DR. SHABANA ALI. Adverse Drug Reactions (ADR) Harm associated with the use of a given medications OR...
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Transcript of DR. SHABANA ALI. Adverse Drug Reactions (ADR) Harm associated with the use of a given medications OR...
Adverse Drug Reactions (ADR)
Harm associated with the use of a given medications
ORUnwanted or harmful reaction experienced
after the administration of a drug or combination of drugs under normal
conditions of use
ADR= significant morbidity & mortalityRange from mild reactions
(drowsiness, nausea, itching& rash); disappear after discontinuation of drug
ORSevere reactions (respiratory
depression, neutorpenia, hepatocellualr injury, hemorrhage, anaphylaxis
Classification of ADR
Rawlin & Thompson classification ABCDTraditional classification A & BAbout 80% of ADR----Type A reactions
1) Type A Reactionsa) Related to pharmacological action of drugExtensions of the principal pharmacological action
of the drugCont.
b) PredictableRelatively easily predicted by preclinical
and clinical pharmacological studies
c) CommonType A reactions not serious---common
d) Dose-dependentUsually 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 paracetamolHeadache with antihypertensiveshypoglycemia with sulfonylurea;
ii) Side EffectsNearly unavoidable secondary drug effect
produced by therapeutic doses
intensity is dose dependentOccur immediately after initially taking drug
or may not appear until weeks after initiation of drug use
E.g., sedation with antihistamines
iii) Secondary EffectsSecondary pharmacological effect
E.g., development of diarrhea with antibiotic therapy due to altered GIT bacterial flora
Orthostatic hypotension with a phenothiazine
iv) Drug InteractionsWhen 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 ReactionsUnrelated to known pharmacological
actions of drugUnpredictableOften caused by immunological &
pharmacogenetic mechanismsUnrelated 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 IntoleranceLower 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 form Type I
hypersensitivity but not involve IgE (non
immunologic reactions)
iv) Idiosyncratic Reactions
An uncommon & abnormal response to drugUsually due to genetic abnormalityAffect drug metabolism & receptor
sensitivityHarmful 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 anticipatedAdaptation occurs = discontinuation
of drug=abstinence syndrome
E.g. opoids, alcohol, barbiturates
4) Type D (delayed) ReactionsCarcinogenic & teratogenic effectsDelayed in onset Very rareCarcinogenic EffectMedication lead to cancer; take >20 y to
develop
Teratogenic EffectDrug- induced birth defects
Sign & Symptoms of ADRMild, moderate, severe or lethalSign & symptoms manifest soon after 1st
dose or only after chronic usee.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 BBiochemical mechanism unrelated to
pharmacologicalImmunologic = 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)