1. Geriatric Pharmacotherapy Linda Farho, Pharm.D. University of Nebraska Medical Center College of Pharmacy

9. Effects of Aging on Volume of Distribution (Vd) diazepam, valproic acid, phenytoin, warfarin  % of unbound or free drug (active)  plasma protein (albumin) quinidine, propranolol, erythromycin, amitriptyline  % of unbound or free drug (active)  plasma protein (  1 -acid glycoprotein) diazepam, trazodone  Vd for lipophilic drugs  fat stores digoxin  Vd for for drugs that bind to muscle  lean body mass ethanol, lithium  Vd for hydrophilic drugs  body water Examples Vd Effect Aging Effect

11. Metabolic Pathways ** NOTE: Medications undergoing Phase II hepatic metabolism are generally preferred in the elderly due to inactive metabolites (no accumulation) lorazepam, oxazepam, temazepam Conversion to inactive metabolites Phase II : glucuronidation, conjugation, or acetylation diazepam, quinidine, piroxicam, theophylline Conversion to metabolites of lesser, equal, or greater Phase I : oxidation, hydroxylation, dealkylation, reduction Examples Effect Pathway

17. Example: Creatinine Clearance vs. Age in a 5’5”, 55 kg Woman 30 1.1 90 41 1.1 70 53 1.1 50 65 1.1 30 CrCl Scr Age

25. The Beers Criteria antihistamines diphenhydramine dipyridamole ergot mesyloids indomethacin muscle relaxants amitriptyline chlorpropamide digoxin >0.125mg/d disopyramide GI antispasmodics meperidine methyldopa pentazocine ticlopidine High Potential for Less Severe ADE High Potential for Severe ADE

30. Common Drug-Drug Interactions Doucet J, Chassagne P, Trivalle C, et al. Drug-drug interactions related to hospital admissions in older adults: a prospective study of 1000 patients. J Am Geriatr Soc 1996;44(9):944-948. Sedation; confusion; falls Benzodiazepine + antidepressant Benzodiazepine + antipsychotic Electrolyte imbalance; dehydration Diuretic + diuretic Bradycardia, arrhythmia Digoxin + antiarrhythmic Hypotension CCB/nitrate/vasodilator/diuretic Electrolyte imbalance; arrhythmia Digoxin + diuretic Antiarrhythmic + diuretic Hyperkalemia, hypotension ACE inhibitor + K sparing diuretic Hyperkalemia ACE inhibitor + potassium Risk Combination

32. Common Drug-Disease Interactions Fluid retention; decreased effectiveness of diuretics NSAIDs + HTN Increased ulcer and bleeding risk NSAIDs + gastropathy Hypoxia; increased risk of lactic acidosis Metformin + CHF Exacerbation of constipation CCB + constipation Narcotics + constipation Anticholinergics + constipation Urinary retention BPH + anticholinergics Fluid retention; CHF exacerbation NSAIDs + CHF Thiazolidinediones + CHF Risk Combination

39. Questions