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Adverse Drug Reaction
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Introduction
Defn: an unwanted or harmful reaction experiencedfollowing the administration of a drug or
combination of drugs under normal conditions of useand suspected to be related to the drug
Trivial OR Serious Or fatal
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Type A: Responsequalitatively normal but
quantitatively abnormalCommon, less serious, dose related,
corrected by dose adjustment
include sideeffect, toxic effect, withdrawal
Type B: Because ofpatient peculiarities; Eg.Allergy, idiosyncrasy
Dose related; uncommon;
Serious withdrawal ofdrug required
Not always predictable / preventable
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Type C
These reactions are associated with long-term drug
therapye.g. Benzodiazepine dependence and
Analgesic nephropathy. Theyare well known andcan be anticipated.
Type D reactionsThese 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 insufficiencyand stoppage of propranolol can produce reboundeffect
Type F Failure of therapy. OCP failure when on
antitubercular therapy
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Severity ofADR: Minor: no need oftherapy, antidote, or
hospitalization
Moderate: requires drug change, specifictreatment, hospitalization
Severe: Potentially life threatening;
permanent damage, and prolongedhospitalization.
Lethal: Directly or indirectly leads to death
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Prevention ofADR:
[1] Avoid inappropriate drugs in the context ofclinical
condition
[2] Use right dose, route, frequency based on patient
variables
[3] Elicit medication history; consider untoward incidents
[4] Elicit history ofallergies [oin patients with allergic
diseases][5] Rule out drug interactions
[6] Adopt right technique: Eg slow iv injection of
aminophylline
7 Carr out a ro riate monitorin E PT with warfarin
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Types ofADRs[1] Side Effects: unavoidable, predictable,qdose
amelioration
Occurs as Extension of thesame therapeutic effect: Eg. Atropine asantisecretory in preanestheticmedication
dry mouth
Occursasa distinctly different effect: Eg. Promethazine asantiallergic sedation
Estrogen asantiovulatory nausea
Sideeffect exploited for a therapeuticuse: Eg Codeine [antitussive] constipating actionused in diarrhoea
Sulfonylureas[tested asantibacterials] were found toqblglucose
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[2] Secondary effects: Indirect effect of
therapy Eg. Iintestinal microflora killed by
tetracycline superinfection
Corticosteroids q 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 oftolerance:osensitivity to low doses
few doses ofcarbamazepine ataxia [ defectivemovement/gait]
single dose oftriflupromazine muscular
dystonia
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[5] Idiosyncrasy: genetically determined
atypical / bizarreeffect
Barbiturate excitement & mental confusion
Streptomycin deafness with single dose
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[6] Drug allergy: [ or hypersensitivity]
Immunologically mediated
Independent ofdose
Occurs in a small proportion;
Prior sensitization required 1-2 weeks required afterfirst dose
Drug acts as an antigen or Hapten
Chemically related drugs may show crosssensitivity
Same drug can cause diffallergic reactions in
diffindividuals
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continued..Type I: urticaria, angioedema, asthma, anaphylactic
shock
Type II: Thrombocytopenia, agranulocytosis, aplasticanemia, SLE
Type III: Arthralgia, lymphadenopathy, Steven Johnson
Synd.
Type IV: contact dermatitis,fever, photosensitisationEg: penicillin, sulfonamides, carbamazepine,
methyldopa
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[7]Photosensitivity:
Phototoxic:Drug accumulates in skin
absorbs light photochemical reaction
photobiological reaction tissue damage [Egerythema,edema, blisteringetc] Eg
tetracyclines
Photoallergic: drug
cell mediated immuneresponse contact dermatitis onexposure
to light. Eg sulfonamides,griseofulvinetc.
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[8]DrugDependence: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 insufficiencyfollowing withdrawal of
corticosteroids