Adverse Drug Reaction. Unnikrishnan M K Additional Prof in Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104. Introduction. Defn: Undesirable effect at normal dose: trivial OR serious Or fatal Requires Treatment in dosing Discontinuation
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Adverse Drug Reaction Unnikrishnan M K Additional Prof in Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104
Introduction • Defn: Undesirable effect at normal dose: • trivial OR serious Or fatal • Requires • Treatment • in dosing • Discontinuation • Caution in future • Occurrence • immediately or after prolonged use • or after termination • Mild ADRs common, [incidence 10-25%] • with polypharmacy • Acceptability: linked to Therap. Use; Risk Benefit Ratio
Type A: Predictable & Type B Unpredictable • Type A: Response qualitatively normal but quantitatively abnormal • Common, less serious, dose related, • corrected by dose adjustment • include side effect, toxic effect, withdrawal • Type B: Because of patient peculiarities; Eg. Allergy, idiosyncrasy • Dose related; uncommon; Serious withdrawal of drug required • Not always predictable / preventable
Severity of ADR: Minor/ moderate/ severe/ lethal • Minor: no need of therapy, antidote, or hospitalization • Moderate: requires drug change , specific treatment, hospitalization • Severe: Potentially life threatening; permanent damage, and prolonged hospitalisation. • Lethal: Directly or indirectly leads to death
Prevention of ADR: [cannot be totally avoided; only minimized]  Avoid inappropriate drugs in the context of clinical condition  Use right dose, route, frequency based on patient variables  Elicit medication history; consider untoward incidents  Elicit history of allergies [in patients with allergic diseases]  Rule out drug interactions  Adopt right technique: Eg slow iv injection of aminophylline  Carry out appropriate monitoring [Eg PT with warfarin; Li levels]
Types of ADRs viz Side effect; Secondary effect; Toxic effect  Side Effects: unavoidable, predictable, dose amelioration • Occurs as Extension of the same therapeutic effect: Eg. • Atropine as antisecretory in preanesthetic medication dry mouth • Occurs as a distinctly different effect: Eg. • Promethazine as antiallergic sedation • Estrogen as antiovulatory nausea • Side effect exploited for a therapeutic use: Eg • Codeine [antitussive] constipating action used in diarrhoea • Sulfonylureas [tested as antibacterials] were found tobl glucose
Secondary Effects & Toxic Effects •  Secondary effects: Indirect effect of therapy • Eg. Iintestinal microflora killed by tetracycline superinfection • Corticosteroids immunity activation of latent tuberculosis •  Toxic effects: [Overdose or prolonged use] • Atropine delirium ; • Paracetamol hepatic necrosis • Barbiturates coma; • Morphine respiratory failure
Intolerance and Idiosyncrasy •  Intolerance: • Opposite of tolerance: sensitivity to low doses • few doses of carbamazepine ataxia [ defective movement/gait] • single dose of triflupromazine muscular dystonia •  Idiosyncrasy: genetically determined atypical / bizarre effect • Barbiturate excitement & mental confusion • Quinine cramps , diarrhoea, purpura, asthma, vascular collapse
Drug allergy: [ or hypersensitivity] •  Drug allergy: [ or hypersensitivity] • Immunologically mediated • Independent of dose • Occurs in a small proportion; • Prior sensitization required • 1-2 weeks required after first dose • Drug acts as an antigen or Hapten • Chemically related drugs may show cross sensitivity • Same drug can cause diff allergic reactions in diff individuals
Drug allergy: continued.. • Variable time course: Sensitive people may later tolerate drug • Type I: urticaria, angioedema, asthma, anaphylactic shock • Type II: Thrombocytopenia, agranulocytosis, aplastic anemia, SLE • Type III: Arthralgia, lymphadenopathy, Steven Johnson Synd. • Type IV: contact dermatitis, fever, photosensitisation Eg: penicillin, sulfonamides, carbamazepine, methyldopa
Photosensitivity: [phototoxic & photoallergic] • Phototoxic: Drug accumulates in skin absorbs light photochemical reaction photobiological reaction tissue damage [Eg erythema, edema, blistering etc] Eg tetracyclines • Photoallergic: drug cell mediated immune response contact dermatitis on exposure to light. Eg sulfonamides, griseofulvin etc.
ADRs continued.. • Drug Dependence: Psychological: (Habituation) & Physical dependence: with withdrawal symptoms • Teratogenicity: Drug use in pregnancy affects offspring Eg Thalidomide phocomelia; phenytoin cleft palate • [10 ]Carcinogenicity & mutagenicity: Anticancer drugs, estrogens •  Drug induced deseases, Iatrogenic diseases : Salicylates peptic ulcer; Phenothiazines parkinsonism; INH hepatitis