Transcript ADVERSE DRUG REACTIONS

DR. SHABANA ALI
Adverse Drug Reactions
(ADR)
Harm associated with the use of a given
medications
OR
 Unwanted or harmful reaction experienced
after the administration of a drug or
combination of drugs under normal
conditions of use
 ADR= significant morbidity & mortality
 Range
from
mild
reactions
(drowsiness, nausea, itching& rash);
disappear after discontinuation of drug
OR
 Severe
reactions
(respiratory
depression, neutorpenia, hepatocellualr
injury, hemorrhage, anaphylaxis
ADR most common in
 Women
 Elderly (>60 y old)
 Very young (1-4 y)
 Patients taking more than one drug
Classification of ADR
 Rawlin & Thompson classification
 Traditional classification
A&B
About 80% of ADR----Type A reactions
ABCD
1) Type A Reactions
a) Related to pharmacological action of drug
Extensions of the principal pharmacological action
of the drug
 Cont.
b) Predictable
Relatively easily predicted by preclinical and clinical
pharmacological studies
c) Common
Type A reactions not serious---common
d) Dose-dependent
Usually dose dependent
Type A reactions
(classes)
i) Toxicity of overdose (Drug overdose)
An adverse drug reaction caused by excessive dosing
e.g., hepatic failure with dose of paracetamol
Headache with antihypertensives
hypoglycemia with sulfonylurea;
ii) Side Effects
Nearly unavoidable secondary drug effect produced
by therapeutic doses
 intensity is dose dependent
 Occur immediately after initially taking drug or may
not appear until weeks after initiation of drug use
 E.g., sedation with antihistamines
iii) Secondary Effects
Secondary pharmacological effect
 E.g., development of diarrhea with antibiotic therapy
due to altered GIT bacterial flora
 Orthostatic hypotension with a phenothiazine
iv) Drug Interactions
When two drugs taken together & they effect each
other’s response pharmacologically or kinetically
 E.g., one drug slow metabolism of 2nd drug
blood
conc.= toxicity
 Theophylline toxicity in presence of erythromycin
2) Type B Reactions
Unrelated
to known pharmacological
actions of drug
Unpredictable
Often caused by immunological &
pharmacogenetic mechanisms
Unrelated to dosage
Comparatively rare & cause serious illness
or death
cont.
 Results
(more
likely)
in withdrawal of
marketing authorization
 Often not discovered until after drug is
marketed
 Both environmental & genetic factors =
important in this reaction
Type B Reactions (classes)
i) Drug Intolerance
Lower threshold to normal pharmacological action of a
drug
e.g., tinnitus (single average dose of aspirin)
ii) Hypersensitivity (immunological reaction)
Immune mediated response to a drug agent in
sensitized patient
e.g., anaphylaxis with penicillin
iii) Pseudoallergic Reaction
 Direct mast cell activation & degranulation by
drugs (opiates, vancomycin & radiocontrast media)
 Clinically
indistinguishable
hypersensitivity
but
immunologic reactions)
not
form
involve
Type
IgE
I
(non
iv) Idiosyncratic Reactions
 An uncommon & abnormal response to drug
 Usually due to genetic abnormality
 Affect drug metabolism & receptor sensitivity
 Harmful even fatal, appear in low doses
E.g., Anemia (hemolysis) by antioxidant drugs
(G6PD deficiency)
Paralysis due to succinylcholine (enzyme
deficiency)
3) Type C (chronic)
Reactions
 Associated with long-term drug therapy
 Well known and can be anticipated
 Adaptation occurs = discontinuation of
drug=abstinence syndrome
E.g. opoids, alcohol, barbiturates
4) Type D (delayed) Reactions
 Carcinogenic & teratogenic effects
 Delayed in onset
 Very rare
Carcinogenic Effect
Medication lead to cancer; take >20 y to develop
Teratogenic Effect
Drug- induced birth defects
Sign & Symptoms of ADR
 Mild, moderate, severe or lethal
 Sign & symptoms manifest soon after 1st dose or
only after chronic use
e.g., Allergic reactions occur soon after drug is taken
usually 2nd time ( itching, rash, eruption, upper or
lower airway edema with dyspnea & hypotension)
Idiosyncratic reactions=any unpredicted symptom
Mechanisms of ADR
Type A =non immunological, reversible with reduction
of dose, non serious, extension of pharmacological
effects
Type B
Biochemical
mechanism
unrelated
to
pharmacological
Immunologic = Hypersensitivity (Type I, II, III, IV)
OR
Non immunologic (direct)=
Pseudoallergic,
idiosyncratic, intolerance
Mechanism of Type B
Reactions
i) Often mediated by a chemically reactive
metabolite
Non detoxification of metabolite
Direct cytotoxicity
Direct tissue damage + necrosis
ii) Bind to NA
altered gene product
 Bind to a larger macromolecule
inducing
immune response (produce Ab & bind to Ab)
Drug Hypersensitivity
(allergic) Reaction
 Common form of adverse response to drugs
Classification (Gell & Coombs)
Type I reactions (IgE-mediated)
Type II reactions (cytotoxic)
Type III reactions (immune complex)
Type IV (delayed, cell mediated)