Pharmacology Flashcards: Drug Safety, Interactions, Pregnancy Categories, Polypharmacy

The most dangerous drug interactions include warfarin with NSAIDs causing severe bleeding, MAOIs with SSRIs causing serotonin syndrome, opioids with benzodiazepines causing fatal respiratory depression, methotrexate with NSAIDs causing methotrexate toxicity, potassium-sparing diuretics with ACE inhibitors causing hyperkalemia, and digoxin with amiodarone causing digoxin toxicity. Fluoroquinolones with corticosteroids increase tendon rupture risk. Statins with certain macrolides and antifungals increase rhabdomyolysis risk.

The FDA replaced the traditional letter categories A through X with narrative labeling in 2015 under the Pregnancy and Lactation Labeling Rule, or PLLR. However, the old system is still widely referenced on exams. Category A had controlled studies showing no fetal risk. Category B had no evidence of risk in humans. Category C had risk not ruled out. Category D had positive evidence of fetal risk but benefits may outweigh risks. Category X was contraindicated because fetal risk clearly outweighs any benefit.

A narrow therapeutic index means the margin between the effective dose and the toxic dose is very small, requiring careful dose adjustment and frequent monitoring. Drugs with narrow therapeutic indexes include warfarin monitored by INR, lithium monitored by serum levels, digoxin monitored by serum levels, theophylline, phenytoin, aminoglycosides like gentamicin monitored by peak and trough levels, and vancomycin monitored by trough levels. Small changes in dose, absorption, metabolism, or drug interactions can push levels from therapeutic to toxic.

The cytochrome P450, or CYP450, system is a family of liver enzymes responsible for metabolizing approximately 75 percent of all medications. The most clinically important isoenzymes are CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2. Some drugs inhibit these enzymes, slowing the metabolism of other drugs and increasing their blood levels and toxicity risk. Other drugs induce these enzymes, speeding metabolism and reducing drug effectiveness. For example, grapefruit juice inhibits CYP3A4, increasing levels of statins, calcium channel blockers, and many other drugs.

Polypharmacy is the concurrent use of five or more medications, common in elderly patients managing multiple chronic conditions. It increases the risk of adverse drug reactions, drug-drug interactions, medication non-adherence, falls, cognitive impairment, and hospitalization. Each additional medication raises the interaction risk exponentially. Medication reconciliation at every clinical encounter identifies unnecessary, duplicate, or interacting medications. The Beers Criteria list potentially inappropriate medications for older adults.

A side effect is any unintended pharmacological effect of a drug at normal therapeutic doses, which may be beneficial, neutral, or harmful. For example, sedation from diphenhydramine is a side effect that is harmful when treating allergies but beneficial when used as a sleep aid. An adverse drug reaction, or ADR, is specifically a harmful and unintended response to a medication. ADRs range from mild, like nausea, to life-threatening, like anaphylaxis or Stevens-Johnson syndrome. Type A reactions are dose-dependent and predictable from pharmacology.

Medication reconciliation is the process of creating and verifying a complete, accurate list of all medications a patient is taking, including prescriptions, over-the-counter drugs, vitamins, and supplements, and comparing it against new orders at every transition of care. Transitions include hospital admission, transfer between units, discharge, and any outpatient visit where medications change. The Joint Commission requires medication reconciliation as a patient safety standard because discrepancies during transitions cause up to 50 percent of medication errors.