II. Physiology: Pharmacokinetics

  1. Absorption
    1. Alcohol absorption is greater in women (same amount of Alcohol results in higher Blood Alcohol Level)
    2. Lower gastric pH decreases absorption in women (e.g. Ketoconazole)
    3. Slower gastrointestinal transit time decreases absorption in women
      1. Examples: Metoprolol, Theophylline, Verapamil
    4. Women should wait longer to eat after taking medications directed to be on an empty Stomache
      1. Examples: Amoxicillin, Levothyroxine, Tetracycline
  2. Distribution
    1. Women have lower Body Mass Index and results in lower medication loading doses
      1. Examples: Antiarrhythmics, Aminoglycosides, Digoxin
    2. Women have higher body fat amounts
      1. Lipophilic medications have longer duration of action (large volume distribution), lower plasma levels
        1. Benzodiazepines
        2. Propofol (may require higher doses, and expect more rapid clearance)
      2. Hydrophilic medications have smaller volumes of distribution, reaching high concentrations faster
        1. Alcohol
        2. Fluoroquinolones
        3. Neuromuscular blocking agents (e.g. Rocuronium, Vecuronium)
  3. Metabolism
    1. Phase I: Women require less Warfarin per week (by as much as 4.5 mg per week) than men
    2. Phase 2: Typically slower in women for medications such as Acetaminophen, Digoxin, Levodopa
  4. Excretion
    1. Glomerular Filtration Rate is as much as 25% slower in women
    2. Renal excreted medications are cleared more slowly
      1. Digoxin
      2. Cefepime
      3. Methotrexate
      4. Aminoglycosides
      5. Fluoroquinolones
      6. Vancomycin

III. Physiology: Pharmacodynamics - Specific differences among Medication Classes

  1. Psychiatric medications
    1. Women respond better to Selective Serotonin Reuptake Inhibitors than Tricyclic Antidepressants
    2. Women respond more to typical Antipsychotic Medications (e.g. Haloperidol) than men
  2. Opioid Analgesics
    1. Women have a greater Opioid response for both analgesia and sedation than men
      1. Start with dose 30-40% lower than for men
    2. Women also have more adverse effects from Opioids (esp. respiratory depression)
  3. Cardiovascular medications
    1. Aspirin has poor Platelet inhibition, CVA and MI prevention in women compared with men
    2. Digoxin is associated with increased mortality in women (target a lower dose if used in women)
    3. Beta Blockers lower Blood Pressure and Heart Rate more in women (especially during Exercise)

IV. Adverse Effects

  1. QT Prolongation
    1. See Drug-Induced Torsades de Pointes
    2. Women have a longer QT Interval than men at baseline
    3. Higher risk of Torsades de Pointes with at risk medications
      1. Women with Prolonged QTc have twice the risk of Torsades de Pointes
      2. Coker (2008) Pharmacol Ther 119(2): 186-94 [PubMed]

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