Adverse Drug Reaction

Aka: Adverse Drug Reaction, Medication Hypersensitivity, Drug Reaction, Medication Allergic Reaction, Drug Hypersensitivity, Drug Eruption, Drug-Induced Skin Reaction, Cutaneous Drug Eruption

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II. Types: Medication-induced Hypersensitivity Reaction

  1. See Gell and Coombs Classification

III. Differential Diagnosis: Non-immune mediated Drug Reaction

  1. Medication Withdrawal (examples)
    1. Antidepressant Withdrawal
    2. Clonidine
  2. Medication intolerance
    1. Significant gastrointestinal upset with Codeine
  3. Sensitization
    1. See Drug-induced Photosensitivity
  4. Idiosyncratic reaction (examples)
    1. G6PD Deficiency
  5. Pseudoallergic reaction (direct Mast Cell activation)
    1. Intravenous Contrast anaphylactoid reaction
  6. Drug Interactions
    1. See Cytochrome P-450
    2. Example: Drug Interactions with Coumadin
  7. Medication Overdose (examples)
    1. Medication Dosing Errors in Children
    2. Dilantin Toxicity
    3. Digoxin Toxicity
  8. Medication toxicity (examples)
    1. Medication Causes of Marrow Toxicity
    2. Medication Causes of Myositis
    3. Nephrotoxic Drugs
    4. Hepatotoxic Medication
    5. Ototoxic Drugs
  9. Medication specific adverse effect (examples)
    1. Medication Causes of Abnormal Uterine Bleeding
    2. Medication Causes of Constipation
    3. Medication Causes of Depression
    4. Medication Causes of Dyspepsia
    5. Medication Causes of Dyspnea
    6. Medication Causes of Edema
    7. Medication Causes of Galactorrhea
    8. Medication Causes of Headache
    9. Medication Causes of Hemolytic Anemia
    10. Medication Causes of Hyperpigmentation
    11. Medication Causes of Impotence
    12. Medication Causes of Jaundice
    13. Medication Causes of Lymphadenopathy
    14. Medication Causes of Macrocytic Anemia
    15. Medication Causes of Myositis
    16. Medication Causes of Neutropenia
    17. Medication Causes of Nightmares
    18. Medication Causes of Phototoxic Reaction
    19. Medication Causes of Pruritus

IV. Risk factors: Immune-mediated Drug Reaction

  1. Drug Hypersensitivity Reaction to related medication
  2. Adults (especially women)
  3. Concurrent Viral Infection
  4. Comorbid condition
    1. HIV Infection
    2. Asthma
    3. Systemic Lupus Erythematosus
    4. Beta Blocker use
  5. Medications with larger more complicated structure
    1. Non-human Proteins
    2. Streptokinase
    3. Insulin

V. Findings: Suggestive of Drug Hypersensitivity

  1. See Life-Threatening Drug-Induced Rashes
  2. Anaphylaxis
  3. Angioedema
  4. Urticaria
  5. Morbilliform rash (80% of drug rashes in adults, 35% in children)
    1. Occurs 4 to 21 days after onset of exposure
    2. See Fixed Drug Eruption
  6. Bullous Disease
    1. See Drug-Induced Bullous Disease
    2. Erythema Multiforme
    3. Toxic Epidermal Necrolysis

VI. Management

  1. Avoid drug responsible for adverse reaction
  2. Consider testing for allergy if suspect immune-mediated
    1. Type 1 Hypersensitivity Reaction
      1. Skin Testing
      2. RAST Testing
    2. Type 2 Hypersensitivity Reaction
      1. Coombs' Test positive
      2. Complete Blood Count
        1. Hemolytic Anemia
        2. Thrombocytopenia
        3. Neutropenia
    3. Type 3 Hypersensitivity Reaction
      1. Erythrocyte Sedimentation Rate (ESR) increased
    4. Type 4 Hypersensitivity Reaction
      1. Patch Testing
  3. Consider Desensitization to offending agent
  4. Consider specific agent management
    1. Penicillin Adverse Drug Reaction
    2. Intravenous Contrast

VII. References

  1. Diasio in Goldman (2000) Cecil Medicine, p. 100-1
  2. Gruchalla (2003) J Allergy Clin Immunol 111:548-59 [PubMed]
  3. Riedl (2003) Am Fam Physician 68:1781-90 [PubMed]

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