SCENARIO 1
CYP2C9 polymorphisms can lead to slower metabolism and a lower dose may be needed.
Patient’s drugs metabolized by CYP2C9- warfarin, fluvastatin, celecoxib
WARFARIN OR apixaban (Eliquis) 5 mg po BID #60
FLUVASTATIN OR rosuvastatin (Crestor) 10 mg po daily #30
Continue HCTZ
CHANGE CELECOXIB TO APAP 500 mg q4-6 hours prn pain and topical NSAID ie diclofenac
gel
DC GOODY’S POWDER (aspirin)
Goody’s power contains aspirin and can increase risk of bleeding with warfarin. Celecoxib
can increase risk of bleeding with warfarin and also increase blood pressure.
Monitor INR if warfarin is continued, liver function, lipid levels, kidney function, bp,
electrolytes, and patient compliance.
SCENARIO 2
propranolol 80 mg
Propranolol has a HIGH FIRST-PASS EFFECT. Metoprolol, verapamil, nitroglycerin,
morphine, lidocaine, insulin, and testosterone are additional examples.
When taken orally, propranolol undergoes extensive first-pass metabolism in the liver. This
means that a significant portion of the drug is metabolized before it reaches systemic
circulation, resulting in LOWER BIOAVAILABILITY.
Drugs that are administered orally (as opposed to IV, IM, SQ, or TDDS) must first pass from
the intestine to the liver before reaching the general circulation.
BIOAVAILABILITY describes the percent at which an active drug is absorbed and becomes
available at the site of action. Essentially, it refers to the amount of a drug that enters the
circulation and is able to have an active effect.
STRATEGIES TO COUNTER THE FIRST-PASS EFFECT and INCREASE BIOAVAILABILITY
Dosage Adjustments: higher oral doses
Extended/controlled-release dosage forms: reduce peak-trough fluctuations and improve
bioavailability over time
