1. Includes adults >65 years old Fastest growing population in US and in the majority of developed nations. 20% of hospitalizations for those >65 are due to medications they’re taking = Adverse Drug Events/Interactions are very common in the elderly. Geriatric Pharmacology: Relevance Clarissa Zaoirov (2009)

2. What is different about geriatric pharmacotherapy? Absorption – Not usually significantly altered with age. Reduced motility and gastric emptying = constipation Distribution – Change in total body composition, vascular changes, lower albumin production (not always) Metabolism – Reduced hepatic blood flow & mass, low CYP-450, slow biotransformation (Phase I metabolic pathways) Excretion = Renal blood flow by age 80, can be reduced by as much as ½. Reduction in tubular function & size.

3. Pharmacodynamic Changes: Disturbed homeostatic mechanisms: - Reduced compensatory tachycardia, baroreceptor and vasomotor response. - Poor thermoregulatory mechanisms - Cardiac Beta receptor sensitivity reduced - Hepatic Beta receptor sensitivity increased - Greater sensitivity to medications affecting the CNS (benzodiazepines and opioids) - Pre-existing depletion of dopamine = Parkinsonism when using anti-psychotic medications.

4. Total Result: These age-related changes result in greater therapeutic effect and increased risk of accumulation & toxicity. (Longer ½ life) Complicated by alterations in metabolism, distribution and clearance. – Example: Benzodiazepines may cause more sedation and poorer psychomotor performance in older adults. Likely cause: reduced clearance of the drug and resultant higher plasma levels, wider volume of distribution of lipophylic drug and active metabolites.

5. Other factors that complicate pharmacotherapy: Polypharmacy including naturaceuticals. (Ginko biloba) Non-Compliance Issues Drug-Disease Interactions - AnticholinergicsBenign. Prostatic Hypertrophy (BPH), constipation, dementia – Antiarrhythmics (Type 1A) CHF (systolic dysfunction) – AmphetaminesHypertension (HTN), insomnia – AspirinPeptic Ulcer disease (PUD) – Atypical antipsychoticsDM (Diabetes Mellitus) – BarbituratesDepression – Benzodiazepines COPD,dementia, falls – Beta-blockersCOPD, DM, syncope – CCB 1 st generation CHF (systolic dysfunction) – ChlorpromazinePostural hypotension, seizures – ClozapineSeizures – CorticosteroidsDM, PUD, COPD – DecongestantsInsomnia

6. Recommendations: Start low and advance dosage slowly. Avoid the prescription cascade! Cockcroft-Gualt Formula (Creatinine Clearance) : Beers Criteria or MAI * ANY new symptom or disease in an elderly patient should be treated as Adverse Drug Event unless proven otherwise. (i.e.. Dementia) Constantly review medications for appropriateness.