Pharmacodynamics-General Pharmacology

1. Pharmacodynamics

2. • Pharmacodynamics means →what the drug does to the body
• It is the study of drugs—their mechanism of action, pharmacological actions and
adverse effects
• Types of Drug Action:-
1. Stimulation: Some drugs act by increasing the activity of specialized cells,
E.g. adrenaline stimulates the heart resulting in ↑HR & FOC.
2. Depression: Some drugs act by decreasing the activity of specialized cells
E.g. alcohol, barbiturates, general anaesthetics, etc. depress the CNS.
3. Irritation: Certain agents on topical application can cause irritation of the skin
and adjacent tissues.
E.g. Counterirritant:- an agent upon topical application to the skin relieves
deep-seated pain e.g. eucalyptus oil, methyl salicylate, etc. useful in sprains,
joint pain, myalgia, etc.

3. • 4. Replacement: When there is a deficiency of endogenous substances, they can
be replaced by drugs
• E.g. Insulin →in diabetes mellitus,
Thyroxine → in cretinism and myxoedema, etc.
• 5. Cytotoxic: Drugs are selectively toxic for the infecting organism/cancer cells,
e.g. antibiotics/anticancer drugs.
• Mechanism of Drug Action:-
Mechanism of action of drugs
-:Non-receptor mediated:-
1.By physical Action:- (A.) Osmosis: Some drugs act by exerting an osmotic
effect, e.g. 20% mannitol in cerebral oedema and acute congestive glaucoma.
Receptor Mediated
Nonreceptor mediated

4. • (B.) Adsorption: Activated charcoal adsorbs toxins→ used in the treatment of
drug poisoning.
• (C.)Demulcent:- Cough syrup produces a soothing effect in pharyngitis by
coating the inflamed mucosa.
• (D.)Radioactivity: Radioactive isotopes emit rays and destroy the tissues, e.g.
131I in hyperthyroidism.
• 2. By chemical action:-
• A. Antacids →neutralize acid in the stomach in peptic ulcer.
• B. Chelation:-Metals like iron, copper, mercury, etc. are eliminated from the body
with the help of chelating agents. They trap the metals in their ring structure and
form water-soluble complexes, which are rapidly excreted from the body.
E.g.-
Dimercaprol (BAL)→ Arsenic poisoning,
Desferrioxamine→ Iron poisoning,
D-penicillamine→ Copper poisoning.

5. • 3. Through enzymes:-Enzymes are Biocatalysts present in the cell.
• Some drugs act either by activating or inhibiting the enzyme activity.
• a. Drug action via enzyme inhibition:-
• Competitive inhibition:-drug is structural analogue of enzyme which prevent the
formation of enzyme-substrate complex.
• Non-Competitive inhibition:- drug binds to allosteric site which prevent the
formation of ES-complex
Enzyme Competitive inhibitors Therapeutic use
Acetyle cholinesterase Physostigmine, Neostigmine Galucoma, Myasthenia gravis
Angiotensin converting enzyme Captopril, Lisinopril Hypertension
Dopa decarboxylase Carbidopa Parkinson disease
Xanthine oxidase Allopurinol Acute Gout
Folate synthetase Sulfonamides conjunctivitis

6. Enzyme Competitive inhibitors Therapeutic use
Aldehyde dehydrogenase Disulfiram Alcohol Aversion therapy
HMG-CoA reductase Atorvastatin Dyslipidaemia
H+ K+ ATPase Lansoprazole Peptic ulcer
Carbonic Anhydrase Acetazolamide Glaucoma
4.Through ion channels:-
minute pores present in the cell membrane.
 common ion channels are of Na+, K+, Ca+2 and Cl –
Some drugs directly bind to ion channels and alter the flow of ions,
Ion channel →have gating properties
 Ligand – gated channels – activated by binding of a chemical ligand.
 Voltage – gated channels – open when the cell membrane is depolarized.
o E.g. LA block sodium channels in neuronal membrane to produce local
anaesthesia, CCB-Diltiazem

7. 5.Through antibody production:-
Vaccines produce their effect by stimulating the formation of antibodies,
E.g.- vaccines against tuberculosis (BCG), oral polio vaccine, etc.
6. Carrier molecules (transporters):-
The transport of ions and small organic polar molecules across cell membranes
generally requires a carrier protein.
• E.g.-Selective serotonin reuptake inhibitors (SSRIs)→ bind to 5-HT
transporter→ block 5-HT reuptake into neurons→ Antidepressant effect
• Others:- Anticancer drugs like cyclophosphamide produce their effect by
binding to nucleic acids

8.  Receptor-mediated Mechanisms:-
• Receptor:- “Receptors are macromolecules present either on the cell surface,
cytoplasm or in the nucleus with which the drug binds and interacts to produce
cellular changes”
• E.g.-adrenergic receptors (α and β), cholinergic receptors (muscarinic and
nicotinic),opioid receptors(μ,κ), etc.
• Drug (D) + Receptor (R) = Drug–receptor complex→ Response
• Terminologies:-
• Affinity:- The ability of the drug to get bound to the receptor
• Intrinsic activity:- The ability of the drug to produce pharmacological action after
combining with the receptor is known as intrinsic activity of the drug.
• Agonist: A drug that is capable of producing pharmacological action after binding
to the receptor is called an agonist.
• Agonist has high affinity + high intrinsic activity (e.g. morphine and adrenaline)

9. • Antagonist:-
• A drug that binds to receptors but is not capable of producing pharmacological
action is called an antagonist.
• Antagonist has high affinity without intrinsic activity
• e.g. naloxone and atropine
• E.g.-
• It produces receptor blockade
• If binding is reversible - Competitive antagonists
• If binding is irreversible - Noncompetitive antagonists
Acetylcholine
Muscarinic
receptor
Atropine
Agonist Antagonist

10. • Partial agonist:-
A drug that binds to the receptor but produces an effect less than that of an
agonist is called partial agonist.
Partial agonist has affinity + less intrinsic activity
• E.g. -Pindolol and buprenorphine
• Inverse agonist: It has full affinity towards the receptor but produces effect
opposite to that of an agonist.
• E.g.-β-carbolines act as inverse agonist at benzodiazepine receptor, and
produce anxiety and convulsions where BZD’s produce antianxiety and
anticonvulsant effects.

11. HOW DO DRUGS WORK BY interacting with CELL SURFACE
RECEPTORS?
Cell Membrane
Unbound Endogenous Activator (Agonist) of Receptor
Inactive Cell Surface Receptor
Extracellular
Compartment
Intracellular
Compartment

12. Cell Membrane
Bound Endogenous Activator (Agonist) of Receptor
Active Cell Surface Receptor
Extracellular
Compartment
Intracellular
Compartment
Cellular Response
HOW DO DRUGS WORK BY interacting with CELL SURFACE
RECEPTORS?

13. •Receptor Families:-
Based on molecular structure & signal transduction- 4 type
1. Ligand-gated ion channels (inotropic receptors).
2. G-protein-coupled receptors (metabotropic receptors).
3. Enzymatic receptors.
4. Receptor regulating gene expression (transcription factors) or the nuclear
receptor

14. Ligand-gated
ion
Channels
G-protein-
coupled
Receptors
Enzymatic
Receptors
Nuclear Receptors
Location Membrane Membrane Membrane Intracellular(cytopl
asm on nuclear
membrane)
Effector Ion channel Channel or enzyme Enzyme Gene transcription
Coupling Direct G-proteins (Gs, Gi,
Gq, etc.)
Direct Via DNA
Examples Nicotinic,
GABAA
–receptors
Muscarinic,
adrenergic
receptors
Insulin, growth
factor, cytokine
receptors
Steroid, thyroid
hormone
receptors
Time required
For Response
Milliseconds Seconds Hours Hours
 Characteristics of Various Receptor Families:-

15. • Ligand-gated Ion Channels (Inotropic Receptors):-
• These are cell surface receptor linked to ion channels
• E.g.- nicotinic (NM) acetylcholine receptors of neuromuscular junction, GABA and glutamate
receptors in the central nervous system (CNS),5-HT3
Agonist binding to the receptor opens the channel & cause hyperpolarization, depolarization
depending on the ion that flows through
Binding of agonist to
ionotropic receptors
Opens the ion channels
(Na+, K+, Ca2+, Cl–)
Flow of ions through
channels
Hyperpolarization/
Depolarization
Tissue
response
Extracellular
Intracellular
Glutamate

16. G-Protein couple receptors(GPCR)/7-pass
receptor/Serpentine receptor:-
They are coupled to intracellular effectors through G-proteins
G-proteins:-
They are membrane proteins
They are called “G” protein because of their interaction with guanine nucleotides,
GTP & GDP
 have three subunits (α,β,ϒ)
α-subunit has GTPase activity that hydrolyzes GTP to GDP
Types of G-protein:- Gs & Gq-(Stimulatory types)
Gi-(Inhibitory types)
second messengers:- cAMP (generated by adenylyl cyclase), cGMP (generated
by guanylyl cyclase), Ca2+, inositol triphosphate–diacylglycerol (IP3–DAG)
(generated by phospholipase C), nitric oxide, etc.

18. • Effector pathways:-
• G-protein-coupled receptors control cell function via
1. Adenylyl cyclase(AC)
↑ Adenylyl cyclase(by Gs)→↑cAMP
↓Adenyl cyclase(by Gi) → ↓cAMP
2.Phospholipase C:-
3.Ion channels:- activated G-protein can open or close ion channels-
Ca++,K+,Na+

19. Gq
Phospholipase-C
↑IP3 & DAG
↑Cytosolic Ca+2 &
Protein kinase-C
Gs
E.g.-M1,M3,H1,α1
M2,M4 receptor

20. Enzyme-linked Receptors:-
For example, receptors for insulin (receptor tyrosine kinase) and growth factors
(epidermal growth factor, platelet derived growth factor, etc.)
Mechanism:-
Binding of agonist to extracellular domain of enzyme linked receptors
↓
Dimerization of the receptor
↓
Stimulates intrinsic/cytosolic kinase activity
↓
Activates intracellular signaling pathways
↓
Gene transcription→ Tissue response

21. Nuclear Receptors
They are distributed in cytoplasm & regulate gene transcription
This is slowest acting transduction mechanism
E.g.-receptors for sex steroids and glucocorticoids, thyroid hormones, Vit-D
receptor
Mechanism:-
If a drug acts on cytoplasmic receptor then after combining with receptor the
drug-receptor complex goes to nucleus leading to gene transcription &
subsequent protein synthesis

22. • Dose–Response Relationship:-
Pharmacological effect of a drug depends on→ its concentration at the site of
action
Which, in turn, is determined by the dose of the drug administered.
Such a relationship is called “Dose–response relationship”
Quantitative measurement of drug effect is very important & helpful to make a
decision on its mode of use.
DRC:- Plots of dose versus response
for drugs(agonist) gives rise to DRC
Types of drug response:-
1.Graded response
2.Quantal response

23. • Graded response:-
• Degree of response changes as per the concentration
• ↑Concentration →↑Response
• Response increases with increase in concentration of agonist till it reaches the
maximum response
• This curve, when plotted on a graph, takes the form of a rectangular hyperbola
• Disadvantage:-
• Difficult to derive statistical
Relationship b/w two
Variable
Thus log-dose(concentration
Response curve) is plotted
Which is sigmoidal.

24. X-axis
Y-axis
A-DRUG B-DRUG
Log dose response Curve
C-DRUG
 A drug having more affinity &
potency than B & C
 C-drug having less efficacy &
potency

25. • Drug Potency:-
• The amount of a drug required to produce a desired response is called the potency
of the drug.
• The lower the dose required for a given response →the drug is more potent.
• E.g.-analgesic dose of morphine is 10 mg and that of pethidine is 100 mg.
Therefore, morphine is ten times more potent than pethidine as an analgesic.
• Drug Efficacy:-
• It is the maximum effect of a drug.
• E.g.-morphine is more efficacious than aspirin as an analgesic
• Therapeutic Window:-It is the range of plasma concentration of the drug that
produces desired response with minimal toxicity

26. • Since middle portion is linear so it can be considered that the response is directly
proportional to log concentration within a wide range of dose
• The effective dose(ED) & effective concentration(EC) can be calculated such as
ED50 & EDmax(maximum effective dose)
• Therapeutic Index:-
• Therapeutic index (TI) is an index of drug safety
• It is the ratio of median lethal dose to the median effective dose
TI=
LD50→ dose that will result in death of 50% of population receiving the drug
Median Lethal dose(LD50) of the drug
Median effective dose(ED50) of the drug

27. • More is LD50→safer is the drug
• ED50→It is the dose of the drug that produces desired effect in 50% of the
population
• More is ED50 →lower is potency
• Wider the value of therapeutic index → safer is the drug
• E.g.- Penicillin has a high
TI, digitalis, lithium and
phenytoin have narrow
TI
Limitation of TI:- effect of drug
In pregnancy cant be predicted on
the basis of T.I.
safety margin

28. Combined Effects of Drugs:-
A combination of two or more drugs can result in an increase or a decrease in
response
Increased response:-
1. Additive effect: The combined effect of two or more drugs is equal to the sum
of their individual effect.
Effect of drugs A + B = Effect of drug A + Effect of drug B
E.g. Ibuprofen and paracetamol as analgesic
Potentiation (supra-additive):-
The enhancement of action of one drug by another drug that is inactive is called
potentiation.
Effect of drugs A + B > Effect of drug A + Effect of drug B
E.g.-levodopa + carbidopa; acetylcholine + physostigmine

29. • Carbidopa and physostigmine inhibit the breakdown of levodopa and
acetylcholine, respectively thus enhancing their effects
• Synergism:- When two or more drugs are administered simultaneously, their
combined effect is greater than that elicited by either drug alone.
• E.g.-sulphamethoxazole + trimethoprim
• Decreased response (drug antagonism):-
• In antagonism, the effect of one drug is decreased or abolished in the presence
of another drug
• 1. Physical antagonism:- The opposing action of the two drugs is due to their
physical property, e.g. activated charcoal adsorbs toxic substances in poisoning.
• 2. Chemical antagonism:- The opposing action of two drugs is due to their
chemical property, e.g. antacids are weak bases that neutralize gastric acid;
chelating agents complex metals and are useful in heavy metal poisoning

30. • 3. Physiological (functional) antagonism:- two drugs act at different receptors or
by different mechanisms on the same physiological system and produce opposite
effects.
• E.g.- insulin and glucagon on blood sugar,
• In Anaphylactic shock- adrenaline helps to reverse bronchospasm in anaphylactic
shock
• Histamine produces→ Bronchoconstriction (via histamine receptors)
• Adrenaline produces → Bronchodilatation (via (β2) receptors)
• 4.Receptor antagonism: The antagonist binds to the same receptor as the agonist
and inhibits its effects.
• Types:- competitive or noncompetitive
• Competitive antagonism (equilibrium type):- both agonist and the antagonist
bind reversibly to the same site on the receptor

31. • Antagonism can be overcome (reversible) by increasing the concentration of
agonist.
• The log DRC of the agonist shows a rightward parallel shift in the presence of
competitive antagonist
• For example:-
• Acetylcholine→ Muscarinic receptors ←Atropine
• Morphine→ Opioid receptors← Naloxone

32. Non-competitive antagonism:-
The antagonist binds to a different site on the receptor and prevents the agonist
from interacting with the receptor.
the antagonistic effect cannot be overcome by ↑↑concentration of the agonist
There is a flattening of DRC in noncompetitive antagonism
E.g. Diazepam and Bicuculline

33. FACTORS MODIFYING DRUG ACTION

34. Drug Factors:-
1. Route of administration:- Quantitative variations common than Qualitative
variations
Quantitative variations:- Oral dose of the drugs are usually larger than
intravenous dose (since i.v. route produces 100% bioavailability)
E.g. intravenous dose of morphine is 5–10 mg, whereas oral dose is 30–60 mg for
analgesic effect.
Qualitative variation:- The drug response differ with different routes.
E.g.-MgSo4 :-
Orally→ Produces purgative effect
Parenterally → it causes CNS depression
Locally →↓oedema in the inflamed area

35. • 2. Presence of other drugs:-
• Additive effect:-
• Potentiation (supra-additive):-
• Synergism:-
• 3. Cumulation: When the elimination of a drug is slower than the rate of
administration, the drug may accumulate in the body causing cumulative toxicity
• E.g.- digoxin, emetine, chloroquine, etc.
•Patient Factors:-
1. Age:- In neonates, the metabolizing function of the liver and excretory function
of the kidney is not fully developed,
• E.g.-Chloramphenicol→ Cause grey baby syndrome in neonates (metabolizing
enzymes are not fully developed)
• Penicillin G→ in infant administered less frequently than adult as the excretory
function is not completely developed

36. • Dose of Aminoglycosides→ in elderly is less than normal adult dose due to the
renal and hepatic functions progressively decline with age.
• The dose of a drug for a child can be calculated as follows:-
• Young’s formula:-
Child dose= × Adult dose
2. Body weight and body surface:- An average dose of a drug is calculated in
terms of body weight(mg/kg).
Dose for an individual = ×Average adult dose
Since it is inconvenient to calculate BSA, routinely dose is calculated on
body weight basis.
Exception:-Dose of anticancer drugs and a few other drugs are calculated on
the basis of BSA
Age
Age + 12
Body weight (kg)
70

37. • 3. Sex:- Drugs like β-blockers, diuretics and clonidine can cause↓ libido in males
not in women
• Alcohol dehydrogenase→ In stomach is less in women than men so effect
of the same amount of alcohol is more as compare to men
• 4. Diet and environmental factors:-
• Milk ↓ absorption of tetracyclines
• Fatty meal ↑absorption of griseofulvin (Antifungal agent).
• Certain environmental pollutants such as DDT, cigarette smoke, insecticides, etc.
induce hepatic microsomal enzymes and ↑metabolism of drugs such as oral
contraceptives, theophylline, etc.
• So the dose of these drugs administered may be inadequate in smokers.
5. Genetic factor:- Isoniazid Peripheral neuritis in slow acetylators, Hepatotoxicity
in fast acetylators

38. 6.Psychological factor:- Personality of the doctor as well as the patient can affect
response to a drug. Some patients even respond to inert dosage forms (placebo) in
conditions like pain, bronchial asthma, anxiety, etc.
7. Pathological states:-
A. GI disorders:-
Achlorhydria→ ↓absorption of acidic drugs in the stomach by causing its
ionization.
In malabsorption syndrome, ↓absorption of some drugs
B. Liver disease:-
In chronic liver diseases- ↓metabolism of drugs resulted ↑BA of drugs having
high first-pass metabolism, e.g. propranolol.
C. Renal failure:- ↓Clearance of drugs by kidney
E.g.-incidence of nephrotoxicity and ototoxicity is more with aminoglycosides in
the presence of renal failure.

39. • 8. Tolerance/Receptor desensitization/Adaptation:-
• Repeated administration of drugs can result in ↓pharmacological effect.
• ↑ doses of such drugs are needed to achieve same response
• e.g. Ephedrine, organic nitrates, opioids, etc.
• Tolerance develops to nasal decongestant effect of ephedrine on repeated use.
Patients on organic nitrates for angina develop tolerance on long-term therapy.
• Tolerance is commonly seen with drugs like morphine, alcohol, amphetamine, etc.
• Types:- (1)Natural (2)Acquired
• Natural tolerance:- Genetically determined reduced/lack of response to a drug
• Species tolerance:-Some species are tolerant to certain drugs, e.g. rabbits can
tolerate large doses of atropine
Racial tolerance:- Some races show tolerance to certain drugs, e.g. blacks are
tolerant to mydriatics

40. Acquired tolerance:-
It develops on repeated exposure to a drug. Sometimes, tolerance develops only to certain
effects,
E.g. on repeated use of morphine, tolerance develops to its euphoriant and analgesic
effects but not to its miotic and constipating effects
• Mechanism of development of tolerance: It could be pharmacokinetic or
pharmacodynamic tolerance.
• (I.) Pharmacokinetic tolerance (Dispositional tolerance): Reduced concentration of the
drug at the site of action may be due to decreased absorption, increased metabolism and
excretion,
• e.g. development of tolerance to phenobarbitone on repeated use is due to enhancement of
Metabolism as a result of enzyme induction
• (II.) Pharmacodynamic tolerance (Functional tolerance):- The drug effect is reduced,
which may be due to a decrease in the number of receptors, decrease in the activity of
receptors and decreased neurotransmitter.
E.g.- Repeated use of opioids, barbiturates, etc. results in the development of tolerance due
to a decrease in the number of receptors (downregulation).

41. • (III.) Cross-tolerance: it is the development of tolerance to drugs having similar action
that may be from same chemical group or different chemical group.
• E.g.- if a person is tolerated to 1 opioid (morphine) shows tolerance to other
opioids(heroin) as well. Others- nitrates, opioids, and between ether and alcohol.
• (IV.) Tachyphylaxis (tachy = rapid; phylaxis = protection; acute tolerance):
• When a drug is administered repeatedly at short intervals, the response diminishes
rapidly and original effect cant be achieved even after increasing the dose. This is
commonly seen with noncatecholamines
• e.g. Tyramine, ephedrine, amphetamine.
• These drugs act by releasing noradrenaline from the adrenergic nerve endings. Repeated
administration of the drug causes gradual depletion of the neurotransmitter and hence
reduction in the response
• (V.) Drug dependance:-a state—psychic and sometimes also physical—resulting from
the interaction between a living organism and a drug, characterized by behavioral and
other response that always includes a compulsion to take the drug on a continuous or
periodic basis in order to experience its psychic effects and sometimes to avoid the
discomfort of its absence.

42. DRUG INTERACTIONS:-
• When two or more drugs are administered simultaneously, the effects of one
drug may be altered by the other drug.
• Drug interactions can occur either in vitro (outside the body) or in vivo (inside
the body).
Resulted-
either beneficial or
harmful effects

43. Pharmaceutical Interactions:-
• These can occur as a result of incompatibility (physical or chemical) of a drug
with an intravenous solution or when two or more drugs are mixed in the same
syringe/i.v. infusion. This may result in precipitation or inactivation of one or
more drugs.
• E.g.-Phenytoin should not be administered in dextrose solution as it gets
precipitated.
• Dextrose solution is not suitable for i.v. infusion of ampicillin, as it is unstable at
acidic pH of dextrose.
• Gentamicin and carbenicillin should not be given in the same infusion as it may
result in loss of their potency.
Pharmacokinetic Interactions:-
• These occur when one drug alters the absorption, distribution, metabolism or
excretion of another drug

44. Absorption:-
• Antacids (containing aluminium, magnesium, calcium, iron, etc.)× tetracyclines
(Antacids interfere absorption of tetracyclines by forming unabsorbable
complexes with it)
• Metoclopramide × Aspirin(Metoclopramide increases the rate of gastric emptying
and promotes absorption of aspirin)
Distribution:-
• Salicylates× warfarin (Salicylates displace warfarin from binding sites resulting
in increased free warfarin levels and an enhanced anticoagulant effect (bleeding).
Metabolism:- enzyme induction & enzyme inhibition
• e.g. Carbamazepine× warfarin (↑Metabolism)→↓ anticoagulant effect
• Erythromycin× carbamazepine (inhibit metabolizing enzyme) →↑Toxicity
Excretion:-
• Salicylates× methotrexate (↓excretion →↑toxicity)

45. • Probenecid decreases the renal tubular secretion of penicillins and prolongs the
duration of action of penicillins (beneficial interaction)
Pharmacodynamic Interactions:-
• The interaction is due to the action of drugs on receptors or physiological
system.
• This may result in either additive, synergistic or antagonistic effects
Harmful effects due to interaction:-
e.g. enhanced nephrotoxicity seen with the concurrent use of aminoglycosides
and amphotericin-B;
Beneficial effect due to interaction:-
e.g. levodopa and carbidopa in parkinsonism.

47. ADR is defined as
“any response to a drug that is noxious, unintended & that occurs at doses
used in man for prophylaxis, diagnosis or therapy’’
Types of ADR:-
1.Predictable reactions (Type A or Augmented reactions):-
 These are predictable dose related reactions to a drug related to its
pharmacological actions.
 They include→ side effects, secondary effects and toxic effects.
The undesirable effects of the drug are called Adverse Drug Reactions

48. Side Effects:-
• Undesired effects in the therapeutic doses are called side effect
• E.g. Atropine used in the treatment of heart block also produces dryness of mouth,
blurring of vision, urinary retention, etc., which are the side effects.
Secondary Effects:-
• The primary action of a drug may result in other effects
• These effects are not the direct effect of drugs but secondary to pharmacodynamic
effect of a drug.
• E.g. immunosuppression by corticosteroids can lead to development of
opportunistic infections like oral candidiasis.
Toxic Effects:-
• These are the effects of a drug that are either due to overdosage or chronic use
• e.g. Bleeding due to chronic use/overdosage of anticoagulants and nephrotoxicity
with aminoglycosides, especially in patients with renal failure

49. • Unpredictable reactions (Type B or Bizarre reactions):
• These are non-dose-related unpredictable reactions to a drug.
• They are not related to the pharmacological actions of the drug.
• They includes-
• Idiosyncrasy:-
• It is usually a genetically determined abnormal reaction to drugs
• E.g.- succinylcholine apnoea, aplastic anaemia caused by chloramphenicol,
haemolytic anaemia seen with primaquine and sulphonamides
• Drug Allergy:-
• It is an abnormal response (local or systemic) to a drug/foreign antigen mediated
by the immune system.
• It is also known as “drug hypersensitivity”.
• Different types of hypersensitivity reactions are discussed below
• Those associated with humoral antibodies: Types I, II and III.

50. • Those associated with cell-mediated immunity: Type IV (delayed
hypersensitivity).
• Type I hypersensitivity (immediate type, anaphylactic shock):-
• It is a rapidly occurring reaction; hence they are called immediate hypersensitivity
reaction.
• The manifestations are itching, urticaria, hay fever, asthma or even anaphylactic
shock.
• Ig-E mediated reactions takes place on the surface of mast cells
• Release of mediators like Histamine, Serotonin, Leukotrienes, Prostaglandins,
Platelet activating factor etc occurs.
• It results in Urticaria, Itching, Angioedema, Asthma, Rhinitis or Anaphylactic
Shock.
• Also known as Immediate hypersensitivity.

51. It is a medical emergency and
should be treated promptly with:
1. Inj. adrenaline (1:1000) 0.3–0.5
mL I.M.
2. Inj. hydrocortisone 100–200 mg
I.V.
3. Inj. pheniramine 45 mg
intramuscularly/intravenously.
4. Intravenous fluids

52. • Type II hypersensitivity (cytotoxic reaction):-
• The antibodies (IgG and IgM) react with cell-bound antigen and cause activation
of complement, which destroys the cells
• E.g.-blood transfusion reactions,
haemolytic anemias produced by quinine,
quinidine, cephalosporins, etc.

53. 3. Type-III reactions (Retarded, Arthus)IgG mediated:-
• In this type of reaction antibodies involved are mainly IgG
AG:AB complexes are formed
↓↓
Fix complement
↓↓
Deposition of complexes on vascular endothelium
↓↓
Destructive inflammatory response.
• E.g.-
• Serum sickness (fever, urticaria, joint pain, lymphadenopathy)→ with penicillins and
sulphonamides
• Acute interstitial nephritis→ with NSAIDs
• Stevens–Johnson syndrome→ with sulphonamides.

54. • Type IV hypersensitivity (cell-mediated or delayed hypersensitivity):
• It is mediated by sensitized T-lymphocytes.
• Re-exposure to the antigen leads to a local inflammatory response.
• The manifestations usually occur 1–2 days after exposure to the sensitizing
antigen, e.g. contact dermatitis due to local anaesthetic creams, topical antibiotics
and antifungal agents.
• Type II, type III and type IV reactions are treated with glucocorticoids.
• Drug Dependence:-
• 1. Psychological dependence:-
• There is an intense desire to continue taking the drug as the patients feel that their
well-being depends upon the drug.
• 2. Physical dependence: Repeated drug use produces physiological changes in
the body that makes continuous presence of the drug in the body necessary to
maintain normal function.
• Abrupt stoppage of the drug results in an imbalance wherein the body has to
readjust to the

55. • Absence of the drug resulting in the development of signs and symptoms known as
withdrawal syndrome.
• The withdrawal signs and symptoms are generally opposite to the effects produced by
the drug
• Principles of treatment of drug dependence are:-
• 1. Hospitalization.
• 2. Substitution therapy: e.g. Methadone/buprenorphine substitution for morphine
addiction.
• 3. Aversion therapy: Disulfiram for alcohol addiction.
• 4. Psychotherapy.
• 5. General measures: Maintain nutrition, family support and rehabilitation.
• Iatrogenic Diseases:-
• It is physician-induced disease (‘Iatros’ is a Greek word, means ‘physician’) due to drug
therapy
• e.g. parkinsonism due to metoclopramide; acute gastritis and peptic ulcer due to
nonsteroidal anti-inflammatory drugs

56. • Teratogenicity:-
• Certain drugs when given during pregnancy may cross the placenta and cause
various dangerous effects in the foetus.
• Or “It refers to the capacity of a drug to cause foetal abnormalities when
administered to a pregnant woman”
• Administration of drugs during early pregnancy (from conception to 16 days)
could result in abortion;
• during 2–8 weeks(18-55 days) of gestation, it can affect organogenesis and
produce structural abnormalities;
• During second and third trimester (56 days onward), drugs can affect growth and
development of the foetus. Hence, drug administration during pregnancy should
be restricted.
• E.g.-

57. • Carcinogenicity and Mutagenicity:-
• The ability of a drug to cause cancer is carcinogenicity and the agent is known as
carcinogen.
• The abnormalities of genetic material in a cell produced by a drug are known as
mutagenicity, e.g. anticancer drugs and oestrogens.
• Photosensitivity Reactions
• It is a drug-induced cutaneous reaction following exposure to ultraviolet radiation, e.g.
demeclocycline,
• doxycycline, etc.
• Hepatotoxicity:-
• Some of the hepatotoxic drugs are isoniazid, rifampicin, pyrazinamide, halothane,
paracetamol, etc.
• Nephrotoxicity:-
• Aminoglycosides, amphotericin B, cisplatin, cyclosporine, heavy metals, etc. are
nephrotoxic drugs.
• Ototoxicity:-
• It can occur with aminoglycosides, loop diuretics, cisplatin, etc.

58. • Ocular Toxicity:-
• Ethambutol, chloroquine, glucocorticoids, etc. can cause ocular toxicity
• Pharmacovigilance:-
• (WHO) define “It is the science and activities relating to Detection, Assessment,
Understanding and Prevention of adverse effects or any other possible drug-
related problems”
Uppsala monitoring centre (sweden)- international Collaborating centre
Central Drugs standard control Organization(CDSCO)-The National
Pharmacovigilance Centre is located at Ghaziabad
• Aim:-
• To improve patient care and safety related to use of drugs,
• Promote rational use of medicines,
• Develop regulations for use of drugs
• Educate healthcare professionals about adverse drug reactions.

59. Indian Pharmacopoeia Commission (IPC) Ghaziabad,
Government of India, is functioning as NCC for PvPI since 15th
April 2011

61. How to decrease the incidence of ADR
• Take detail drug history of patient.
• In case of prescribing more than one drug, rule out the drug
interaction between two drugs.
• Use accurate drug administration technique.
• For drugs with narrow safety margin go for TDM.

63. Question paper
1.Giving suitable examples discuss factors modifying Drug responses.(8M/4M)
2.Discuss the following:-
A. Mechanisms of action of drugs
B. Drug-drug interaction with suitable example(4M)
3.Write a short note on:-
A. Adverse drug reactions (3M)
B. Tolerance (3M/5M/4M)
C. Signal transduction mechanism (5M)
D. Partial agonist (3M)
E. Drug receptor Antagonism(5M)
F. Therapeutic index(2.5M)
G. G protein couple receptors (5M)
4.Write the difference between:-(3M)
A. Physical dependance & psychological dependance
B. Competitive & Non-competitive antagonists