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Drug Interactions & Polypharmacy

Each of a patient's medications can look safe alone, yet together one silently doubles the blood level of another. Drug interactions occur through three mechanisms: pharmacokinetic (one drug changes how another is absorbed, distributed, metabolized, or excreted), pharmacodynamic (two drugs amplify or oppose each other at the target site), and pharmaceutical (physical/chemical incompatibility in the tubing — a mixing problem, not a body problem). The most heavily tested pathway is the cytochrome P450 liver enzyme system: an inhibitor slows metabolism and raises a second drug toward toxicity, while an inducer speeds metabolism and can drop a drug below therapeutic range. Polypharmacy — concurrent use of five or more medications — multiplies interaction risk, especially in older adults with declining renal and hepatic function. The nurse reviews the full list (including OTCs, herbals, and supplements) at every encounter and reports unexpected changes in drug effect.

pharmacokinetic interaction Hallmark
one drug alters absorption, distribution, metabolism, or excretion of another — e.g., CYP450 effects
pharmacodynamic interaction
two drugs amplify or oppose each other at the target site
pharmaceutical incompatibility
physical/chemical — IV drugs precipitate in the tubing, not in the patient
additive effect
1 + 1 = 2 — two CNS depressants causing oversedation
synergistic effect
1 + 1 = 3 — amplification beyond simple addition
inhibitors increase drug levels Hallmark
slow metabolism → toxicity risk; 'Inhibitor = Increase'
erythromycin
CYP450 inhibitor
fluconazole
CYP450 inhibitor
grapefruit juice
CYP450 inhibitor
inducers decrease drug levels
speed metabolism → therapeutic failure risk
rifampin
classic inducer — revs the engine, burns drugs faster
carbamazepine
CYP450 inducer
St. John's wort
potent inducer — drops INR on warfarin; reduces oral contraceptive efficacy
five or more concurrent medications Hallmark
the usual definition of polypharmacy
older adults at highest risk
declining renal and hepatic function
multiple prescribers
no single provider sees the whole list
review the full list every encounter
include OTCs, herbals, supplements
the nurse assesses for new supplements
independent responsibility between pharmacist reviews
tell every provider all your medications
include OTCs, herbals, and supplements
do not start herbals without asking
St. John's wort, ginkgo, and garlic are pharmacologically active
avoid grapefruit juice unless cleared
it raises levels of many drugs
use one pharmacy when possible
lets the pharmacist screen for interactions
report new drowsiness or falls
a clue to additive CNS depression
Report Nowescalate immediately
additive CNS depression Hallmark
opioid + benzodiazepine + muscle relaxant → sedation and falls in older adults
tyramine-rich food with an MAOI
aged cheese + phenelzine → hypertensive crisis
potassium supplement with an ACE inhibitor
lisinopril retains potassium → dangerous hyperkalemia
NSAID with warfarin
ibuprofen + warfarin → markedly increased bleeding risk
subtherapeutic INR after starting an inducer
St. John's wort dropped INR 2.5 → 1.4 — clot risk
new falls or sedation on polypharmacy
review meds immediately — not age-related decline to watch

Clinical Pearl

Inhibitors Increase levels, Inducers decrease them — the 'I-I' pair: Inhibitor = Increase. Rifampin is the classic inducer that revs the engine and burns drugs faster. And in an older adult on five-plus drugs, new drowsiness or a fall is a medication review, not just aging.

NurseSavvy™·nursesavvy.com

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