IC5 - I

Cards (34)

  • Adverse drug reactions (ADRs) are undesirable or harmful effects of drugs given in conventional therapeutic settings
  • ADRs can range from minor to serious to potentially fatal
  • ADRs can mimic many disease conditions
  • ADRs are not the same as drug-drug interactions
  • Type A (Augmented ADR):
    • Due to excess of normal, predictable effects
    • Dose-related
    • Common and occurs in everyone if sufficient dosage is taken
    • Examples: Warfarin (anticoagulant) leading to bleeding, Digoxin causing nausea
  • Type B (Bizarre ADR):
    • Uncommon
    • Not predictable from the drug's primary action
    • Not dose-related
    • Includes idiosyncratic reactions due to genetic abnormalities and immunologic reactions like allergic reactions
    • Examples: Anaesthetics causing malignant hyperthermia, Penicillin leading to anaphylaxis
  • Type C (Continuous use ADR):
    • Predictable in most cases
    • Due to long-term use
    • Examples: NSAIDs causing nephropathy, Corticosteroids leading to Cushing syndrome
  • Type D (Delayed ADR):
    • Delayed effects that may occur even after cessation of drug use
    • Examples: Alkylating agents causing carcinogenesis, Retinoids and Thalidomide leading to teratogenesis
  • Type E (End of use ADR):
    • Occur after withdrawal of the drug, especially with abrupt withdrawal
    • Usually predictable
    • Examples: Corticosteroids leading to adrenocortical insufficiency
  • Hypersensitivity reactions include allergic reactions categorized into 4 types: Type I to Type IV
  • Type I (IgE-mediated):
    • Immediate hypersensitivity with maximal response within 30 minutes
    • Clinical manifestations include allergic reactions like rhinitis, angioedema, and systemic anaphylaxis
    • Examples: B-lactam antibiotics causing anaphylaxis
  • Type II (Cytotoxic ADR):
    • Involves cytotoxic antibodies against drug hapten-coated cells
    • Clinical effects include haemolytic anaemia, neutropenia, and thrombocytopenia
    • Examples: Penicillin leading to haemolytic anaemia
  • Type III (Immune complex-mediated):
    • Also known as Arthus reaction
    • Clinical manifestations include serum sickness, lymphadenopathy, and nephropathy
    • Examples: Penicillins, cephalosporins, and sulfonamides causing immune complex-mediated reactions
  • Type IV (Delayed cell-mediated):
    • Mediated by Th1 cells
    • Clinical manifestations include erythema and induration
    • Examples: Allergic contact dermatitis, TB dermal test
  • Common drugs giving rise to ADRs include Oestrogens, NSAIDs, and Corticosteroids
  • Oestrogens:
    • Therapeutic uses include Hormone Replacement Therapy (HRT) and Oral Contraceptive Pills (OCP)
    • ADRs include thromboembolism, hypertension, breast cancer, endometrial cancer, and hepatic adenoma
  • NSAIDs:
    • Therapeutic uses include reducing pain, fever, and inflammation by inhibiting cyclo-oxygenase (COX)
    • ADRs include GI bleeding, tinnitus, pulmonary eosinophilia, GI ulceration, vertigo, and renal failure
  • NSAIDs Adverse Drug Reactions (ADRs):
    • GI bleeding
    • Tinnitus
    • Pulmonary eosinophilia
    • GI ulceration
    • Vertigo
    • Alveolitis
    • Nausea
    • Headache
    • Stevens-Johnson Syndrome
    • Vomiting
    • Renal failure
    • Toxic epidermal necrolysis (TEN)
    • Pancreatitis
    • Papillary necrosis
    • Haematuria
    • Liver damage
    • Fluid retention
    • Hypersensitivity
    • Gastric ulceration due to inhibition of COX-1, preventing the creation of prostaglandins that protect the gastric mucosa
  • Corticosteroids Therapeutic uses:
    • Cortisol (glucocorticoid) and aldosterone (mineralocorticoid) produced in the adrenal cortex
    • "Corticosteroids" generally refers to glucocorticoids
    • Anti-inflammatory agents (systemic or topical) inhibit molecules promoting inflammation
    • Uses: Autoimmune disease, asthma, allergic rhinitis, urticaria (hives), atopic eczema
    • Replacement therapy for pituitary or adrenal insufficiency
    • Effects: Immunosuppressive, anti-inflammatory effects, Metabolic effects affecting carbohydrate, fat, and protein metabolism
  • Corticosteroids Adverse Drug Reactions:
    • Mental disturbances
    • Suppression of growth in children
    • Adrenocortical atrophy
    • Diabetes (iatrogenic)
    • Immunosuppression
    • Cushing syndrome symptoms:
    • Moon facies
    • Central obesity
    • Violaceous striae (purple stretch marks)
    • Easy bruising
    • Hirsutism
    • Male pattern balding
    • Acne
    • Acanthosis nigricans
    • Peptic ulcer
    • Proximal muscle weakness
    • Osteoporosis
    • Avascular necrosis of the hip
    • Weight gain
  • Liver Dose-related reactions:
    • Pathology and associated drugs:
    • Hepatocellular necrosis: Paracetamol, Cytotoxic drugs (e.g., Methotrexate), Salicylates, Vitamin A
    • Acute fatty liver: Tetracycline (IV)
    • Granulomatous hepatitis: Phenylbutazone, hydralazine, allopurinol
    • Focal Nodular Hyperplasia: Oral contraceptives (OCP)
    • Liver cell adenoma (benign tumour): OCP, anabolic steroids
    • Fatty liver
  • Gastrointestinal tract ADRs:
    • Gastritis: NSAIDs
    • Peptic ulcers: NSAIDs, Corticosteroids
    • Jejunal ulcers: Enteric-coated potassium
    • Pseudomembranous colitis: Antibiotics
    • Gingival hyperplasia: Phenytoin
  • Urinary Tract ADRs:
    • Acute tubulo-interstitial nephritis: Methicillin, rifampicin, sulphonamides
    • Acute tubular necrosis: Gentamicin
    • Analgesic nephropathy (papillary necrosis): Compound analgesics containing phenacetin, acetaminophen, NSAIDs
    • Haemorrhagic cystitis: Cyclophosphamide
  • Bone Marrow ADRs:
    • Many drugs affect the bone marrow, usually cytotoxic/anti-neoplastic drugs
    • Myelosuppression (usually reversible)
    • Normal marrow vs. Aplastic marrow
  • Principles of avoiding and minimizing ADRs (in clinical practice):
    • Patient factors: Intrinsic (age, gender, genetic factors, organ dysfunction, previous ADRs, habits), Extrinsic (environmental factors, nutrition)
    • Prescriber factors: Drug-drug interactions, Incorrect administration, Dose, Duration
    • Drug factors: Interactions, Pharmaceutical issues
    • Vulnerable patient groups: Elderly, Neonates, infants, Women, Renal or hepatic impairment history of ADRs
  • Steps to minimize ADRs in clinical practice:
    • Appropriate use of drugs
    • Prescribe correct dose, route, and frequency
    • Check previous ADR history and allergies
    • Be cautious of polypharmacy and interactions
    • Perform necessary lab monitoring
    • Communicate common ADRs clearly
  • How to reduce the incidence of ADRs:
    • Always check for allergies and drug interactions
    • Advise discontinuation of medication if an ADR occurs
  • Summary:
    • Definition of ADRs and types
    • Hypersensitivity reactions
    • Commonly used drugs and affected organ systems
    • Principles of preventing/minimizing ADRs
  • types of adverse drug reactions
    A: Augmented; common
    B: Bizarre; idiosyncratic; infrequent
    C: Chronic, continuous; rare
    D: Delayed; rare
    E: End of use; rare
  • Type A (Augmented ADR) mechanism
    1. due to the drug's primary pharmacological effect: warfarin causing bleeding
    2. due to low therapeutic index: digoxin causing nausea
    3. predictable, dose related, preventable
  • Type B (bizarre ADR) mechanism (poorly understood)
    1. immunologic mechanism (allergic/hypersensitivity reaction): penicillin causing anaphylaxis
    2. idiosyncratic. genetic basis; how the drug is metabolised: anaesthetics causing malignant hyperthermia
    3. not predictable, not dose related, can be life threatening
  • Type C (chronic, continuous ADR) mechanism:
    1. continuous reaction to long-term use
    2. analgesics causing nephropathy
    3. neuroleptics causing tardive dyskinesia
    4. predictable, dose dependent
  • Type D (delayed ADR) mechanism
    1. delayed reactions
    2. alkylating agents causing carcinogenesis
    3. predictable and dose dependent
  • type E (end-of-use ADR) mechanism
    1. end of use reactions
    2. glucocorticoid withdrawal symptoms like adrenocortical deficiency
    3. benzodiazepine withdrawal causing insomnia and anxiety
    4. predictable and dose related