adverse drug reactions

Adverse Drug Reaction : 

Adverse Drug Reaction Dr. Manjunath

Introduction : 

Introduction Defn: “an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug” Trivial OR Serious Or fatal

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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

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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

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Type “C” These reactions are associated with long-term drug therapy e.g. Benzodiazepine dependence and Analgesic nephropathy. They are well known and can be anticipated. Type “D” reactions These reactions refer to carcinogenic and teratogenic effects. These reactions are delayed in onset

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Type E End of dose effect for example abrupt cessation of corticosteroids produces acute adrenal insufficiency and stoppage of propranolol can produce rebound effect Type F Failure of therapy. OCP failure when on antitubercular therapy

Severity of ADR: : 

Severity of ADR: Minor: no need of therapy, antidote, or hospitalization Moderate: requires drug change , specific treatment, hospitalization Severe: Potentially life threatening; permanent damage, and prolonged hospitalization. Lethal: Directly or indirectly leads to death

Prevention of ADR: : 

Prevention of ADR: [1] Avoid inappropriate drugs in the context of clinical condition [2] Use right dose, route, frequency based on patient variables [3] Elicit medication history; consider untoward incidents [4] Elicit history of allergies [in patients with allergic diseases] [5] Rule out drug interactions [6] Adopt right technique: Eg slow iv injection of aminophylline [7] Carry out appropriate monitoring [Eg PT with warfarin; Li levels]

Types of ADRs : 

Types of ADRs [1] 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 tobl glucose

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[2] Secondary effects: Indirect effect of therapy Eg. Iintestinal microflora killed by tetracycline superinfection Corticosteroids  immunity  oral candidiasis

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[3] Toxic effects: [Overdose or prolonged use] Atropine  delirium ; Paracetamol  hepatic necrosis Barbiturates  coma; Morphine  respiratory failure

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EVALUATION AIRWAY BREATHING CIRCULATION DEGREE OF CONSCIOUSNESS HISTORY OF EXPOSURE/ INGESTION PHYSICAL EXAMINATION DECONTAMINATION GASTRIC LAVAGE INDUCTION OF EMESIS CONTRAINDICATIONS TO EMESIS ACTIVATED CHARCOAL OTHER DECONTAMINATION SUPPORTIVE CARE RESPIRATORY CARDIOVASCULAR CNS

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DIAGNOSTIC STUDIES BLOOD TESTS ECG X RAYS SPECIFIC DRUG LEVELS ENHANCING ELIMINATION ACTIVATED CHARCOAL FORCED ALKALINE DIURESIS HAEMODIALYSIS/PERFUSION ANTIDOTES Organophosphates – atropine, oximes Morphine – naloxone Benzodiazepines – flumazenil Paracetamol – N- acetyl cysteine

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[4] Intolerance: Opposite of tolerance: sensitivity to low doses few doses of carbamazepine  ataxia [ defective movement/gait] single dose of triflupromazine  muscular dystonia

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[5] Idiosyncrasy: genetically determined atypical / bizarre effect Barbiturate  excitement & mental confusion Streptomycin  deafness with single dose

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[6] 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

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continued.. 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

[7]Photosensitivity: : 

[7]Photosensitivity: 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.

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[8]Drug Dependence: Psychological: Physical dependence:

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[9]Teratogenicity: Drug use in pregnancy affects offspring Eg Thalidomide  phocomelia; phenytoin  cleft palate

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[10 ]Carcinogenicity & mutagenicity: Anticancer drugs, estrogens

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[11] Drug induced deseases, Iatrogenic diseases : Salicylates  peptic ulcer; Phenothiazines  parkinsonism; INH  hepatitis

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12. Drug withdrawal reaction Propranolol  hypertension Acute adrenal insufficiency following withdrawal of corticosteroids