💊Intro to Pharmacology Unit 12 – Drug Interactions and Medication Safety

Key Concepts and Terminology

• Pharmacodynamics studies how drugs affect the body by binding to receptors, altering biochemical processes, and modifying physiological functions
• Pharmacokinetics examines how the body processes drugs through absorption, distribution, metabolism, and excretion (ADME)
• Drug interactions occur when one substance alters the pharmacokinetics or pharmacodynamics of another drug, potentially leading to adverse effects or reduced efficacy
  • Additive interactions result in an enhanced effect when two drugs with similar actions are combined
  • Synergistic interactions produce an effect greater than the sum of the individual drug effects
• Adverse drug events (ADEs) are unintended and harmful outcomes resulting from medication use, including side effects, allergic reactions, and medication errors
• Medication reconciliation is the process of comparing a patient's medication orders to all the medications they have been taking to avoid omissions, duplications, or potential interactions
• Polypharmacy refers to the concurrent use of multiple medications by a patient, which increases the risk of drug interactions and adverse events
• Cytochrome P450 (CYP) enzymes are a family of proteins primarily found in the liver that play a crucial role in drug metabolism and are often involved in drug interactions

Types of Drug Interactions

• Drug-drug interactions (DDIs) occur when two or more drugs interact with each other, potentially altering their effects or causing adverse reactions
  • Pharmacokinetic DDIs involve changes in absorption, distribution, metabolism, or excretion of one drug by another
  • Pharmacodynamic DDIs result from the combined pharmacological effects of two drugs on the body
• Drug-food interactions happen when certain foods or beverages affect the absorption, metabolism, or excretion of a drug (grapefruit juice)
• Drug-supplement interactions can occur between medications and dietary supplements, such as vitamins, minerals, or herbal products (St. John's Wort)
• Drug-disease interactions arise when a medication exacerbates or worsens a pre-existing medical condition (beta-blockers and asthma)
• Drug-alcohol interactions can lead to increased side effects, altered drug metabolism, or reduced drug effectiveness
• Drug-laboratory test interactions may cause false-positive or false-negative test results, potentially leading to misdiagnosis or inappropriate treatment
• Drug-lifestyle interactions involve the impact of certain lifestyle factors on drug efficacy or safety (smoking and oral contraceptives)

Mechanisms of Drug Interactions

• Absorption interactions occur when one drug alters the absorption of another drug in the gastrointestinal tract
  • Formation of insoluble complexes can reduce drug absorption (tetracyclines and calcium)
  • Changes in gastric pH can affect drug solubility and absorption (antacids and antibiotics)
• Distribution interactions involve competition for plasma protein binding sites or altered tissue distribution
  • Displacement of a drug from plasma proteins can increase its free concentration and effects (warfarin and NSAIDs)
• Metabolism interactions happen when one drug induces or inhibits the metabolic enzymes responsible for breaking down another drug
  • CYP enzyme induction can lead to reduced drug levels and efficacy (rifampin and oral contraceptives)
  • CYP enzyme inhibition can cause increased drug levels and toxicity (ketoconazole and simvastatin)
• Excretion interactions occur when one drug affects the renal elimination of another drug
  • Competition for active tubular secretion can lead to increased drug levels (probenecid and penicillins)
  • Changes in urine pH can alter drug ionization and reabsorption (ammonium chloride and amphetamines)
• Pharmacodynamic interactions result from drugs with similar or opposing pharmacological effects
  • Additive or synergistic effects can occur when drugs have similar mechanisms of action (alcohol and benzodiazepines)
  • Antagonistic effects happen when drugs have opposing actions (beta-agonists and beta-blockers)

Common Drug-Drug Interactions

• Warfarin, an anticoagulant, interacts with numerous drugs that can increase or decrease its effects, leading to bleeding or clotting risks (NSAIDs, antibiotics, and antifungals)
• Digoxin, a cardiac glycoside, has a narrow therapeutic index and can interact with drugs that alter its absorption or elimination (quinidine, verapamil, and amiodarone)
• Monoamine oxidase inhibitors (MAOIs), used for depression, can cause severe hypertensive crises when combined with sympathomimetic drugs or tyramine-rich foods (decongestants, certain cheeses, and cured meats)
• Selective serotonin reuptake inhibitors (SSRIs) can interact with other serotonergic drugs, leading to serotonin syndrome (tramadol, triptans, and St. John's Wort)
• Statins, used for lowering cholesterol, can interact with drugs that inhibit their metabolism, increasing the risk of muscle toxicity (fibrates, macrolide antibiotics, and azole antifungals)
• Oral contraceptives can interact with drugs that induce or inhibit CYP enzymes, leading to reduced contraceptive efficacy or increased side effects (rifampin, carbamazepine, and grapefruit juice)
• Angiotensin-converting enzyme (ACE) inhibitors, used for hypertension and heart failure, can interact with potassium-sparing diuretics, causing hyperkalemia (spironolactone and triamterene)

Drug-Food and Drug-Supplement Interactions

• Grapefruit juice inhibits CYP3A4 enzymes, leading to increased levels of drugs metabolized by this pathway (statins, calcium channel blockers, and cyclosporine)
  • Patients should avoid grapefruit juice when taking these medications or seek alternative drugs
• Vitamin K-rich foods (green leafy vegetables and soybean oil) can reduce the effectiveness of warfarin by promoting blood clotting
  • Patients on warfarin should maintain a consistent intake of vitamin K-rich foods
• Calcium supplements can interfere with the absorption of certain antibiotics (tetracyclines and fluoroquinolones)
  • Patients should take these antibiotics at least 2 hours before or 6 hours after calcium supplements
• St. John's Wort, a herbal supplement used for depression, induces CYP3A4 enzymes and can reduce the effectiveness of various drugs (oral contraceptives, antiretrovirals, and immunosuppressants)
  • Patients should avoid St. John's Wort or consult their healthcare provider before using it
• Iron supplements can reduce the absorption of levothyroxine, used for treating hypothyroidism
  • Patients should take levothyroxine at least 4 hours apart from iron supplements
• High-fat meals can delay the absorption of certain drugs (propranolol and spironolactone), while enhancing the absorption of others (griseofulvin and itraconazole)
  • Patients should follow the specific food intake instructions for their medications

Factors Affecting Drug Interactions

• Age can influence drug interactions due to changes in organ function, body composition, and polypharmacy
  • Elderly patients are more susceptible to drug interactions due to reduced drug clearance and increased sensitivity
• Genetics play a role in drug interactions through variations in drug-metabolizing enzymes and transporters
  • Polymorphisms in CYP enzymes can lead to poor, intermediate, extensive, or ultra-rapid metabolizers
• Comorbidities can affect drug interactions by altering drug pharmacokinetics or pharmacodynamics
  • Renal or hepatic impairment can lead to reduced drug clearance and increased risk of interactions
• Polypharmacy increases the likelihood of drug interactions due to the concurrent use of multiple medications
  • Regular medication reviews and deprescribing can help minimize polypharmacy-related interactions
• Dosage and duration of therapy can influence the severity and onset of drug interactions
  • Higher doses and longer durations of treatment are associated with a greater risk of interactions
• Route of administration can affect the potential for drug interactions
  • Intravenous administration bypasses first-pass metabolism and can lead to higher drug levels and increased interaction risk
• Environmental factors, such as smoking and alcohol consumption, can alter drug metabolism and contribute to interactions
  • Smoking induces CYP1A2 enzymes, while alcohol can inhibit various CYP enzymes

Medication Safety Principles

• Prescribing medications based on evidence-based guidelines and individual patient factors to ensure appropriate and safe use
• Conducting thorough medication reconciliation at each patient encounter to identify and resolve discrepancies
  • Obtaining an accurate and complete medication history, including prescription drugs, over-the-counter medications, and supplements
  • Comparing the medication history with current prescriptions and reconciling any differences
• Monitoring patients for adverse drug events and drug interactions through regular follow-up and laboratory testing
  • Assessing patient response to therapy, side effects, and any signs of toxicity
  • Adjusting medication regimens as needed based on patient response and monitoring results
• Educating patients and caregivers about their medications, including proper use, potential side effects, and the importance of adherence
  • Providing clear, written instructions and encouraging patients to ask questions
  • Emphasizing the significance of reporting any adverse reactions or concerns to their healthcare provider
• Collaborating with an interprofessional team, including physicians, pharmacists, and nurses, to optimize medication management
  • Utilizing the expertise of each team member to ensure comprehensive patient care and medication safety
• Maintaining accurate and up-to-date medication records in electronic health record systems to facilitate communication and reduce errors
  • Documenting medication changes, allergies, and adverse reactions in a timely and consistent manner
• Implementing medication safety technologies, such as computerized physician order entry (CPOE) and barcode medication administration (BCMA), to reduce medication errors
  • CPOE systems can alert prescribers to potential drug interactions, allergies, and dosing errors
  • BCMA helps ensure the right patient receives the right medication at the right time

Strategies for Preventing Adverse Drug Events

• Utilizing clinical decision support systems (CDSS) that provide real-time alerts and recommendations for drug interactions, dosing, and monitoring
  • Integrating CDSS into electronic health record systems to assist healthcare providers in making informed decisions
• Implementing pharmacist-led medication reviews and interventions to identify and resolve drug-related problems
  • Conducting comprehensive medication reviews for high-risk patients, such as those with polypharmacy or complex medical conditions
  • Collaborating with prescribers to optimize medication regimens and minimize the risk of adverse events
• Establishing standardized medication administration protocols and double-check processes to reduce errors
  • Using independent double checks for high-alert medications, such as insulin and anticoagulants
  • Developing and adhering to standardized protocols for medication preparation, labeling, and administration
• Promoting a culture of medication safety through ongoing education, training, and quality improvement initiatives
  • Providing regular education and training for healthcare professionals on medication safety principles and best practices
  • Encouraging open communication and reporting of medication errors and near-misses to identify system-level improvements
• Engaging patients and caregivers as active partners in medication safety by encouraging open communication and shared decision-making
  • Empowering patients to ask questions, report concerns, and participate in their medication management
  • Providing patient-friendly resources and tools to support medication adherence and self-management
• Regularly updating and reviewing medication formularies and order sets to ensure the inclusion of safe and effective drug therapies
  • Evaluating new medications and removing or restricting the use of high-risk or outdated drugs
  • Standardizing order sets and protocols to promote consistent and evidence-based prescribing practices
• Implementing a robust adverse drug event reporting and monitoring system to identify trends and opportunities for improvement
  • Encouraging healthcare professionals to report adverse drug events and near-misses through user-friendly reporting systems
  • Analyzing reported events to identify contributing factors and develop targeted interventions to prevent future occurrences