Session 10 Pharmacovigilance, drug interactions and response

• Type A (augmented reactions) ADR?

  • Predictable from knowledge of how a medication works.
  • Dose related.
  • Reversible
  • Example: Bleeding with anticoagulants, Hypoglycaemia with insulin
• Type B (bizarre reactions) or idiosyncratic ADR?

  • Not related to the pharmacological action of the drug.
  • Not predictable, uncommon, often fatal.
  • Not dose dependent in the therapeutic range.
  • Often immunological
  • Often linked to genetic variation
  • Examples: Anaphylaxis and penicillin
• Type C (continuous reactions) ADR?

  • Persist relatively long time
  • Example: Steroid therapy and osteoporosis
• Type D (delayed reactions) ADR?

  • Apparent sometime after use of a medicine.
  • Example: Azathioprine immunosuppression and malignancy
• Type E (end of use reactions)?

  Example insomnia, anxiety, perceptual disturbances following benzodiazepine withdrawal.
• Type F (failure)?

  Failure of oral contraceptive and enzyme inducer
• Types of ADR?

  • Type A - augmented reactions
  • Type B - bizarre reactions
  • Type C - continuous reactions
  • Type D - Delayed reactions
  • type E - End of use reactions
  • Type F - Failure
• Suspected drug allergy is any reaction caused by a drug with clinical features compatible with an immunological mechanism.
• Types of hypersensitivity reactions

  A) IgE

  B) IgG or IgM

  C) T

  
• Know common/ serious adverse drug reactions

  • ACEi– cough, hyperkalaemia
  • Amlodipine – oedema
  • Amiodarone – pulmonary fibrosis, thyroid dysfunction
  • Carbamazepine – hyponatraemia
  • Metformin – lactic acidosis
  • Statins – myalgia
• Common ADRs

  • Antibiotics (penicillin) - Nausea, diarrhoea
  • Anticoagulants (warfarin) - Bleeding
  • Aspirin - Dyspepsia, bleeding
  • Benzodiazepines (diazepam) - Drowsiness, falls
  • Beta blockers (atenolol) - Cold peripheries, bradycardia
  • Digoxin - Nausea, anorexia, bradycardia
  • Insulin - Hypoglycaemia
  • Diuretics (furosemide) - Dehydration, electrolyte disturbance
  • NSAIDs (ibuprofen) - Dyspepsia, bleeding, renal impairment
  • Opioid analgesia (morphine)- Nausea, vomiting, confusion, constipation
• Pharmacogenomics: role of the components of the genome (genetic variation like specific DNA polymorphism) on the response to a drug.
• Single nucleotide polymorphisms (SNPs) - variation at a single base pair.
• Drug Metabolism?

  • Phase 1- polar groups added to lipophilic molecules by oxidation, reduction, or hydrolysis to make water-soluble. Catalyzed by the cytochrome P450 superfamily of mixed function oxidases (CYPs).
  • Phase 2- compounds not hydrophilic enough for excretion- further processing conjugation - readily excretable, nontoxic substances.
• Clopidogrel treatment failure - thrombotic/ischemic event during clopidogrel therapy.
• Clopidogrel - Independent of cyclooxygenase pathway – synergistic with aspirin (Inhibit COX - reduced thromboxane – reduce platelet aggregation).
• Codeine is a prodrug it is metabolized by CYP2D6 to morphine and codeine-6-glucuronide.
• Increased risk of bone marrow suppression and infection - Polymorphisms in the TPMT (Thiopurine methyltransferase) gene
• START(Screening Tool to Alert to Right Treatment) can be used to prevent omissions of indicated, appropriate medicines in older patients with specific conditions.
• STOPP(Screening Tool of Older Persons' potentially inappropriate Prescriptions) aims to reduce the incidence of medicines-related adverse events from potentially inappropriate prescribing and polypharmacy.