usually results from ingestion of contaminated food. The long chain and aryl forms of
organic mercury have similar characteristics of inorganic mercury toxicity. The onset of
symptoms usually is delayed (days to weeks) after exposure. Symptoms related to
toxicity are typically neurological, such as visual disturbance (eg, scotomata, visual field
constriction), ataxia, paresthesias (early signs), hearing loss, dysarthria, mental
deterioration, muscle tremor, movement disorders, and, with severe exposure,
paralysis, and death. Organic mercury targets specific sites in the brain, including the
cerebral cortex (especially visual cortex), motor and sensory centers (precentral and
postcentral cortex), auditory center (temporal cortex), and cerebellum.
4- Chronic toxicity: The classic triad found in chronic toxicity is tremors, gingivitis, and
erethism.
A) Elemental Mercury: chronic exposure causes cutaneous and neurological symptoms.
Chronic exposure usually results from prolonged occupational exposure to elemental
Hg that is converted into the inorganic form, topical application of mercurial salves, and
the chronic use of diuretics or cathartics.
B) Inorganic Mercury: chronic exposure may occur directly or after release of mercuric
salts due to oxidation of elemental or organic mercury. It results in:
1- GIT: metallic taste, burning sensation in the mouth, gingivostomatitis, hypersalivation.
2- Neurologic Manifestations: Neurasthenia & Erethism.
 Neurasthenia: fatigue, depression, hypersensitivity to stimuli, and loss of
concentration.
 Erethism: insomnia, shyness, memory loss, emotional instability, depression,
anorexia, vasomotor disturbance, uncontrolled perspiration.

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3- Renal failure.
4- Acrodynia (Pink disease): it is considered to be a mercury allergy, presents with
erythema of the palms and soles, edema of the hands and feet, desquamating rash,
hair loss, pruritus, diaphoresis, tachycardia, hypertension, photophobia, irritability,
anorexia, insomnia, poor muscle tone, and constipation or diarrhea.
5- All forms of mercury are toxic to the fetus, but methylmercury most readily passes
through the placenta. Even with an asymptomatic patient, maternal exposure can lead
to spontaneous abortion or retardation.
Investigations
Blood mercury levels are usually less than 2 µg/dL in unexposed individuals
(exceptions may be individuals with a high dietary intake of fish). Blood Hg levels are
helpful for recent exposures and for determining if the toxicity is secondary to organic or
inorganic mercury, but not as useful guide to therapy. Hair has high sulfhydryl content.
Mercury forms covalent bonds with sulfur and, therefore, can be found in abundance in
hair samples. However, the rate of false-positive results is high with hair analysis
secondary to environmental exposure.
Treatment
1- ABCs, especially when managing the inhalation of elemental mercury and the
ingestion of caustic inorganic mercury, both of which may cause the onset of airway
obstruction and failure.
2- Removal of contaminated clothing and copious irrigation of skin.
3- Do not induce emesis if the compound ingested is caustic inorganic form.
4- Gastric lavage for organic ingestion, especially if the compound is observed on the
abdominal x-ray.
5- Use chelating agents if the patient is symptomatic, if systemic absorption is
anticipated, or if increased blood or urine levels are present.
a) Dimercaprol (BAL): not with methyl mercury.
b) Penicillamine
c) Succimer [DMSA (2,3-dimercaptosuccinic acid)] is used in inorganic and organic
mercurials.
d) CaNa2EDTA is contraindicated. It makes with Hg a nephrotoxic complex.
6- Hemodialysis is used in severe cases of toxicity when renal function has declined.

III- ARSENIC TOXICITY

Arsenic is a heavy metal with a name derived from the Greek word arsenikon, meaning
potent. Arsenic is found in air, water, fuels, and marine life. The daily human intake of
arsenic contained in food ranges from 0.5-1 mg, with the greatest concentrations
coming from fish. Arsenic was considered the perfect poison because it is odorless,
tasteless, and resembles sugar.
Pathophysiology:
Arsenic exists in:
1- Metalloid: inorganic arsenite (trivalent), and organic arsenate (pentavalent) valences
2- Arsine gas.
The inorganic (trivalent) compound is absorbed more readily than the organic
(pentavalent) forms because of its high lipid solubility. Absorption occurs mainly through
the GIT. It binds to hemoglobin, plasma proteins, and leukocytes and is redistributed to

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the liver, kidney, lung, spleen, and intestines. Over a period of weeks, deposits may be
found in skin, hair, nails, bone, muscle, and nervous tissue.
Arsenic produces cellular damage through a variety of mechanisms:
1- Arsenic binds to enzyme SH groups and forms a stable ring, which deactivates the
enzyme.
2- Massive transudation of fluid into the bowel lumen, mucosal vesicle formation, and
tissue sloughing may result in large gastrointestinal fluid losses.
3- Arsenic blocks the conversion of pyruvate to acetyl coenzyme A and inhibits
gluconeogenesis.
4- In some forms, arsenic is caustic, exerting a direct toxic effect on blood vessels and
large organs.
5- Long-term exposure results in nerve damage and may lead to lung, skin, or liver
cancer.
6- Once inhaled, arsine gas combines with hemoglobin severe hemolysis and anemia.
Cinical Manifestations
Acute Toxicity
1- GIT: nausea, vomiting, abdominal pain, and profuse watery or bloody diarrhea.
Patients may complain of a metallic taste in their mouth and have a garlic odor on their
breath.
2- CVS: myocardial depression, prolonged QT interval, hypotension, shock.
3- Renal: acute tubular necrosis.
4- Liver: central hepatic necrosis.
5- CNS: encephalopathy, delirium.
6- Blood: anemia due to hemolysis and GIT hemorrhage.
7- Other effects: rhabdomyolysis, fever, acute myopathy.
Chronic Toxicity
1- Peripheral Neuropathy: it affects sensory part more than the motor one. Patients with
chronic arsenic exposure often present with the complaint of painful paresthesias.
2- Black Foot Disease: it is a peripheral vascular disease due to peripheral vascular
obliteration appearing with acrocyanisis, Raynaud’s phenomenon.
3- Dermatologic Effects: alopecia, hypo- or hyperpigmentation, palmoplantar keratosis.
Mee’s lines: transverse white lines in the nails appear several weeks after mercury
exposure.
Investigations:
1- CBC, 2- Urea & electrolytes 3- Serum arsenic levels
4- Urinalysis: for hemoglobinuria and proteinuria. pH should be > 7.5 to treat
rhabdomyolysis.
1. Arsenic excretion, 24-hour urine test: This test is believed to be the most reliable
indicator of toxicity. This test is used to test for chronic toxicity only after the patient
has abstained from consuming seafood for at least 7 days.
5- Arsenic levels in hair, nails, and other tissue, if necessary
1- Abdominal radiograph: radiopaque on x-ray and may appear as bariumlike
opacities.
2- ECG may show prolonged QT interval and T-wave changes.

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Treatment

Chelation therapy is the definitive treatment for arsenic poisoning. Chelation may be of
greatest benefit to patients exposed to high levels of arsenic over short periods or to
patients with chronic poisoning who recently were exposed to high levels that were
superimposed on their chronic toxicity.
Chelating agents are:
1- Dimercaprol 2- Succimer (DMSA) 3- Dimerval (DMPS) 4- D-penicillamine

TOXIC GASES AND BLOOD POISONS

TOXIC GASES
Introduction:
- These are chemical toxins that are present in the gaseous form at room
temperature and normal atmospheric pressure.
- High risk of these gases is due to:
1- Most of these gases are colorless and odorless.
2- The major route of administration is via inhalation, which is difficult to control.
3- They are widely used in many industrial and household products.
4- Most of these gases are elaborated naturally.
5- Most of these agents are highly toxic at very low concentrations.
6- Most of cases are present late in the course of toxicity.
7- Lack of principal information about the methods of detoxification particularly
among the personnel of the medical field.
8- Some of them are used as war gases.
Classification: according to mechanism of action:
1- Chemical asphyxiants (blood gases):
- They result in histotoxic anoxia due to affection of blood proteins.
- Best examples of this group are CO, Cyanide gas & Hydrogen sulfide.
2- Simple asphyxiants (Inert gases):
- They result in anoxic anoxia due to in simple substitution of air.
- The best examples of this group are CO2, methane, and butane.
3- Irritant gases (Vesicants):
- Produce their effects via local corrosive effect on skin & mucous membranes that
come in contact with, especially mucosa of respiratory passages.
- Best examples of this group of gases are: Chlorine, phosphine & ammonia.
4- Nerve gases:
-  respiratory failure.
- The best examples of this group are Sarin, soman and tabon.

Both carbon monoxide and cyanide exert their toxicity through their toxic effect on blood
(blood poisons) and by causing asphyxia (asphyxiant poisons).

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CARBON MONOXIDE

Carbon monoxide is a colorless odorless non irritating gas. Its density (0.968 relative to
air), allows it to disperse homogeneously within a room as it is released.

Sources:

1. Endogenous:

 Normally the body produces small amount of CO during catabolism of

protoporphyrin ring of Hb. Carboxyhemoglobin (COHb) normally dose not exceed 4-
6%.
2. Exogenous:

 Incomplete combustion of carbonaceous materials.

 The major source is automobile exhaust.
 At home, oil and gas heaters, kerosene heaters, charcoal grills all emit CO.
 Industrial: pulp mills, steel foundries.
 Tobacco cigarette smoking.
 Fires.
Factors Affecting CO Toxicity:

1- Physical factors: CO is tasteless, odorless, colorless and non-irritating so not

noticed.
2- Duration of exposure.
3- Concentration of the gas in the inspired air.
4- Muscular activity of the person.
5- Decreased PO2 as in high altitude.
6- Individuals with cardiovascular or pulmonary diseases tolerate CO intoxication
poorly.
7- Lowered Hb% as in anemia.
8- Neonates and fetus are more vulnerable to CO toxicity because fetal Hb has
increased affinity to CO. In addition, fetal elimination of CO is much slower than that of
the mother. Also there is a natural leftward shift of the oxyhemoglobin dissociation curve
which causes decreased O2 delivered to tissues.
Pathophysiology of CO

 Hypoxia: due to high affinity of Hb to CO which is greater than that of O2, and to the
leftward shift of oxyHb dissociation curve i.e, decrease O2 release from Hb to
tissues.
 Myoglobin impairment: myoglobin functions as short O2 reservoir, and facilitates O2
transport from blood stream to mitochondria. Myoglobin affinity to CO is 40 times
greater than that to O2. In the heart, carboxymyoglobin causes direct myocardial
depression and arrhythmias.
 Mitochondrial impairment: CO interferes with cellular respiration at the mitochondrial
level: Blockade of cytochrome C oxidase.

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 Brain reperfusion injury: CO causes brain lipid peroxidation and leukocyte mediated
inflammatory changes in the brain with delayed neurologic sequelae.
Clinical Manifestations

(A) CNS: is most sensitive to CO poisoning

1- Acutely, headache, dizziness and ataxia.

2- With longer exposure, syncope, seizures and coma may occur.

3- Recurrent symptoms syndrome: Occur in 10-20% of patients with moderate CO

toxicity:

 Patient may have lucid interval of 1-40 days followed by recurrence of symptoms
as headache dizziness, irritability, confusion, disorientation, and memory
problems.
 Delayed neuropsychiatric sequelae: It is a severe form of secondary deterioration
characterized by appearance of overt signs of neurologic or psychiatric
impairment .
 Children may show behavioral changes and learning difficulties after severe
poisoning.
 Other neuropsychiatric problems include depression, emotional liability,
hallucinations, personality changes, verbal aggressiveness.
(B) Cardiovascular System:

1- Palpitation and chest pain.

2- Patchy myocardial infarction with ECG changes of ischemia.

3- Tachycardia is common. Bradycardia occurs in severe cases due to cardiac or CNS

hypoxia.

4- Atrial and ventricular arrhythmias.

5- Hypotension.

C. Other Systems:

1. Dermal:

 Cherry red skin is rarely seen clinically (a sign of non survivors), pallor or cyanosis
are more frequent.
 Blisters resembling 2nd degree burn may be seen in severe CO poisoning. These
bullae are thought to be due to pressure necrosis and direct effects of CO on the
epidermis.
2. Eye:

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 Blurring of vision, decreased dark adaptation

 In severe cases frank blindness due to effect of CO on CNS.
 Retina: Bright red retinal veins is an early sensitive sign.
 Other findings include: Congested tortuous retinal veins, disk edema, flame shaped
hemorrhages.
3. Respiratory: Noncardiogenic pulmonary edema due to fluid shift through alveolar-
epithelial junction caused by direct effect of CO on the capillaries. There may be
cardiogenic pulmonary edema due to myocardial depression.

4. Renal: Oliguric and non oliguric renal failure.

5. Blood: - Disseminated intravascular coagulation (DIC). Thrombocytopenic purpura.

6. Metabolic: - Lactic acidosis, hyperglycemia and hypercalcaemia.

7. Muscles: Rhabdomyolysis.

8. GIT: Nausea, vomiting, abdominal pain and may be diarrhea so may be

misdiagnosed as gastroenteritis or food poisoning specially in children or in a group of
patients.

Investigations

1. Carboxy hemoglobin (COHB) level; the most helpful diagnostic test:

 COHb level is 0-5% in normal individuals.

 Smokers may have COHb levels up to 10%.
 No difference between arterial and venous COHb.
 Measured by cooximeter which spectrophotometrically measures the percentage of
total hemoglobin saturated with CO.
2. Arterial blood gases:

 PO2 may be normal

 Pulse oximeter shows falsely elevated O2 saturation and cannot be relied on.
 Metabolic acidosis if present is usually due to lactic acidosis which is a bad
prognostic sign.
Management

1- Rapid removal from continued exposure and maintain airway patency.

3- 100% O2 should be provided immediately either by non rebreather mask or ET tube.

100% O2 shortens CO t 1/2 and increases O2 delivered to tissue in physical solution.

4- Cardiac monitoring and IV access are necessary with rapid treatment of any
arrhythmias.

5- Do not aggressively treat acidosis with pH above 7.15 as this can increase tissue

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hypoxia by left shift of oxyhemoglobin dissociation curve.

6- Hyperbaric oxygen (HBO): Oxygen at 2-3 times atmospheric pressure. It is the

treatment of choice in significant CO exposure. HBO decreases half life (t½) of CO to
20 min.

Postmortem Appearance

1. Cherry red appearance, especially in the areas of postmortem lividity. In dark

people the color can be made out in lips, nail beds, tongue, palms and soles.
2. Skin blisters are seen sometimes in calves, buttocks, wrists, and knees.
3. Cherry pink color of blood and tissues
4. Pulmonary edema
5. In delayed deaths; necrosis and cavitation of basal ganglia, especially globus
pallidus

CYANIDE TOXICITY

Cyanide is a rare source of poisoning but it is one of the most rapidly acting lethal
poisons.

Sources

1. Plants: cherry green unripe guava, seeds of bitter almond. These contain amygdalin
which is converted into cyanide in the small intestine by bacteria.
2. Fires: cyanide exposure occurs frequently in patients with smoke inhalation from fires.
3. Industrial: metal refining, mining, electroplating, jewelry manufacture, and x-ray film
recovery.
4. Cyanides may be used as suicidal agents, particularly among health care workers.
5. Iatrogenic: from nitroprusside administration.
Pathophysiology

Cyanide reversibly binds to a number of proteins and enzymes with a metallic

component. It has a special affinity for iron in its ferric state and is capable of binding to
all enzymes and proteins containing iron, including hemoglobin, myoglobin, catalase,
and the cytochrome system. Its most significant interaction is its binding to the ferric iron
of the mitochondrial cytochrome oxidase system. The most sensitive organ systems to
cyanide toxicity are CNS and the myocardium.

Pharmacokinetics

Hydrogen cyanide is a colorless gas with a faint, bitter almond-like odor. Sodium
cyanide and potassium cyanide are both white solids with a bitter, almondlike odor in
damp air. Rapidly absorbed from skin and mucous membranes, after ingestion it is
transferred into HCN through the action of hydrochloric acid in the stomach. Cyanide is

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metabolized by rhodanese (sulfurtransferase), which catalyzes its combination with

sulfur to form thiocyanate, a much less toxic compound that is readily excreted in the
urine. Hydrogen cyanide also may be converted to a nontoxic compound by its
combination with hydroxocobalamin (vit B-12a), which produces cyanocobalamin
(vitamin B-12).

Clinical Manifestations

Cyanide should be considered in the differential diagnosis of sudden death and sudden
global neurologic deficit (i.e. coma, convulsions and encephalopathy, severe acidosis
and shock). Clinical features of acute cyanide toxicity may include:

1- Weakness, asthenia, loss of energy, and pain throughout the body.

2- CNS: headache, dizziness, weakness, confusion, and nausea and vomiting. These
are followed by confusion, agitation, convulsions, paralysis, and coma.

3- Cardiac: Chest pain may be due to myocardial ischemia or pulmonary disease.

Palpitations due to tachyarrhythmias, dizziness due to tachyarrhythmias, and
bradyarrhythmias have been reported.

4- Respiratory: The patient may complain of shortness of breath, cough, and difficulty
breathing.

5- GI: Nausea and vomiting may be due to stimulation of the CNS vomiting center and
to the direct irritant effects of cyanide compounds on the GI tract.

6- Skin & Fundoscopy: cherry red appearance due to increased Hb saturation in venous
blood because of inability to utilize O2. Funduscopy shows same color.

Treatment

1. Supportive therapy is extremely important.

2. Decontamination by removal of the patient from the source, removal of all clothes,
and rapid irrigation of the body with copious amounts. This will protect also the health
workers that must be protected from contamination with the cyanide-laced vomitus.
3. Antidote therapy
Methemoglobin dependent antidote:

Cyanide antidote kit consists of: Amyl nitrite, sodium nitrite, sodium thiosulfate. Cyanide
antidote consists of:

Phase I: attempts to induce methemoglobinemia so that cyanide, which has a high

affinity for the ferric iron (Fe3+) moiety, may attach to it to form cyanomethemoglobin,
rather than the ferric iron of the cytochrome, thus restoring or allowing cellular
respiration to continue. This is can be achieved by using amyl nitrite (inhalation) &

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sodium nitrite (infusion). MtHb levels must be monitored because the antidote relies on
the induction of methemoglobinemia. Sodium nitrite infusion should be stopped if
patient develops cyanosis or Methemoglobin levels exceed 30%

Phase II: involves the detoxification of the newly formed cyanomethemoglobin

compound so that it may be excreted. This is the role of sodium thiosulfate. The infusion
of sodium nitrite is generally followed by the infusion of sodium thiosulfate. The
presence of thiosulfate in the blood allows rhodanese to detoxify the
cyanomethemoglobin by catalyzing the formation of thiocyanate, which is nontoxic and
rapidly excreted in the urine. Rhodanese catalyzes the combination of cyanide moiety of
cyanomethemoglobin with the thiosulfate group provided intravenously.

Mixed Cyanide & CO Toxicity

Patients who have high levels of carboxyHb may not tolerate any further reduction of
their circulating oxyhemoglobin. The induction of methemoglobin in these patients may
be dangerous and may lead to further tissue hypoxia. The infusion of sodium nitrite in
these patients should be performed with extreme caution and should probably be
preceded by HBO therapy. If there is no HBO sodium thiosulfate should be used alone
and gives good effects.

Postmortem appearance

• External
▫ Odor of bitter almonds
▫ Brick red color of skin and mucous membranes
▫ Cyanosis of extremeties
▫ Froth at mouth and nostrils
• Internal
▫ Hemorrhagic gastritis. Stomach wall may be hardened
▫ Pulmonary and cerebral edema
▫ Disseminated petechiae in brain, meninges, pleura, lungs, and
pericardium.

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TOXICITY OF ALKALOIDS

Alkaloids are group of nitrogenous basic compounds of vegetable origin with wide
difference in properties and constitution. In addition to their toxicological interest, they
have medical uses.

Alkaloids are not true alkalies (they do not turn litmus paper blue), but they form salts
with acids. They can be found in one or more parts of the plant (leaves, fruits, seeds, or
whole plant), and they are, generally, non-soluble in water but can be extracted by
organic solvents in alkaline media.

The most important alkaloids of toxicological interest are: opium, atropine, cocaine,
strychnine, nicotine, aconite, ergot, digitalis, cannabis, cathin, and myraticin.

OPIATES

Opiates are a group of narcotic analgesics that represent one of the most important
groups of CNS depressants. All members of opiates have similar pharmacological
actions of natural opiates.

Classification:

1- Natural 2- Semisynthetic 3- Synthetic

1- Natural Opium Alkaloids

There are about 25 alkaloids that are present naturally in opium. Opium is the juice
taken from the unripe capsule of poppy plant fruit (Papever somniferum). Poppy plant is
present mainly in Asia and South America, but can be cultivated anywhere either in hot
or cold countries. The unripe green poppy capsules are scratched at early night and left
to collect opium at early morning. Fresh opium is plastic, moist, smooth, reddish-brown,
with characteristic odor, then becomes hard, brittle, and dark-brown. Dry-ripe poppy
capsules contain a trace of opium. Opium is used for sedative, antitussive, and
constipating effects. Opium alkaloids are combined with meconic acid, and divided into
2 groups:

A- Hypnotic (depressant) alkaloids: morphine (10%); codeine (0.5%); narceine

(0.2%).
B- Convulsant (stimulant) alkaloids: papaverine (1%); narcotine (6%); thebaine (0.3%).

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2- Semisynthetic Opium Derivatives:

Semi-synthetic derivatives of opium are chemically and pharmacologically related to

opium, such as:

a) Heroin: diacetylmorphine (addictive drug).

b) Dionin: ethylmorphine hydrochloride (for corneal ulcer).
c) Apomorphine: central emetic agent.
d) Dilaudid: dihydroxymorphine (potent analgesic with short duration).
e) Metopan: methyldilaudid (potent analgesic with short duration).
3- Synthetic Opiates:

A group of chemically synthesized drugs, which are remote in chemical structure from
that of opium but have similar pharmacologic effect, such as:

a) Pethidine: potent analgesic usually used as postoperative analgesic and for

labor pain.
b) Methadone: potent analgesic usually used to antagonize withdrawal
manifestations during treatment of heroin and morphine dependence.
Pharmacokinetics of opiates:

 Well absorbed from GIT, nasal mucosa, pulmonary mucosa, subcutaneous and
intramuscular routes.
 Widely distributed into liver, kidneys, lungs, spleen, brain, placenta, and intestinal
mucosa.
 Biotransformation occurs mainly in liver by conjugation with glucuronic acid,
hydrolysis, & oxidation.
 Excretion mainly by kidneys, where more than 50% are excreted within 8 hours,
about 40% up to 24 hours, and traces are still detectable in urine after 48 hours by
classic methods of detection and for longer periods by sophisticated techniques. Small
percentage is excreted in bile, saliva, sweat, & milk.
Pharmacodynamics of opiates:

Opiate Receptors: Mode of action of opiates is still unclear completely but they act on
specific receptors. Opioid receptors are concentrated in the periaqueductal gray matter
of the brainstem, medial thalamus, solitary nucleus, amygdala, substantia gelatinosa of
the spinal cord, area postrema of the chemoreceptor trigger zone, and vagal nerve
fibers. These areas are involved with either pain transmission or perception. The
receptors are classified as mu (μ), kappa (ĸ), and delta (δ). The mu receptor has 2
types (μ1 & μ2). The kappa receptor has 3 types (K 1, K2, K3). The delta receptor has 2
types (δ1, δ2). All receptors subtypes are capable of modulating pain perception. mu1,
kappa3, and delta2 are located in the brain, while mu2, kappa1, and delta1 are located
in the spinal cord. Opioids react with the three receptors as antagonists, agonists, or
partial agonists.

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Table: Pharmacologic effects of opiod receptors

Pharmacologic Effect Receptor

Supraspinal analgesia, Prolactin release μ1

Spinal analgesia, Respiratory depression, Bradycardia, Pruritis, Decreases GIT motility, CV μ2

effects, Physical dependence, Euphoria

Spinal analgesia, Sedation, Miosis, hunger, Dysphoria, Psycotomimetic, Diuresis (ADH ĸ1

inhibition)

Supraspinal analgesia, Sedation, Miosis, Dysphoria, Psychomimetic, Diuresis (ADH ĸ3

inhibition)

Spinal analgesia, Modulation of mu receptors Δ

Most opiates are agonists for mu and kappa receptors.

 Opiate agonist – antagonist: a group of synthetic drugs, which have both agonist
and antagonist effects i.e. they oppose the effect of opiates when they are given
simultaneously, but when given alone they produce similar effects. They are agonists at
kappa3 and kappa1 pain receptors. They may precipitate withdrawal by their antagonist
effects on mu1 and mu2 and possibly delta receptors. Examples: Pentazocine
(Sosegone, Talwin, Fortwin). Buprenorphine (Norphine). Nalbuphine (Nubain). These
drugs are used widely as potent analgesics.
 Pure opiate antagonist:These drugs reverse the toxic and pharmacologic effects
of opiates by blocking all opiate receptors. They are used in the treatment of opiate
toxicity, and can give milder effects in acute ethanol toxicity. It is given as a routine
emergency treatment in cases of coma of unknown origin particularly those associated
with respiratory depression. Examples: Naloxone (Narcan); Naltroxone.
Action of Opiates

 Morphine & Heroin: They act on different areas of CNS as stimulators or inhibitors:
Inhibit Stimulate

1- Sensory cortex (analgesia). 1- Pupillo-constrictor center (pin-point

2- Medullary respiratory center (respiratory pupil).
depression). 2- Vagal center (slow full pulse &
3- Cough center (suppression of cough). hypotension).
3- Medullary CTZ (vomiting).
 Codeine: mainly suppress cough center and produce weak euphoria.
 Papaverine: mainly as spasmolytic and could be used as local vasodilator.
 Thebaine & Narcotine: have strychnine-like effect producing convulsions.
Acute Toxicity:

 Mainly accidental overdose among addicts or may be iatrogenic.

 May be suicidal.

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 Rarely homicidal.
 Hot-shoot phenomenon.
The triad of opiate intoxication is: pin-point pupil, respiratory depression, and coma.
Classical clinical picture is:

1- Initially, there is a relief of distress and pain, and euphoria that may be followed by
dysphoria.
2- Gradual drowsiness passing into sleep. Large doses may produce coma rapidly.
3- Slow sterterous respiration & slow full regular bounding pulse and hypotension.
4- Pin-point pupil affecting both eyes, which are sluggish and fixed.
5- Nausea and vomiting.
6- Subnormal temperature or even hypothermia.
7- Decreased all body secretions except sweating leading to moist cold skin (cold
sweat).
8- Cyanosis.
9- Rhabdomyolysis: elevated CPK.
10- Cardiac conduction defects including LBBB, wide QRS.
11- Noncardiogenic pulmonary edema, particularly with heroin, and codeine.
12- Terminally, irregular respiration (Chyne-stoke respiration), cyanosis deepens,
dilated pupils, and death from central asphyxia. Death may be due to cardiac arrest
secondary to cardiac arrhythmias.
Codeine: causes hypeirritability and convulsions. Cerebral hypoxia lowers seizure
threshold.

Treatment of Acute Opiate Toxicity

1- ABC management for vital function stabilization.

2- Antidote: Naloxone IV in doses 0.2-4 mg, then observe for positive response
(changes in respiratory rate & level of consciousness, and size of pupils).
3- Convulsions can be controlled by IV diazepam.
4- Gastric lavage and AC if opium is ingested.

HEROIN (Diacetyl Morphine)

It was synthesized from morphine in 1874, but become popular after the discovery of
Mexican heroin (black tea) in 1970, which is much more potent and cheaper than the
first one. Heroin can be taken well absorbed by any route; this is because of its high
lipid solubility. Heroin distributes to all tissues and converted to morphine by hepatic
enzymes and it is eliminated by kidneys as morphine in free and conjugated forms.

Clinical Manifestations

Heroin abuser can be presented with any of the following:

1- Acute overdose.

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2- Withdrawal syndrome: heroin is the most addictive drug with highest dependence
potential among all available abuse agents.
3- Medical complications of drug abuse.
Clinical presentation of acute heroin toxicity is, generally, the same of that of morphine
but more seriously and mainly in a picture of acute respiratory distress and non-
cardiogenic pulmonary edema. Pulmonary edema may be due to hypoxia, which leads
to pulmonary vasoconstriction and increased pulmonary capillary pressure with leakage
of fluids into interstitium and alveoli. The patient may have wheezing, rales, ronchi, and
pink frothy secretions. IV crude heroin may lead to sever muscle injury with increased
CPK, hyperkalemia, pulmonary edema, renal failure. It may cause also cold pulseless
extremities, and acute cardiomyopathy. Sometimes, addict may try self-treatment of
acute overdose by IV injection of milk, which may lead to pulmonary edema and fat
embolism.

COCAINE

Cocaine is present in the leaves of Erythroxylon coca, which grows in South America. It
represents about 1% of coca leaves. Cocaine is a powerful CNS stimulant and
sympathomimetic agent with local anesthetic effect but chemically related to atropine.
Its medical use is local anesthetic (paralysis of nerve endings & local vasoconstriction).

Its abuse is to its stimulant effect, it also reduces fatigability and increases mental
ability, libido, alertness, sociability.

Clinical Picture

 Acute Cocaine Toxicity

Excessive central & systemic neural stimulation

1- Autonomic & Neuromuscular Effects: tachycardia, hypertension, hyperthermia,

tachypnea, nausea, vomiting, mydriasis, seizures.
2- CNS Effects: behavioral and psychiatric disorders such as irritability, hyperactivity,
insomnia, agitation, psychosis (often paranoid), delirium, stupor, coma. CVA either
ischemic or hemorrhagic.
3- Arrhythmias: sympathetic stimulation of the heart may lead to tachyarrhythmias,
myocardial ischemia, myocarditis, impaired cardiac conduction (local anesthetic effect).
4- Organ Ischemia: it may produce myocardial, renal, and/or intestinal infarction limb
ischemia.
5- Shock: hypotension and shock may occur due to:
 Depletion of noradrenaline.
 Vasodilatory effect on brainstem.
 Myocardial ischemia and resultant decreased cardiac output.
 Local anesthetic effect (vasodilatation & depressed cardiac contractility).

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 Hyperthermia and hypovolemia due tp agitation.

6- Pulmonary Effects: the reported effects include pneumomediastineum,
pneumothorax, pulmonary edema (cardiogenic), adult respiratory distress syndrome
(ARDS).
7- Other Effects: rhabdomyolysis, coagulopathy.
Cocaine Body-Packer Syndrome

A person who takes cocaine-containing packets orally, rectally, or vaginally, is prone to develop cocaine
intoxication due to rupture of the packets. This condition is known as cocaine body-packer syndrome.
Cocaine packets can be classified into 3 types:

Type 1: condoms, toy balloons, or fingers of latex gloves, well-defined in abdominal plain X-ray. It is the
most liable type to rupture.

Type 2: light yellow multi-layered (5-7 layers) latex bundles contain powdered cocaine and appear in
plain x-ray.

Type 3: yellow hardened cocaine paste in aluminum foil with multilayered (3–5) latex cover. It does not
appear in x-ray.

If a case is suspected, do plain X-ray. If a case is confirmed, either:

 Observe & give laxatives.

 Surgical interference: presence of signs of toxicity, passage of ruptured bag, or intestinal
obstruction.
Management

There is no specific antidote, but treatment is emergency and supportive with the goal
to control:

1- Hypertension: sedation, nitroprusside infusion, IV labetolol (propranolol should be

avoided as the reversal β2-mediated vasodilatation may result in unopposed α-
mediated vasoconstriction).
2- Cardiac arrhythmias: selective β blockers as labetolol.
3- Seizures: IV diazepam, general anesthesia.
4- Hyperthermia: external cooling, neuromuscular paralysis.
5- Agitation & Psychosis: restrain, IV diazepam, IM haloperidol.
6- Myocardial Ischemia & Infarction: nitroglycerine & calcium channel blockers.
7- Correct acidosis, which improves cardiac functions.
8- Prevention of further absorption if ingested.

CANNABIS

(HASHISH; HASH OIL; BANGO; MARIJUANA)

Most widely abused substance. Most active ingredient over 61 cannabinoid compounds
is delta-tetrahydrocannabinol (δ-THC).

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Source: flowering-tops of the female hump plant Cannabis sativum & C. indica.

Cannabis is received by : Smoking (main route),Ingestion, Parentrally (unusual).

Pharmacology:

 After absorption, THC is rapidly metabolized in the lungs and liver. Absorption rate
is 10-15% after inhalation and 3-6% after ingestion.
 THC is highly lipophilic, so it deposits in fatty tissue.
 Peak blood level is reached after few minutes by inhalation but declines rapidly,
while after ingestion PBL is reached after 2 hours and declines slowly.
 Metabolites of carboxylic acid can be detected in blood for several days after
consumption using radio-immunoassay (RIA) but urine is the more reliable sample for
detection.
 The only therapeutic use of THC is as antiemetic in cases chemotherapy.
Poisoning occurs accidentally, with undetermined fatal dose, and the fatal period is few
hours.

Action of THC: THC is a hallucinatory agent with mixed stimulatory and depressive CNS
effects.

Acute effects:

1- Psychological & Neurological: affects behavior, cognition, perception, and

performance. These effects are dose-dependent:
 Euphoric, talkative, joking and pleased with himself, may have fear of death and
dysphoria.
 Accentuation of auditory perception.
 Hyperphagia, especially to sweets.
 A dreamy semiconscious state may be associated with aphrodisiac and other types of
hallucinations.
 Disorientation in time and place.
 Nervous disorders such as dilated reactive pupils (with conjunctival injection), ataxia,
tinnitus, Hyperreflexia, Hypothermia.
With large doses, the effect varies from mild anxiety to paranoid behavior to acute
psychosis with impaired complex motor functions.

2- Cardiovascular: tachycardia with blood pressure changes and increase in

myocardial O2 demand (may be due to autonomic NS stimulation).
3- Respiratory: chronic bronchitis, rhinitis, pharyngitis, horsiness of voice (due to
smoking).
Clinical Manifestations

 Extremely rare.
 Mostly due to accidental ingestion of huge dose in empty stomach, especially in
children leads to toxic metabolites by the effect of gastric hydrolysis.

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 Mental confusion followed by deep sleep, coma and death due to:
o Central asphyxia & respiratory failure.
o Rarely, over distension of stomach from eating.
Chronic Effects of THC:

1- Chronic pulmonary diseases and cancer.

2- Hormonal & reproductive disorders:
Male: Temporary decrease in testosterone. Semen abnormalities (decrease in count &
motility, increase of abnormal forms) decrease the fertrility.

Female (transient effect): Decrease of GTH with subsequent decrease of pituitary and
ovarian hormones.

Pregnancy (chronic abuse): Abruptio placenta. Premature labor. Low birth weight.

3- Immunological problems: THC appears to suppress interferon.

4- Neuropsychological effects: acute brain syndrome, cloud mentality,
disorientation, short memory impairment.
5- Tolerance & Dependence: psychological dependence with withdrawal
manifestations including irritability, restlessness, sleep disturbances, and diarrhea.
Treatment

 Marked phobia (IV diazepam).

 Symptomatic treatment of acute cases.
 Chronic cases are treated with sudden withdrawal with psychiatric support.

ANTICHOLINERGICS

Classification:

1- Natural Alkaloids:

A) Atropine (Atropa belladonna).

B) Hyoscyamine (Hyoscyamus muticus).

C) Hyoscine (Datura fastiusa & D. stramonium).

Substances are present in all parts of the plants.

2- Parmacological Preparations:

a) Tricyclic antidepressants (imipramine).

b) Antipsychotics (phenothiazines, haloperidol)

c) Antihistaminics (chlorephenhydramine).

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d) Antiparkinsonism (benzotropine).

e) Antispasmodics (propantheline).

f) Ophthalmic solutions (cyclopentolate).

Clinical Manifestations of Anticholinergic Syndrome:

Peripheral (muscarinic Central

parasympatholytic)

1- Vasodilatation & flushing of skin. 1- Agitation and/or restlessness, Anxiety.

2- Decreased secretions 2- Twitching or jerky movements.
3- Decreased GIT motility. 3- Hypereflexia, ataxia, and muscle
4- Fixed dilated pupils (blurred vision). incoordination.
5- Tachycardia. 4- Seizures
6- Hypertension. 5- Purposeless movements.
7- Hyperthermia. 6- Hallucinations.
8- Urinary retention. 7- Staggering gate.
8- Coma; respiratory & circulatory center
depression.

Hyoscine differs from atropine and hyoscyamine in that it has:

Depressant effect from the start.

 Milder peripheral action

Circumstances of acute toxicity

 Mainly accidental especially in children and drug abusers. Can be suicidal.

 Can be used with sweets to facilitate ropary.
 Fatal dose: Atropine & Hyoscyamine: 120 mg (100 datura seeds). Hyosine: 60 mg.
Management of anticholinergic syndrome

 ABC management & prevention of absorption (see principles of management).

 Arrhythmias: phenytoin, lidocaine. Better to avoid:
o Propranolol; may cause complete heart block.
o Digoxine; may cause tachycardia, ventricular irritability.
o Quinindine & procaineamide; increase electric disturbance.
STRYCHNINE

It is the main alkaloid found in the seeds of Strychnos Nux vomica. The seeds are hard,
flat biconcave discoid in shape, 1-2 cm in diameter, brownish-gray and covered with
hair (velvet appearance). The toxicity is mainly accidental.

Pharmacology

 Absorption through GIT & nasal mucosa.

 After absorption, about half of the dose is distributed in all tissues in about 5 min.

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 Metabolized in the liver.

 5-20% of the dose excreted unchanged with urine within 24 hrs.
 Action: causes stimulation of the spinal cord, brainstem, & thalamus by competitive
inhibition of postsynaptic glycine receptors (an inhibitory neurotransmitter in the spinal
cord).
Clinical Manifestations

1. Onset of symptoms after 15-30 minutes.

2. Starting as restlessness, increased visual & auditory acuity, nausea,
vomiting, and muscle twitching, then sudden onset of generalized, extremely
painful tonic fits while patient is fully conscious.
3. Strychnine fits are characterized by:
 Sudden onset.
 Generalized tonic convulsions.
 Last 0.5-2 min with 10-15 min intervals of complete relaxation between fits.
 Retraction of the jaw gives peculiar complexion called rhesus sardonicus (devil's
laugh).
 Body takes extensor position called opisthotonus.
 During fits there may be apnea, bulging of eyeballs, cyanosis, bloody froth,
dilated pupils, bradycardia, hypertension, hyperthermia, lactic acidosis, and
rhabdomyolysis.
 Patient cannot tolerate frequent fits; they die from exhaustion or asphyxia.
TOXIDROME: Symmetrical generalized fits + Epithotonus + Rhisus saedonicus + Full
consciousness

Differential Diagnoses

1- Tetanus. 2- Head injury. 3- Meningitis. 4- Epilepsy. 5- Hysteria.

Differential points between strychnine & tetanus poisoning:

Tetanus Strychnine

Wound Taking food with bitter taste History

Gradual Sudden Onset

Start at lower jaw; Tonic contraction Generalized fits; Relaxation Clinical

with fixation of chest in between features

Delayed (24hr) Rapid (2hr) Death

Bacterial isolation Chemical detection Diagnosis

Management

 Control of convulsions & Dark quite room.

 Antidote: Mephenisine (20-30 mg IV); suxamethonium 0.06-0.1 mg/kg IV.
 Treatment of complications.

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CORROSIVES’ TOXICITY

Corrosives (caustics) are substances which have local, rapid and destructive action on
any tissues which come in contact with. Although the generation of heat often
contributes to the damage, these are not classic hyperthermic burns. Caustics have no
remote action except organic acids.

Classification:

Other Corrosives Alkalies Acids

a) Salts: Hg Chloride, Antimony NaOH a) Inorganic: sulfuric, hydrochloric,

trichloride. nitric.
KOH
b) Hydrogen peroxide. b) Organic: oxalic, carbolic, acetic
Ammonia
c) Potassium permanganate.

Factors Affecting the Severity of the Injury:

1. Amount ingested: The more the amount the more is the severity of the injury.

2. pH: Alkalis with pH greater than 11.5-12 & acids with pH less than 2 cause serious
injuries.

3. Concentration: concentrated caustics are more destructive.

4. Form of the agent: ingestion of solid pellets of alkaline substances result in impaction
in normal anatomical sites of narrowing with prolonged contact and may cause
perforation.

5. Contact time.

Childhood ingestions: Approximately 80% of caustic ingestions occur in children

younger than 5 years. Serious solid ingestion is rare because children generally do not
swallow the burning particles. Liquid ingestions however can be quite serious.

Adult ingestion: Most intentional ingestions occur in adults. Adult exposures have more
morbidity than childhood exposures because of significant volume and possibility of
coingestion of other harmful agents. Occupational exposures are often more severe
because industrial products are concentrated.

Sources:

• Common acid containing sources:

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- Toilet bowel cleaners.

- Rust removing products.

- Metal and cement cleaning products.

• Common alkaline containing sources:

- Drain cleaning products.

- Oven cleaning products.

- Swimming pool sanitizers.

- Automatic dishwasher detergent.

- Bleaches.

- Hair relaxes.

- Clini- test tablets.

Pathophysiology:

A. Alkaline Ingestion:

Alkalis cause liquefactive necrosis and saponification of fats resulting in deep tissue
destruction. Further injury is caused by thrombosis of the blood vessels. Alkalis most
severely affect the squamous epithelium of the esophagus but the stomach is also
involved in about 20% of cases.

Ingestion of liquid alkalis usually result in multiple long strictures, while ingestion of solid
alkalis frequently leads to short dense strictures, often localized at the level of the carina
or the aortic arch, an anatomically narrow part of the esophagus where impaction of
solids occurs.

Immediately after alkali ingestion, tissue edema occurs and may persist for 48 hours.
Granulation tissue replaces the necrotic tissue. Over the next 2-4 weeks, scar tissue
thickens and contracts to form strictures.

The incidence of stricture formation depends on the depth of burn. Superficial burns
result in strictures in less than 1% of cases while full thickness burns result in strictures
in nearly 100% of cases. Severe burns also may cause esophageal perforation.

B. Acid Ingestion:

Acid ingestions cause tissue injury by coagulation necrosis with formation of coagulum
or eschar. The stomach is the most commonly involved organ in acid ingestion. The

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esophagus is affected in 6-20% of cases of acid ingestion. In initial phase of the injury
the eschar may limit further penetration and control the extent of the injury. However,
delayed sloughing of large surface areas may lead to bleeding and frank perforation.

Clinical Manifestations

1. Pharyngeal pain is the most common presenting symptom. Dysphagia. Drooling of

saliva and may be vomiting.Pain in the chest or abdomen usually reflects more severe
tissue damage. Shock may be the presenting symptom in severe cases.

2- Erythema, edema, erosions may be apparent in the oropharynx, lips, tongue and
mouth cavity. They are the most common findings on physical examination however,
significant esophageal involvement may occur in absence of oropharyngeal lesions.

3- Respiratory distress may be caused by aspiration and mediastinitis as well as acute

upper airway obstruction. Glottic and subglottic edema are rare and manifest as stridor
and dyspnea.

4- Hypotension, tachycardia and changes in mental status signify shock.

5- Sepsis may develop shortly after presentation.

Complications of Caustic Ingestion:

Acute Complications:

1. Upper airway obstruction. 2. GIT hemorrhage. 3. Perforation.

Chronic or Late Complications:

1. Esophageal obstruction secondary to stricture formation.

2. Malnutrition, dehydration and cachexia.

3. Increased risk of esophageal carcinoma which occurs in 1-4% of serious caustic

ingestions.

4. Scarring, Infection and Poor Healing may occur with Dermal Burns.

Management:

ABCDE

Dermal exposure: irrigation with tap water after removal of contaminated clothes.

Eye exposure: Copious irrigation with water.

Ingested caustic: Do not induce emesis or attempt to neutralize the substance. Dilution

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with water or milk if there are no signs of perforation or airway involvement.

Corticosteroids may inhibit collagen formation in wound healing, effective to decrease
strictures if started at 24-48 hrs.

ORGANIC ACIDS

I- CARBOLIC ACID (PHENOL)

Pure carbolic acid is a colorless crystals with specific odor, and it is soluble in alcohol.
The commercial forms: Dettol cresol lysol and phenol detergent. Both forms are
absorbed after ingestion and skin contact. Toxicity may occur as:

1. Suicidal: cheap, has local anesthetic effect and rapidly fatal.

2. Accidental: ingestion in children or absorption through the skin.

Clinical Manifestations

It is a general protoplasmic poison, it has dual action:

1. Local action:

a) Mild corrosive with anaesthetic effect on sensory nerve endings.

b) Coagulative necrosis of the superficial layer of the tissue proteins. However,

detachment of these layers may lead to hemorrhage and stricture on healing.

c) May cause skin gangrene if applied for long period.

d) After ingestion there is hot burning pain extending from mouth to stomach but rapidly
disappears due to local anaesthetic effect so there is no vomiting.

2. Remote action:

a. CNS stimulation followed by depression: Headache, convulsion, drowsiness,

confusion, coma. Constricted pupil.

b. Respiratory depression with slow breathing cyanosis and central respiratory failure.

c. Heart: myocardial depression with weak rapid or irregular pulse.

d. Kidney: acute glomerulonephritis with oliguria, albuminuria, casts, anuria and renal
failure. Urine turns dark green on exposure to air due to oxidation of the excreted
products of phenol

Causes of Death.

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1. Immediate (within hours) due to central respiratory depression.

2. Delayed (within days) renal failure.

Management:

1. Care of respiration and coma if present.

2. Gastric lavage may be done in early presentation.

II- OXALIC ACID POISONING

It is in the form of white crystals easily soluble in water and alcohol. It is used as
bleacher and metal cleaner in industry and houses.

Toxicity could be:

1. Accidental: Commonest form especially in children.

2. Suicidal; very rare.

Pathophysiology

1. Local mild corrosive effect.

2. Remote decalcification: it combines with blood ionized calcium forming calcium

oxalate resulting in cardiac arrhythmias, tetany, convulsions, blocking of renal tubules
with calcium oxalates.

Clinical Manifestations

I. Local Corrosive: hot burning pain in the mouth, esophagus and stomach together
with repeated vomiting.

II. Remote Hypocalcemia: tingling and numbness, muscle twitches in the face and
extremities with carpopedal spasm, convulsions, arrhythmias or cardiac arrest. Dysuria
oxaluria, hematuria, oliguria and anuria.

Chronic Exposure: skin contact lead to local erosion which may lead to cyanosis and
gangrene.

Management:

Gastric lavage. Calcium should be given rapidly by every route 10% Ca gluconate
slowly IV or orally.

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VOLATILE POISONS

ETHANOL TOXICITY
Alcohols can be prepared by fermentation of carbohydrates e.g. beer from grains, wine
from grapes or apples. Modern types of alcohol such as rum, gin, whisky, and brandy
contain ethyl alcohol in different percentages. Clinically, ethanol is used as an
ingredient of many elixirs, surgical spirits, antiseptic preparations, and mouthwashes.
The illegally manufactured whiskey is called moonshine, poteen, etc. The illegal types
are dangerous because of the possibility of adding other compounds to increase its
intoxicating effect. These compounds may be antifreeze (ethylene glycol), methyl
alcohol, etc. This has resulted in many complications such as hepatotoxicity, blindness,
and death. Ethyl alcohol is a colorless, volatile liquid, with a characteristic aromatic
odor.

Absorption

About 20% of alcohol are absorbed from the stomach, and 80% from the upper
small intestine. Absorption is more rapid when the stomach is empty or contains
water. Accelerated gastric emptying increases the rate of absorption due to rapid
passage to the small intestine. Solutions with concentrations above 20% are
absorbed slowly because high concentrations of alcohol inhibit gastric peristalsis
and cause pylorospasm, thus delaying gastric emptying
Concentration:
Presence of alcohol in the blood can be detected after 5 minutes, and maximum
concentration is seen within 30-90 minutes (average 60 minutes). One unit of alcohol
will increase the blood level in females more than that in males. This is can be
explained because of; 1- Smaller body mass in women, higher proportion of fats, and
lesser proportion of fluids in the body, 2- Diminished “first-pass” metabolism of alcohol
in the gastric mucosa.
Distribution & Equilibrium: After entering blood, the alcohol enters various organs of the
body as well as spinal fluid, urine, and pulmonary alveolar air, etc. Alcohol is distributed
in body water. Tissues rich in water take up more alcohol than those rich in fat do.
Equilibrium between tissues and blood takes place within 1-2 hours. The available
water for distribution depends on the body weight and build. A lean person with greater
muscle bulk has a larger volume of distribution of the alcohol than that in an obese
person of similar weight.
Elimination: About 10% of alcohol are excreted as such mainly through urine and breath
and only negligible amount in sweat and faeces.
Metabolism: The metabolism takes place mainly in the liver by efficient systems located
in the subcellular compartments of hepatocytes; about 90% of the ingested alcohol are
oxidized in the cytoplasm by the enzyme alcohol dehydrogenase to form acetaldehyde
the cofactor is NAD. Microsomal ethanol-oxidizing system (MEOS) is another way by
which smaller amount of alcohol is converted to acetaldehyde. This oxidase system
increases in activity with chronic exposure to ethanol or inducing agents such as
barbiturates.

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The next step is the metabolism of acetaldehyde, which is converted to acetate by the
effect of aldehyde dehydrogenase and the presence of NAD as cofactor. This pathway
takes place in mitochondria. Aldehyde dehydrogenase can be inhibited by disulfirum,
metronidazole, oral hypoglycemics, and cephalosporins. Acetate will be further
metabolized into water and carbon dioxide. Acetaldehyde has a number of unique
effects that are not produced by the alcohol and this has led to speculation that
acetaldehyde might be responsible for the manifestations of alcohol intoxication and
addiction.
Following consumption of a single alcoholic drink, the combined effects of different
factors affecting absorption, metabolism, and excretion, result in a characteristic alcohol
curve:

a) The alcohol concentration rises steeply to a distinct maximum (absorption phase).

Peak concentration is reached after 30-90 minutes (average 60 minutes).
b) Irregularly curved fall due to a period of diffusion within the tissues to equilibrium
(15-30 minutes).
c) The BAC then falls progressively in linear fasion (elimination phase). At very high
concentrations > 200mg%, the decrease is not linear due to greater loss in breath and
urine. Over 12 hours are required to eliminate 200mg%.
Pathophysiology
1- The most important effect is the depression of CNS. Depression of higher centers of
the brain, leads to release of lower centers from the cortical control, this is called
releasing inhibition. Alcohol acts on the frontal lobe, psychic area, cerebellum, spinal
cord, and finally the medulla. It inhibits (1) higher nervous centers, which control
conduct and judgment, (2) motor centers and lastly (3) the vital organs.
2- The effect on the spinal cord leads to the initial increase in deep tendon reflexes.
3- The motor performance is affected from the simple standing posture to the more
complex skilled movements. The movement will be slower, inaccurate, and random.
4- Impairment in the efficiency of mental function by interfering with the speed of
perception and the mental processing: slower learning, decrease in ability of focusing,
concentration, judgment, discrimination, & thinking.
5- Acid-base disturbances.
6- Abnormalities of glucose metabolism either hypoglycemia or hyperglycemia.
Hypoglycemia is the most common and may lead to hypoglycemic seizures.
7- Impairs central thermal regulation and increases cutaneous blood flow, which lead
to hypothermia.
Types of Toxicity
Acute Ethanol Poisoning
Three phases have been recognized in acute ethanol intoxication. These are:
Phase I: Excitation: The person has the feeling of well being, excitement, euphoria,
and increased confidence. He is talkative and argues on every point right or wrong.
There is lack of restrain and inhibition of self-control. The face is flushed and the
conjunctiva is injected, while the pupils are dilated with sluggish light and
accommodation reactions. The judgment is impaired while mental alertness can be
retained. Blood alcohol is about 50-150 mg/100ml.
Phase II: Incoordination (Confusion): This stage is important for medicolegal

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purposes where different crimes and accidents are committed. There is incoordination
of thought, speech, and action. The speech is slurred, with difficulty in pronouncing
consonants. The pupils are dilated and react sluggishly to light and accommodation.
The sense of perceptions and skilled movements are affected. Nausea and vomiting are
common followed by sleep and recovery. There may be ataxia. There may be hangover
due to brain edema, toxic effects of alcohol on the brain, GIT, and liver. Blood alcohol
concentration is up to 300mg/100ml.
Phase III: Coma (Narcosis): The motor and sensory cells are deeply affected. The
speech becomes thick and slurring, incoordination is more marked the person staggers
and falls. Gradually, he enters into coma and cannot be awakened by deep stimuli and
reflexes are abolished. The breathing is stertorous. There is tachycardia and
hypotension. Pupils may be constricted. Blood alcohol concentration is more than
400mg/100ml. If coma continues more than 5 hours, the prognosis is likely to be worse.
Death occurs from respiratory failure.
The fatal dose is variable depending upon habit, age, health, and other factors affecting
pharmacokinetics. Usually, the dose of 300-400 ml of absolute alcohol ingested in a
period less than ½ hour is fatal.
Management
1- ABCs. Insert an IV catheter and withdraw blood for laboratory studies. Begin
intravenous infusion of dextrose to treat possible hypoglycemia. Since dextrose alone
may precipitate or worsen Wernicke’s encephalopathy in thiamine-deficient persons,
100 mg of thiamine should be given IV.
2- In noncomatose patients, lavage can be done, at the beginning, with plain water,
from which a sample should be sent for chemical analysis, the next wash will be done
by NaHCO3. This will prevent further absorption and help for acidosis.
3- Maintain body temperature, especially in cold weather.
4- Others causes of coma should be excluded.
5- Treat acidosis if ABG results show low pH.
6- Hemodialysis or hemoperfusion may be considered in severe cases.
CHRONIC ALCOHOLISM (Alcohol Dependence)
Alcohol abuse and dependence are, by far, the most common substance-related
disorders. Alcohol abuse and dependence are commonly referred as alcoholism.
Complications of Alcohol Withdrawal
1- Withdrawal Seizures: seizures are generalized tonic-clonic in character. If seizures
are focal, we should expect a lesion that is usually posttraumatic.
2- Impending Delirium Tremens: the most common alcohol withdrawal syndrome.
There is mild to moderate agitation, tremor, insomnia, loss of blood pressure control.
Features of acute alcoholic hallucinations, with auditory hallucinations. Generalized
tremor is the most obvious feature of the illness. Its frequency is 6-8 Hz, irregular,
variable in severity, decreases with quietness, and increases with motor activity or
emotion. There many be diminished amplitudes of sensory-evoked potentials, and
prolonged latencies of BAEP.
3-Delirium Tremens: the most severe form of withdrawal syndrome. It is a medical
emergency. It is said to be due to severe cortical and brainstem hyperexcitability,
cerebral edema, and increased pressure of CSF. Onset follows 3-5 days after cessation
of drinking. Mortality is 20% if untreated, usually as a result of an intercurrent medical

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illness such as pneumonia, renal disease, hepatic insufficiency, pancreatitis, or heart

failure.

METHANOL TOXICITY
It is used commonly in the form of methylated spirit. It is also called wood alcohol or
wood naphta and is obtained by destructive distillation of wood. It is widely used as
solvent and found in paint, varnish, etc.
Action

Methanol is slowly metabolized and up to one third may still be detected after 48 hours.
So, there is cumulative effect, which accounts for continuo damage and higher death
rate. It is metabolized in to formaldehyde and formic acid, which causes toxic effects
and acidosis.

In first few hours: inebriation, gastritis.

After a latent period (8-36 hours): There is nausea, vomiting, abdominal pain,
headache, severe metabolic acidosis, visual disturbances, blindness, cerebral edema,
seizures, coma, and death may occur. The severity of symptoms varies with dose, and
individual variation.

Optic neuritis leads to blindness. The pupils are dilated and fixed.

In over dose, death is caused by respiratory paralysis.

Treatment

Induction of emesis or gastric lavage may be done if the patient is seen early after
ingestion

Ethyl alcohol as the antidote. The new antidote Fomepizole is better than ethanol in
that there are no side effects of ethanol treatment (hypoglycemia, impairment of
consciousness, respiratory depression). The new antidote Fomepizole is better than
ethanol in that there are no side effects of impaired consciousness, hypoglycemia, or
respiratory depression.

ETHYLENE GLYCOL TOXICITY

It is colorless, odorless, with sweet taste, and water-soluble compound. It is a
component of antifreeze. The nonmetabolized form affects the CNS in a way similar to
that of the alcohol. It is metabolized in the liver by alcohol dehydrogenase into
glycoaldehyde and which then converted into glycolic, glyoxylic, and oxalic acids.
Kidneys and brain are mainly affected as calcium oxalate crystals and oxalic acid
crystals accumulate in these organs. There is oxaluria and oxalic acidemia.

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Clinical Manifestations
3-4 hours: gastritis, vomiting, abdominal pain.
4-12 hours: headache, acidosis, convulsions, arrhythmias, and coma.

12-24 hours: renal failure, pulmonary edema, cerebral edema,

Treatment

1-Stomach lavage with calcium salts.

2-Forced diuresis:In the IV infusion, 10% calcium gluconate as antidote to oxalic acid.

3-Ethyl alcohol to prevent further oxidation: 5% solution of 0.5g/kg body weight.

Fomepizole is the newer antidote.

4-Correction of metabolic acidosis.

5-Treatment of complications; pulmonary edema, shock, etc.

6-Peritoneal dialysis better than hemodialysis and hemoperfusion.

HYDROCARBONS (Petroleum Distillates)

Hydrocarbons or petroleum distillates are comprised of aliphatic (straight chain) form,

which includes kerosene, gasoline, furniture polish, petroleum ether, petroleum
naphtha, lubricating oils, etc. the other type is the aromatic (containing a benzene ring)
hydrocarbons and includes benzene, xylenes, etc. The toxicity of hydrocarbons is
generally indirectly proportional to the agent’s viscosity.
Mechanism of Toxicity
A-Pulmonary Aspiration: Chemical peumonitis.
B-Ingestion:
1- Aliphatic (kerosene) poorly absorbed by GIT giving less systemic toxicity.
2- Aromatic (benzene) are capable of causing systemic toxicity after ingestion such as
convulsion, coma, cardiac arrhythmias.
C-Inhalation: vapors in an enclosed space may cause systemic intoxication.
Clinical Manifestations
A) After Inhalation:
1. Gasoline and kerosene produce symptoms resembling alcoholic
intoxication.
2. The difficulty is not the toxic effects by GIT absorption but the effects of the
vapour on the tracheobronchopulmonary tree.
3. The early effects of exposure are: headache, nausea, vomiting, dyspnea,
and variety degrees of cyanosis and confusion.
4. Within few hours may progress to tachypnea, wheezing, severe chemical

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pneumonitis.
5. Muscular incoordination, convulsions, coma.
6. With more severe injury, pulmonary edema, hemoptysis.
7. Cardiorespiratory arrest.
8. Death may also ensue from secondary bacterial infection.
9. Kerosene is 100 times more toxic when inhaled rather than when ingested.
The fatal dose is 100ml, but death may occur after ingestion of 15 ml.
Recovery has occurred even after 250 ml. Aspiration of 0.2 ml may cause
major pulmonary pathology.
B) After Ingestion
1. Often causes- abrupt nausea, vomiting.
2. Irritation of upper GIT.
3. Occasionally hemorrhagic gastroenteritis.
4. Diarrhea (may be bloody), less common.
5. Some compounds may be absorbed and produce systemic toxicity.
C) Systemic Toxicity
1. Highly variable, depending on the compound.
2. There may be confusion, ataxia, lethargy, headache.
3. With severe exposure; syncope, coma, and respiratory arrest.
Treatment
1-Saline cathartics such as magnesium or sodium sulfate can be given.
2-Oil administration may result in higher incidence of aspiration pneumonia. Gastric
lavage is contraindicated for hydrocarbon ingestion to avoid the risk of aspiration, which
may result from vomiting around the lavage tube. In cases of high amount ingestion,
and to avoid CNS depression, gastric lavage may be done after endotracheal
intubation.

TOXICITY OF PESTICIDES

Pesticide is a world that is consisted of 2 parts:

Pest = unwanted creature or living

Cide = killing or elimination

Pesticides include several categories such as hebicides, insecticides, fungicides,

bacteriocides, etc.

The 3 major groups to be studied in our course are:

1- Insecticides: organophophates.
2- Herbicides: paraquat.
3- Rodenticides: anticoagulants

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ORGANOPHOSPHATE TOXICITY

Organophosphate insecticides are widely used as garden and household pesticides,

and in agriculture. Formulations include liquids, sprays, and powders. In veterinary
medicine they are found in pedicullicide lotions. Shampoos, aqueous and alcoholic
lotions are also used as human pedicullicides and scabicides.
Organophosphate nerve agents may be used as chemical warfare agents. An example
was sarin used in the Tokyo subway attacks of 1995.
Although most patients with organophosphate poisoning have a good prognosis, severe
poisoning is potentially lethal. Early diagnosis and initiation of treatment are important.
Parathion is an organophosphate insecticide that is widely used in agriculture in Libya.
Pathophysiology
Organophosphates bind to one of the active sites of acetylcholinesterase (AChE) and
inhibit the function of this enzyme. The main purpose of AChE is to hydrolyze
acetylcholine (ACh) to choline and acetic acid. Therefore, the inhibition of AChE causes
an excess of ACh in synapses and neuromuscular junctions, resulting in muscarinic and
nicotinic symptoms and signs. Excess ACh in the synapse can lead to 3 sets of
symptoms and signs:
 First, accumulation of ACh at postganglionic muscarinic synapses lead to
parasympathetic activity of smooth muscle in lungs, the GI tract, heart, eyes, bladder,
and secretory glands, and increased activity in postganglionic sympathetic receptors for
sweat glands. This results in the symptoms and signs that can be remembered with the
mnemonic SLUDGE/BBB.
 Second, excessive ACh at nicotinic motor end plates causes persistent
depolarization of skeletal muscle resulting in fasciculations, progressive weakness, and
hypotonicity.
 Third, as organophosphates cross the blood-brain barrier, they may cause
seizures, respiratory depression, and CNS depression for reasons not completely
understood.
Organophosphates bind to erythrocyte cholinesterase (RBC cholinesterase) on RBCs
and plasma cholinesterase (pseudocholinesterase) in the serum. This binding seems to
have only minimal clinical effects but is useful in confirmatory diagnostic studies.
The kinetics of the enzyme will reach zero within 10 hours i.e. all enzyme will be in the
form of OP-AchE complex, this situation is called aging phenomenon.
Causes
Agricultural exposure is the most common cause of organophosphate poisoning. The
WHO classifies these poisonings as class I (extremely toxic) to class III (slightly
hazardous). The WHO advocates banning or strong restrictions on the use of class I
pesticides and a reduction in the use of pesticides to a minimal number of compounds
that are less hazardous than others. Organophosphates may also be encountered in
the military setting or the result of a terrorist attack with nerve agents such as sarin, VX,
or soman.

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Clinical Manifestations
Pesticides can rapidly be absorbed through the skin, lungs, GI tract, and mucous
membranes. The rate of absorption depends on the route of absorption and the type of
organophosphate. Symptoms usually occur within a few hours after GI ingestion and
appear almost immediately after inhalational exposure.
Patients often present with evidence of a cholinergic toxic syndrome (toxidrome). It is
useful to remember the toxidrome in terms of the 3 clinical effects on nerve endings:
1- Muscarinic effects: SLUDGE/BBB mnemonic
S = Salivation L = Lacrimation U = Urination D =
Defecation
G = GI symptoms E = Emesis B = Bronchorrhea
B = Bronchospasm B = Bradycardia
2- Nicotinic effects at neuromuscular junctions and autonomic ganglia: weakness,
fasciculations, and paralysis.
3- CNS effects may lead to seizures and CNS depression.
Investigations
The most common tests to determine organophosphate poisoning are measurements of
serum AChE and RBC AChE activity, which are used to estimate neuronal AChE
activity. Although the RBC AChE test may not as readily available as the other, it
provides a better indicator of neuronal AChE activity than serum AChE. In many places,
neither of these tests is immediately available and therefore is of no assistance in the
acute setting or in guiding therapy.
Other Tests:
ECG may be considered. Many retrospective studies have shown that:
 Prolonged QTc interval is the most common ECG abnormality.
 Elevation of the ST segment, sinus tachycardia, sinus bradycardia, and
complete heart block (rare) may also occur.
 Sinus tachycardia occurs just as commonly as sinus bradycardia.
Treatment
1- Airway, breathing, and circulation (ABCs):
Care of the ABCs should be initiated first because intubation may be necessary in
cases of severe poisoning.
2- Decontamination:
Decontamination is an important part of the initial care. In general, the importance of
decontamination depends on the route of poisoning. Patients with dermal and inhalation
exposures are more likely to cause nosocomial poisoning than patients with GI
exposure. Patients with GI exposure should also be decontaminated, but ED staff
should not delay urgent treatment with excessive decontamination. Patients with dermal
and inhalation poisonings must be decontaminated before being brought into the ED.
Case reports have described nosocomial poisoning in staff members treating patients
who have been exposed to OP; one describes OP toxicity from mouth-to-mouth
resuscitation.
3- Atropine:
Atropine is a pure muscarinic antagonist that competes with ACh at the muscarinic
receptor. Atropine is most commonly given in intravenous (IV) form at the
recommended dose of 2-5 mg for adults and 0.05 mg/kg for children with a minimum

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dose of 0.1 mg to prevent reflex bradycardia. Atropine may be repeated every 5-10
minutes. Severe organophosphate poisonings often require hundreds of milligrams of
atropine.
Most sources recommend starting atropine on patients with anything more than ocular
effects and then observing 3 major signs: dryness of mouth, flushing of face, and
dilatation of pupils.
4- Oximes {Pralidoxime (2-PAM)}:
Organophosphates bind and phosphorylate one of the active sites of AChE and inhibit
the functionality of this enzyme. Oximes bind to the organophosphate, causing the
compound to break its bond with AChE. Most of the effects are on the peripheral
nervous system because entry into the CNS is limited.
Atropine does not bind to nicotinic receptors; therefore, it is ineffective in treating
neuromuscular toxicity (particularly weakness of respiratory muscles).

PARAQUAT TOXICITY

Paraquat is a non-selective, water soluble herbicide. It is used since 1962. It is available

as an aqueous concentrate and in granular formulations, all require dilution with or
dissolving in water before use. The manufacturers recommend that the maximum
strength used should not exceed 0.5% (5g/L).
In Libya there are 2 compounds:
1- Gramaxone (yellowish liquid)
2- Weedol (granulation form)

Pathophysiology
Paraquat is very toxic when ingested. The exact mechanisms of toxicity is not fully
understood, but are thought to be a combination of NADPH depletion and free radical
formation. This free radical reacts with molecular oxygen to reform the cation and
produce a superoxide free radicals and will continue to do this in the presence of
NADPH and oxygen. The superoxide free radicals disrupt cell function and may cause
its death.
The lethal dose is 1-4 grams. In massive paraquat toxicity, death may occur within
hours after ingestion due to multiorgan failure. Lower doses may cause lung damage
with death after days to weeks postingestion. Lungs are the main target of paraquat due
to active, energy-dependent uptake by alveolar type I and II cells.
Ingestion is the most common route of toxicity and such exposure can be divided into:
A) Mild: ingestion of less than 20 mg/Kg body weight. Patients are usually
asymptomatic or may have vomiting and diarrhea. They may have transient fall
of gas transfer factor and vital capacity but complete recovery.
B) Moderate to severe: ingestion of 20-40 mg/Kg. patients may suffer from
vomiting, diarrhea, systemic toxicity (commonly renal failure and occasionally
hepatic dysfunction). Pulmonary fibrosis develops in all cases. Death may occur
2-3 weeks later in the majority.
C) Very severe: ingestion of more than 40 mg/Kg. death may occur within 24 hours
but never after more than 7 days.

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Clinical Manifestations
There are 3 phases:
Phase 1: (GIT phase): this phase can start immediately till 72 hours; intense pain in
mouth, pharynx, and stomach due to the corrosive effect of paraquat. There may be
bloody vomiting or diarrhea.
Phase 2: (systemic; renal or hepatic phase): severity depends on the dose of paraquat,
where manifestations of renal and or hepatic failure appear.
Phase 3: (respiratory phase): in which signs of respiratory illness appear such as cough
or cyanosis.
Management
There is no specific specific treatment for paraquat toxicity, and management consists
of supportive therapy.
1) Gastric lavage: with aqoues suspension of clay (Fuller Earth or Bentonite clay).
2) Careful oxygen administration
3) Hemodialysis.

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ANIMAL POISONS

SCORPION STING

Animal poisons are not common but lifeithreatening toxicities. Venoms are poisons of
snakes and scorpions. Scorpions belong to phylum Arthropoda, class Arachnida and to
order scorpionida, with 9 living families; Buthidae, Scorpionidae, Diplocentridae,
Chaerilidae, Ischnuridae, Bothruridae, Chactidae, Iuridae, and Vaejovidae. The most
dangerous species are found in Africa, Middle East, Asia, and Latin America, and they
belong to the Buthidae family.

In Libya, nine different species have been recognized; most of them belong to Buthidae
family whereas others belong to the family Scorpionidae. The 9 different species in
Libya are:

1. Leiurus quinquestriatus: the most abundant and toxic species in Libya and it is
restricted to the southern parts e.g. Aujla, jkharra, Elkufra.
2. Androctonus amoreuxi: the second most abundant and toxic species, they are found
in the same areas with L. quinquestriatus forming a co-occurrence.
3. Androctonus aneas: widely distributed in low numbers, especially in Wadi Elshati,
Bengazi, Jdabia, Zawia, Tripoli, Sirt.
4. Androctonus australis: in costal and southern parts of Libya, but more abundant in
Sirt, Algariat, and Shwerif.
5. Buthacus leptochelys: mainly in Jalow, Aujla, and Jekhirrah.
6. Buthus occitanus: inTajoura, and some other costal regions but not in the southern
parts.
7. Buthacus arenicola: found in same areas with Buthus occitanus but in small
numbers.
8. Orthochirus innesi: found in restricted areas mainly at Morzug, Marhaba, and
Tsawah.
9. Scorpion maurus: the least toxic species and it is restricted to Khums and Msillata.
Pathophysiology
Scorpions use their pincers to grasp their prey; then, they arch their tail over their body
to drive their stinger into the prey to inject their venom, sometimes more than once. The
scorpion can voluntarily regulate how much venom to inject with each sting. The striated
muscles in the stinger allow regulation of the amount of venom ejected, which is usually
0.1-0.6 mg. The potency of the venom varies with the species. Generally, the venom is
distributed rapidly into the tissue if it is deposited into a venous structure. Venom
deposited via the intravenous route can cause symptoms only 4-7 minutes after the
injection, with a peak tissue concentration in 30 minutes and an overall toxin elimination
half-life of 4.2-13.4 hours through the urine. The more rapidly the venom enters the
bloodstream, the higher the venom concentration in the blood and the more rapid the
onset of systemic symptoms.
Scorpion venom is a water-soluble, antigenic, heterogenous mixture, as demonstrated
on electrophoresis studies. This heterogeneity accounts for the variable patient
reactions to the scorpion sting. Furthermore, the various constituents of the venom may

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act directly or indirectly and individually or synergistically to manifest their effects.

The venom is composed of varying concentrations of neurotoxin, cardiotoxin,
nephrotoxin, hemolytic toxin, phosphodiesterases, tryptophan, phospholipases,
hyaluronidases, glycosaminoglycans, histamine, serotonin, and cytokine releasers. The
most potent toxin is the neurotoxin causing cell impairment in nerves, muscles, and the
heart by altering ion channel permeability.
The long-chain polypeptide neurotoxin causes stabilization of voltage-dependent
sodium channels in the open position, leading to continuous, prolonged, repetitive firing
of the somatic, sympathetic, and parasympathetic neurons, while the short polypeptide
neurotoxin blocks the potassium channels.
Clinical Manifestations

The toxicity, variation, and duration of the symptoms depends on the following factors:

 Scorpion species
 Scorpion age, size, and nutritional status
 Healthiness of the scorpion's stinging apparatus (telson)
 Number of stings and quantity of venom injected
 Depth of the sting penetration
 Composition of the venom
 Site of envenomation: Closer proximity of the sting to the head and torso results
in quicker venom absorption into the central circulation and a quicker onset of
symptoms.
 Age of the victim
 Health of the victim
 Weight of the victim relative to amount of venom
 Presence of comorbidities
 Treatment effectiveness
Generally, intrathecal and intravenous routes have immediate effects, while
subcutaneous and intramuscular routes take effect several minutes to hours later.

Nonlethal scorpion species tend to produce local reactions while lethal scorpion species
tend to produce systemic symptoms. The duration to progress to systemic symptoms
ranges from 5 minutes to 4 hours after the sting. The symptoms generally persist for 10-
48 hours. The signs of the envenomation are determined by the scorpion species,
venom composition and the victim's physiological reaction to the venom. The signs
occur within a few minutes after the sting and usually progress to a maximum severity
within 5 hours. The signs last for 24-72 hours and do not have an apparent sequence.
Thus, predicting the evolution of signs over time is difficult. Furthermore, a false
recovery followed by a total relapse is common.

The grading of these scorpion envenomations depends on whether or not neurological

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signs predominate and is as follows:

Clinical Picture Grade

Local pain and/or erythema and/or paresthesia at site of envenomation I

Pain and/or paresthesia remote from the site of the sting and/or tachycardia and II
mild hypertension in addition to local findings

Cranial nerve or somatic skeletal neuromuscular dysfunction: III

Cranial nerve dysfunction: blurred vision, wandering eye movement, dysphagia,

tongue fasciculation, problems with upper airway, slurred speech, and/or ptosis.

Somatic skeletal neuromuscular dysfunction: jerking extremity, restlessness,

severe involuntary shaking and jerking that may be mistaken for a central seizure
disorder.

Any combination of cranial nerve dysfunction, somatic skeletal neuromuscular IV

dysfunction.

1-Local effects

a) Neurotoxic local effects

 A sharp burning pain at the sting site, followed by pruritus, erythema, local tissue
swelling, and ascending hyperesthesia. The tap test is administered by tapping at
the sting site. A positive result is when the paresthesia worsens with the tapping
because the site is hypersensitive to touch and temperature.
b) Cytotoxic local effects

 A macule or papule appears initially at the sting site, occurring within the first
hour of the sting.
 The diameter of the lesion is dependent on the quantity of venom injected.
 The lesion progresses to a purpuric plague that will necrose and ulcerate.
 Lymphangitis results from the transfer of the venom through the lymphatic
vessels.
2- Systemic effects
A- Neurologic signs: Most of the symptoms are due to either the release of
catecholamines or the release of acetylcholine from postganglionic parasympathetic
neurons. However, dual manifestations of adrenergic and cholinergic signs are
possible.

a) Central nervous system signs

 Paresthesia occurs in all 4 limbs.

 Patients experience venom-induced cerebral thrombosis strokes.
 The level of consciousness is altered, especially with restlessness, confusion, or
delirium.

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b) Autonomic nervous system signs: sympathetic, parasympathetic, or a combination of

signs

 Sympathetic signs: hyperthermia; tachypnea; tachycardia; hypertension;

hyperglycemia- Diaphoresis- Piloerection- Restlessness - Hyperexcitability -
convulsions
 Parasympathetic signs: bronchoconstriction; bradycardia; hypotension; SLUDGE;
Rhinorrhea and bronchorrhea. Loss of bowel and bladder control - Priapism -
Dysphagia – Miosis.
c) Somatic signs

o Rigid spastic muscle of the limbs

o Involuntary muscle spasm, twitching, clonus, and contractures
o Alternating episthotonos and opisthotonus
o Increased tendon reflexes, especially prolongation of relaxation phase
d) Cranial nerve signs

oClassic rotary eye movement may result in ptosis, nystagmus, and blurred vision.
oMydriasis is a sign.
oPatients may have tongue fasciculations.
o Dysphagia, dysarthria, and stridor occur secondary to pharyngeal reflex loss or
muscle spasm.
o Patients may present with excessive salivation and drooling.
B- Nonneurologic systemic signs

a) Cardiovascular signs: usually follow a pattern of hyperdynamic phase followed by

hypodynamic phase

 Hypertension is observed as early as within 4 minutes after the sting and lasts for
few hours
 Hypotension - Less commonly occurs secondary to excess Ach or catecholamine
depletion
 Tachycardia is greater than 130 beats per minute, although bradycardia can be
observed.
 Cardiovascular collapse occurs secondary to biventricular dysfunction and profuse
loss of fluids from sweating, vomiting, diarrhea, and hypersalivation.
b) Respiratory signs

 Tachypnea may be present.

 Pulmonary edema with hemoptysis and a normal-sized heart is observed in 7-32%
of respiratory cases. This is secondary to a direct toxin-induced increased
pulmonary vessel permeability effect and is also secondary to catecholamine-
induced effects of hypoxia and intracellular calcium accumulation, which leads to a
decrease in left ventricular compliance with resultant ventricular dilation and
diastolic dysfunction.
 Respiratory failure may occur secondary to diaphragm paralysis, alveolar
hypoventilation.

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c) Allergic signs

 Patients may have urticaria, Angioedema, or bronchospasm.

 Anaphylaxis is possible.
d) Gastrointestinal signs

 Patients may present with excessive salivation, Dysphagia, Nausea and vomiting.
 Acute pancreatitis may lead to hyperglycemia.
e) Genitourinary signs

 Patients have decreased renal plasma flow, acute tubular necrosis.

 Priapism may occur secondary to cholinergic stimulation.
f) Hematological signs

 Platelet aggregation may occur because of catecholamine stimulation.

 DIC with massive hemorrhage may result from venom-induced defibrination.
g) Metabolic signs

 Hyperglycemia.
 Increased lactic acidosis from hypoxia and increased lactase dehydrogenase
activity.
 Patients may have an electrolyte imbalance and dehydration.
Management

1- General measures:

a) Ice bags may reduce pain and slow the absorption. This can be effective during the
first 2 hours.
b) Immobilizing the affected part below level of heart may delay venom absorption.
c) Application of a local anesthetic to the wound decreases paresthesia.
2- Systemic treatment is instituted by giving scorpion antivenom and by directing
supportive care toward the organ specifically affected by the venom.

a) Continuous monitoring of vital signs (pulse oximetry; HR, BP, and RR).
b) Antivenom: antivenom is recommended in grades III and IV envenomation and is
said to be the treatment of choice for severe neuromuscular hyperactivity. The quantity
of antivenom to be used is determined by the clinical severity of patients and by their
evolution over time. The antivenom significantly decreases the level of circulating
unbound venom within an hour. The persistence of symptoms after the administration of
antivenom is due to the inability of the antivenom to neutralize scorpion toxins already
bound to their target receptors.
c) IV fluids to prevent hypovolemia in cases with vomiting, diarrhea, sweating, and/or
hypersalivation.
d) Hyperdynamic CVS effects: administration of an α-blockers is effective in reversing
this venom-induced effect. β-blockers alone are not recommended as they may lead to
an unopposed α-adrenergic effect. Nitrates can be used for hypertension and
myocardial ischemia.

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e) Hypodynamic CVS effects: monitored fluid infusion with afterload reduction reduces
mortality. A diuretic may be used for pulmonary edema in absence of hypovolemia, but
an afterload reducer (e.g. prazosin, nifedipine, nitroprusside, hydralazine, or Angiostin
CE inhibitors) may give better results. Prazosin is a postsynaptic α- blocker that
reverses both inotropic and hypokinetic phases and, also, reverses the metabolic
effects caused by depressed insulin secretion. Although prazosin use in children is not
approved yet, some studies have showed its efficacy in the treatment of both adults and
children with scorpion envenomation. Inotropic medications, such as digitalis, have little
effect, while dopamine aggravates the myocardial damage through catecholamine-like
actions. Dobutamine seems to have better effects in cases with acute pulmonary
edema when given with sodium nitroprusside for children .
f) Insulin administration in scorpion envenomation has helped in preventing
multisystem failure. Some auhors have showed the efficacy of insulin in humans with
scorpion envenomation; they found that early start of insulin-glucose infusion has
resulted in the recovery of cardiac, respiratory and metabolic derangements, and in
significant decrease of mortality rate.

BLACK WIDOW SPIDER BITE

There are more than 30,000 species of spiders, most of which are venomous, but they
cannot cause serious bites due to delicate mouthparts and short fangs. Many spiders
produce toxic venoms that can cause skin lesions, systemic illnesses, neurotoxicity, and
death. The term "arachnidism" is often used to refer to envenoming spider bites.
There are many families each containing many species but the most important of
them in Libya is the family Latrodectus (black widows), examples of these families:
1- Family Latrodectus (Black widows)
2- Family Loxosceles: (L. reclusae, L. parrami)
3- Family Atrax and other funnel-web spiders: Atrax species are large, aggressive
spiders. Most notorious is Australian Atrax robustus or Sydney funnel-web
spider
4- Family Pheneutria: P. keyserlingi
5- Family Lycosa: L. tarantula
Latrodectus spiders (black widows) have a wide distribution. There are several species
and subspecies:
Latrodectus mactans
L. mactans hasseltii (Australian black widow)
L. m. tridecimguttatus (Europe and South America), etc.
The black widow, or hourglass, spider is dangerous because of its potent venom.
Pathophysiology
The venom of the black widow is a neurotoxin. It primarily causes systemic symptoms
with little local damage at the bite site and no local necrosis. The venom mediates its
effects through an initial release of massive amounts of acetylcholine at neuromuscular
junctions. Latrotoxin is specific to nerve terminals.
Clinical Manifestations
Envenomation can occur in people of any age. Initially, a severe pain in local muscle
groups occurs, which then spreads to regional muscle groups. Severe cramps and
contraction of musculature may extend throughout the body. The abdominal pains are

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frequently most severe, mimicking appendicitis, colic, or food poisoning. Other

symptoms include headache, restlessness, anxiety, fatigue, and insomnia.
Signs of latrodectism include:
1- Salivation 2 –Lacrimation 3- Diaphoresis 4- Tremors 5- Tachycardia 6- Bradycardia
7- Hypertension 8- Shock 9- Coma.
Slight erythema, piloerection locally, mild edema or urtication, local perspiration, and
lymphangiitis are the primary local features that may be present.

Management
The outcome, even in untreated cases of black widow bites, generally is favorable with
supportive care, and symptoms subside in approximately 2 days. Children, old people,
and patients with cardiovascular disease have higher risk for complications.
Treatment centers on alleviating pain and muscle cramping. The 3 main treatments are:
1- Pain relievers such as narcotics
2- Muscle relaxants
3- Intravenous calcium gluconate. Mechanism of action remains uncertain.
Moderates nerve and muscle performance and facilitates normal cardiac
function. Can be administered IV initially, and calcium levels maintained with
high-calcium diet.

SNAKEBITES

VENOMOUS (POISONOUS) SNAKES

Most snakebites are delivered by nonpoisonous species. Worldwide, only about 15% of
the more than 3000 species of snakes are considered dangerous to humans.

Poisonous snakes belong to 5 families

1- Elapidae: have forward grooved fangs, which are fixed in the upper jaw below or in
front of the eyes. The nostrils are lateral and there are large scales over the head. This
family includes:
A) Cobras (Naja and other genera) of Asia and Africa
B) Mambas (Dendroaspis) of Africa
C) Kraits (Bungarus) of Asia
D) Coral snakes (Micrurus) of the Americas
2- Viperidae: at rest the long canalized fangs lie along the palate pointing posteriorly but
during act of biting they are rotated forwards. This family includes:
A) Rattlesnakes (Crotalus)
B) Moccasins (Agkistrodon)
C) Lance-headed vipers (Bothrops) of the Americas
D) Saw-scaled vipers (Echis) of Asia and Africa
E) Russell's viper (Daboia russellii) of Asia;
F) Puff adder (Bitis arietans)
3- Colubridae: many are non-poisonous but, also include the Opisthglypha which are
poisonous but rarely dangerous because the grooved gangs are the most posterior
teeth in the upper jaw. Examples are tree snakes.

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4- Crotalidae: include
A) Pit viper (pit between the nose and the eye)
5- Hydrophidae: poisonous see snakes.
Pathophysiology

Venom is produced and stored in paired glands below the eye. It is discharged from
hollow fangs located in the upper jaw. Fangs can grow to 20 mm in some large
rattlesnakes. Venom dosage per bite depends on:
1- Elapsed time since the last bite
2- Degree of threat the snake feels
3- Size of the prey
Coral snakes have shorter fangs and smaller mouths. This allows them less opportunity
for envenomation than the crotalids, and their bites more closely resemble chewing
rather than the strike for which the pit vipers are famous. Both methods inject venom
into the victim to immobilize it quickly and begin digestion.
Venom is mostly water. Enzymatic proteins in venom impart its destructive properties.
Venoms are different in action according to the family:
1- Vipridae and Crotalidae: produce cytolytic and hemolytic venoms.
2- Elapidae: most of them produce neurotoxic venom.
3- Colubridae: produce cytolytic venoms.
4- Hydrophidae venom contains myotoxin that causes muscle necrosis.
Enzyme concentrations vary among species, thereby causing dissimilar
envenomations. Rattlesnakes can leave impressive wounds and cause systemic
toxicity. Coral snakes may leave small wounds that later result in respiratory failure from
the typical systemic neuromuscular blockade.
The local effects of venom serve as a reminder of the potential systemic disruption of
organ system function. One effect is local bleeding; coagulopathies are not uncommon
with severe envenomations. Another effect, local edema, increases capillary leak and
interstitial fluid in the lungs. Pulmonary mechanics may be altered significantly. The final
effect, local cell death, increases lactic acid concentration secondary to changes in
volume status and requires increased minute ventilation. The effects of neuromuscular
blockade result in poor diaphragmatic excursion. Cardiac failure can result from
hypotension and acidosis. Myonecrosis raises concerns about myoglobinuria and renal
damage.

Family Elapidae (Cobra)

Most cobras are large snakes, 1.2-2.5 m in length. The king cobra, which may reach 5.2
m, is the largest venomous snake in the world. Cobras live throughout most of Africa
and southern Asia. Most of these snakes elevate the head and spread the neck as a
threat gesture. Most snakebites are inflicted on body extremities. In addition to biting,
some cobra species have a unique defense; they eject jets of venom toward an enemy,
usually at the eyes. The fangs of these species are specially modified with the
discharge orifice on the anterior face rather than at the tip.
Cobra envenomation is an extremely variable process. Necrosis is typical of bites by the
African spitting cobras (e.g. Naja nigricollis), and Naja sumatrana (Sumatran spitting

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cobra). Although the venoms of these cobras contain neurotoxins, necrosis often is the
chief or only manifestation of envenoming in humans. Occasionally, a combination of
neurologic dysfunction and tissue necrosis is observed. Cobra venoms are
multicomponent systems whose toxins are mostly proteins and polypeptides.
Venoms can be divided into the following categories:
1- Neurotoxins: competitively bind to nicotinic acetylcholine receptors to produce
depolarizing neuromuscular blockade.
2- Cardiotoxins: generalized cell-membrane poisons that produce irreversible cell
depolarization, leading to dysrhythmia, hypotension, and death.
3- Toxins that activate complement via the alternative pathway (C3-C9 sequence).
4- Enzyme toxins, such as phospholipase A2 (variable toxicity), hyaluronidase
(facilitates tissue dispersion of other toxins), L-amino acid oxidase (gives many
venoms a characteristic yellow coloration), and acetylcholine acetylhydrolase
(unknown toxicity).

Clinical Features
The onset of symptoms and signs following a cobra bite can be extremely variable.

 Immediate, local pain, soft tissue swelling (may be progressive). Signs of

necrosis appear within 48hrs. The area around fang punctures darkens, Blistering may
follow.
 Neurologic findings, which may begin early or may be delayed in onset as long
as 24 hours
 Respiratory distress or weakness, Cyanosis
 Neurologic dysfunction; Altered mental status
 Ptosis (may be earliest sign of systemic toxicity
 Generalized weakness or paralysis
 Cardiovascular collapse
Investigations
Laboratory studies offer no diagnostic benefit. Baseline labs may be reasonable in
severe bites or if the patient has significant underlying medical problems. Coagulopathy
is rare with cobra bites, though prolonged bleeding and failure of clot retraction have
been reported following bites by African spitting cobras.
Management
1- In some regions of the world, clothing is wrapped around a bitten extremity proximal
to the bite site. However, prolonged use of arterial tourniquets is unwise and has
caused loss of limb function.
An alternative first aid procedure is the Australian pressure immobilization technique.
This technique has been shown to be helpful in delaying systemic absorption of elapid
venoms, but its use in cobra bites remains controversial. An elastic compress (eg, crepe
bandage) is wrapped rapidly around the bitten extremity, beginning distally and
progressing proximally to encompass the entire limb. The extremity is splinted and kept
at heart level.
2- Incisions are not helpful. Using a mechanical suction device is unlikely to return any
significant amount of venom, and it could increase local tissue damage when
necrotizing venom is involved. Suction should, therefore, be avoided.

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3- Avoid cooling measures and ice application. They have been associated with
increased necrotic complications.
4- Antivenom is the only proven therapy for significant snakebites, most are polyvalent
against venoms of all the important snakes of a region. It should be started as soon as
possible if evidence of systemic envenoming is present. Administer antivenom
according to the manufacturer’s instructions. While most currently available commercial
antivenoms are of equine origin, work is currently underway in several countries to
produce new, fragment antigen binding (Fab)-based ovine antivenoms for various cobra
species. These new antivenoms may be much safer to use, with less risk of allergic
phenomena.
Adult and child doses are similar. Dilute in 500-1000 mL isotonic crystalloid, and begin
IV at a slow rate with the physician in immediate attendance, if no reaction, increase
rate in order to administer full starting dose in 1-2 h.

Food poisoning
Definition:
It is an acute illness of acute onset following the ingestion of food, and usually occurs in a
group of person sharing the same type of food.
Pathogenesis:
There are three ways by which the illness can occur:
1- Contamination of food with organisms or their products (toxins) resulting into 2 main
syndromes:
- Acute gastroenteritis: bacterial.
- Neurological syndrome: botulism, paralytic shell-fishes.
2- Contamination of food with chemicals as;
- Heavy metals: lead, cadmium, phosphorus, zinc…etc.
- Simple salts: Na-fluoride, K-chloride, etc.
- Organic compounds: insecticides.
3- Naturally occurring poisonous food:

- Poisonous animals: poisonous fishes, shell-fish…etc.

- Poisonous plants: datura, mushroom, akee fruit…etc.
Classification: according to the nature of the poison:
1- Microbial food poisoning.
2- Animal food poisoning.
3- Plant food poisoning.

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4- Chemical food poisoning.

1- Microbial food poisoning
Types:
a- Bacterial: there are 2 types:
1- Infective (entero-invasive): the illness is due to the ingestion of the living bacteria as
salmonella, shigella, E. coli, and campylobacter.
2- Toxogenic: illness is due to previously formed toxin in the food before the ingestion as
staphylococcus, bacillus cereus, botulism, and cholera.
b- Viral: there are more than 1000 types of viruses produce food poisoning.
c- Parasitic: giardiaasis, amebiasis, trichinosis.
Botulism
Etiology:
- Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by
Clostridium botulinum (not by the bacterium itself).
- It is gram +ve anaerobe, spore-forming bacillus. It grows everywhere; releases 7 types of
toxins (A, B, C, D, E, F, and G). They are the most dangerous and powerful poison known. The
spores are heat-resistant. Under anaerobic conditions, botulinum spores can germinate, and
the bacterium grows and produces the toxin.
Types:

1- Food-born botulism:
- It is related to ingestion of preformed toxin in the food.
- Toxin: Resistant to proteolysis in stomach.
- Absorption: Alkaline pH of intestine helps absorption.
- Occurs usually in adults.
- Associated foods: home canned vegetables, potatoes fish & preserved sea food.
2- Infant botulism: (GI colonization syndromes):
- It is due to the ingestion of the spores which germinate in GIT.
- Raw honey is a common source of type B organisms.
3- Wound botulism:
- Toxin is produced locally in wound or abscess after proliferation of bacterial spores.
- Drug abuse is the most common cause.
- Clinically it's similar to food borne form, but may take up to 2 wks to appear.

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4- Undetermined botulism:
Usually involves adult cases where no food or wound source can be identified. It has been
suggested that these cases are comparable to infant botulism and may occur when the normal
gut flora has been altered as a result of surgical procedures or antibiotic therapy.
Clinical picture of food born botulism:
1- Onset: They usually appear within 12 to 36 hours after exposure.

2- The characteristic early symptoms and signs are: marked fatigue, weakness, and vertigo,
usually followed by blurred vision, dry mouth, and difficulty in swallowing and speaking.
Vomiting, diarrhea, constipation and abdominal swelling may occur.
3- The disease can progress to weakness in the neck and arms, after which the respiratory
muscles and muscles of the lower body are affected. The paralysis may make breathing
difficult.
4- There is no fever and no loss of consciousness.
Infant botulism:
- Age: from 1 to 6 months.
- Predisposing factors: Low acidity,  the bacterial type and number and lack of mature
mucosal immune system of lysosome.
- Clinically: - Initial sign: Constipation
- Poor suckling & hypotonia
- Parasympathetic change: hypotension; tachycardia.
Undetermined Botulism: it’s an adult variant of infant botulism.
predisposing factors: achlorydria, chronic antibiotics, gastrectomy & intestinal surgery.
Mechanism of action:
The toxin binds irreversibly to neuromuscular junction (NMJ)  prevents the release of
acetylcholine and produces block.

Differential diagnosis:
1- Gillian-Barre syndrome: paralysis start in limbs.
2- Organophosphorus toxicity.
3- Cerebrovascular accidents: focal asymmetric findings & diagnosed by CT.

4- Poliomyelitis: fever, bulbar involvement, but ascending paralysis.

5- Encephalitis: fever, coma and abnormal CSF.
6- Ciguatera: sensory affection, vertigo.

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Management:
Investigations:
1- Detection of toxins in serum: 1/3 of patients will have +ve test.
- False -ve occurs when sample is taken late or antibiotics are given.
2- Stool examinations for toxins and botulinum organism is very helpful.
Treatment:
1- Supportive care: Respiratory; cardiovascular.
2- Early: - Emetics: Avoid magnesium containing ones.
- Lavage. - Enemas: Not used in paralytic ileus.
3- Antitoxin: - Most useful in 1st 24 hours.
- Trivalent ABE.
- Use on clinical diagnosis without waiting for lab confirmation.
- Dose: 1 vial (10 mg)/4hr., till the patient is clinically free.
Staphylococcus aureus:
It is the most common cause of food poisoning. It is produced by one of 6 Heat stable
endotoxius produced by the staph. Organism. Symptoms: triad of abdominal pain, followed by
vomiting or diarrhea. It is a self limited disease. Treatment: only supportive treatment.

Clostridium perfringens:
The disease occurs when the heat stable spores germinate in the meat. Heating the food to
75°C or greater will inactivate the heat labile toxin.
Symptoms: the enterotoxins cause fluid, sodium and chloride secretion into the gut lumen. The
symptoms occur in 12-24 hs. Diarrhea and abdominal cramps are usually the only symptoms.
Treatment: usually supportive
Vibrio:
It is motile gram negative rods; endemic in water of many countries. The illness is due to
enterotoxin called the cholera toxin which block Na + absorption & enhance Cl- excretion by
direct stimulation of adenylate cyclase enzyme in the gut epithelium. It causes intense watery
diarrhea that may result in fluid loss up to 1 L/h. Treatment: aggressive fluid replacement.
Bacillus cereus:
B. cereus is anaerobic spore forming gram positive rod. It elaborates 2 types of enterotoxins;
one causes diarrheal type illness and the other affect the upper GIT tract (called the emetic
form). Emetic form has more rapid onset and shorter clinical course, it closely resembles staph

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food poisoning but diarrhea & abdominal cramps may occur. The diarrheal form produces
cholera like diarrhea. Treatment: usually mild & self limited so treatment is supportive.

2- Animal food poisoning:

1- Shell-fish poisoning:
Etiology: produced by eating shell fish that has ingested toxic species of Dianoflagellates
which produce a potent neurotoxin with curare-like action (neuromuscular paralysis).
Clinical picture:
1- Numbness and tingling of the lips, tongue, face, and limbs.
2- GIT upset: nausea, vomiting, and diarrhea.
3- Drowsiness, tremors, and even convulsions may occur.
4- Respiratory distress, paralysis of respiratory muscle, and death from respiratory failure.
Treatment: symptomatic and supportive:
1- Emesis, gastric lavage, activated charcoal and saline purgative.
2- Respiratory support: O2 therapy, artificial respiration.
3- Correction of acid base and electrolyte disturbances.
4- Benzodiazepines for convulsions if present.
2- Poisonous fish:
There are about 300 species of fishes that have poisonous flesh, commonest are:
a- Ciguatera fish poisoning:
- It results from ingestion of fish harboring cigatoxin in its flesh.
- They include: surgeon fish, mackerel fish, and barracuda fish.
Clinical picture:
1- GIT upset: nausea, vomiting and may be diarrhea.
2- Paraethesia of face, mouth & limbs with characteristic reversed temperature sensation.
3- Dizziness, ataxia, and incoordination.
4- Muscle weakness or even paralysis, and myalgia.
5- Death from respiratory failure.
If the patient recovers, paraesthesia and muscle weakness may persist for several weeks.
b- Scombroid fish poisoning:

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It is caused by ingestion of fish as mackerel and tuna secondary to improper storage before
cooking. It is caused by bacterial decarboxylation of histidine normally present in fish tissue
converting it to histamine.
Symptoms: produces histamine like reaction; there are headache, nausea, diarrhea, flushing,
palpitations, tachycardia and wheezing.

3- Plants food poisoning:

There are many poisonous plants including:
1- Belladonna (datura). 2- Ergot fungus.
3- Toxic mushroom. 4- Castor bean.
5- Akee fruit. 6- Ivey (Oak) fruit.
Toxic mushroom
- They are the sexual organs or fruiting bodies of fungi.
- The word “Mushroom” is derived from early Greek term roughly meaning “mucus”.
- From over 10,000 known species, only 50-100 are known to be toxic.
- The clinical picture differ greatly according to the type of toxic mushroom, as follows:
1- Cyclopeptide-containing mushroom: (Amantadine group):
Example: Amanita phalloides.
Toxic effects: potent hepato-toxic as amatoxin and phallotoxin.

Clinical picture
1 Stage 1: cholera-like diarrhea.
2 Stage 2: quiescent stage with elevation of liver enzymes.
3 Stage 3: fulminant hepatic, cardiac and renal failure.
Fatalities: 50% of all cases.
2- Gyromitrin group:
Example: gyromitra species.
Active principle: hydrazone which is metabolized to monomethyl hydrazine which produces
toxicity similar to isonicotenic acid hydralyzine (INH) overdose. It inhibits the formation of GABA
in the brain by inducing state of pyridoxine deficiency.
Clinical picture:
1 Nausea, vomiting, and diarrhea.

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2 Hemolysis & hepatorenal failure.

3 Convulsions and coma are terminal events.
Fatalities: 20-40% of all case.

3- Muscarine containing mushroom:

Example: amanita muscaria.
Toxic effect: peripheral cholinergic effects.
Clinical picture:
1- Nausea, vomiting and diarrhea.
2- Salivation, lacrimation, and bronchorrhea.
3- Bronchospasm and miosis.
4- Hypotension, Bradycardia and arrhythmia.
Fatalities: 5% of all cases.
4- Ibotenic acid containing mushroom.
Example: amanita pantherina.

Toxic effects: anticholinergic effects.

Clinical picture:
1- Delirium, drowsiness, and dizziness.
2- Tremors, confusion, and ataxia.
3- Slow bounding pulse and arrhythmia.
Fatalities: rare.
5- Coprine containing mushroom:
Example: coprine species.
Toxic effects: disulfuram like action. Symptoms occur after ingestion of ethanol several days
after ingestion of the fungus.
Clinical picture: flushing, palapation, dyspnea, chest pain & hypotension.
Fatalities: rare.
6- Psilocybin-containing mushroom:
Example: psilocypbe species (magic mushroom).
Toxic effects: LSD-like action (hallucinogen).

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Clinical picture:
1- Abdominal pain.
2- Atropine like action.
3- Hyperkinesias, ataxia, and muscle weakness.
4- Hallucinations.
Fatalities: rare.
7- Gastrointestinal irritant:
They are large group.
It produces gastroenteritis like picture.
It has no systemic effects.
Treatment:
1- General measures:
Emesis, gastric lavage, & serial activated charcoal in 70% sorbitol.
2- Specific measures:
1) Amantadine group: thioctic acid.
2) Muscarinic group: atropine sulphate.
3) Gyromitrin group: pyridoxine.
4) Disulfuram group: propranolol.
3- Symptomatic and supportive measures:

4- Chemical food poisoning:

Source:
Contamination of food with chemical can occur as:
1- Canning food in enameled metal pans.
2- Excess food preservatives.
3- Household chemicals: insecticides, solvents, antibiotics….etc.
Toxic chemicals:
The most commonly met including:
1- Metals: arsenic, barium, lead, iron, cadmium, and silver.
2- Insecticides: household or agriculture.

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3- Excess food preservatives: benzoic acid, hydrogen peroxide.

4- Antibiotics: usually mistaken by children for candy.
Clinical picture:
- Acute onset of nausea, vomiting, diarrhea, and abdominal pain.
- Specific manifestations: according to the causative chemical.
Treatment: usually symptomatic and supportive.

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