DRUG REACTIONS

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DRUG REACTIONS

• A drug may be defined as a chemical substance, or
  combination of substances, administered for the
  investigation, prevention or treatment of
  diseases or symptoms, real or imagined.
• The distinction between drugs and 'other
  chemicals' is not always easily

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• Chemicals of very diverse structure are
  increasingly added to foods and beverages as
  dyes, flavours or preservatives.
• Chemicals used in agriculture or in veterinary
  medicine may contaminate human
• Advent of therapeutic agents that may be useful
  for improving the appearance, e.g minoxidil for
  androgenetic alopecia and tretinoin for
  photo-aged skin,
• the distinction between drugs and cosmetics has
  become blurred

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• An adverse drug reaction - defined as an
  undesirable clinical manifestation resulting from
  administration of a particular drug at doses
  normally used for prophylaxix,diagnosis threapy
  of diseases WHO 1972
• this includes reactions due to overdose,
  predictable side-effects and unanticipated
  adverse manifestations.
• Adverse drug reactions are the inevitable price
  we pay for the benefits of modern drug therapy.
• They are costly both in terms of -
• the human illness caused
• in economic terms,
• can undermine doctor-patient relationship.

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• Adverse drug reactions contribute to the need for
  hospitalization in 10-17 of elderly inpatients
• Inappropriate medication is a major cause of
  adverse drug reactions in elderly patients
• 27 of elderly patients on medication admitted to
  a teaching hospital experienced adverse drug
  reactions,
• Adverse drug reactions occur in between 6 and 17
  of children admitted to specialist paediatric
  hospitals

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• The incidence of adverse drug reactions varies
  from 6 to 30, with at least 90 million courses
  of drug treatment given yearly
• The reported percentage of patients who develop
  an adverse drug reaction during hospitalization
  varies markedly from 1.5 to 44,
• Although in most studies the incidence is about
  10-20
• It has been estimated that about one in 40
  consultations in general practice is the result
  of adverse drug reactions.
• the percentage of consultations involving an
  adverse drug reaction increased from 0.6 for
  patients aged 0-20 years to 2.7 for patients
  aged over 50 years

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• The elderly persons have a significantly higher
  incidence of adverse drug reactions, related to
  decreased organ reserve capacity
• Altered pharmacokinetics and pharmacodynamics,
• polypharmacy

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Classification of adverse drug reactions.

• Non-immunological
• Predictable
• Overdosage
• Side-effects
• Cumulation
• Delayed toxicity
• Facultative effects
• Drug interactions
• Metabolic alterations
• Teratogenicity
• Non-immunological activation of effectors
  pathways
• Exacerbation of disease
• Drug-induced chromosomal damage
• Unpredictable
• Intolerance
• Idiosyncrasy

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Immunological (unpredictable)

• IgE-dependent drug reactions
• Immune complex-dependent drug reactions
• Cytotoxic drug-induced
• Cell-mediated reactions
• Miscellaneous
• Jarisch-Herxheimer reactions
• Infectious mononucleosis-ampicillin reaction

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Immunological drug reactions

• IgE-dependent (type I) drug reactions
• urticaria and anaphylaxis
• Antibody-mediated (type II) drug reactions
• Immune complex-dependent (type III)
• Vasculitis
• The Arthus reaction
• Cell-mediated reactions (type IV reactions)
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• "Lichenoid drug eruptions
• Lupus erythematosus (LE)-like syndrome induced by
  drugs
• Drug-induced pemphigus Pemhigoid
• Fixed drug eruptions

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Drugs causing exanthematic reactions.

• Ampicillin and penicillin
• Cephalosporins
• Phenylbutazone and other pyrazolones
• Barbiturates
• Sulphonamides
• Thiazides
• Phenytoin
• Naproxen
• Carbamazepine
• Isoniazid
• Gold
• Phenothiazines
• Gentamicin

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exanthematous reactions
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exanthematous reactions
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urticaria or anaphylaxis

• Drugs causing are
• Animal sera
• Dextrans
• Antibiotics
• Angiotensin converting enzyme inhibitors
• Vasopressin
• Radiographic contrast media
• Non-steroidal anti-inflammatory drugs
• opiates, codeine, amphetamine, polymyxin B,
  tubocurarine, atropine, hydralazine, pentamidine,
  quinine and radiocontrast media - may release
  mast-cell mediators directly.
• Cyclo-oxygenase inhibitors, such as aspirin and
  indomethacin,

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Drugs causing photosensitivity.

• Amiodarone
• Ampicillin
• Phenothiazines
• Antidepressants
• ChlorpromazineTetracyclines
• Griseofulvin
• Demeclocyclin

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lichenoid eruptions

• Drugs causing lichenoid eruptions.
• Antitubercular drugs
• Ethambutol
• Antimalarials
• Mepacrine (quinacrine, atebrin)
• Frusemide,
• diazoxide,
• tetracyclines,

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STEVENS-JOHNSON SYNDROME (S.J.S)TOXIC
EPIDERMAL NECROLYSIS (TEN)
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MULTIPLE MUCOSAL LESION
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SjS-TEN
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SJS-TEN
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STEVENS-JOHNSON SYNDROME (S.J.S)TOXIC
EPIDERMAL NECROLYSIS (TEN)

• Anti-epileptic drugs (phenytoin, barbiturates,
  carbamazepine and lamotrigine
• Ampicillin and other lactam antibiotics
• Sulphonamides (sulphadiazine, trimethoprim-sulpham
  ethoxazole, sulphadoxine),
• phenobarbital,
• chlormezanone

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Drugs reported to exacerbate psoriasis

• Antimalarials
• Lithium salts
• Non-steroidal anti-inflammatory drugs
• Buprofen
• Indomethacin
• Meclofenamate sodium
• Pyrazolon derivatives (phenylbutazone,
  oxyphenbutazone)

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Acne form eruption

• Lesions are papulopustular but comedones are
  usually absent.
• Adrenocorticotrophic hormone (ACTH),
  corticosteroids
• Dexamethasone in neurosurgical patients,
• Anabolic steroids for bodybuilding
• Isoniazid may induce acne
• Danazol

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Fixe drug eruptions

• Fixed eruptions characteristically recur in the
  same site or sites each time the drug is
  administered
• Cross-sensitivity to related drugs may occur,
  such as between phenylbutazone and
  oxyphenbutazone and between tetracycline type
  drugs.
• Acute lesions usually develop 30 min to 8h after
  drug administration
• sharply marginated, round or oval itchy plaques
  of erythema and oedema becoming dusky violaceous
  or brown, and sometimes vesicular or bullous
• Lesions are solitary at first, but with repeated
  attacks new lesions usually appear and existing
  lesions may increase in size.
• Bullous fixed drug eruption
• Co-trimoxazole (trimethoprim-sulphamethoxazole),
• Tetracycline
• Ampicilline

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FDE GENITEL LESION
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FDE
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• Hair changes
• Drug-induced alopecia
• Drug-induced hypertrichosis
• Drug-induced hair discoloration
• Nail changes
• Onycholysis
• Oral conditions
• Xerostomia

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The management of drug reactions

• Diagnosis
• Drug history
• Drug elimination
• Skin testing
• Patch testing
• In vitro tests
• Tests for IgE antibody - RAST

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• Challenge tests
• Treatment
• Anaphylaxis
• Exfoliative dermatitis/erythroderma