II. Physiology: Pharmacokinetics
- Absorption
- Alcohol absorption is greater in women (same amount of Alcohol results in higher Blood Alcohol Level)
- Lower gastric pH decreases absorption in women (e.g. Ketoconazole)
- Slower gastrointestinal transit time decreases absorption in women
- Examples: Metoprolol, Theophylline, Verapamil
- Women should wait longer to eat after taking medications directed to be on an empty Stomache
- Examples: Amoxicillin, Levothyroxine, Tetracycline
- Distribution
- Women have lower Body Mass Index and results in lower medication loading doses
- Examples: Antiarrhythmics, Aminoglycosides, Digoxin
- Women have higher body fat amounts
- Lipophilic medications have longer duration of action (large volume distribution), lower plasma levels
- Benzodiazepines
- Propofol (may require higher doses, and expect more rapid clearance)
- Hydrophilic medications have smaller volumes of distribution, reaching high concentrations faster
- Alcohol
- Fluoroquinolones
- Neuromuscular blocking agents (e.g. Rocuronium, Vecuronium)
- Lipophilic medications have longer duration of action (large volume distribution), lower plasma levels
- Women have lower Body Mass Index and results in lower medication loading doses
- Metabolism
- Phase I: Women require less Warfarin per week (by as much as 4.5 mg per week) than men
- Phase 2: Typically slower in women for medications such as Acetaminophen, Digoxin, Levodopa
- Excretion
- Glomerular Filtration Rate is as much as 25% slower in women
- Renal excreted medications are cleared more slowly
III. Physiology: Pharmacodynamics - Specific differences among Medication Classes
- Psychiatric medications
- Women respond better to Selective Serotonin Reuptake Inhibitors than Tricyclic Antidepressants
- Women respond more to typical Antipsychotic Medications (e.g. Haloperidol) than men
- Opioid Analgesics
- Cardiovascular medications
- Aspirin has poor Platelet inhibition, CVA and MI prevention in women compared with men
- Digoxin is associated with increased mortality in women (target a lower dose if used in women)
- Beta Blockers lower Blood Pressure and Heart Rate more in women (especially during Exercise)
IV. Adverse Effects
-
QT Prolongation
- See Drug-Induced Torsades de Pointes
- Women have a longer QT Interval than men at baseline
- Higher risk of Torsades de Pointes with at risk medications
- Women with Prolonged QTc have twice the risk of Torsades de Pointes
- Coker (2008) Pharmacol Ther 119(2): 186-94 [PubMed]
V. References
- Madsen, Walter and McGregor (2018) Crit Dec Emerg Med 32(3): 15-24
- Schwartz (2007) Clin Pharmacol Ther 82(1): 87-96 [PubMed]
- Schwartz (2003) Clin Pharmacokinet 42(2): 107-21 [PubMed]
- Whitley (2009) Am Fam Physician 80(11): 1254-8 [PubMed]