Drug Interactions: Intro

Faculty of Health - Drug Interactions Introduction

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Welcome to Country

  • Acknowledgment of Traditional Owners:
    • Recognizes the Turrbal, Jagera/Yuggera, Kabi Kabi, and Jinibara Peoples as Traditional Owners of the land.
    • Acknowledges their ongoing role in the QUT community and pays respect to their Elders past, present, and emerging.

Learning Objectives

By applying the information from the drug interaction presentations and activities, you should be able to:

  • Summarize the likelihood and significance of drug interactions (DI).
  • Identify susceptible patients.
  • Discuss the definition of a drug interaction.
  • Recognize clinically important drug interactions.
  • Document suspected adverse drug interactions.
  • Utilize available drug interaction resources.

Likelihood and Significance of Drug Interactions

  • Estimated incidence of drug interactions:
    • 5-6% if a person is taking 2 drugs.
    • Approximately 56% incidence for 6 drugs.
    • Nearly 100% chance of interaction when taking 8 drugs.
  • Important note: Not all drug interactions are clinically significant!
    • Potential Clinical Significance: When a therapeutic combination leads to unexpected changes or complications in a patient’s condition.
  • Individual variability: Not everyone will experience a given interaction.

Susceptible Patients

  • Certain populations are at higher risk for drug interactions:
    • Patients experiencing poly-pharmacy and those using complementary and alternative medicine (CAM).
    • Patients with hepatic or renal disease.
    • Individuals on drugs with narrow therapeutic indices, such as:
    • Digoxin
    • Insulin
    • Lithium
    • Antidepressants
    • Warfarin
    • Patients on long-term therapy for chronic diseases (e.g., epilepsy, diabetes).
    • Intensive care patients, transplant recipients, and complicated surgical patients.
    • Patients with multiple prescribers or those not communicating with their prescriber.
    • The elderly and critically ill, due to impaired homeostatic mechanisms.

Previous Experiences of Drug Interactions

  • Engage with questions about past drug interactions, considering:
    • Severity of the interaction.
    • Methods used to resolve the interaction.
    • Relevance to patient symptoms (theoretical vs. real).
    • Resources used for information.
    • Areas needing further assistance.

Definition of a Drug Interaction

  • An interaction occurs when the effects of one drug are altered by any of the following:
    • Another drug.
    • Herbal medicine.
    • Food or drink.
    • Medical condition.
    • Environmental chemical agents.
    • Source: Stockley's Drug Interactions (2016).

Mechanism of Drug Interactions

  • Drug interactions mainly occur through two processes:
    • Pharmacokinetic interactions:
    • One drug affects the absorption, distribution, metabolism, and excretion of another drug.
    • Example 1: Antacids decrease the dissolution of Ketoconazole (an acidic drug); they should be separated by 2 hours.
    • Example 2: Tetracycline interacts with iron preparations.
    • Pharmacodynamic interactions:
    • The pharmacological activity of one drug interacts with another drug.
    • Examples include:
      • Synergism
      • Antagonism
      • Altered cellular transport effects on the receptor sites.
    • Example: Phenytoin increases hepatic metabolism of theophylline, resulting in decreased levels of theophylline and reduced action.

MESS Framework for Drug Interactions

  • M – Mechanism: Thiazide diuretic increases sodium reabsorption, decreasing lithium clearance and increasing lithium concentration.
  • E – Evidence:
    • Various case reports and studies, including:
    • Macfie AC (1975) - Letter to BMJ about lithium poisoning with diuretics.
    • Solomon JG (1980) - Lithium toxicity due to diuretics.
    • Kerry RJ et al. (1980) - Warning about diuretics and lithium.
    • Jefferson JW et al. (1979) - Study on lithium levels with long-term diuretic use.
    • Jakobsson B & Berg U (1994) - Effects on renal function in nephrogenic diabetes insipidus.
    • Crabtree BL et al. (1991) - Comparison of diuretics' effects on lithium disposition.
  • S – Severity: Significant interaction possible; close monitoring of lithium is required.
  • S – Symptoms:
    • Signs of lithium toxicity, including weakness, worsening tremor, mild ataxia, poor concentration, and diarrhea.
    • Recommended management: Halve the lithium dose, monitor levels, and adjust accordingly based on monitoring results.

Drug-Disease Interactions

  • Examples of drug-disease interactions include:
    • Tricyclic Antidepressants (TCA) in patients with a history of postural hypotension.
    • Long-term NSAID use in osteoarthritis patients with chronic renal failure.
    • Use of anticholinergic drugs to prevent extrapyramidal side effects (EPSE) of antipsychotic medications.
    • Long-term prescription of benzodiazepines in patients with insomnia, dementia, or anxiety.

Potential Outcomes of Drug Interactions

  • Drug interaction combinations may lead to several net effects:
    • Additive effects: Increase in exposure or effects of one or more drugs leading to increased side effects (e.g., ACE inhibitors with thiazide diuretics leading to hypertension).
    • Reduced exposure: Decrease in effectiveness of one or more drugs (e.g., NSAIDs reducing blood-pressure-lowering effect of ACE inhibitors).
    • Antagonistic effects: One drug diminishes the effect of another (e.g., Omeprazole inhibiting CYP2C19, which reduces Clopidogrel activation).
    • Any other alteration in the effects of one or more drugs.

Understanding Drug Interactions

  • Not all drug interactions are harmful; some can be beneficial.
  • The significance of potential drug interactions needs to be identified and assessed.
  • Consider all medications, including dietary supplements and non-prescription drugs.
  • Most hospitalization cases due to drug interactions could be prevented with early intervention.

Clinical Considerations

  • Medications frequently involved in important drug interactions:
    • Drugs with narrow therapeutic indices (e.g., theophylline, lithium, digoxin, warfarin).
    • Drugs with steep dose-response curves (e.g., verapamil, sulfonylureas, levodopa).
  • Factors to consider:
    • Patient’s clinical state (e.g., renal or hepatic impairment).
    • Pharmacology of drugs (additive or antagonistic effects).
    • Timeline for interactions; effects may not be immediately evident.
    • Severity of interaction and individual variability (some genetically more susceptible).

Documenting Adverse Drug Interactions

  • Document and report suspected adverse drug interactions to regulatory authorities (e.g., TGA “blue-card”).
  • Some potentially interacting drugs may be given together if monitored carefully and dose adjustments are made when necessary.

Drug Interaction Resources

  • Recommended resources include:
    • AMH (Australian Medicines Handbook)
    • AusDI
    • Drugs.com
    • Drug Interaction Facts (annually updated)
    • Drug-Reax® (available through Micromedex)
    • eMIMs
    • Hansten and Horn
    • Medscape
    • Product information sources like Stockley's Drug Interactions
    • TGA website (http://www.tga.gov.au)

Top 10 Dangerous Drug Interactions in Long-Term Care

  1. Warfarin - NSAIDs
  2. Warfarin - Sulfa drugs
  3. Warfarin - Macrolides
  4. Warfarin - Quinolones
  5. Warfarin - Phenytoin
  6. ACE inhibitors - Potassium supplements
  7. ACE inhibitors - Spironolactone
  8. Digoxin - Amiodarone
  9. Digoxin - Verapamil
  10. Theophylline - Quinolones

Summary

  • Drug interactions exist; some are obvious, while others are not.
  • It is crucial to anticipate potentially clinically significant drug interactions.
  • Understanding drug interaction mechanisms facilitates recognition of actual or potential interactions.
  • Develop strategies to manage drug interactions to mitigate patients' risks.
  • Know “how” and “when” to act in the event of a drug interaction.
  • Educating patients about drug interactions is critically important.

References

  • Australian Medicines Handbook 2016/2017.
  • Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 2007; 76:391-6.
  • McLeod P et al. Defining inappropriate practices in prescribing for the elderly. Can Med Assoc J 1997; 156(3):385-91.
  • Snyder B et al. Drug Interactions: principles and practice. Aust Prescr 2012; 35:85-8.
  • Walker and Whittlese. Clinical Pharmacy and Therapeutics. Drug interactions 2012 pages 50-61.
  • Finley PR et al. Clinical relevance of drug interactions with lithium. Clinical pharmacokinetics. 1995 Sep; 29:172-91.