Toxicology is a discipline overlapping with biology, chemistry, pharmacology, medicine and nursing, that
involves the study of the adverse effects of chemical substances on living organisms and the practice of
diagnosing and treating exposure to toxins.
Clinical /Medical Toxicology is a separate specialty in Bulgaria, as in many former Soviet Union or eastern
European countries, whereas its part of the Emergency medicine in the western countries.
Unlike the latter , where intoxicated patients are triaged in A&Es and the severe ones admitted in ICUs, in
Bulgaria there are several specialized poison centers- toxicology departments at the bigger university hospitals
- Clinical Toxicology department of the National Institute of emergency medicine “Pirogov”Sofia
-Clinical Toxicology department- Military Academy Hospital Sofia
-Clinical Toxicology departments of University Hospitals in Plovdiv, Varna, Pleven
Epidemiology
The annual number of intoxicated patients treated in the Toxicology clinic Plovdiv is on steady decline after it
peaked in mid 80s and the scope of the intoxications has changed drastically.Due to the expansion of
industrial /chemical plants back then industrial poisonings and chronic professional intoxications prevailed,
plus the population was at its highest hence proportionally the number of patients was bigger.
After the economic collapse in the early 90s we see an increasing number of intentional self harming poisonings
and accidental drug overdoses or substance misuse due to many factors as easy, uncontrolled access to
prescription medications, popularity of less toxic new brands of drugs. Most common intoxications nowadays
include the misuse of psychoactive drugs such as benzodiazepines, antipsycotics,anticonvulsants, NSAIDS incl
aspirin/paracetamol, antihypertensives and oral hypoglycaemic drugs, followed by acute poisonings with
alcohols- ethanol/methanol/etylenglycol, pesticides, domestic products- corrosives , as well as toxic gases after
fires, falloid mushroom poisoning, and envenomations- insect stings, snake bites . We treat more than 600 or
100-150/100 000 patients annually with a mortality rate of around 1%
Frequently used terms:
xenobiotics- chemical substance not familiar /deriving out of a living organism
Toxin-xenobiotic with potentially harmful effect on an organism
toxicants – synthetic poisons created by artificial processes
venoms- form of toxin secreted by an animal for the purpose of causing harm to another and deliver ed by a
certain means like bites or stings
poison- a generalized term for any substance that could have adverse effects on an organism
toxicity- the degree to which a poison can damage the organism, including the effect on the whole orgaism or
on a substructure- hepatotoxicity, cytotoxicity, nephrotoxicity
Paracelsus- everything could be poison or the dose makes the poison
types of toxins
chemical toxicants – inorganic/organic,most of the known poisons in practice, excluding radioactive
substances
nonliving biological toxicants are called toxins if produced by bacteria,plant or fungus and venoms if
produced by animals
physical toxicants – substances that interfere with biological processes – coal dust, asbestos, inert gases, water
acute poisoning –exposure to a poison on one occasion or during short period of time
chronic poisoning –long term repeated or continuous exposure to a posion where symptoms do not occur
immediately or after the exposure
acute toxicity lethal or harmful effects after oral dermatological or inhalation exposure to
environmental and occupation hazards
median toxic dose – TD50- the dose at which toxicity occurs in 50% of the cases. It should be greater than the
half maximum effective concentration and less than LD50
median lethal dose LD50- the dose required to kill half of the members of the tested population, lower Ld50
greater toxicity
therapeutic index TI the ratio between the efficacious and the lethal dose of drug that causes adverse effects
TI= Ld50/ED50 morphine 70/1 diazepam 100/1cocaine 15/1 ethanol 10/1 digoxin 2/1( paracetamol warfarin
lithium, gentamicin vancomicin, amphotericin B)
lowest published toxic concentration and lethal dose TCLo and LDLo
severity /grade –
Anaphylaxis/Shock
DEFINITION- an acute allergic, potentially fatal multiorgan system reaction caused by release of chemical
mediators from mast cells and basophils
PATOGENESIS traditional nomenclature- IgE mediated reactions- anaphylaxis, non IgE mediated-
anaphylactoid
World Allergy Organization- immunologic ( IgE meadiated and non IgE-mediated like IgG and complement
mediated) and nonimmunologic –direct release of mediators( opiodis, dextrans, vancomycin)
Ethyology
IGE mediated-classic form- sensitizing antigen elicits IgE response, that bind to the mast cells and basophils Fc-
receptors. Subsequent exposure to the allergen causes cross linking of the cell bound IgE and degranulation.
Non IgE mediated anaphylaxis- involves complement cascade activation of C3a C4a C5a- anaphylatoxins that
cause degranulation
Histamine and leucotriens/Pg and PAF are released
Causative agents
food –peanuts, treenuts,fish, shellfish,dairy,eggs, wheat,soy
drugs- penicillin,ACTS AS HAPTEN and other beta lactams,,cephalosporins,MUSCLE
RELAXANTS,HYPNOTICS,OPIODS,COLLOIDS,LATEX, nsaids,ACE inhibitors
blood products+iv immunoglobuline
contrast media
insects
miscellaneous- exercise induced, idiopathic (more than 6 episodes per year)
Anamnesis and clinical manifestation -most commonly involves the cutaneous respiratory cardiovascular and
GI systems
onset- within seconds to minutes, but 1-8-10hours if delayed, less than 1 to max of 23% recurrence in different
reports
risk factors- atopy as rhinitis, dermatitis, asthma,
route of administration food<parenteral,
shorter intervals between exposures,
concomitant use of medication especially ACE (2x greater risk)
skin/mucoses 80-90% some combination of urticaria, pruritus ,erythema,flushing or angioedema, SOME OF THE
MORE SEVERE CASES CAN PRESENT WITHOUT CUTANEOUS SYMPTOMS
-rhinorrhea, sneezing throat tightness, wheezing, SOB, cough, hoarsenes, severe angioedema of lips and
tongue, tachypnea, stridor, dysphonia
-dizziness, weakness, chest pain, [palpitations, syncope,tachycardia,hypotension, shock- occurring immediately
without any other findings sometimes
-nausea, vomiting, diarrhea
-altered mental state, depressed LOC (level of consciousness) or agitated/combative, feeling of
impending doom
Testing – not usually required as an emergency but if syndrome recurring-
-serum triptase, urinary 24-histamine, skin testing for food, drug or other IgE-independent reactions
Treatment
-call for help, lie patient flat, raise legs
-ABCDE in case of established cardiac arrest
-in case of refractory or very severe anaphylaxis –CVS and resp symptoms ,patients should be admitted and
treated/observed for a longer period in A$E or ICU for
*airway management,high flow oxygen
*cardiac monitoring,pulse oxymetry,fluid resuscitation and medication
Medication
1.OXYGEN-HIGH FLOW
2.Adrenergic agonists- adrenaline(epinephrine)
adult and child >12y/o 500mcg per dose of the 1:1000 ampules im
child 6-12 y 300mcg of 1:1000 amp im
child less than 6y 150mcg of 1:1000 amp im
REPERAT DOSES EVERY 5-1OMINS
IV ADRENALINE ONLY BY EXPERIENCED SPECIALISTS 50MCG PER DOSE –ADULTS, 1MCG/KG PAED
EPIPEN AUTOINJECTORS 300MCG PER DOSE- APPLY TO OUTER MID THIGH , REPEAT DOSE IN 5-10MINS
3. Fluid resuscitation 500-1000ml/boluses 20ml/kg in paed
4.Antihistamines diphenhydramine- Benadryl, chlorpenamine- piriton, hydroxyzine
Chlorphenamin adults/children >12 y 10mg iv stat or im followed by 4mg po q4-6h
child 6-12y 5mg iv/im
child <6y 2,5 mg iv/im
5.Corticosteroids
HYDROCORTISONE ADULTS /children >12y 200mg iv/im stat followed by 100mg q6h
child 6-12 100mg iv/im stat
child 6m to 6y 50mg iv/im stat
METHYLPREDNISOLON 1MG/KG
6.Bronchodilators-salbutamol nebulized 0,5 mg/2,5mls NS
7.Vasopressors dopamine 5-20mcg/kg/min, noradrenaline 0,01-2mcg/kg/min
monitor- pulsoxymetry, ECG,blood gases, BP
*in extreme situations- crycothyrotomy
Follow up
mortality rate 0,65-2%, in the UK half of the fatlities are iatrogenic in origin, most common cause of death is
airway obstruction, cardiac arrest averages 20-30min in onset, 5mins inhospital, 10mins insects, 10-20mins
prehospital
prevention patient education, identification tags, epinephfrine autoinjectors- not stored in fridge and avoid exp
to heat
