PHARMACOLOGY

Tony stark
 Introduction, Routes of Drug Administration
INTRODUCTION-
Pharmacology-
→Pharmacology is derived from two Greek words-

Pharmacon- Drugs, logos- study

→Pharmacology is the science of drugs.

→Father of pharmacology- Oswald Schmiedeberg.

The two main divisions of pharmacology-

1. Pharmacodynamics

2. Pharmacokinetics

1. Pharmacodynamics (dynamis—power)-
-What the drug does to the body.
→This includes physiological and biochemical effects of drugs and
their mechanism of action at organ system/subcellular/
macromolecular levels.

E.g.-Adrenaline → interaction with adrenoceptors.

2. Pharmacokinetics (Kinesis—movement)-
-What the body does to the drug.
→This refers to movement of the drug in and alteration of the drug
by the body; includes-

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-Absorption

-Distribution

-Metabolism

-Excretion.

e.g. - PCM.

Drugs-
Definition—“Drug is any substance or product that is used or is
intended to be used to modify or explore physiological systems or
pathological states for the benefit of the recipient.”

Route of drug administration-

→Routes can be broadly divided into two types-

1. Local

2. Systemic

1. Local routes-
→These routes can only be used for localized lesions at accessible
sites and for drugs whose systemic absorption from these sites are
minimal or absent.

They are following route-

(1)Topical-
→This refers to external application of the drug to the surface for
localized action.

(2) Deeper tissues-

→Certain deep areas can be approached by using a syringe and

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needle, but the drug should be in such a form that systemic
absorption is slow.

(3) Arterial supply-

→Close intra-arterial injection is used for contrast media in

angiography; anticancer drugs can be infused in femoral or brachial
artery to localize the effect for limb malignancies.

2. Systemic routes-
(1). Oral

(2). Sublingual/Buccal

(3). Rectal

(4). Cutaneous

(5). Inhalation

(6). Nasal

(7) Parenteral

(a) S.C

(b) I.M

(c) I.V

(d) I.D

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 Pharmacokinetics
Pharmacokinetics-
→Pharmacokinetics is the quantitative study of drug movement in,
through and out of the body.

→All pharmacokinetic processes involve transport of the drug

across biological membranes.

Biological membrane-
→This is a bilayer (about100 Å thick) of phospholipid and
cholesterol molecules, the polar groups (glyceryl phosphate
attached to ethanolamine/choline or hydroxyl group of cholesterol)
of these are oriented at the two surfaces and the nonpolar
hydrocarbon chains are embedded in the matrix to form a
continuous sheet.

→Drugs are transported across the membranes by:

(1) Passive diffusion and filtration

(2) Specialized transport

(1). Passive diffusion-

→The drug diffuses across the membrane in the direction of its
concentration gradient, the membrane playing no active role in the
process.

Filtration-
→Filtration is passage of drugs through aqueous pores in the
membrane or through paracellular spaces. This can be accelerated
if hydrodynamic flow of the solvent is occurring under hydrostatic

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or osmotic pressure gradient, e.g. across most capillaries including
glomeruli.

(2). Specialized transport-

→This can be carrier mediated or by pinocytosis.

(a).Facilitated diffusion-
→The transporter, belonging to the super-family of solute carrier
(SLC) transporters, operates passively without needing energy.

→e.g. the entry of glucose into muscle and fat cells by the glucose
transporter GLUT.

(b).Active transport-
→It requires energy, is inhibited by metabolic poisons, and
transports the solute against its electrochemical gradient (low to
high), resulting in selective accumulation of the substance on one
side of the membrane.

(i).Primary active transport-

e.g. - endoplasmic reticulum.

(ii).Secondary active transport-

e.g. - sodium transport.

Absorption-
→Absorption is movement of the drug from its site of
administration into the circulation. Not only the fraction of the
administered dose that gets absorbed, but also the rate of
absorption is important.
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Factors affecting absorption are-

1. Aqueous solubility
2. Concentration
3. Area of absorbing surface
4. Vascularity of the absorbing surface
5. Route of administration.
Bioavailability-
→Bioavailability refers to the rate and extent of absorption of a
drug from a dosage form as determined by its concentration-time
curve in blood or by its excretion in urine.

→Bioavailability of drug injected i.v. is 100%, but is frequently

lower after oral ingestion because—

(a). The drug may be incompletely absorbed.

(b).The absorbed drug may undergo first pass metabolism in the

intestinal wall/liver or be excreted in bile.

Fig. - Plasma concentration-time curves depicting bioavailability

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Distribution-
→Once a drug has gained access to the blood stream, it gets
distributed to other tissues that initially had no drug, concentration
gradient being in the direction of plasma to tissues.

→Distribution of a drug depends on its:

• Lipid solubility

• Ionization at physiological pH (a function of its pKa)

• Extent of binding to plasma and tissue proteins

• Presence of tissue-specific transporters

• Differences in regional blood flow.

Redistribution-
→Highly lipid-soluble drugs get initially distributed to organs with
high blood flow, i.e. brain, heart, kidney, etc. Later, less vascular
but more bulky tissues (muscle, fat) take up the drug—plasma
concentration falls and the drug is withdrawn from the highly
perfuse sites.

Penetration into brain and CSF-

→The capillary endothelial cells in brain have tight junctions and
lack large paracellular spaces.

→Together they constitute the so called Blood-Brain Barrier (BBB).

→A similar blood-CSF barrier is located in the choroid plexus.

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 Fig.-Passage of drugs across capillaries

A. Usual capillary with large paracellular spaces through which even

large lipid-insoluble molecules diffuse.

B. Capillary constituting blood brain or blood-CSF barrier. Tight

junctions between capillary endothelial cells and investment of glial
processes or choroidal epithelium do not allow passage of non
lipid-soluble molecules/ions.

Passage across placenta-

→Placental membranes are lipoidal and allow free passage of
lipophilic drugs, while restricting hydrophilic drugs.

→Placenta is a site for drug metabolism as well, which may

lower/modify exposure of the fetus to the administered drug.

Biotransformation/Metabolism-
→Biotransformation means chemical alteration of the drug in the
body.

→It is needed to render nonpolar (lipid-soluble) compounds polar

(lipidinsoluble) so that they are not reabsorbed in the renal tubules
and are excreted. Most hydrophilic drugs, e.g. streptomycin,
neostigmine.

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First pass metabolism-
→This refers to metabolism of a drug during its passage from the
site of absorption into the systemic circulation.

→All orally administered drugs are exposed to drug metabolizing

enzymes in the intestinal wall and liver (where they first reach
through the portal vein).

Attributes of drugs with high first pass metabolism:

(a) Oral dose is considerably higher than sublingual or parenteral

dose.

(b) There is marked individual variation in the oral dose due to

differences in the extent of first pass metabolism.

(c) Oral bioavailability is apparently increased in patients with

severe liver disease.

Excretion-
→Excretion is the passage out of systemically absorbed drug. Drugs
and their metabolites are excreted in:

(1).Urine-
→Through the kidney. It is the most important channel of excretion
for majority of drugs.

(2).Faeces -
→Apart from the unabsorbed fraction, most of the drug present in
faeces is derived from bile.

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(3).Exhaled air-
→Gases and volatile liquids (general anaesthetics, alcohol) are
eliminated by lungs, irrespective of their lipid solubility.

(4).Saliva and sweat-

→These are of minor importance for drug excretion.

(5).Milk-
→The excretion of drug in milk is not important for the mother, but
the suckling infant inadvertently receives the drug.

Plasma half-life-
→The Plasma half-life (t½) of a drug is the time taken for its plasma
concentration to be reduced to half of its original value.

→Taking the simplest case of a drug which has rapid one

compartment distribution and first order elimination, and is given
i.v. a semi log plasma concentration-time plot.

Fig. - Semi log plasma concentration-time plot of a drug elimination.

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 Pharmacodynamics
Pharmacodynamics-
→Pharmacodynamics is the study of drug effects.

Principles of drugs action-

The basic types of drug action can be broadly classed as:

(1).Stimulation-
→It refers to selective enhancement of the level of activity of
specialized cells, e.g. adrenaline stimulates heart.

(2).Depression-
→It means selective diminution of activity of specialized cells.

E.g. barbiturates depress CNS, quinidine depresses heart.

(3).Irritation-
→This connotes a nonselective, often noxious effect and is
particularly applied to less specialized cells.

(4).Replacement-
→This refers to the use of natural metabolites, hormones.
E.g. Insulin in diabetes mellitus, iron in anemia.

Mechanism of action-
1. Receptor-
→It is defined as macromolecules or the sites on them which bind
and interact with the drug are called ‘receptors’.

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Drug + Receptor → Bind (complex) → Response to affected body
part.

2. Affinity-
→The ability to get bound of drug to receptor that is known as
affinity.

3. Drug- receptor interaction-

→The ability of the drug pharmacological action after combined
with receptor is known as drug- receptor interaction.

(a).Agonist-
→An agent which actives a receptor to produce an effect similar to
that of the physiological singal molecules.

(b).Antagonist-
→An agent which prevents the action of an agonist on a receptor or
the subsequent response, but does not have any effect of its own.

(c).Partial agonist-
→An agent which actives a receptor to produce sub maximal effect
but antagonizes agonist.

Therapeutic index (TI)-

→The TI is measure of a drug’s safety because a larger value
indicates a wide margin between doses that are effective & doses
that are toxic.

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Drug potency-
→Potency is a measure of the amount of drug necessary to prduce
an effect of a given magnitude.

Drug efficacy-
→Efficacy is the magnitude of response a drug causes when it
interacts with receptor.

Factors modifying drug action-

(1).Body size-
→It influences the concentration of the drug attained at the site of
action. The average adult dose refers to individuals of medium
built.

(2).Age-
→It can also calculate the drug dose different age of people on
body weight & body surface area.

(3).Sex-
→Females have smaller body size and require doses that are on the
lower side of the range.

(4).Genetics-
→The dose of a drug to produce the same effect may vary by 4–6
folds among different individuals.

(5).Route of administration-
→Route of administration governs the speed and intensity of drug
response.

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(6).Environmental factors-
→Several environmental factors affect drug responses.

(7).Psychological factors-
Placebos-Placebos are used in two situations:
1. As a control device in clinical trial of drugs (dummy medication).

2. To treat a patient who, in the opinion of the physician, does not

require an active drug.

(8).Pathological states-
→Not only drugs modify disease processes, several diseases can
influence drug disposition and drug action:

-G.I disease

-Kidney disease etc.

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 Adverse drug effect
Adverse drug effect-
→Adverse effect is ‘any undesirable or unintended consequence of
drug administration’.

→It is a broad term includes all kinds of noxious effect—trivial,

serious or even fatal.

Adverse drug reaction (ADR)-

→Adverse drug reaction (ADR) has been defined as ‘any noxious
change which is suspected to be due to a drug, occurs at doses
normally used in man, requires treatment or decrease in dose or
indicates caution in the future use of the same drug’.

→This definition excludes trivial or expected side effects and

poisonings or overdose.

Category of adverse drug effect-

(1).Side effects

(2).Secondary effects

(3).Toxic effects

(4).Intolerance

(5).Idiosyncrasy

(6).Drug allergy

(7).Photosensitivity

(8).Drug dependence

(9).Drug withdrawal reactions

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(10).Teratogenicity.

(1).Side effects-
→These are unwanted but often unavoidable pharmacodynamic
effects that occur at therapeutic doses.

E.g. atropine is used in pre-anesthetic medication for its

antisecretory action.

(2).Secondary effects-
→These are indirect consequences of a primary action of the drug.
E.g. suppression of bacterial flora by tetracycline’s paves the way
for super infections.

(3).Toxicity-
→Toxicity may result from extension of the therapeutic effect itself,
e.g. coma by barbiturates, complete A-V block by digoxin, bleeding
due to heparin.

(4).Intolerance-
→It is the appearance of characteristic toxic effects .of a drug in an
individual at therapeutic doses.

e.g. - One tablet of chloroquine may cause vomiting and abdominal

pain in an occasional patient.

(5).Idiosyncrasy-
→It is genetically determined abnormal reactivity to a chemical.

e.g. - Barbiturates cause excitement and mental confusion in some

individuals.

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(6).Drug allergy-
→It is an immunologically mediated reaction producing stereotype
symptoms which are unrelated to the pharmacodynamic profile of
the drug.

(7).Photosensitivity-
→It is a cutaneous reaction resulting from drug induced
sensitization of the skin to UV radiation.

(8).Drug dependence-
→Drugs capable of altering mood and feelings are liable to
repetitive use to derive euphoria, recreation, withdrawal from
reality, social adjustment etc.

(9).Drug withdrawal reactions-

→Apart from drugs that are usually recognized as producing
dependence, sudden interruption of therapy with certain other
drugs also results in adverse consequences.

(10).Teratogenicity-
→It refers to the capacity of a drug to cause fetal abnormalities
when administered to the pregnant mother. The placenta does not
constitute a strict barrier, and any drug can cross it to a greater or
lesser extent.

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 Miscellaneous drugs

Immunosuppressant Drugs-
→Immunosuppressant’s are drugs which inhibit cellular/humoral or
both types of immune responses, and have their major use in organ
transplantation and autoimmune diseases.

Classification-
1. Calcineurin inhibitors (Specific T-cell inhibitors)-
-Cyclosporine
-Tacrolimus

2. m-TOR inhibitors-
-Sirolimus
-Everolimus

3. Antiproliferative drugs (Cytotoxic drugs)

-Azathioprine
-Methotrexate

4. Glucocorticoids
-Prednisolone

5. Biological agents
(a) TNFα inhibitors: Etanercept
(b)Polyclonol antibiotics: Rho (D) immunoglobin.

(1).CALCINEURIN INHIBITORS (Specific T-cell inhibitors)-

Cyclosporine-
→It is a cyclic polypeptide with 11 amino acids, obtained from a
fungus and highly selective immunosuppressant which has
markedly increased the success of organ transplantations.

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(2).m-TOR INHIBITORS-
Sirolimus-
→This new and potent immunosuppressant is a macrolide
antibiotic (like tacrolimus) which was earlier named Rapamycin.

(3).ANTIPROLIFERATIVE DRUGS (Cytotoxic

immunosuppressant’s)-
Azathioprine-
→It is a purine antimetabolite which has more marked
immunosuppressant than antitumor action.

(4).Glucocorticoids-
→Glucocorticoids have potent immunosuppressant and anti-
inflammatory action; inhibit several components of the immune
response.

(5)BIOLOGICAL AGENTS-
(a).TNFα inhibitors-
→TNFα is secreted by activated macrophages and other immune
cells to act on TNF receptors.

(b).Polyclonal antibodies-
Antithymocyte globulin (ATG)-
→It is a polyclonal antibody purified from horse or rabbit
immunized with human thymic lymphocytes which contains
antibodies against many CD antigens as well as HLA antigens.

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 Antiseptics & Disinfectants
1. Antiseptic-
→The chemical substances that are on living surfaces (skin, mouth)
& inhibit the growth of microbes that is called antiseptics.

2. Disinfectant-
→The chemical substances that are used on the objects
(instruments) are called disinfectant.

3. Germicide-
→An agent used to kill/inhibit microbes but not spore included.

4. Sterilization-
→Sterilization means complete killing of all forms of micro-
organism.

Classification-

1. Phenol derivatives: Phenol, Cresol

2. Oxidizing agents: Hydrogen peroxide, Benzoyl peroxide

3. Halogens: Iodine, Iodophores, Chlorine

4. Biguanide: Chlorhexidine

5. Soaps: of Sodium and Potassium

6. Alcohols: Ethanol, Isopropanol

7. Aldehydes: Formaldehyde, Glutaraldehyde

8. Acids: Boric acid, Acetic acid

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9. Metallic salts: Silver nitrate, Zinc oxide

10. Dyes: Gentian violet, Proflavine

1. PHENOLS-
Phenol (Carbolic acid)-
→It is one of the earliest used antiseptics and still the standard for
comparing other germicides.
→It acts by disrupting bacterial membranes and denaturing
bacterial proteins.

2. Oxidizing agent-
Hydrogen peroxide-
→It liberates nascent oxygen which oxidizes necrotic matter and
bacteria.

3. HALOGENS-
Iodine-
→It is a rapidly acting, broad-spectrum (bacteria, fungi, viruses)
microbicidal agent; has been in use for more than a century. Acts
by iodinating and oxidizing microbial protoplasm.

4. BIGUANIDE-
Chlorhexidine-
→A powerful, non-irritating, cationic antiseptic that disrupts
bacterial cell membrane. A secondary action is denaturation of
microbial proteins. It is relatively more active against gram-positive
bacteria.

5. SOAPS-
→Soaps are anionic detergents; weak antiseptics, affect only gram-
positive bacteria. Their usefulness primarily resides in their
cleansing action.

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6. ALCOHOLS-
Ethanol-
→It is an effective antiseptic and cleansing agent at 40–90%
concentration.
→It acts by precipitating bacterial proteins.
→It is a poor disinfectant for instruments—does not kill spores and
promotes rusting.

7. ALDEHYDES-
Formaldehyde-
→It is a pungent gas—sometimes used for fumigation. A 37%
aqueous solution called Formalin is diluted to 4% and used for
hardening and preserving dead tissues.

8. ACIDS -
Boric acid-
→It is only bacteriostatic and a very weak antiseptic. But being
nonirritating even to delicate structures, saturated aqueous
solutions (4%) have been used for irrigating eyes, mouthwash,
douche, etc.

9. METALLIC SALTS-
Silver nitrate-
→It rapidly kills microbes, action persisting for long periods
because of slow release of Ag+ ions from silver proteinate formed
by interaction with tissue proteins.

10. DYES-
Gentian violet (crystal violet)-
→A dye active against staphylococci, other gram-positive bacteria
and fungi, but gram-negative organisms and mycobacteria are
insensitive. Aqueous or alcoholic solution (0.5–1%) is used on
furunculosis, bedsores, chronic ulcers, infected eczema, thrush,
Vincent’s angina, ringworm, etc.
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Objectives of antiseptic/disinfectant-

-Chemical stable.
-Nonstaining with agreeable color & odour.
-Active against all pathogens.
-Require brief time.
-Nonabsorable produces minimum toxicity if absorbed.
-Non-sensitizing.

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 GI SYSTEM
Emesis-
→Emesis Vomiting occurs due to stimulation of the emetic
(vomiting) centre situated in the medulla oblongata.

Chemoreceptor trigger zone (CTZ)-

→The CTZ located in the area postrema and the nucleus tractus
solitarius (NTS) are the most important relay areas for afferent
impulses arising in the G.I.T. throat and other viscera.

ANTIEMETICS-
→These are drugs used to prevent or suppress vomiting.

Classification-
1. Anticholinergics-
-Dicyclomine

2. H1 anti-histaminics-
-Diphenhydramine

-Doxylamine

3. Neuroleptics-
-Chlorpromazine

-Haloperidol

4. Prokinetic drugs-
-Domperidone, Itopride

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5. 5-HT3 antagonists-
-Ondansetron

-Granisetron

6. Adjuvant antiemetics-
-Dexamethasone

-Benzodiazepines

1. Anticholinergics-
Dicyclomine-
→It has been used for prophylaxis of motion sickness & for morning
sickness.

→ 10-20 mg orally.

Morning sickness-
→It is also called nausea & vomiting of pregnancy is a symptoms of
pregnancy that involves nausea & vomiting.

Motion sickness-
→Nausea/vomiting caused by motion, especially by travelling.

2. H1 Antihistaminics-
→Some antihistaminics are antiemetics.

→They are useful mainly in motion.

Diphenhydramine- These drugs afford protection of motion

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Sickness for 4–6 hours, but produce sedation and dryness of mouth.

Doxylamine-
→It is a sedative H1 antihistaminic with prominent anticholinergic
activity.

→It is specifically promoted in India for ‘morning sickness’

(vomiting of early pregnancy).

→ 10-20 mg at bed time.

3. Neuroleptics-
→The neuroleptics are potent antiemetics act by blocking D2
receptors in the CTZ.

Prochlorperazine-
→This D2 blocking phenothiazine is a labyrinthine suppressant has
selective antivertigo and antiemetic actions.

R & D- 5–10 mg BD/TDS oral.

4. Prokinetic drugs-
→These are drugs which promote gastrointestinal transit and speed
gastric emptying by enhancing coordinated propulsive motility.

Mechanism of action:
→Metoclopramide acts through both dopaminergic and
serotonergic receptors blocking.

Domperidone-
→It is a D2 receptor antagonist, chemically related to haloperidol,
but pharmacologically related to metoclopramide.

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→Domperidone is absorbed orally.

Side effect-
-Dry mouth

-Loose stools

-Headache

-Rashes

Dose: 10–40 mg (Children 0.3–0.6 mg/kg) TDS.

5. 5-HT3 antagonists-
Ondasteron-
→It blocks the depolarizing action of 5-HT exerted through 5-HT3
receptors on vagal afferents in the GIT as well as in NTS and CTZ.

Side effect-
-Headache

-Dizziness

-Hypotension

-Chest pain

R & D- 4-8 mg I.V.

6. Adjuvant antiemetics-
Corticosteroids-
Dexamethasone-
→ 8–20 mg I.V. It can partly alleviate nausea and vomiting due to
moderately emetogenic.
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Anti-diarrheal drugs-
Diarrhea-
→It is defined by WHO as 3 or more loose/watery stools in a 24
hours period.

Management-
Oral rehydration salt/solution-
NaCl- 2.6 gm

KCl- 1.5 gm

Sodium citrate- 2.9 gm

Glucose- 13.5 gm

Water- 1 liter

Drugs therapy-
1. Specific antimicrobial drugs-
→One or more antimicrobial agent is almost routinely prescribed to
most patient of diarrhea.

e.g.- Rifaximin, Metronidazole

2. Drugs for inflammatory bowel disease (IBD)-

→IBD is a chronic relapsing inflammatory disease of the ileum,
colon or both.

e.g. - Sulfasalazine, Mesalazine

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3. Non-specific anti-diarrheal drugs-
Anti-motility drugs-
→These are opioid drugs which increase small bowel tone &
segmenting activity reduce propulsive movements & diminish
secretion while enhancing absorption.

e.g. - Diphenoxylate, Loperamine

Drugs for constipation treatment-

Laxatives-
→These are drugs that promote evacuation of bowels.

→A distinction is sometimes made according to the intensity of

action.

(a) Laxative or aperient: - Milder action, elimination of soft but

formed stools.

(b) Purgative or cathartic: - Stronger action resulting in more

fluid evacuation.

CLASSIFICATION-
1. Bulk forming-
Dietary fibre:- Bran, Psyllium (Plantago)

2. Stool softener-
-Docusates (DOSS)

-Liquid paraffin

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3. Stimulant purgatives-
(a).Diphenylmethanes- Sodium picosulfate

(b)Fixed oil- Castor oil

4. Osmotic purgatives-
Magnesium salts: sulfate, hydroxide

Sodium salts: sulfate, phosphate

MECHANISM OF ACTION-
→All purgatives increase the water content of the faeces by:

(a).A hydrophilic or osmotic action, retaining water and electrolytes

in the intestinal lumen—increase volume of colonic content and
make it easily propelled.

(b). Acting on intestinal mucosa, decrease net absorption of water

and electrolyte.

(c). Increasing propulsive activity as primary action-allowing less

time for absorption of salt and water as a secondary effect.

1. BULK PURGATIVES-
→Dietary fibre: Bran Dietary fibre consists of unabsorbable cell
wall and other constituents of vegetable food—cellulose, lignin’s,
gums, pectin’s, glycoprotein’s and other polysaccharides.

Route & dose- 20-40 mg, orally

2. STOOL SOFTENER-
Docusates (Dioctyl sodium sulfosuccinate: DOSS) - It is an
anionic detergent, softens the stools by net water accumulation in
the lumen by an action on the intestinal mucosa.
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→It emulsifies the colonic contents and increases penetration of
water into the faeces.

Route & dose-

Laxicon- 100-150 mg tab., Doslax- 150 mg cap.

Side effect-
-Cramps

-Abdominal pain

-Hepatotoxicity.

Liquid paraffin-
→It is a viscous liquid; a mixture of petroleum hydrocarbons, that
was introduced as a laxative at the turn of 19th century.

Rout & dose- 15-30mg, orally, OD

Disadvantages
→It is bland but very unpleasant to swallow because of oily
consistency.

→While swallowing it may trickle into lungs—cause lipid

pneumonia.

3. STIMULANT PURGATIVES-
→They are powerful purgatives: often produce griping.

→They irritate intestinal mucosa and thus were thought to

primarily stimulate motor activity.

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Diphenylmethanes-
Sodium picosulfate -
R & D- 5-10 mg orally, syr.
Castor oil-
→The primary action is now shown to be decreased intestinal
absorption of water and electrolytes.

Dose- 15-25 ml adult, 5-15 ml children

4. OSMOTIC PURGATIVES-
→Solutes that are not absorbed in the intestine retain water
osmotically and distend the bowel—increasing peristalsis indirectly.

-Mag. sulfate (Epsom salt): 5–15 gm

-Mag. Hydroxide- 30 ml

Drugs for peptic ulcer-

Peptic ulcer-
→Peptic ulcer occurs in that part of the gastrointestinal tract which
is exposed to gastric acid and pepsin, i.e. the stomach and
duodenum.

→Peptic ulcer due to an imbalance between the aggressive (acid,

pepsin, bile and H. pylori) and the defensive (gastric mucus and
bicarbonate secretion, prostaglandins, nitric oxide, high mucosal
blood flow, innate resistance of the mucosal cells) factors.

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Classification-
1. Reduction of gastric acid secretion-
(a).Proton pump inhibitors:-
-Omeprazol

-Lansoprazole

-Pantoprazole

(b).H2 antagonist-
-Cimetidine

-Ranitidine

(c).Prostaglandin analogue-
- Misoprostol

2. Neutralization of gastric acid (Antacids-)-

(a).Systemic-
-Sodium bicarbonate

-Sod. Citrate

(b). Nonsystemic-
-Magnesium hydroxide

-Aluminium hydroxide gel

3. Ulcer protectives-
- Sucralfate

-Colloidal bismuth subcitrate (CBS)

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4. Anti-H. pylori drugs-
-Amoxicillin

-Metronidazole

-Tinidazole

-Tetracycline

1. Reduction of gastric acid secretion-

(a).Proton pump inhibitors (PPI)-
→All PPI are administered orally in enteric coated form to protect
them from molecular transformation in the acidic gastric juice.

→PPI are maintaining H+/K+ ATPase in the GIT.

Uses-
(1).Peptic ulcer-
→Omeprazole 20 mg OD is equally or more effective than H2
blockers. Relief of pain is rapid and excellent.

(2).Zollinger-Ellison syndrome-
→Omeprazole is more effective than H2 blockers in controlling
hyperacidity in Z-E syndrome.

Dose- 60-120 mg/day

Adverse effect-
→PPIs produce minimal adverse effects.

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→Nausea, loose stools, headache, abdominal pain, muscle and joint
pain.

Note- PPI is uses in empty stomach.

(b).H2-Antagonist-
→These are the first class of highly effective drugs for acid-peptic
disease.

→Their interaction with H2 receptors has been found to be

competitive in case of cimetidine, ranitidine.

Uses- To treat the peptic ulcer.

Adverse effect-
→Cimetidine is well tolerated by most patients: adverse effects
occur-

→Headache, dizziness, bowel upset, dry mouth, rashes.

(c).Prostaglandin analogue-
→PGE2 and PGI2 are produced in the gastric mucosa and appear to
serve a protective role by inhibiting acid secretion and promoting
mucus as well as HCO3¯ secretion.

Dose- 200μg QID.

2. Antacids-
→These are basic substances which neutralize gastric acid and raise
pH of gastric contents.

→Peptic activity is indirectly reduced if the pH rises above 4.

36
(a).Systemic Antacids-
Sodium bicarbonate-
→It is water soluble, acts instantaneously, but the duration of
action is short.

→It is a potent neutralizer (1 g → 12 mEq HCl), pH may rise above 7.

Sodium citrate-
→Properties similar to sod. bicarbonate; 1 g neutralizes 10 mEq
HCl, CO2 is not evolved.

(b).Non-systemic Antacids-
→These are insoluble and poorly absorbed basic compounds; react
in stomach to form the corresponding chloride salt.

→Mag. Hydroxide (MILK OF MAGNESIA) 0.4 g/5 ml suspension: 5

ml neutralizes 12 mEq acid.

Antacid combinations-
→A combination of two or more antacids is frequently used.

(a) Fast (Mag. hydrox.) and slow (Alum. hydrox.) acting components
yield prompt as well as sustained effect.

(b) Mag. salts are laxative, while alum. Salts are constipating:
combination may annul each other’s action and bowel movement
may be least affected.

Drugs- Acidin, Allugel, Digene.

Uses-
→Antacids are no longer used for healing peptic ulcer, because they

37
are needed in large and frequent doses, are inconvenient, can
cause acid rebound and bowel upset.

3. Ulcer protective’s-
→It is basic aluminium salt of sulated sucrose.

→Sucralfate has no acid neutralizing action, but delays gastric

emptying—its own stay in stomach is prolonged.

Dose- 1 gm for 4–8 weeks.

Colloidal bismuth subcitrate (CBS; Tripotassium
dicitratobismuthate)-
→It is a colloidal bismuth compound; water soluble but precipitates
at pH < 5.

Dose- Trymo, denol-120 mg tab.

4. Anti-Helicobacter Pylori drugs-
→Antimicrobials that are used clinically against H. pylori are:
amoxicillin, clarithromycin, tetracycline and metronidazole/
tinidazole.

38
 Nervous system
1. Neurotransmitter in CNS-
A. These are inhibitory effect on CNS-
→GABA (Gamma amino butyric acid)

→Glycine

→Dopamine

B. Stimulatory effect on CNS-

→Glutamate

→Aspartate

C. Mediate both inhibitory as well as excitory effect-

→Acetyle choline

→Nor-adrenaline

→Serotonone(5HT)

2. Sedative & Hypnotics-

Sedative-
→ Sedative is a drug that reduce excitement & calms the person
without induce sleep.

Hypnotics-
→A drug that produce sleep resembling normal sleep.

39
Classification:-
1. Benzodiazepines(BzDs)-
E.g. →Diazepam

→Oxazepam

→Lorazepam

→Flurazepam

→Nitrozepam

→Clonazepam

→Chlorodizepam

→Alphrazolam.

2. Barbiturates-
(1).Long acting-
→Phenobarbitone

→Mephobarbitone

(2).Short acting-
→Pentobarbitone

→ Secobarbitone

(3).Ultra short acting-

→Thiopentone

→ Methohexitone

40
3. Nonbenzodiazepam hypnotics-
→Zolpidem

→Zopiclone

4. Miscellaneous-
→Promethzine

→Neuroleptics

→Opiods

1. Benzodaizepine:-
→Benzodiazepines have a wide therapeutic index.

Mechanism of action-
BZDs →potential the inhibitory effect of GABA→CNS depress.

Side effects-
→Drowsiness

→Vertigo

→Amnesia

→ Blurred vision

Uses-
→Sedation and hypotics are uses for short term insomnia.

→Anticonvulsant-

→diazepam

→lorazepam

41
Benzodaizepine are:-
→Diazepam

→Oxazepam

→Lorazepam

→Flurazepam

→Nitrozepam

→Alphrazolam.

Muscle Relaxant: - The reduce muscle tone and are use fell in
spinal injury & spasm due to joint injury.

2. Barbiturates:-
→They are uses to hypnotics and sedative but are not use now
because they have a low therapeutic index.

They cause marked respiratory depression, they produce marked

hangover effect.

Adverse effect-
→drowsiness

→confusion

→Headache

→Respiratory depression

→Skin rashes

42
Pharmacological action and uses of barbiturates:-
1. Sedation & hypnotics-
→Barbiturates are uses to reaction of insomnia but present time
not recommended.

2. As general anesthesia-
→Thiopentone is uses for general anesthesia.

3. Non benzodiazepine hypnotics:-

Zaleplone -
→The drug produces near normal sleep like benzodiapine.

Route and dose-

7.5 to 10 mg at bed time orally.

Side effect-
-Headache

-Confusion

-Nausea

-Vomiting

43
 General Anaesthetics
→General anaesthetics (GAs) are drugs which produce reversible
loss of all sensation and consciousness. The cardinal features of
general anaesthesia are:

• Loss of all sensation, especially pain

• Sleep (unconsciousness) and amnesia

• Immobility and muscle relaxation

• Abolition of somatic and autonomic reflexes.

CLASSIFICATION OF ANESTHESIA:-
1. Inhalational-
(1).Gas-
→Nitrous oxide

(2).Volatile liquids-
→Ether

→Halothane

→Isoflurane

→Desflurane

→Sevoflurane

44
2. Intravenous:-
(1)Fast acting drugs-
→Thiopentone sodium

→Methohexitone sod.

→Propofol

→Etomidate

(2)Slower acting drugs-

→Benzodiazepines

→Diazepam

→Lorazepam

→Midazolam

→Dissociative anaesthesia

→Ketamine

→Opioid analgesia

→Fentanyl

1. INHALATIONAL ANAESTHETICS
(1). Nitrous oxide (N2O)-
→It is a colourless, odourless, heavier than air, non-inflammable
gas supplied under pressure in steel cylinders. It is non-irritating,
but low potency anaesthetic; unconsciousness cannot be produced
in all individuals without concomitant hypoxia.

45
→Patients maintained on 70% N2O +30% O2 along with muscle
relaxants often recall the events during anaesthesia, but some lose
awareness completely.

Uses-
→ Nitrous oxide is generally used as a carrier and adjuvant to other
anaesthetics

→ N2O (50%) has been used with O2 for dental and obstetric
analgesia.

Side effect-
→ N2O has little ceffect on respiration, heart and BP.

(2). Ether (Diethyl ether):-

→ It is a highly volatile liquid, produces irritating vapours which are
inflammable and explosive.

(C2H5 — O — C2H5)

→ Ether is a potent anaesthetic, produces good analgesia and

marked muscle relaxation by reducing ACh output from motor
nerve endings.

2. INTRAVENOUS ANAESTHETICS-
(1) FAST ACTING DRUGS:-These are drugs which on i.v. injection
produce loss of consciousness in one arm-brain circulation time
(~11sec). They are generally used for induction because of rapidity
of onset of action.

46
1. Thiopentone sod.-
→It is an ultra-shortacting thiobarbiturate, highly soluble in water
yielding a very alkaline solution, which must be prepared freshly
before injection.

Route & dose- Injected i.v. (3–5 mg/kg).

Redistribution of thiopentone-
Thiopentone → CNS(-ve) → BBB → suppressed → CNS → skeletal
muscle, adipose tissue→→REDISTRIBUTED→→depressed→→ CNS.

Adverse effect-
→ It is depressed respiratory center

→ It is poor analgesic

Uses –
→Occasionally used for rapid control of convulsions.

→ Gradual i.v. infusion of sub anaesthetic doses can be used to

facilitate verbal communication with psychiatric patients and for
‘narcoanalysis’ of criminals; acts by knocking off guarding.

2. Propofol-
→It is an oily liquid employed as a 1% emulsion.

→Currently, propofol has super seded-thiopentone as an i.v.

anesthetic, both for induction as well as maintenance.

Route & dose- 2mg/kg I.V.

Side effect-
→Metabolic distanstion.
47
→Cardiac heart failure.

→Pain during injection (due to oily.)

Uses-
→It is uses for induction and maintenance of anesthesia.

SLOWER ACTING DRUGS:-

1. Ketamine-
→This unique anaesthetic is pharmacologically related to the
hallucinogen phencyclidine.

→It induces a so called ‘dissociative anaesthesia’ characterized by

profound analgesia, immobility, amnesia with light sleep.

Route & dose- 1.5mg/kg I.V. & 0.5mg/kg I.M.

Adverse effect-
→Increase blood pressure

→Increase cranial pressure

→Hallucination

→Contraindication-

→HTN (hypertension)

→Ischemia

→Glaucoma

Uses- →For minor operation of the heart, neck and face.

→For dressing wound.
48
Difference b/t general & local anesthesia-

POINT GENERAL LOCAL

ANESTHESIA ANESTHESIA

1. Site of action CNS Peripheral nerve

2. Area of body Whole body Restricted area

involved

3. Consciousness Lost No changes

4. Care of vital Essential Usually not

functions needed

5. Physiological High Low

trespass

6. Poor health Risky Safe

patient
7. Use in non-
cooperative Possible Not possible
patient

49
 Local anesthesia
→Local anaesthetics (LAs) are drugs which upon topical application
or local injection cause reversible loss of sensory perception,
especially of pain, in a restricted area of the body.

→They block generation and conduction of nerve impulse at any

part of the neurone with which they come in contact, without
causing any structural damage.

CLASSIFICATION-
1. Injectable anaesthetic-
Low potency, short duration-

→Procaine

→Chloroprocaine

2. Intermediate potency and duration-

→Lidocaine (Lignocaine)

→Prilocaine

3. High potency, long duration-

→Tetracaine (Amethocaine)

→Bupivacaine

→Ropivacaine

→Dibucaine (Cinchocaine)

50
4. Surface anesthesia
Soluble Insoluble
Cocaine Benzocaine
Lidocane Butylaminobezoate
Tetracaine Oxethazaine
benoxinate

MECHANISM OF ACTION-
→The LAs block nerve conduction by decreasing the entry of Na+
ions during upstroke of action potential (AP). As the concentration
of the LAis increased the rate of rise of AP and maximum
depolarization decreases causing slowing of conduction.

Local anesthesia→→Block Na+ channels in the nerve fibers→ No

generation & conduction & impulse to CNS.

Adverse effect-
1. CNS
→Light headache

→Dizziness

→Mental confusion

→Respiratory arrest

2. CVS
→Bradycardia

→Cardiac arrhythmias

51
→Hypotension

→Hypersensitivity reaction

1. Lidocaine (Lignocaine)-
→Introduced in 1948, it is currently the most widely used LA. It is
versatile LA, good both for surface application as well as injection
and is available in a variety of forms.

Route & dose- 4% solution surface, 2% jelly form,5% ointment,2-

4% spray.

Uses-
→Burn

→Minor surgery

→Skin surgery

→Stomatitis

→Sore throat

2. Long acting with high potency-

→A potent & long lasting amides linked local anesthesia used for
infiltration, nerveblock, epidural& spinal anesthesia of long
duration.

Route & dose-

→0.5%-1% for spinal & 0.25-2.5% epidural.

52
Adverse effect-
→Cardiac arrest
→Swelling

Uses-
→Suturing of cut wound
→Episiotomy.

USES AND TECHNIQUES OF LOCAL ANAESTHESIA-

1. Surface anaesthesia-
→It is produced by topical application of surface anaesthetic
tomucous membranes and abraded skin. Only the superficial layer
is anaesthetised and there is no loss of motor function.

2. Infiltration anaesthesia-
→Dilute solution of LA is infiltrated under the skin in the area of
operation—blocks sensory nerve endings.

3. Conduction block-
→The LA is injected around nerve trunks so that the area distal to
injection is anaesthetized and paralyzed.

(a). Field block-

→It is produced by injecting the LA subcutaneously in a manner
that all nerves coming to a particular field are blocked—as is done
for herniorrhaphy, appendicectomy, dental procedures, scalp
stitching, operations on forearms and legs, etc.

53
(b). Nerve block-
→It is produced by injecting the LA around the appropriate nerve
trunks or plexuses. The area of resulting anaesthesia is still larger
compared to the amount of drug used. Muscles supplied by the
injected nerve/plexus are paralyzed.

4. Spinal anaesthesia-
→The LA is injected in the subarachnoid space between L2–3 orL3–
4 i.e. below the lower end of spinal cord. The primary site of action
is the nerve roots in the cauda equina rather than the spinal cord.
Lower abdomen and hind limbs are anaesthetized and paralyzed.
The level of anaesthesia depends on the volume and speed of
injection, specific gravity of drug solution and posture of the
patient. The drug solution could be hyperbaric (in 10%glucose) or
isobaric with CSF.

5. Epidural anaesthesia-
→The spinal dural space is filled with semi liquid fat through which
nerve roots travel. The LA injected in this space—acts primarily on
nerve roots (in the epidural as well as subarachnoid spaces to
which it diffuses) and small amount permeates through inter
vertebral foramina to produce multiple para-vertebral blocks.

6. Intravenous regional anaesthesia (Intravascular

infiltration anaesthesia)-
→It consists of injection of LA in a vein of a tourniquet occluded
limb such that the drug diffuses retrograde from the peripheral
vascular bed to nonvascular tissues including nerve endings. The
limb is first elevated to ensure venous drainage by gravity.

54
 ANALGESIC
Analgesic-
→A drug that selectively relieves pain by acting in the CNS or on
peripheral pain mechanisms, without significantly altering
consciousness.

Algesia (pain) -
→Pain is an ill-defined, unpleasant bodily sensation, usually evoked
by an external or internal noxious stimulus. Pain is a warning signal,
primarily protective in nature, but causes discomfort and suffering;
may even be unbearable and incapacitating. It is the most
important symptom that brings the patient to the physician.

Analgesics are divided into two groups-

A. Opioid/narcotic/morphine-like analgesics.
B. Non-opioid/non-narcotic/aspirin-like/antipyreticor anti-
inflammatory analgesics.
A.OPIOID ANALGESICS -
→Opium a dark brown, resinous material obtained from poppy
(Papaver somniferum) capsule. It contains two types of alkaloids.

1. Phenanthrene derivatives-
-Morphine (10% in opium)
-Codeine (0.5% in opium)

2. Benzoisoquinoline derivatives (non analgesic) -

-Papaverine (1%)
-Noscapine (6%)

55
CLASSIFICATION OF OPIOIDS-
1. Natural opium alkaloids:
-Morphine

-Codeine

2. Semi synthetic opiates:

-Diacetylmorphine (Heroin)

-Pholcodeine

-Ethylmorphine

3. Synthetic opioids:
-Pethidine (Meperidine)

-Fentanyl

-Methadone

-Tramadol

1. MORPHINE-
→Morphine is the principal alkaloid in opium and widely used till
today. Therefore, it is described as prototype.

Mechanism of action-
→Morphine is depressed pain impulses transmission in the brain
intracting with opioids receptor (the receptor located at spinal,
supra-spinal site).

Route & dose -

→10-50mg orally/IM/Sc, 2-6mg IV.

56
PHARMACOLOGICAL ACTIONS-
1. CNS-
→Morphine has site specific depressant and stimulant actions in
the CNS by interacting primarily with the μ opioid receptor (for
which it has the highest affinity), as a full agonist.

The depressant actions are:

(1). Analgesia-
→Morphine is a strong analgesic. Though dull, poorly localized
visceral pain is relieved better than sharply defined somatic pain;
higher doses can mitigate even severe pain; degree of analgesia
increasing with dose.

(2). Mood and subjective effects (Euphoria)-

→These are prominent. Morphine has a calming effect; there is loss
of apprehension, feeling of detachment, lack of initiative, limbs feel
heavy and body warm, mental clouding and inability to concentrate
occurs.

(3). Sedation-
→Sedation is different from that produced by hypnotics is seen.
Drowsiness and indifference to surroundings as well as to own
body occurs without motor in coordination, ataxia or apparent
excitement (contrast alcohol). Higher doses progressively induce
sleep and then coma.

(4). Respiratory centre-

→Morphine depresses respiratory centre in a dose dependent
manner; rate and tidal volume are both decreased. Death in
morphine poisoning is due to respiratory failure.
57
(5). Cough centre-
→It is depressed by morphine, and is more sensitive than
respiratory centre.

Morphine stimulant-
(1).CTZ-
→Nausea and vomiting occur as side effects especially if stomach is
full and the patient stands or moves about. Thus, morphine
appears to sensitize the CTZ to vestibular and other impulses.

(2).CVS-
→Morphine causes vasodilatation due to:
(a) Histamine release.
(b) Depression of vasomotor centre.
(c) Direct action decreasing tone of blood vessels.

(3).GIT-
→Constipation is a prominent feature of morphine action.

(4).Other smooth muscles-

(a).Biliary tract-
→Morphine causes spasm of sphincter of Oddi → intrabiliary
pressure is increased several fold → may cause biliary colic.

(b).Urinary bladder-
→Tone of both detrusor and sphincter muscle is increased urinary
urgency and difficulty in micturition. Contractions of
ureter are also increases.

Adverse effect-
-Nausea

-vomiting

58
-Hypertension

-Confusion & drowsiness

-Adverse effect drug dependency.

Contraindication-
1. Infants and the elderly are more susceptible to the respiratory
depressant action of morphine.

2. It is dangerous in patients with respiratory insufficiency

(emphysema, pulmonary fibrosis); sudden deaths have occurred.
Morphine accentuates sleep apnea; hypoxic brain damage can
occur.

3. Bronchial asthma: Morphine can precipitate an attack by its

histamine releasing action.

2. CODEINE-
→It is methyl-morphine, occurs naturally in opium, and is partly
converted in the body to morphine.

→It is analgesic & cough suppressant.

→It is administered orally 10-30 mg.

Side effect-
→Constipation & sedation

3. Pethidine (Meperidine)-
→Pethidine was synthesized as an atropine substitute in 1939, and
has some actions like it.

→It is well absorbed from the GIT widely distributed in the body.
→Cross the placenta barrier & is metabolite in the liver.
59
Route & dose- 50-100mg IM & SC, orally
Side effect-
→Over dose of pethidine produce many effect-

-Tremors

-Mydriasis

-Hyper reflexia

-Convulsions

Uses –
→Pethidine is primarily used as an analgesic (substitute of
morphine) and in pre-anaesthetic Medication.

→It has also been used to control shivering during recovery from
anaesthesia or that attending i.v. infusion.

→Use during labor pain.

(B).NSAID/Non-opioids-
→All drugs grouped in this class have analgesic, antipyretic and
anti-inflammatory actions in different measures.

→In contrast to morphine they do not depress CNS, do not produce

physical dependence, has no abuse liability and is weaker
analgesics (except for inflammatory pain). They are also called non-
narcotic, non-opioid.

60
CLASSIFICATION OF NSAID-
1. Non-selective COX inhibitors (traditional NSAIDs)-
(1). Salicylates-

-Aspirin
(2). Propionic acid derivatives-
-Ibuprofen

-Naproxen

-Ketoprofen

-Flurbiprofen

(3). Acetic acid derivatives-

-Diclofenac
-Acetaminophen

(4). Fenamate-
-Mephenamic acid
(5). Oxican derivatives-
-Piroxicam

-Tenoxicam

(6). Pyrrolacetic acid-

-Ketorolac

61
(7). Indolacetic derivatives-
-Indomethacin

-Sulindac

2. Preferentail COX-2 inhibitors-

-Nimesulide

-Meloxicam

-Nabumetone

3. Highly selective COX-2 inhibitors-

-Etoricoxib

-Parecoxib

4. Analgesic-Antipyretics with poor anti-inflammatory

action-
-Paracetamole (PCM)

-Nefopam

Aspirin (prototype)-
→Aspirin is acetylsalicylic acid. It is rapidly converted in the body to
salicylic acid which is responsible for most of the actions.

→It is one of the oldest analgesic- 62 anti-inflammatory drugs and

is still frequently used.

62
Mechanism of action-
→Aspirin inhibit both COX-1 & COX-2 isoform their by decrease PGs
(Prostaglandis) & prombacton synthesis.

→Aspirin caused irreversible inhibition COX activities & other

NSAID caused reversible inhibition of enzyme.

Route & dose-

→As analgesic 0.32-0.60gm, orally

→Rheumatic fever-75-100mg/kg/day

→Rheumatic arthritis- 2-5gm/day

Adverse effect of aspirin-

1. GIT-
-Peptic ulcer

-Nausea & vomiting

-Epigestric pain

-GI bleeding

2. Hypersensitivity-
→Reactions include rashes, fixed drug eruption, urticaria,
rhinorrhoea, angioedema, asthma and anaphylactoid reaction.

3. Acute salicylate poisoning-

→Vomiting, dehydration, electrolyte imbalance, acidotic breathing,
hyper/ hypoglycemia.

63
4. Reye’s syndrome-
→Reye’s syndrome’, a rare form of hepatic encephalopathy seen in
children having viral (varicella, influenza) infection.

5. Pregnancy-
→The drug inhibit PGs synthesis there are dealing onset of labor &
increase chance of PPH (Post-partum hemorrhage).

Uses-
1. As analgesic-
-Headache

-Toothache

-Joint pain

-Backache

2. As antipyretics-
→Aspirin is effective in fever of any origin, dose is same as for
analgesia.

3. Acute rheumatic fever-

→Aspirin is the preferred in reduced fever, relief in swelling& joint
pain.

4. Rheumatoid arthritis-
→NSAID analgesic & anti-inflammatory effect on the symptomatic
relief.

64
6. Osteoarthritis-
→It affords symptomatic relief only, may be used on ‘as and when
required’ basis, but paracetamol is the first choice analgesic for
most cases.

PHARMACOLOGICAL ACTIONS-
1. Analgesic effect-
→The analgesic action is mainly due to obtunding of peripheral
pain receptors and prevention of PG-mediated sensitization of
nerve endings. A central sub cortical action raising threshold to pain
perception also contributes, but the morphine-like action on
psychic processing or reaction component of the pain is missing.

2. Acid-base and electrolyte balance-

→Anti-inflammatory doses produce significant changes in the acid-
base and electrolyte composition of body fluids. Aspirin stay in a
state of compensated respiratory alkalosis.

3. GIT-
→Aspirin and released salicylic acid irritate gastric mucosa.

→Cause epigastric distress, nausea and vomiting.

4. CVS-
→Aspirin has no direct effect on heart or blood vessels in
therapeutic doses. Larger doses increase cardiac output to meet the
increased peripheral O2 demand, and cause direct vasodilatation.

65
5. Blood-
→Aspirin, even in small doses, irreversibly inhibits TXA2 synthesis
by platelets.

Other NSAID-
1. Ibuprofen (Brufen)-
→It has moderate anti-inflammatory effect.

→It is better tolerating than aspirin.

→It can be used in children but doesn’t use cause Reye’s syndrome.

Route & dose-

→400mg-600mg (TDS) orally, Topic gel.

2. Diclofenac (Voveran)-
→It has potent anti-inflammatory effect.

→Incidence of hepatotoxocoty is more.

→Combination of diclofenac misprostal is available, which reduced

GI irritation & peptic ulcer.

Route & dose-

→50mg BD & 100mg OD, orally, IM, Topical gel & ophthalmic in eye
drop.

3. Indomethacin (Inocid)-
→It has not selective COX inhibitor & potent anti-inflammatory
effect.

66
→It has prominent GI side effects.

Route & dose-

→Orally, eye drop & suppository, 50mg (TDS)

4. Piroxocam (Pirox)-
→It has potent anti-inflammatory & long acting.

Route & dose-

→IM, Topically gel, 20md (OD)
5. Ketorolic (Torolac)-
→It has analgesic effect.

→It relieve pain without casing respiratory depression,

hypotension & drug dependency.

Route & dose-

→Orally, IM, IV, 10-20mg (QID)

6. Selective COX-2 inhibitor-

→Peracoxib is administered parentral & etoricoxib is enteral route.

Route & dose-

→Peracoxib – 40mg IM, IV

→Etoricoxib- 60-120mg Orally, OD

67
Competitive feature non-selective COX-1 & selective COX-2
inhibitor-
S.N. Non-selective COX-1 Selective COX-2 inhibitor
1. Analgesic effect Present
present
2. Antipyretic effect Present
present
3. Anti-inflammatory present
effect present
4. Anti-platelets effect No effect
present
5. GI side effects are GI side effects are rare(Less
more effect ulcergenic potential)

Paracetamol(PCM)/Acetaminophen-
→It is administered by orally, rectum, IM/IV route.

→It is well absorbed & widely distributed all over the body.

→Metabolism in the liver & metabolite are excreted in urine.

Phenacetin-
→Phenacetin is introduced in 1887.

→PCM the active metabolic of the last century but has come into
common used since 1950.

Route & dose- 0.5-1mg TDS

→Infant-50mg, children (1-3 years) 80-160mg-orally.

68
Uses-
→As an anti-pyretic- reduce body temperature during fever.

→As Analgesic-

-Relieve pain

-Headache

-Toothache

-Muscle pain

-Dysmenorrhea

→It is the preferred the analgesic & anti-pyretic in patient with

peptic ulcer, bronchial asthma.

Acute paracetamol poisoning-

→Acute overdose mainly causes hepatotoxicity.

→These symptoms are nausea, vomiting, diarrhea.

Treatment-
→Anti-dot of PCM-

N-acetylcysteine

→Universal anti-dot – Active charcoal.

→Activated charcoal administered to decrease absorption PCM

from the Gut.

69
Gout-
→It is a metabolic disorder characterized by hyper uricaemia
(normal plasma urate 2–6 mg/dl). Uric acid, a product of purine
metabolism, has low water solubility, especially at low pH.

→When blood levels are high, it precipitates and deposits in joints,

kidney and subcutaneous tissue (trophy).

Uric acid raised Arthritis Deposition sodium

urate(crystallized in joint).
Drugs used in gout are:
1. For acute gout-
(a).NSAIDs

(b).Colchicine

(c).Corticosteroids

2. For chronic gout/hyperuricaemia-

(1). Uricosurics (2). Synthesis inhibitors

(a). Probenecid (a). Allopurinol

(b). Sulfinpyrazone (b). Febuxostat

1. Acute gout-
→Acute gout manifests as sudden onset of severe inflammation in
a small joint (commonest is metatarso-phalangeal joint of great
toe) due to precipitation of urate crystals in the joint space.

70
(a). NSAIDs-
→One of the strong anti-inflammatory drugs, e.g. naproxen,
piroxicam, diclofenac, indomethacin or etoricoxib is given in
relatively high and quickly repeated doses.

(b). Colchicine-
→Colchicine is used to relive acute attack of gout.

Route & dose- 0.5-1.5mg orally.

Adverse effect-
-Nausea & vomiting

-Diarrhea

-Abdominal pain

Use-
→It is used in acute gout.

→It is used as prophylaxis.

(c). Corticosteroids-
→Intra-articular injection of a soluble steroid suppresses symptoms
of acute gout.

Route & dose- 40-6-mg IV/orally (OD).

2. Chronic gout-
→In majority of patients, hyper uricaemia is due to under secretion
of uric acid, while in few it is due to over production.

71
(1). Uricosuric drugs-
→Increase uric acid excretion by direct action of renal tubule.

R/D- 0.5- 1.5gm BD.

Adverse effect-
-Dyspepsia

-Toxic dose

-Conversion

-Respiratory failure.

(2). Synthesis inhibitor-

Allopurinol-
→Allopurinol itself is a short-acting (t½ 2 hrs) competitive inhibitor
of xanthine oxidase, but its major metabolite all oxanthine
(oxypurine) is a long-acting (t½ 24 hrs).

R & D- 100-300mg orally (BD).

Mechanism of action-
Allopurinol xanthine oxidase xanthine uric acid.
→It present the synthesis of uric acid by inhibiting the enzyme
xanthine oxidase thus reduce plasma urete.

→It reduce crystal in the kidney, joint, soft tissue.

Adverse effect-
-Skin rashes

72
-Nausea & vomiting

-Diarrhea

Uses-
→Allopurinol is the first drug of choice for gout.

Anti-rheumatoid drugs-
Rheumatoid arthritis-
→Rheumatoid arthritis (RA) is an autoimmune disease in which
there is joint inflammation, synovial proliferation and destruction
of articular cartilage.

→ Immune complexes composed of IgM activate complement and

release cytokines (mainly TNFα and IL-1) which are chemotactic for
neutrophils.

Classification-
1. NSAIDs-
-Aspirin

-Ibuprofen

2. Glucocorticosteroid-
-Predinisolone

3. Disease modifying anti-rheumatic drugs (DMARDs)-

A. Non-biological drugs
1. Immunosuppressants: Methotrexate, Azathioprine, Cyclosporine

73
2. Sulfasalazine

3. Chloroquine or Hydroxychloroquine

4. Leflunomide

B. Biological agents
1. TNFα inhibitors: Etanercept, Infliximab,Adalimumab

2. IL-1 antagonist: Anakinra.

1. NSAIDs-
→NSAIDs are analgesic, Anti-pyretics, Anti-inflammatory drugs.

2. Glucocorticoids-
→Predinisolone

Predinisole-
→Glucocorticoids have potent immunosuppressant and anti-
inflammatory activity: can be inducted almost at any stage in RA
along with first or second line drugs, if potent anti-inflammatory
action is required while continuing the NSAID ± DMARD.
Symptomatic relief is prompt and marked but they do not arrest
the rheumatoid process, though joint destruction may be slowed
and bony erosions delayed.

3. Disease modifying anti-rheumatic drugs (DMARDs)-

(1). Methotrexate (Mtx)-
→This dihydrofolate reductase inhibitor has prominent
immunosuppressant and anti-inflammatory property. Beneficial
effects in RA are probably related to inhibition of cytokine
production, chemotaxis and cell-mediated immune reaction.
74
Route & dose- 7.5- 15mg, orally.
Adverse effect-
-Nausea

-Vomiting

-Hepatotoxicity

Uses-
-Psoriasis

-Organs transplantation, Ectopic pregnancy.

(2). Chloroquine and hydroxychloroquine-

→These are anti-malarial drugs found to induce remission in up to
50% patients of RA.

Route & dose- 150mg (base)/day IM/IV.

Adverse effect-
-Nauseas

-Vomiting

-Skin rashes

(3). Gold -
→Injected I.M. as gold sodium thiomalate, gold is the oldest drug
capable of arresting progression of RA. Because of high toxicity
(hypertension, dermatitis, stomatitis, kidney/ liver/bone marrow
damage) it has gone out of use.

75
(4). d-Penicillamine-
→It is a copper chelating agent with gold like action in RA. Toxicity
is also similar and it is no longer used in this disease.

(5). Leflunomide-
→This immunomodulator inhibits proliferation of stimulated
lymphocytes in patients with active RA. Arthritic symptoms are
suppressed and radiological progression of disease is retarded.

Route & dose- 20mg/day, orally

Adverse effect-

-Diarrhea
-Loss of hair

-Liver toxicity

-Thrombocytopenia

NOTE- It is not to be used in children and pregnant/lactating

women.

76
Drugs Used in Mental Illness-Antipsychotic drugs or
Neuroleptics drugs-
These are drugs having a salutary therapeutic effect in psychoses.

CLASSIFICATION
1. Phenothiazines-
-Chlorpromazine
-Triflupromaze
-Thioridazine
2. Butyrophenones
-Haloperidol

-Trifluperidol

-Penfluridol

3. Thioxanthenes
-Flupenthixol

4. Atypical antipsychotics
-Clozapine

-Aripiprazole

-Risperidone

-Ziprasidone

Mechanism of action-
1. Conventional antipsychotic-
→Mainly block dopamine (D2) receptor in the limbic system.

77
2. Aptical antipsychotic-
→DA over activity in the limbic area is not the only abnormality in
schizophrenia. Other monoaminergic (5-HT) as well as amino acid
(glutamate) neurotransmitter systems may also be affected.

Pharmacological action-
1. CNS-
-Reduce hesitation & aggressive

-Reduce spontaneous movement

-Suppress hallucination

-Reduce anxiety.

2. Endocrine system-
→Neuroleptics consistently increase prolactin release by blocking
the inhibitory action of DA on pituitary lactotropes. This may result
in galactorrhoea and gynaecomastia.

3. Skeletal muscle-
→Neuroleptics have no direct effect on muscle fibres or
neuromuscular transmission.

Adverse effect-
1. Parkinsonism with typical manifestations—
→Rigidity, tremor, hypokinesia, mask like facies, shuffling gait;
appears between 1–4 weeks of therapy and persists unless dose is
reduced.

78
2. Acute muscular dystonias-
→Bizarre muscle spasms, mostly involving linguo-facial muscles —
grimacing, tongue thrusting, torticollis, locked jaw; occurs within a
few hours of a single dose or at the most in the first week of
therapy.

3. Akathisia -
→Restlessness, feeling of discomfort, apparent agitation
manifested as a compelling desire to move about, but without
anxiety, is seen in some patients between 1–8 weeks of therapy: up
to 20% incidence.

3. Tardive dyskinesia-
→It occurs late inneuroleptic: manifests as purposeless involuntary
facial and limb movements like constant chewing, pouting, puffing
of cheeks, lip licking, choreoathetoid movements.

Other side effect-

-Weight gain
-Skin rashes
-Agranulocytosis
-Dermatitis

Therapeutic uses-

1. Schizophrenia-
→The antipsychotics are used primarily in functional psychoses.
They have an indefinable but definite therapeutic effect in all forms
of schizophrenia: produce a wide range of symptom relief.

2. Mania -
→Antipsychotics are required in high doses for rapid control of
acute mania, and mania patients tolerate them very well.
79
3. As antiemetic-
→The typical neuroleptics are potent antiemetics.

4. Anxiety-
→Antipsychotics have antianxiety action but should not be used for
simple anxiety because of psychomotor slowing, emotional
blunting, autonomic & effect side.

Anti-depressant drugs-
→These are drugs which can elevate mood in depressive illness.
Practically all antidepressants affect monoaminergic transmission
in the brain in one way or the other, and many of them have other
associated properties.

Classification-

1. Tricyclic antidepressants (TCAs)-

-Imipramine
-Amitriptyline
-Trimipramine
-Doxepin
-Dothiepin
-Clomipramine

2. Selective serotonin reuptake inhibitors (SSRIs)

-Fluoxetine
- Fluvoxamine
- Paroxetine
-Sertraline
-Citalopram

80
3. Atypical antidepressants-
-Trazodone

-Mianserin

-Mirtazapine

4. MAO inhibitors-
-Moclobemide
1. Tricyclic antidepressants (TCAs)-
→Imipramine, an analogue of CPZ was found during clinical trials
(1958) to selectively benefit depressed but not agitated psychotics.
In contrast to CPZ, it inhibited NA and 5-HT reuptake into neurones.
A large number of congeners were soon added and are called
tricyclic antidepressants (TCAs).

Mechanism of action-
→The TCAs and related drugs inhibit NET and SERT which mediate
active reuptake of biogenic amines NA and 5-HT into their
respective neurons and thus potentiate them. They, however, differ
markedly in their selectivity and potency for different amines.

Eg. Amitriptyline 50-200mg orally.

Adverse effect-
-Dry mouth

-Weakness

-Conversion

-Constipation

81
2. Selective serotonin reuptake inhibitors (SSRIs)-
→The major limitations of TCAs (first generation Anti-depressants)
are:
→Frequent anti-cholinergic, cardiovascular and neurological side
effects.
→Relatively low safety margin. They are hazardous in overdose;
fatalities are common.
Side effect-
-Nausea
-vomiting
-Insomnia
-Loss of libido (loss of sexual desire)

3. Atypical antidepressants-
Trazodone-
→It is the first atypical antidepressant; less efficiently blocks 5-HT
uptake and has prominent α adrenergic and weak 5-HT2
antagonistic actions. The latter may contribute to its antidepressant
effect, which nevertheless is modest.

Adverse effect-
-Nausea

-Vomiting

-Bradycardia

4. MAO inhibitors-
→MAO is a mitochondrial enzyme involved in the oxidative
deamination of biogenic amines (Adr, NA, DA, 5-HT). Two
isoenzyme forms of MAO have been identified.

82
(a). MAO-A: Preferentially deaminates 5-HT and NA, and is
inhibited by clorgyline, moclobemide.

(b). MAO-B: Preferentially deaminates phenylethylamine and is

inhibited by selegiline. Dopamine is degraded equally by both
isoenzymes.

Route & dose- 150mg BD, orally

Adverse effect-
-Nausea

-Dizziness

-Headache

-Insomnia

-Rarely excitement and liver damage.

Uses-
-Antidepressant, social phobia.

Anti-anxiety drugs-
Anxiety-
→It is an emotional state, unpleasant in nature, associated with
uneasiness, discomfort and concern or fear about some defined or
undefined future threat. Some degree of anxiety is a part of normal
life.

83
Anti-anxiety drugs-
→These are an ill-defined group of drugs, mostly mild CNS
depressants, which are aimed to control the symptoms of anxiety,
produce a restful state of mind without interfering with normal
mental or physical functions.

Classification-
1. Benzodiazepines-
-Diazepam

-Chlordiazepoxide

-Oxazepam

-Lorazepam

- Alprazolam

2. Azapirones -
-Buspirone

-Gepirone

-Ispapirone

3. Sedative anti-histaminic-
-Hydroxyzine

4. β-blocker-
-Propranolol

84
1. Benzodizepines(BZDs)-
→Some members have a slow and prolonged action; relieve anxiety
at low doses without producing significant CNS depression.

2. Buspirone-
→It is the first azapirone, a new class of antianxiety drugs, distinctly
different from BZDs.

→Buspirone relieves mild-to-moderate generalized anxiety, but is

ineffective in severe cases, in those showing panic reaction.

→The therapeutic effect develops slowly; maximum benefit may be

delayed up to 2 weeks.

→Antagonistic action at certain postsynaptic 5-HT1A receptors has

also been demonstrated.

Route & dose- 5 – 15mg OD/TDS, orally.

3. Hydroxyzine-
→An H1 antihistaminic with sedative, antiemetic, antimuscarinic
and spasmolytic properties.

→It is claimed to have selective anxiolytic action, but the

accompanying sedation is quite marked.

Route & dose- 50 – 200mg, orally.

4.β-Blockers-
→Many symptoms of anxiety (palpitation, rise in BP, shaking,
tremor, gastrointestinal hurrying, etc.) are due to sympathetic over
activity and these symptoms reinforce anxiety.

85
→They do not affect the psychological symptoms such as worry,
tension and fear, but are valuable in acutely stressful situations
(examination fear, unaccustomed public appearance, etc.).

→The role of β blockers in anxiety disorders is quite limited.

86
 Respiratory system
DRUGS FOR BRONCHIAL ASTHMA-
→Bronchial asthma is characterized by hyper responsiveness of
trachea-bronchial smooth muscle to a variety of stimuli, resulting in
narrowing of air tubes, often accompanied by increased secretion,
mucosal edema and mucus plugging.

→Mast cells (present in lungs) and inflammatory cells recruited as a

result of the initial reaction produce a multitude of mediators by
the following processes:

• Release of mediators stored in granules (immediate): histamine,

protease enzymes, TNF-α.

CLASSIFICATION-
I. Bronchodilators-
A. β2 Sympathomimetics-
-Salbutamol

-Terbutaline

-Salmeterol

-Formoterol

B. Methylxanthines-
-Theophylline (anhydrous)

-Aminophylline

87
-Choline theophyllinate

C. Antchollinergics-
-Ipratropium bromide

-Tiotropium bromide

II. Leukotriene antagonists-

-Montelukast

-Zafirlukast

III. Mast cell stabilizers-

-Sodium cromoglycate

-Ketotifen

IV. Corticosteroids-
A. Systemic-
-Hydrocortisone

-Prednisolone

B. Inhalational-
-Beclomethasone dipropionate

-Budesonide

-Fluticasone propionate

-Flunisolide

88
1. Bronchodilator-
Sympathomimetics-
(1)Salbutamol (Albuterol) -
→A highly selective β2 agonist; cardiac side effects are less
prominent.

→An inhalation they have a rapid onset (1-5 minute) & short
duration of action.

→They are mostly useful for acute attack of asthma.

Mechanism of action-
Adrenergic drugs are broncho dilatation through β2 receptor
stimulation → increased cAMP formation in bronchial muscle cell
→ relaxation.

Route & dose-

→2-4mg orally, 0.25- 0.50mg I.M & SC, 100-200μg inhalation.

Note-
→Inhance salbutamole produced broncho-dilation with 5minute &
the action last for 2 – 4 hours.

Adverse effect-
-Muscle trimmer

-Bradycardia

-Palpitation

-Throat irritation

-Restlessness

89
Uses- Asthmatic condition.
(2)Terbutaline-
→It is similar to salbutamol in properties and use.

→Route &Dose: 5 mg oral, 0.25 mg SC, 250 μg by inhalation.

(3)Salmeterol-
→It is the first long acting selective β2 agonist with a slow onset of
action.

→Route & dose- 25 μg twice daily inhalation.

Adrenalin-
→It is produced powerful bronchodilation, uses in acute attack of
asthma.

Mechanism of action-
Sympathomimetics→ Bronchioles → Bronchodilator.

Route & dose- 0.2-0.5 ml solution, SC.

Side effect-
→Causes of adrenaline
→Cardiac side effect.

Therapeutic uses-
A-Anaphylatic shock

B-Bronchial asthma

C-Cardiac arrest
90
D-Prolonged Duratin of action

E-Control of epitasis (Bleeding in nose).

Methylxanthines-
→Theophylline and its compounds have been extensively used in
asthma, but are not considered first line drugs any more. They are
used more often in COPD.

- Theophylline (anhydrous)
-Aminophylline

Mechanism of action-
Theophylline (anhydrous), Aminophylline

Inhibit phosphodiesterase

Bronchodilation

Route & dose-

Theophylline (anhydrous) – 100-300 mg TDS orally

Aminophylline - 250-500 mg orally.

Adverse effect-
-Insomnia

-Conversion

-Trimmer

-Nausea

-Headache.

91
Anticholinergics-
→Atropinic drugs are bronchodilatation by blocking M3 receptor
mediated cholinergic constrictor tone; act primarily in the larger
airways which receive vagal innervations.

→some recent evidence points to presence of M3 receptors on

peripheral bronchiolar muscles as well, though they are not vagally
innervated.

→Ipratropium bromide is a short acting (duration 4–6 hours)

inhaled anticholinergic bronchodilator, while tiotropium bromide is
long acting (duration 24 hours).

→Both are less efficacious than inhaled β2 sympathomimetics in

bronchial asthma.

Mechanism of action-
→The inhibit the physiological action acetylcholine at a receptor
side.

2. Leukotriene antagonists-
-Montelukast
- Zafirlukast

→ leukotriene are important mediators of bronchial asthma.

92
Mechanism of action-
Montelukast,Zafirlukast

Leukotriene receptor

Inhibit bronchial cell

Reduce bronchial asthma

Route & dose-

-Montelukast- 10mg orally
- Zafirlukast-20 mg orally

Adverse effect-
-Headache

-Skin rashes

-Eosinophilia

Uses- In the bronchodilator & suppressed asthma.

3. Mast cell stabilizers-

Sodium cromoglycate (Cromolyn sod.)-
→It is a synthetic chromone derivative which inhibits degranulation
of mast cells (as well as other inflammatory cells) by trigger stimuli.
→Release of mediators of asthma like histamine, LTs, PAF,
interleukins, etc. is restricted.

→The basis of this effect is not well understood, but may involve a
delayed Cl¯ channel in the membrane of these cells.
93
Mechanism of action-
Sodium cromoglycate

Inhibit degrenulation of mast cell & release of histamine, PGs etc

Reduce inflammation

Route & dose- 1.5 mg OD, Inhalation

Adverse effect-
-Throat irritation

-Skin rashes

-Dizziness

-Dry mouth.

Ketotifen-
→ It is an antihistaminic (H1) with some cromoglycate like action.

Route & dose- 1-2 mg BD, orally.

Drugs uses for cough-

→Cough is a protective reflex, its purpose being expulsion of
respiratory secretions or foreign particles from air passages.

→Cough may be useful or useless. Useless (nonproductive) cough

should be suppressed. Useful (productive) cough serves to drain the
airway, its suppression is not desirable, may even be harmful,
94
except if the amount of expectoration achieved is small compared
to the effort of continuous coughing.

Classification-
1. Pharyngeal demulcents-
-Lozenges
-linctuses containing syrup
-liquorice

2. Expectorants (Mucokinetics)-
-Sodium or Potassium citrate
-Potassium iodide
-Guaiphenesin

3. Mucolytics-
-Bromhexine
-Ambroxol
-Acetyicysteine

4. Anti-tussives (Cough centre suppressants)-

(a) Opioids: Codeine, Pholcodeine

(b) Nonopioids: Noscapine, Dextromethorphan

(c) Antihistamines: Chlorpheniramine, Diphenhydramine,

Prenoxdiazine

95
1. Pharyngeal demulcents-
→Pharyngeal demulcents sooth the throat and reduce afferent
impulses from the inflamed/irritated pharyngeal mucosa, thus
provide symptomatic relief in dry cough arising from throat.

2. Expectorants (Mucokinetics)-
→Expectorants (Mucokinetics) are drugs believed to increase
bronchial secretion or reduce its viscosity, facilitating its removal by
coughing.

E.g. Sodium and potassium citrate are considered to increase

bronchial secretion by salt action. Potassium iodide is secreted by
bronchial glands and can irritate the airway mucosa.

3. Mucolytics-
→These agent breaks the thick sputum & viscosity of sputum. So
that he sputum comes out easily with less effort.

Mechanism of action-
Bromohexine/acetylcysteine

Decrease viscosity of sputum

Cough becomes less tiring & productive

96
(1). Bromhexine-
→A derivative of the alkaloid vasicineobtained from Adhatoda
vasica (Vasaka), is a potent mucolytic and mucokinetic, capable of
inducing thin copious bronchial secretion.

R/D- 8 mg, orally, TDS

Side effect-
-Rhinorrhoea
-Lacrimation
-Nausea
-Gastric irritation
-Hypersensitivity

(2). Ambroxol-
R/D- 15 -30 mg TDS
(3). Acetylcysteine-
→It opens disulfide bonds in mucoproteins present in sputum—
makes it less viscid, but has to be administered directly into the
respiratory tract.

4. Antitussive-
→These are drugs that act in the CNS to raise the threshold of
cough centre or act peripherally in the respiratory tract to reduce
tussal impulses or both these actions.

(a). Opioid-
(1). Codine-
→It has cough centre suppressed

97
R/D- 10-30 mg orally.
Side effect-
-Respiratory depressed
-Drowsiness
-Constipation

Uses-
-Pain killer
-Muscle relaxant

Contrainditon-
→children’s & asthmatic patient

(2). Pholcodeine-
→Pholcodeine It has practically no analgesic or addicting property,
but is similar in efficacy as antitussive to codeine and is longer
acting—acts for 12 hours.

(b). Nonopioids-
(1). Noscapine (Narcotine)-
→An opium alkaloid of the benzoisoquinoline series . It depresses
cough but has no narcotic, analgesic or dependence inducing
properties. It is nearly equipotent antitussive as codeine, especially
useful in spasmodic cough.

R/D- 15-30 mg Orally.

Uses- It uses in spasmodic cough.

98
Side effect-
-Headache
-Nausea

Contraindication- Asthma
(2). Dextromethorphan-
→A synthetic central NMDA (N-methyl D-aspartate) receptor
antagonist; the d-isomer has antitussive action while l-isomer is
analgesic. Dextromethorphan does not depress mucociliary
function of the airway mucosa and is practically devoid of
constipating action.

R/D- 10-20 mg orally.

Side effect-
-Dizziness
-Nausea
-drowsiness

(c). Anti-histamines-
→Many H1 antihistamines have been conventionally added to
antitussive/expectorant formulations. They afford relief in cough
due to their sedative and anticholinergic actions, but lack selectivity
for the cough centre.

(1). Chlorpheniramine-
→It is white crystalline power with bitter taste. It is soluble in
water. It decreases allergic reaction by blocking histamine.

99
R/D- 2-4 mg orally,
Indication- cough, rhinitis.
Contraindication- hypersensitive reation.
Side effect-
-Drowsiness
-Anxiety
-Chest tightness

(2). Diphenhydramine-
Dose- Adult 25-50 mg orally, 6 hours.
Children’s orally 5 mg per kg body weight.

(3). Prenoxdiazine-
Dose-
-Adult orally 20-50 mg OD.
-Children up to 1 year age 5-10 mg OD.
-1-5 year age 10-15 mg.
-6-12 year 15-25 mg daily.

100
 BLOOD
Drugs Affecting Coagulation, Bleeding-
Haemostatic agents-
→They arrest bleeding either by vasoconstriction or by promoting
coagulation of blood.

Classification-
Haemostatic

1. Local agents (styptics) 2. Systemic agent

-Adrenaline -Vitamin-K

-Thrombin -Fibrinogen

-Fibrin -Antihemophilic factor

-Gelatins -Monosemicarbozone

-Calcium alginate -Ethamsylate

-Oxidized cellulose -Demopressin

-Russell’s, viper venom -Tranexaemic acid

-Tranexaemic acid -Epsilon amino caproic acid

-Hemocoagulase -Hemocoagulase

101
1. Local agent-
1. Adrenaline-
→It is local haemostatic use to control bleeding from capillaries &
minute vessels.

→It causes vasoconstriction when applied locally, a cotton pad

shocked in 0.1% adrenaline solution is use to control capillary
leakage.

→Epitasis tooth extraction.

Contraindication-
-Hypertension

-Rhythmus

-Angina

2. Thrombin-
→It is used topically to control bleeding term capillaries.

3. Fibrin-
→It is consisting of fibrin factor-B, thrombin, calcium & other
clotting component.

4. Gelatin-
→It is used as a haemostatic in surgical procedure.

5. Oxidized cellulose-
→It is an absorbable, it should be applied dry.

102
2. Systemic agent-
(1). Vitamin-K-
→It is a fat soluble & it is found in different from vitamin-k1, k2, k3.

→It is used in synthesis of clotting factor.

Daily requirement-
→ 3-4 microgram per day from any sources.

→In adult requriment 50-100 microgram.

Deficiency of vitamin-k-
→Its deficiency due to liver disease, obstructive jaundice,
malabsorption etc.

Uses-
→To control bleeding due to oral anticoagulant therapy.

→In obstructive jaundice with hemorrhagic symptoms parental

vitamin-k is preferred.

Adverse effect-
-Sweating

-Dyspnea

-Cynosis

Indication-
→It is I.M or S.C route may causes severe pain & bleeding at the
site of injection.

103
Anti-coagulant drugs-
→These are drugs used to reduce the coagulability of blood. They
may be classified into:

1. Used in vitro-
A. Heparin:

B. Calcium complexion agents: Sodium citrate

2. Used in vivo-
A. Parenteral anticoagulants-
-Heparin

-Low molecular weight heparins

-Danaparoid

B. Oral anticoagulants-
(i) Coumarin derivatives: dicumaron, Warfarin sod.

(ii) Indandione derivative: Phenindione.

1. Heparin-
→It is strongest organic acid in the body commercial, it is obtain
from OX lungs & pig intestinal mucosa.

→It is a natural anticoagulant.

→Common rote of administration I.V or subcutaneous.

Dose- 0.5-1 mg per kg body weight.

→Heparin safe use in pregnancy & lactation

104
Mechanism of action-
Heparin → increase activity of antithrombin-3→inhibit activated
clotting factor

2. Coumarin derivatives-
Warfarian-
→These are commonly use for oral anticoagulant.

→Warfarin is use to prevent myocardial infarction, stroke &

thrombosis.

→It is contraindicating in pregnancy.

Anti-platelets-
→Drug that inhibit platelets aggregation are called antiplatelets
drugs.

e.g. - Aspirin, Dipyridamole, Abciximab.

1. Low dose aspirin-

→It is irreversible inhibit platelets COX & produce anti-platelets
effect.

Uses- Acute MI.

Adverse effect-
-Gastric irritation

-Bleeding

2. Abciximab-
→It produce antiplatelets effect by acting in platelets surface.

105
→It administered by parentral.

Thrombolytic-
→The promote the conversion of plaminogen to plasmic & plasmic
break fibrin & rapidly dissolve the blood clot.

E.g.-streptokinase

-eurokinase

Streptokinase-
→It is obtaining Beta hemolytic streptococci group-c.

R & D- 7.5-15mg for I.V

Uses- In acute MI.
Adverse effect-
-Allergic reaction

-Bleeding

-Fever

-Chills

106
 CARDIOVASCULAR SYSTEM
Haematinics-
→These are substances required in the formation of blood, and are
used for treatment of anemia.

→Haematinics are such as iron, vitamin-B12, folic acid etc.

e.g. - Iron-

→It is essential element of blood are sources are liver,

fish, fruits, jiggery, banana, green leafy vegetables etc.

Preparation of Iron-
(1). Oral preparation-
→Oral iron is preferred for the treatment of iron deficiency anemia.

Various preparations are-

(a). Ferrous sulfate-
→It is the oldest iron preparation.

(b). Ferrous gluconate-

→It is less gastric irritant.

→Other oral preparation are ferrous fumarate, ferrous succinate,

ferric ammonium citrate.

Adverse effect-
-Nausea & Vomiting

-Epigastric pain

107
-Constipation

-Diarrhea

-Staining of teeth (Discoloration)

Uses- Used for the treatment of iron deficiency anemia.

(2). Parental preparation-
(a). Iron sorbitol citric acid complex (Jactofer)-
→It is given I.M but never administered I.V because
hypersensitivity reaction appears.

Iron dextrin (Imferon)-

→It is most commonly used parentral preparation & can be
administered I.V or I.M.

(b). Sodium ferric gluconate & iron sucroses-

→Uses in I.V.

→Intolerance to oral iron.

Adverse effect-
-Nausea & vomiting

-Painful injection

-Headache

-Pyrexia

-Arthritis

Uses- To treat iron deficiency anemia.

108
(3). Prophylactics-
→Prophylactics drug therapy used in pregnancy.

(a). Oral-
Ferrous sulphate-
→Dose- 100 mg TDS.
→The iron liquid form available for prevention of teeth
discoloration.

→Iron start second trimester (16 weeks).

→100 mg Tab. Ferrous sulphate 90 mg Tab. Excreted only 10 mg are

absorbed so stool color are clay.

→Iron absorbed in duodenum.

(b). I.V.-
→It is dilute 500 ml in normal saline & it can be given I.V slowly in
small dose of 2 ml daily.

(c). I.M.-
→100 mg daily & the iron administer to I.M. so apply the method of
zig-zag manner because prevention of drug leakage.

Folic acid-
→100 mg → 100 day → TDS start too mainly before 3 month.

109
Anti-hypertensive drugs-
→These are drugs used to lower BP in hypertension.

Classification-
1. Diuretics-

(a). Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide

(b). Loop diuretics: Furosemide (Lasix)
(c). K+ Sparing: Spironolactone, Amiloride
2. ACE inhibitors-
Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Fosinopril

3. Angiotensin (AT1 receptor) blockers-

Losartan, Candesartan, Valsartan

4. Calcium channel blockers-

Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine

5. α-Adrenergic blockers-
Phentolamine, Phenoxybenzamine

6. β-Adrenergic blockers-
Propranolol, Metoprolol, Atenolol, etc.

7. Vasodilators-
Arteriolar: Hydralazine, Minoxidil, Diazoxide
Arteriolar + venous: Sodium nitroprusside

110
8. Central sympatholytics- Clonidine, Methyldopa
1. Diuretics-
(a). Thiazides-
→It is a type of molecules and class of diuretics, To tract
hypertensive edema, heart failure & renal failure.

E.g. - Hydrochlorothiazide, Chlorthalidone

Mechanism of action (MOA)-

→It is a powerful diuretic drug.

→It is reabsorbtion of inhibiting of Na+, H2O & calcium ion from

the DCT in kidney.

Pharmacokinetics-
→It is mainly absorb their action star within one hours, but the
duration is various from 8-14 hours.

Uses-
-Hypertension

-Edema

-Retention of urine

Side effect-
-Hypotension

-Hyponatremia

-Allergic condition

Contraindication- Pregnancy
111
Dose & route- 10, 25, 50 mg orally
(b). Loop diuretics-
Frusamide-
MOA-
→It is mainly act on loop of henle & it is mainly action to the inhibit
reabsorption of the Na+, Cl, in the kidney tubules & it increase the
urine production.

Pharmacokinetics-
→It is rapidly absorbed orally but bioavailability is about 60% & it’s
metabolizing in liver & excretion through the kidney.

Uses-
-Hypertension

-Edema

-Heart failure

-Liver cirrhosis

Side effect-
-Hypotension

-Nausea & vomiting

-Diarrhea

Dose & route- 20-50 mg orally, 2 ml I.V/I.M.

(c). K+ spearing diuretics-
Spironolactone-They are used only in conjunction with a thiazide
112
diuretic to prevent K+ loss and to augment the antihypertensive
action.

Pharmacokinetics-
→The oral bioavailability of spironolactone is about 75% &
complete metabolite in liver.

Uses-
-Hypertension

-Chronic heart failure

-Edema

Dose & route- 25-50 mg orally BD & TID

2. Vasodilator-
Sodium nitroprusside-
→it is rapidly & constantly acting vasodilator & it mainly act on
blood vessels.

→It is also decreasing cardiac output & TPR.

Pharmacokinetics-
→It is absorbed orally, first metabolism in liver & excrete by urine.

Uses- Antihypertensive in emergency condition.

Side effect-
-Palpation, nervousness, vomiting

D&R- 5 ml in infusion.

113
MOA-
Sodium nitroprusside-

Arteriolar dilator Veno dilator

Decrease PVR Decrease venous return

(Peripheral vascular resistance)

Decrease B.P.

Hydralazine-
→It is used with or without other medication to treat high B.P. help
to prevent stroke, kidney problems.

Dose- 25-50 mg OD orally.

Diazoxide-
→It is administered by rapid I.V in fraction dose repeated every 5-
10 minutes as per required.

3. Central sympatholytics-
Methyldopa-
→It is central acting drugs & is available for oral administration.

114
→Uses in pregnancy.

MOA-
Methyldopa → activated → α-methyl nor-androgenic

Act on vasomotor center

Decrease heart rate

Decrease B.P

Pharmacokinetics-
→It is metabolite in liver & partially excreted by urine.

Uses- Anti-hypertensive.
Adverse effect-
-Dryness of mouth

-Headache

-Weight gain

D & R- 0.25-0.5 gm BD-QIT, Orally.

115
4.α-Adrenergic blockers-
α-Adrenergic blockers-

Selective blockers Non selective blockers

-Prezosin - Phenoxybenzamine

Block selective α-1 vascular receptor Both block α-1, 2

Decrease B.P.

5. β-Adrenergic blockers-
→This block β- receptor, thus inhibiting the β- receptor indicates
affect of sympathetic stimulation.

e.g.-

-Atenolol

-Propanolol

-Metoprolol

116
MOA-
β- Blocker agent

β- Blocker blocked

Decrease heart rate

Decrease B.P.

Pharmacokinetics-
→Propenolol is highly lipid soluble in well absorbed from GIT.

6. ACE Inhibitor-
→It is one of the first choice of drug.

e.g. - Ramiprine, Keptoprine.

MOA- Angiotensine

Angiotensine -1

Angiotensine converting enzyme

ACE inhibitor

Angiotensine -2 vasoconstriction increase B.P

→ACE inhibit this process.

117
D & R- Ramiprine- 1.25-20 mg OD, orally
Adverse effect-
-Dryness of mouth

-Protein urea

-Hypotension.

-Skin rashes

Contraindication- in pregnancy.
7.Angiotensin Receptor blockers-
E.g. - Losartan, Candesartan, Valsartan

MOA-

Decrease PVR→ Decrease aldosterone production & this lead to

decrease sodium & water retention.

Uses- Anti-hypertension.
Adverse effect-
-Headache

-Hypotension

-Skin rashes

Contraindication- Pregnancy
D & R- 25-50 mg OD orally.

118
8. Calcium channel blockers-
→Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine

MOA-
→In the heart & vascular smooth muscles, calcium channel blocker
block the voltage sensitive calcium channel, decrease cardiac work
& relax vascular smooth muscles.

1. It has prominent action on heart.

2. It decrease force of contraction.

3. It decrease heart rate.

4. Suppress the SA node & slow AV conduction.

D & R- 200 mg OD, Orally.

Pharmacokinetics-
→All calcium blockers are well absorbed through GIT & all are
highly bound to plasma protein & metabolize in liver & excrete in
urine.

Uses-
-Anti-hypertensive

119
Anti-anginal drugs-
Angina pectoris-
→Angina pectoris is the main symptoms of ischemic heart disease.
It is due to an imbalance between O2 supply & O2 demand of the
myocardium.

Classification-
1. For the treatment of acute angina attack-
→Nitroglycerin-sublingual

→ Isosorbide dinitrate-sublingual

2. For chronic prophylaxis-

Nitrates-

-Glyceryl trinitrate (GTN, Nitroglycerine)

-Isosorbide dinitrate

-Isosorbide mononitrate

2. β Blockers- Propranolol
3. Calcium channel blockers-
(a)Potassium channel opener Nicorandil

(b)Miscellaneous agent- Low dose aspirin

120
Nitrates-
→ All organic nitrates share the same action; differ only in time
course. The only major action is direct nonspecific smooth muscle
relaxation.

MOA-
Vasodilator Arterial Dilation coronary

Dilation vessels

Decrease decrease after increase blood

Preload load flow

Decrease cardiac work

Decrease O2 demand Relieve angina

D & R-
GTN (Nitroglycerine) - 0.5 mg sublingual, 0.4–0.8 mg, spray

Isosorbide dinitrate - 5–10 mg sublingual

Adverse effect-
-Redness

-Swelling

121
-Palpitation

-Flushing face

Uses- MI, Angina pectoris, CHF.

Potassium channel opener-
→Minoxidil and diazoxide are K+ channel openers which were used
earlier in severe hypertension and hypertensive emergencies.

Nicorandil-
→This dual mechanism anti-anginal drug activates ATP sensitive K+
channels (KATP) thereby hyperpolarizing vascular smooth muscle.
The vasodilator action is partly antagonized by K+ channel blocker
glibenclamide.

D & R- 5–20 mg BD, Orally

Side effect-
-Flushing
-Palpitation

-Weakness

-Headache

-Dizziness

-Nausea

122
Anti-arrhythmic drugs-
Arrhythmias-
→Disturbances in the cardiac rhythm, it means abnormality in the
site of origin of impulse, its rate, regularity over common is known
as arrhythmias.

Anti-arrhythmic agent-
1. Quinidine-
→It is depressed/excitability slow conduction velocity.

D & R- 100-200 mg TDS orally

MOA-
→ Quinidine blocks myocardial Na+ channels in the open state—
reduces automaticity and maximal rate of 0 phase depolarization in
a frequency dependent manner. Quinidine decreases the
availability of Na+ channels as well as delays their reactivation.

Uses- Though quinidine is effective in many atrial and ventricular

arrhythmias.

2. Amiodarone-
→It is structurally related to thyroid hormone.

R & D- 400-600 mg/day,Orally.

Adverse effect-
-Hypotension

-Headache

- Peripheral neuropathy
123
Drug interaction- Amiodarone + beta-blocker
3. Adenosine-
→It decrease conduction in the AV node.

→It is give I.V route.

→it is useful in supravantricular arrythmics.

→The duration of action of adenosine is less than 1 ml.

Adverse effect-
-Bronchiospasm

-Chest pain

-Dyspnea

-Flushing of face

Plasma volume expenditure-

→Plasma volume expenditure is solution for temporary maintains
of blood volume in emergency situation.

→Colloidal plasma expender has high molecular weight.

→The important plasma volume expenditure are-

1. Dextrose

2. Hexastrach

3. Polyinaylpyrrolidone

4. Degraded gelatin polymer

124
Drug used in CPR-
1. Adrenaline-
→1 mg I.V use in cardiac arrest& due to drowning or electrocution
& should not because not use in myocardial infarction because it is
powerful cardiac stimulant.

2. Atropine-
→It is used I.V in cardiac systole use to tract heart block.

3. Lignocaine-
→It is use to I.V or to tract ventricular arrhythmias.

4. Vasopressers-
→Dopamine by I.V infusion is use to tract cardiogenic shock.

5. Adenosive-
→It is used I.V paroxysmal supra-ventricular to cardiac.

Anti-snake or Anti-venom drugs-

→Anti-venom polyvalent for snake bite.

→Resure the patient that all snakes are not poisons.

Symptomatic treatment-
→The site should be clean with a clean cloth & PCM can be use to
control pain & patient should be given TT & embellished the bitten
limb with a sling & splint to prevent spread of the venom from the
bite area.

125
→Moniter BP, heart rate, urine output & respiration of patient.

→It is available as purified in 10 ml ampul of distal water-

- 0.6 mg standard cobra (Nasa)

- 0.6 mg standard rusell’s wiper.

→Establish I.V line in suspected venomous snake bite.

→Prophylatic antibiotic can be use to prevent infection.

→Blood transfusion if necessary in wiper bite.

→I.V neostigmine to given in case of cobra bite, to reverse

neuromuscular blockage.

Alternative system of medicine-

AYUSH-
→Alternative system of medicine includes ayurveda, Homeopathy,
Siddha, Unani.

1. Ayurveda-
→Ayu means life & Veda means science in Sanskrit (science of life).

→This system originated in India 5000 year back, according to

ayurveda the disease & their symptoms depend on 3 basic
physiological symptoms-

-Vata

-Pitta

-Kapha

126
→The imbalance of these three gives to disease. It aim not only
treat the disease but to treat the person as a whole & present the
disease.

2. Homeopathy-
→It is a system of medicine based on the concept of treating the
disease with minute dose of the drugs which enlarge dose are
capable of providing the same symptoms in health individual.

→The dilute form of drug stimulates immunity & help to fight

against the disease.

3. Siddha-
→Siddha is a traditional medicine was first developing in tamil-
nadu.

→According to siddha medicine the function in body depend on

seven elements-

(1).Plasma

(2).Blood

(3).Muscle

(4).Fatty tissue

(5).Bone

(6).Brain

(7).Semen

→The basic concept of ayurveda & siddha are similar.

4. Unani- Unani a traditional medicine widely practices in south

Asia & it based on the Blood, Phlegm, Yellow bile, Black bile.
127
Anti-tubercular drug-
Classification-
1. First line drugs-
1. Isoniazid (H) 2. Ethambutol (E)

3. Rifampin (R) 4. Streptomycin (S)

5. Pyrazinamide (Z)

2. Second line drugs-

Ethionamide (Eto) Fluoroquinolones
• Prothionamide (Pto) • Ofloxacin (Ofx)

• Cycloserine (Cs) • Levofloxacin (Lvx/Lfx)

• Terizidone (Trd) • Moxifloxacin (Mfx)

• Para-aminosalicylic • Ciprofloxacin (Cfx)

-acid (PAS) Injectable drugs

• Rifabutin • Kanamycin (Km)

• Thiacetazone (Thz) • Amikacin (Am)

Standard drug-
→They are chief more effective, routinely uses & less toxic.

1. Isoniazid-
→It is the most widely used anti-tubular agent & has is oral
effective, chief & it has tuberculoidal activity.

128
→It is rapidly absorbed from the gut & metabolize by acetyl ion &
the excreted in urine.

R & D- 300mg, orally.

2. Rifampin-
→It is a first line anti-tubercular drugs.

→It is rapidly kill the tubercular bacilli.

→Rifampin interrupts RNA synthesis by binding to β subunit of

mycobacterial DNA-dependent RNA polymerase and blocking its
polymerizing function.

R & D- 450mg, orally.

3. Pyrazinamide-
→It has tuberculoidal activity like a isonized & it is given orally
absorbed from GIT & it is metabolize in liver & excreted in urine.

R & D- 1500mg, orally.

4. Streptomycin-
→It is an amino glycoside antibiotic & it was first effective drug
developed for the treatment of T.B.

R & D- 1000mg, I.M

5. Ethambutol-
→It is first line anti-tubercular drugs.

→It is well absorb after oral administration & distributed widely in

the body & metabolite in liver & excreted by urine.

R & D- 0.1 – 1mg, orally.

129
 Chemotherapy
Chemotherapy-
→Chemotherapy is the use of any drug to treat any disease. But to
most people, the word chemotherapy means drugs used for cancer
treatment. It's often shortened to “chemo.”

→Chemotherapy is the treatment of infectious disease or

malignant with drug to destroyed micro-organism or cancer cell
damage the tissue of host.

Antibiotics-
→These are substance produce by micro-organism which
selectively suppresses the growth or kill other micro-organism at
very low concentration.

Antibodies-
→These are natural substance produce in the body which have high
concentration or high molecular weight.

Note- Antibody molecular weight- 25kDa.

Classification of anti-microbial agent-

1. On the basis of mechanism of action-
(1). Inhibit cell wall synthesis:
-Penicillins

-Cephalosporins

-Vancomycin

130
(2). Cause leakage from cell membranes:
-Polypeptides—Polymyxins, Colistin, Bacitracin.

-Polyenes—Amphotericin B, Nystatin, Hamycin.

(3). Inhibit protein synthesis:

-Tetracyclines

-Chloramphenicol

-Erythromycin

-Clindamycin

(4).Interfere with DNA function:

-Rifampin

(5). Interfere with DNA synthesis:

-Acyclovir
-Zidovudine

(6). Interfere with intermediary metabolism:

-Sulfonamides

-Sulfones

-Pyrimethamine

-Metronidazole

(7). Cause misreading of m-RNA code and affect

permeability: - Amino glycosides— Streptomycin, Gentamicin.

131
2. On the basis of type of organisms against-
(1). Antibacterial drug:
-Penicillins

-Aminoglycosides

-Erythromycin

(2). Antifungal drug:

-Griseofulvin
-Amphotericin-B

-Ketoconazole

(3). Antiviral drug:

-Acyclovir
-Amantadine

-Zidovudine

(4). Antiprotozoal drug:

-Chloroquine
-Pyrimethamine

-Metronidazole

(5). Antihelminthic drug:

-Mebendazole
-Pyrantel

-Niclosamide
132
3. On the basis of Spectrum of activity-
(A). Narrow-spectrum-

-Penicillin G

-Streptomycin

-Erythromycin

(B). Broad-spectrum-
-Tetracyclines

-Chloramphenicol

4. Other types-
(1).Bacteriostatic-
-Sulfonamides

-Erythromycin

-Tetracycline

-Clindamycin

-Chloramphenicol

(2).Bactericidal-
-Penicillins

-Cephalosporins

-Aminoglycosides

-Vancomycin

133
1. PENICILLINS-
→Penicillin was the first antibiotic to be used clinically in 1941. It is
a miracle that the least toxic drug of its kind was the first to be
discovered. It was originally obtained from the fungus Penicillium
notatum, but the present source is a high yielding mutant of
P. chrysogenum.

Mechanism of action-
→All β-lactam antibiotics interfere with the synthesis of bacterial
cell wall. The bacteria synthesize UDP-N-acetylmuramic acid
pentapeptide, called ‘Park nucleotide’ (because Park in 1957 found
it to accumulate when susceptible Staphylococcus was grown in the
presence of penicillin) and UDP-N-acetyl glucosamine.

Uses-
1. Streptococcal infection-
-Pharyngitis

-Otitis media

-Scarlet fever

- Rheumatic fever

2. Pneumococcal infections-
-Pneumonia

-Meningitis

3. Gonococcal infection-
-Syphilis

134
4. Diphtheria
5. Tetanus and gas gangrene
Adverse effect-
-Rash

-Itching

-Urticaria

-Fever

-Wheezing

-Angioneurotic edema

-Serum sickness

Dose-
Natural penicillin-
→Sod. penicillin G (crystalline penicillin) injection 0.5– 5 MU
i.m./i.v. 6–12 hourly.

SEMISYNTHETIC PENICILLINS-
(1). Acid-resistant alternative to penicillin G-
-Phenoxymethyl penicillin (Penicillin V).

(2). Penicillinase-resistant penicillins-

-Methicillin

-Cloxacillin

-Dicloxacillin

135
(3). Extended spectrum penicillins-
→Aminopenicillins:

-Ampicillin

-Bacampicillin

-Amoxicillin

2. CEPHALOSPORINS-
→These are a group of semi synthetic antibiotics derived from
‘cephalosporin-C’ obtained from a fungus Cephalosporium. They
are chemically related to penicillin’s.

Types-
1. FIRST GENERATION CEPHALOSPORINS-
→These were developed in the 1960s, have high activity against
gram-positive but weaker against gram-negative bacteria.

e.g. - Cefazolin, Chiphalexin, Cefadroxil.

2. SECOND GENERATION CEPHALOSPORINS-

→These were developed subsequent to the first generation
compounds and are more active against gram-negative organisms.

e.g.- Cefuroximine, Cefprozil.

3. THIRD GENERATION CEPHALOSPORINS-

→These compounds introduced in the 1980s have highly
augmented activity against gram-negative bacteria.

e.g.- Ceftizoxime, Cefotaxime

136
Uses-
1. As alternatives to penicillins for ENT, upper respiratory and
cutaneous infections, one of the first generation compounds may
be used.

2. Respiratory, urinary and soft tissue infections caused by gram-

negative organisms, especially Klebsiella, Proteus, Enterobacter,
Serratia. Cephalosporins preferred for these infections are
cefuroxime, cefotaxime, ceftriaxone.

3. Penicillinase producing staphylococcal infections.

4. Septicaemias caused by gram-negative organisms: an

aminoglycoside may be combined with a cephalosporin.

5. Meningitis.

Adverse effect-
-Pain

-Allergic reaction

-Diarrhea

-Vomiting

-Bleeding

3. Aminoglycosides drugs-
→They includes streptomycin, Gentamycin, Amikacin, Kanamycin,
Neomycin.

137
Classification-
1. Systemic aminoglycosides-
-Streptomycin

-Amikacin

-Gentamicin

-Sisomicin

-Kanamycin

2. Topical aminoglycosides-
-Neomycin

-Framycetin

Mechanism of action-
→The aminoglycosides are bactericidal antibiotics, all having the
same general pattern of action which may be described in two main
steps:

(a) Transport of the aminoglycoside through the bacterial cell wall

and cytoplasmic membrane.

(b) Binding to ribosomes resulting in inhibition of protein synthesis.

Uses-
-Acute bacterial infection

-Tuberculosis

-Post operative care- Meningitis

138
Adverse effect-
-Hypersensitivity

-Ototoxicity

-Nephotoxicity

-Neuromuscular blocking

Dose-
→ Inj. - Streptomycin-1gm

→ Gentamycin cream for skin infection, eye, ear etc.

Neomycin-
→It is highly nephrotoxic drug.

Uses-
-Infection in mucus membrane skin.

-Ulcer

-Wound

-Burn

-Infection in ear & eye

Gentamycin-
→It is most commonly used aminoglyside antibiotic for gram -ve
bacterial infection.

→It is also effective against gram +ve bacteria.

139
Uses-
-Upper urinary tract infection

-Pneumonia

-Meningitis

-Infected burn

4. Tetracycline (Broad-Spectrum Antibiotics)-

→They have 4 cyclic rings in their structure common drugs available
in India.

-Tetracycline

-Doxycycline

-Oxytetracycline

-Minocycline

-Demeclocycline

Mechanism of action-
→The tetracyclines are Primarily bacteriostatic; inhibit protein
synthesis by binding to 30S ribosomes in susceptible organism.
Subsequent to such binding, attachment of aminoacyl-t-RNA to the
acceptor (A) site of mRNA-ribosome complex is interferred with. As
a result, the peptide chain fails to grow.

Pharmacokinetics-
→Tetracycline drug absorption better taken in empty stomach.
Doxycycline & minocycline are completely absorbed irrespective of
food. Tetracyclines are widely distributed in the body & excreted in
urine.
140
Uses-
-In the venereal disease

-Pneumonia

-Cholera

-Plaque

-UTI

Adverse effect-
-Epigestric pain

-Nausea

-Vomiting

-Diarrhea

-Liver damage

-Kidney damage

Dose- Capsule 250mg & 500mg, 50mg I.M

Chloramphenicol-
→Chloramphenicol is a broad spectrum antibiotic. It is uses in
limitation then few side effects.

Mechanism of action-
→Chloramphenicol inhibits bacterial protein synthesis by
interfering with ‘transfer’ of the elongating peptide chain to the
newly attached aminoacyl-tRNA at the ribosome-mRNA complex.

141
Uses-
-In typhoid fever

-Bacterial meningitis

-Eye & ear infection

Adverse effect-
-Hypersensitivity reaction

-Bone marrow suppression

-Nausea & vomiting

-Abdominal distension

Dose- capsule 200mg for 6 days adult, children 25-50mg/ kg body

weight, 0.1% eye ointment, 0.2% eye drops.

Antiamoebic drug-
→These are drugs useful in infection caused by the anaerobic
protozoa Entamoeba histolytica.

Classification-
1. Tissue amoebicides-
→These drugs are highly concentration in blood & tissues.

(A).Metronidazole

-Tinidazole

-Ornidazole

142
(B).Emetine

(C).Chloroquine

2. Luminal amoebicides-
(A).Diloxanide furoate

(B).Quiniodochlor

(C).Lodoquinol

(D).Tetracyclines

Metronidazole-
→It is highly effective most bacterial or protozoal infection such as
Entamoeba histolytica, trimonas vaginatis.

Mechanism of action-
→Metronidazole enter into the micro-organism & damage DNA for
active metabolite & causes death of the organism (bacterial effect).

Pharmacokinetics-
→Metronidazole is almost completely absorbed from the small
intestines; little unabsorbed drug reaches the colon. It is widely
distributed in the body. Metabolism occurs in liver primarily by
oxidation and glucuronide conjugation followed by renal excretion.

Dose- 400-800mg for TDS.

Uses-
(1). Amoebiasis- It is use in the treatment of intestine.

(2). Trimonas vaginitis- Metranidazole 100mg orally for 7 days.

(3). Anaerobic infecton- Pelvic inflammatory disease.

143
Adverse effect-
-Anoreixa

-Headache

-Dizziness

-Abdominal cramps

-Dry mouth

Tinidazole-
→Most of the feature are similar to metranidazole.

→It has longer duration of action & better toleratability then

metranidazole.

Dose- 500mg tinidazole tab. BD.

Antimalarial Drugs-
→These drugs are use for prophylaxis & treatment of
malaria.
Classification-
1. Chemical classification-
(a). 4-Aminoquinolines-
-Chloroquine (CQ)

(b). 8-Aminoquinoline-
-Primaquine

144
(c). Quinoline-methaol-
-Mefloquine

(D). Cinchona alkaloid-

-Quinine

(E). Antibiotics-
-Tetracycline

-Doxycycline

2. Clinical classification-
(a). Tissue schizonticidal agent-
-Primoquine

(b). Blood schizonticidal agent-

-Chloroquine

(c). Gametocidal agent-

-Quinine

Chloroquine-
→It is a rapidly acting erythrocytic schizontocide against all species
of plasmodia; controls most clinical attacks in 1–2 days with
disappearance of parasites from peripheral blood in 1–3 days.

Mechanism of action-
→Chloroquine is taken up by plasmodium & inhibit the
conversation.

145
Pharmacokinetics-
→Oral absorption of CQ is excellent. About 50% gets bound in the
plasma. Chloroquine is partly metabolized by liver and slowly
excreted in urine.

Uses-
-Malaria

-Amoebiasis

-Rheumatic arthritis

-Autoimmune disease

Adverse effect-
-Nausea & vomiting

-Headache

-Hypotension

-Depression

-Loss of vision

Dose- 500mg Tab. Chloroquine, 40mg in I.V.

Contraindication-
-Neurological disease

-Hematological disease

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Anthelmintic Drug-
→Anthelmintics are drugs that either kill (vermicide) or expel
(vermifuge) infesting helminths.

Antihelmintic drugs are-

-Mebendazole

-Albendazole

-Levamisole

-Niclosamide

Mebendazole-
→It has a broad spectrum antihelmintic drug. It is inhibit
microtubules synthesis in the parasite causing immobilization or
death of the intestinal parasite.

→It is administration orally & absorb from the GIT & metabolism in
liver than excreted in feaces.

Adverse effect-
-Anorexia

-Nausea

-Vomiting

-Diarrhea

-Skin rashes

-Itching

Dose- 100mg Tab. Mebex.

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Antiviral drug-
→Antiviral drugs are a class of medication used specially for
treating viral infections rather than bacterial ones.

→Most anti-virals are used for specific viral infection, while a

broad-spectrum antiviral is effective against a wide range of
viruses.

1. Anti-Herpes virus-
-Idoxuridine

-Trifluridine

-Acyclovir

2. Anti-Retrovirus-
(a). Nucleoside reverse transcriptase inhibitors (NRTIs):
-Zidovudine (AZT)

-Lamivudine

(b). Nonnucleoside reverse transcriptase inhibitors

(NNRTIs): -
-Nevirapine

-Efavirenz

(c). Protease inhibitors:

-Ritonavir

-Atazanavir

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3. Anti-Influenza virus-
-Amantadine

-Rimantadine

4. Anti-Hepatitis virus/Nonselective antiviral drugs-

-Lamivudine

-Tenofovir

Acyclovir
→This deoxiguanosine analogue antiviral drug requires a virus
specific enzyme for conversion to the active metabolite that
inhibits DNA synthesis and viral replication.

Mechanism of action-
→Herpes virus specific thymidine kinase Acyclovir monophosphate
Cellular kinases Inhibits herpes virus DNA polymerase competitively
gets incorporated in viral DNA and stops lengthening of DNA
strand. The terminated DNA inhibits DNA polymerase irreversibly.

Pharmacokinetics-
→Only about 20% of an oral dose of acyclovir is absorbed. It is little
plasma protein bound and is widely distributed attaining CSF
concentration that is 50% of plasma concentration. Acyclovir is
primarily excreted unchanged in urine.

Uses-
-In Genital Herpes simplex

-In Mucocutaneous H. simplex

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-In Herpes zoster

-In Chickenpox

Dose- Oral acyclovir 400 mg 4 times a day for 7 days given during
the incubation period.

Adverse effect-
-Headache

-Nausea

-Skin rashes

-Sweating

-Hallucinations

-Kidney disease

Contraindication-
-In pregnancy

-During lactation.

END
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