Understanding Drug Interactions & Contraindications

Clinical Significance of Drug Interactions

Drug interactions are alterations in a drug’s effect caused by concomitant administration of another substance. For nurses, preventing these interactions is a safety imperative. Interactions can cause therapeutic failure or toxicity. This guide details pharmacokinetic and pharmacodynamic mechanisms to ensuring safe medication administration.

Authoritative research, such as this systematic review on drug interactions, highlights the complexity of polypharmacy. Understanding the rationale behind contraindications empowers effective patient advocacy.

Pharmacokinetic Interactions (ADME)

These affect drug concentration by altering Absorption, Distribution, Metabolism, or Excretion.

Metabolism: The CYP450 System

Hepatic Cytochrome P450 enzymes are the primary site of interactions.
Inducers: Accelerate metabolism, reducing drug levels (Therapeutic Failure).
Example: Rifampin induces enzymes metabolizing Warfarin, increasing clot risk.
Inhibitors: Slow metabolism, increasing drug levels (Toxicity).
Example: Grapefruit juice inhibits CYP3A4, causing toxic Statin or Calcium Channel Blocker levels.

Absorption Interactions

Binding Agents: Dairy (Calcium) binds Tetracyclines in the gut, blocking absorption.
pH Alteration: Antacids raise gastric pH, reducing absorption of acid-dependent drugs (e.g., Iron).

Pharmacodynamic Interactions

These alter the drug’s effect at the receptor level without changing concentration.

• Synergism (1+1=3): Combined effect exceeds the sum.
  Example: Alcohol + Benzodiazepines = Respiratory Depression.
• Antagonism (1+1=0): One drug blocks another.
  Example: Naloxone displaces Opioids, reversing sedation.
• Additive (1+1=2): Combined effect equals the sum.
  Example: Beta-blocker + Diuretic = Enhanced antihypertensive effect.

QT Prolongation Risks

Certain drugs delay ventricular repolarization (prolong the QT interval), increasing the risk of Torsades de Pointes, a fatal arrhythmia.

Contraindications: Absolute vs. Relative

Distinguishing between absolute prohibitions and cautionary use is vital.

Absolute Contraindication

Risk of life-threatening harm outweighs any benefit.
Example: Isotretinoin in pregnancy (Teratogenic). Aspirin in children with viral fever (Reye’s Syndrome).

Relative Contraindication

Benefit may outweigh risk if monitored closely.
Example: Non-selective Beta-blockers in mild asthma (Bronchospasm risk).

Drug-Disease Interactions

Drugs can exacerbate existing medical conditions.

• NSAIDs + Heart Failure: Cause fluid retention, worsening HF.
• Beta-Blockers + Asthma: Cause bronchoconstriction.
• Anticholinergics + Glaucoma/BPH: Increase intraocular pressure and urinary retention.
• Metformin + Renal Failure: Increases lactic acidosis risk.

Polypharmacy in the Elderly

Multiple medications increase interaction risk exponentially. Age-related renal/hepatic decline exacerbates this.
Intervention: Perform medication reconciliation at every transition. Consult the Beers Criteria for potentially inappropriate medications in older adults.

Herbal and OTC Interactions

“Natural” does not mean safe. Many supplements interact with prescriptions.

• St. John’s Wort: Potent CYP3A4 inducer. Reduces efficacy of oral contraceptives, Cyclosporine, and Digoxin. Risk of Serotonin Syndrome with SSRIs.
• The “G” Herbs (Garlic, Ginger, Ginkgo, Ginseng): Increase bleeding risk. Contraindicated with Warfarin/Antiplatelets before surgery.
• NSAIDs: OTC use increases bleeding risk with anticoagulants and renal failure risk with ACE inhibitors.

Drug-Nutrient Interactions

Food alters drug effects.

• Vitamin K + Warfarin: High intake (spinach, kale) antagonizes Warfarin. Consistent intake is key.
• Tyramine + MAOIs: Tyramine (aged cheese, wine) causes hypertensive crisis.
• Dairy + Ciprofloxacin: Calcium binds antibiotic, reducing efficacy.

Black Box Warnings

The FDA’s strictest warning alerts to serious risks.
Example: Fluoroquinolones (tendon rupture). Antidepressants (suicidality in young adults). Educate patients on specific warning signs.

FAQs: Safety Protocols

Conclusion

Preventing drug interactions requires vigilance. Understanding CYP450, recognizing high-risk combinations, and conducting thorough medication reconciliations allows nurses to prevent harm. Always consult a pharmacist when in doubt.