Drug Interactions Final

8/6/2019 Drug Interactions Final

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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

Drug Interactions Final

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