Drug-Disease Interactions

Drug-Disease Interactions - Defining Dangers & Renal Risks

Drug-disease interaction: drug harms patient due to an existing disease. Kidneys are often affected.

• Altered physiology in disease → altered drug response.
• Renal Risks:
  • Reduced drug elimination → ↑ toxicity.
  • Increased drug sensitivity.
  • Drugs directly causing nephrotoxicity.

⭐ NSAIDs can precipitate acute renal failure in patients with pre-existing kidney disease or heart failure by inhibiting prostaglandin synthesis, leading to renal vasoconstriction.

• Key Renal Interactions:
  • Metformin: Risk of lactic acidosis if GFR < 30 mL/min.
  • ACE inhibitors/ARBs: Can worsen renal function in bilateral renal artery stenosis.
  • Aminoglycosides: ↑ nephrotoxicity risk in CKD.
  • Contrast media: Risk of contrast-induced nephropathy (CIN).

Drug-Disease Interactions - When Organs Complain

• Hepatic Impairment:
  • Altered drug pharmacokinetics:
    • ↓ Metabolism of drugs like warfarin, theophylline, benzodiazepines → ↑ toxicity.
    • ↓ Activation of prodrugs (e.g., codeine, enalapril) → ↓ efficacy.
  • Avoid/dose-adjust hepatotoxic drugs (e.g., paracetamol, isoniazid, methotrexate).
• Cardiac Conditions:
  • Heart Failure (HF):
    • Avoid: NSAIDs (Na⁺/H₂O retention), non-dihydropyridine CCBs (e.g., verapamil, diltiazem in HFrEF), Class I antiarrhythmics.
  • Ischemic Heart Disease (IHD):
    • Avoid drugs ↑ myocardial O₂ demand (e.g., non-selective β-agonists).

⭐ Amiodarone use should be cautious in patients with thyroid dysfunction (both hyper- and hypothyroidism) due to its high iodine content and direct toxic effects on the thyroid gland.

Drug-Disease Interactions - Lungs, Glands, Nerve Alerts

• Lungs:
  • NSAIDs & Aspirin: Risk of bronchospasm in asthma (AERD).
  • ACE Inhibitors: Dry cough; can worsen existing cough.
• Glands (Endocrine):
  • Thiazide diuretics:
    • Diabetes: ↑Glucose.
    • Gout: ↑Uric acid.
  • Corticosteroids:
    • Diabetes: ↑Glucose.
    • Osteoporosis: Worsen.
  • Beta-blockers (in Diabetes): Mask hypoglycemia symptoms (sweating may persist).
• Nerve (CNS/PNS):
  • Anticholinergics (e.g., TCAs, 1st gen antihistamines):
    • BPH: Urinary retention.
    • Narrow-angle glaucoma: Precipitate attack.
    • Elderly: Confusion, delirium.
  • Benzodiazepines/Opioids:
    • COPD: Respiratory depression.
    • Elderly/Dementia: ↑Sedation, confusion.
  • Dopamine antagonists (e.g., metoclopramide, typical antipsychotics): Worsen Parkinson's symptoms.

⭐ Non-selective beta-blockers (e.g., propranolol) are generally contraindicated in patients with asthma or severe COPD as they can cause bronchoconstriction by blocking beta-2 receptors in the lungs.

Drug-Disease Interactions - Age & Polypharmacy Perils

• Geriatric Vulnerability (≥65 yrs):
  • Altered Pharmacokinetics (PK): ↓ renal clearance, ↓ hepatic metabolism (Phase I), ↑ Volume of Distribution (Vd) for lipophilic drugs.
  • Altered Pharmacodynamics (PD): ↑ sensitivity to CNS depressants (e.g., opioids, benzodiazepines).
  • ↑ Adverse Drug Reaction (ADR) risk.
• Polypharmacy Perils (≥5 drugs):
  • Common in elderly; significantly ↑ risk of Drug-Drug Interactions (DDIs) & Drug-Disease Interactions (DDxIs).
  • Leads to ↑ pill burden, ↓ adherence, and ADR cascades.
• Beers Criteria & PIMs:
  • Lists Potentially Inappropriate Medications (PIMs) for older adults to minimize ADRs.

  ⭐ Benzodiazepines are on the Beers Criteria list of potentially inappropriate medications for older adults due to increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes.

• Mitigation Strategies:
  • Comprehensive medication review (e.g., "brown bag" review).
  • Deprescribing non-essential/harmful drugs.
  • "Start low, go slow" dosing approach.
  • 📌 Utilize tools like STOPP/START criteria for medication appropriateness assessment in older adults.

High‑Yield Points - ⚡ Biggest Takeaways

• Beta-blockers (e.g., propranolol) are contraindicated in asthma/COPD due to bronchoconstriction risk.
• NSAIDs can exacerbate heart failure, hypertension, and renal insufficiency.
• Metformin is contraindicated in severe renal impairment due to lactic acidosis risk.
• ACE inhibitors/ARBs are teratogenic (pregnancy) and contraindicated in bilateral renal artery stenosis.
• Thiazide diuretics may worsen gout (hyperuricemia) and diabetes (hyperglycemia).
• Corticosteroids can worsen diabetes, osteoporosis, and ↑ infection risk.
• Aminoglycosides: nephrotoxic/ototoxic; caution with renal disease or hearing loss.