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Geriatric Pharmacology
Physiology, Pharmacology, and Prescribing
Roy Krishna, Ph.D. FCP.
Touro University, Nevada. Challenges of Prescribing for Older Adults • Multiple chronic medical problems • Multiple medications and prescribers • Different metabolism and responses • Adherence and cost • Supplements, herbals, and OTC drugs • POLYPHARMACY!!!!!!!!! Lancet. 1995;346(8966):32–36. 2 Physiologic Changes Associated with Normal Aging • Less Water • More Fat • Less muscle mass • Slowed hepatic metabolism • Decreased renal excretion • Decreased responsiveness and sensitivity of the baroreceptor reflex
3 Absorption Not affected by the normal aging process Can be altered by drug interactions Antacids Iron Can be affected by pathophysiology Lack of intrinsic factor (B12 absorption) Delayed gastric emptying GERD, Crohns, Ulcerative Colitis.
4 Distribution Less water = ↓ volume of distribution = higher concentration of water soluble drugs (aminoglycosides?)
More fat = ↑ volume of distribution = prolonged action
of fat soluble drugs (increased half-life, redistribution- barbiturates, benzodiazepines))
Lower serum proteins (like albumin) increases the
concentration of unbound (free or active) form of drugs-Digoxin, Theophylline, NSAID,s. 5 Metabolism Slowed Phase I, cytochrome P450, reactions Oxidation, reduction, dealkylation Warfarin and phenytoin levels may be higher because of altered metabolism
Renal Renal clearance may be reduced Serum creatinine may not be an accurate reflection of renal clearance in elderly patients (decreased lean body mass).
normal or increased GFR 2 Kidney damage with 60-90 mild decreased GFR 3 Moderate decreased 30-59 GFR 4 Severe decreased GFR 15-29 5 Kidney failure < 15 11 Physiologic Changes Associated with Disease States Cardiac Disease Impaired cardiac output (decreased absorption, metabolism, clearance) Greater susceptibility to cardiac adverse effects
Drugs Care Adverse Drug Events (ADEs) Adverse symptoms
Adverse patient outcomes
Doctor visits or hospitalizations Falls Functional decline Changes in cognition (delirium) Death
↑ number of medications = ↑ risk of ADEs
(even if all the meds are “clinically indicated”)
16 Medications Which Account for Most ADEs in Older Adults Cardiovascular medications
Psychotropic medications
Antibiotics
Anticoagulants
Non-opioid analgesics (NSAIDS)
Anti-seizure medications
(JAGS 2004;52:1349-1354 and NEJM 2003;348:1556-64)
17 Risk Factors for Adverse Drug Events (ADE) >6 chronic disease >12 doses/day ≥ 9 medications Low BMI (<22kg/m2) Age >85 years Creatinine clearance < 50 mL/min History of prior ADE
Consult Pharm 1997;12:1103-11.
18 Do You Need to prescribe? • Does every condition need a drug? • Is it a benign or self limited condition? • How does this condition bother the patient?
• Consider non-drug alternatives
• Diet • Exercise • Lifestyle modification
• Consider “Over The Counter” (OTC) medications
• Not necessarily safer than prescription drugs • Be very careful with herbals and supplements 19 Clinical Case: Mr. Johnson Mr. Johnson is 83 years old. He has a history of benign prostatic hypertrophy (BPH) and hypertension. After visiting his grandchildren, he developed a viral upper respiratory infection. He took an over-the-counter cold remedy containing a decongestant and diphenhydramine. He now comes to the office because he is unable to urinate. His blood pressure is 190/80.
What happened?
20 Urinary Retention and Hypertension Parasympathetic Nervous System Mediates detrusor muscle contraction Blocked by anticholinergic medications like diphenhydramine
Sympathetic Nervous System
α-adrenergic activity causes the urethral sphincter to contract (retaining urine) α-adrenergic activity increases systemic vascular resistance (raises blood pressure) Decongestants are alpha-adrenergic agonists (ex. pseudoephedrine and phenylephrine) 21 Clinical Case: Mr. Johnson Since Mr. Johnson has a history of benign prostatic hypertrophy, his physician prescribes terazosin, a peripherally-acting α1-adrenergic antagonist, to help with his urinary retention and to help reduce his blood pressure.
Two days later, Mr. Johnson falls in the middle of
the night, on the way to the bathroom. He fractures his hip.
What happened?
22 Orthostatic Hypotension and Hip Fracture Barorecptor sensitivity decreases with age
α-adrenergic blockade can worsen
postural hypotension and increase the risk of falls
Falls and Hip fractures are associated with
significant morbidity and mortality in older adults 23 Prescribing Cascade: Prescribing a new drug to treat an ADE
• Establish the diagnosis
• Diphenhydramine and the decongestant precipitated urinary retention in a older male with prostatic enlargement • Urinary retention is an ADE
• Stop (or reduce) the offending medications
• OTC cold medicine • Need to ask about ALL medications
• Avoid prescribing new medications (terazosin)
24 Before making a new diagnosis: “Think Drugs” • Consider ADE as etiology of new signs/symptoms
• Remember that OTC drugs, supplements, and herbals
can cause ADEs
• Consider discontinuing or dose-reducing medications
rather than treating an ADE with another medication
25 Clinical Case: Mr. Johnson Mr. Johnson arrives in the emergency department and is given meperidine (Demerol) for his pain.
He is also very anxious, so he receives diazepam
(Valium).
A few hours later, Mr. Johnson becomes very
confused and somnolent.
What happened? 26 Drug-Induced Delirium Meperidine Can cause confusion Active metabolites Slow renal clearance in older adults
Diazepam Long-acting benzodiazepine Lipophilic Extended half-life in elderly Increased sensitivity in the elderly Increased risk of falls and fractures
27 Anticholinergic Medications • Drug classes • Antihistamines • Tricyclic antidepressants • Antispasmodics and muscle relaxants
28 Cardiovascular Drugs Dihydropyridines-greater response in treatment-naïve elderly. Non-dihydropyridines: Enhanced HR and BP responses
29 Autonomic Agents β-sensitivity decreases with age - prevalence of high-affinity receptors ↓ with age; does not explain diminished response to β antagonists - may be related to G proteins -adrenoceptors couple with G proteins (G proteins ↓ with age) exception: activity of β-blockers in elderly with very high blood pressure α-sensitivity has shown varied responses Interacting Drugs Impact Mechanism Prevention Warfarin, NSAIDs Increased risk of NSAIDs irritate gastric lining & Monitor weekly INR and for bleeding impair platelet function s/s of bleeding Warfarin, sulfa Increased warfarin Change in gut flora responsible Dec. warfarin dose by 50% activity for K production during and 1 wk after abx Warfarin, macrolide Increased effect of E-mycin inhibits warfarin metab. If macrolide necessary, (highly probably, often delayed) warfarin and clearance; change in gut monitor INR qod. ID flora pathogen to confirm need. Warfarin, quinolones Increased effect of Change in gut flora; decrease in Monitor INR qod if warfarin hepatic warfarin metabolism quinolone is necessary Warfarin, phenytoin Increased effects of Keep INR at lower end of both drugs thx range. Monitor INR and PTN lvl. ACE-inhibitors, K+ supplements Elevated serum K+ Decreased aldosterone/K+ Monitor K+; are both drugs secretion necessary? ACE-inhibitors, aldactone/ Elevated serum K+ Probably additive effect Monitor K+; are both drugs spironolactone necessary? Digoxin, amiodarone Digoxin toxicity ? amio ↓ clearance of digoxin; ? Dig lvl prior to amiodarone; additive effect at sinus note decrease dig dose and monitor weekly Digoxin, verapamil Digoxin toxicity, Synergistic effect of slowed Monitor HR and EKG (PR bradycardia, heart impulse conduction and interval) block reduced contractility Theophylline, quinolones Theophylline toxicity Quinolones inhibit hepatic Monitor theophylline lvl metabolism of theophylline AND watch for s/s Serotonin Syndrome Caused by elevated levels of serotonin -too high a dose of some medications -medication combinations -some illicit drugs and herbal supplements Signs/Symptoms: agitation, confusion, tachycardia, headache, diaphoresis, diarrhea POTENTIAL INTERACTIONS BETWEEN HERBAL MEDICINES AND CONVENTIONAL MEDICINES St. John’s wort is a potent inducer of the CYP3A4 and the P-glycoprotein drug transporter.
Inhibit HIV protease inhibitors
Inhibit some immunosuppressants Inhibit antineoplastic agents Interact with antidepressants Interact with warfarin POTENTIAL INTERACTIONS BETWEEN HERBAL MEDICINES AND CONVENTIONAL MEDICINES
Other potential (frequently used) herb-drug
interactions
Ginkgo and Aspirin
Ginkgo and Trazodone Ginseng and Amlodipine Valerian and Lorazepam Antiepileptics and herbals! Suggested Maximum Daily Dosages for Older Adults Benzodiazepines/ Hypnotics • Lorazepam, 3 mg --Temazepam, 15 mg • Oxazepam, 60 mg -- Zolpidem, 5 mg • Alprazolam, 2 mg -- Triazolam, 0.25 mg Iron Supplements, 325 mg Digoxin, 0.125 mg Avoiding Potentially Dangerous Drugs:
