Dr.U.P.

Rathnakar
MD.DIH.PGDHM
Adverse Drug Effects

Any undesirable or unintended consequence
of drug administration

“Any response to a drug that is noxious and
unintended and that occurs at doses used
in man for the prophylaxis, diagnosis, or
therapy of disease or for modification of
physiological function” – WHO

Adverse event: Any untoward event that
occurs during treatment not necessarily
with causal relation ship to treatment
ADE: Predictable and Unpredictable

Predictable: Type A : Augmented

Augmented pharmacological properties

Side effects, toxic effects, Drug withdrawal
effects

Common, dose related, Reversible

Unpredictable: Type B: Bizarre Reactions

Not known action of drug

Idiosyncracy, Allergy

Less common, Non dose related
ADE: Severity

Minor:

No tt required

Moderate:

Requires change in tt, change of drug

Severe:

Potentially life threatening,
permanent damage

Lethal:

Directly or indirectly contributes to
death
ADE
1. Side effects:
Unwanted ,unavoidable pharmacodynamic effects
at therapeutic doses
Eg. Antihistaminics cause sedation
2. Secondary effects:
Indirect consequence of primary action of a drug
Eg. Tetracyclines cause superinfection
3. Toxic effects:
Due to overdose or prolonged use
Eg. Respiratory failure by morphine
Coma by barbiturates
 ADE
4. Intolerance:

Low threshold to the action of drug

Eg. EPS with single dose of Metoclopromide
5. Idiosyncrasy:

A genetically determined reaction

An unusual individual reaction to food or a drug
Eg. Barbiturates cause excitement and mental
confusion
Chloramphenicol causes aplastic anemia
6. ADE:Drug allergy (drug hypersensitivity)

Immunologically mediated reaction

Types of drug allergy
1. Anaphylactic- -Type I
2. Cytolytic -Type II
3. Immune complex mediated[Arthus]:
-Type III
4. Delayed hypersensitivity
-Type IV
Type 1
 Drug allergy-Type I [Anaphylaxis]

Exposure to IgE AB
drug Fixed to Reexposure AG+AB
Eg.Penicillin mast cells

Release of
Treatment: mediators:
•Medical emergency Histamine, 5-HT,
•Inj.Adrenaline[1:1000] .3 to .5 ml PGs, LTs, PAF
i.m.
•Inj.Hydrocortisone 100 mgi.v.
Anaphylactic shock:
•Inj.Diphenhydramine 25mg i.v.
Hypotension,
•Oxygen
Bronchospasm,
•i.v. fluids
Urticaria Etc.
Type 2
Drug allergy-Type II [Cytolytic]

Exposure to Drug+Tissue=
Re Tissue+AB
drug AG
exposure
Eg.Quinine IgG, IgM- AB

Complement
Eg. Hemolysis by
Quinine, Quinidine
Cell
destruction
Type 3
Drug allergy-Type III[Immune mediated]
AG+AB
IgG Eg.
• Serum sicknes
[Fever, urticaria,
joint pain,
lymphadenopathy]
Complement •Penicillin, Sulfa
fixation •NSAIDs

Deposited on
vascular
endothelium

Destructive inflammatory
response
Type 4
Drug allergy-Type IV
[Delayed]

•Inflammatory respone
•Delayed by 2-3 days
•Contact dermatitis with LA creams
•Not AB related
•Cell mediated
7. Photosensitivity

Sensitization of the skin by drugs

UV radiation

Cutaneous reaction-Photosensitivity
8. Carcinogenicity & mutagenicity:

Ability of the drug to cause cancer and genetic
defects respectively
Eg. Tobacco, anticancer drugs
9. Iatrogenic diseases:
iatros = physician
(physician induced diseases):
Parkinsonism – Phenothiazines
Peptic ulcer – Aspirin,corticosteroids
Hepatitis - Isoniazid
Drugs frequently cause allergic reactions

Penicillins
Carbamazapine

Cephalosporins
ACE inhibitors

Sulfonamides
Local

Tetracyclines anesthetics

Quinolones

Antitubercular
drugs

Salicylates
10. Teratogenicity: terataos = monster
Capacity of the drug to cause fetal abnormalities
when administered to pregnant mother

I. Preimplantation:conception to 17 days-Abortion
ii.Organogenesis:18-55 days-Deformities
iii.Growth and development:56 days onwards

Thalidomide –Phocomelia
Corticosteroids – Cleft lip
TC-Discolouration of teeth, retarded bone growth
 17 D 17-55 D >56D
Implantation
Organogen Growth&Dev
Death Growth
Fetus Malform retard
 Human teratogenic drugs

Cleft Palate Hydrocephalus Phocomelia Neural tube

Anticancer drugs Thalidomide Defects
Valproate

Fetal alcohol
Hand defects syndrome Hydantoin syndrome
Warfarin Alcohol Phenytoin
Tetracycline

Staining

After Tt
11.Organ toxicity

Hepatotoxicity: INH, Rifampicin

Nephrotoxicity: Aminoglycosides

Ototoxicity: Aminoglycosides,
Frusemide

Ocular toxicity: Ethambutol,
Chloroquine
12. Drug dependence

A state

Psychological or physical

Due to interaction - living organism+Drug

Characterised by behavioral and other responses

Always includes a compulsion to take the drug
continuously or periodically

Psychological: Intense desire to take drug and

immense satisfaction later

Physical: Physiological equilibrium is maintained by

drug
Poisoning
“Poisons in small doses are the best medicines; and
useful medicines in too large doses are poisonous”

William Withering 1789

Poisoning

Large enough dose of a drug

Sub.which endagers life

Accidental or suicidal

Treatment

Hospitalization

Gastric lavage

Airway-Suction, Endotracheal tube

Breathing-Mechanical ventilation

Circulation-i.v.Fluids

Diuretics or Dialysis

Antidote-OP poisoning-Atropine
 Poisoning
1. Resuscitation and maintainance of vital functions
Airway, BP, Body temp., Blood sugar
2. Termination of exposure
Fresh air, remove wet clothes, wash,
3. Prevention of absorption
Gastric lavage, Activated charcoal,
4. Hastening elimination
Diuresis, Altering urine pH, Hemodialysis
 Prevention of adverse effects

Right dose, route, frequency

Previous history drug allergy and
allergic diseases

Rule out drug interactions

Correct technique of
administration

TDM if appropriate
 Pharmacovigilance

Actively look for adverse drug effects

“Activities relating to detection, assessment,
understanding and prevention of adverse effects or
any other drug related problem”

Information collected by
Regional centers to
Zonal centers to
National centers to
Uppsala monitoring center
(Sweden)
Uses

Educating doctors about ADE

Assessing safety of drugs