Pitfalls in Pharmacotherapy of Geriatrics DR Ali M. Alyami (M Pharm., PhD)
Case Study An 85 year old female with a history of atrial fibrillation, stroke, dementia, and hypertension, who is receiving chronic therapy with warfarin. Her primary care provider has been closing her warfarin to maintain her at an INR of 2.
Case study One evening, a covering physician is called with a report that the patient has developed a fever. The patient is initiated on empiric antibiotic therapy with cephalexin (500 PO TID for 7 days) to treat a presumed Urinary tract infection.
Case study The next morning the primary care physician is called with the previous day s INR, 1.75. He increased the daily warfarin dose from 4 mg to 5 mg per day. He is not notified of cephalexin ordered the previous evening by the covering physician.
Case study One week later, the INR comes back at 13.8 and a covering physician is notified. That evening s warfarin dose is held. The INR the following day is 16.1. The warfarin continues to be held. No vitamin K is administered.
Case study The very next day the patient develops congestion and shortness of breath. A chest X- ray reveals an infiltrate and the covering physician orders Augmentin 875 mg PO q12 hours for 10 days. The next day the patient passes tarry stool and omeprazole is initiated.
Case study The following morning the patient s hematocrit is 25 and her INR is 11.3. The primary care physician is notified, and vitamin K 10 mg SC is administered for 3 days with a decrease in INR to 0.9. The physician writes that warfarin will not be reinitiated because anticoagulation has been difficult to control for unclear reasons.
Major contributing factors to ADRs: Poor communication increase < ADRs Multiple care prescribing cascade (lack interface reconciliation)
Prescribing Cascade A new drug is prescribed to treat an adverse reaction to another drug in the mistaken belief that a new medical condition requiring treatment has developed.
A Prescribing cascade An 50 year old female with a history of parkinson s Disease treated with long term sinemet therapy (25-100 TID). She has suffered occasional hallucinations attributed to the sinemet therapy, which have recently increased in frequency. The hallucinations sometimes involve large animals & can be quite terrifying.
A Prescribing cascade The patient is initialed on olanzapine 2.5 mg at bed time. Due to agitation & continued hallucinations, the olanzapine dose is increased to 5 mg and lorazepam 0.5 mg PO q4 hours prn is added to the medication regimen. The hallucinations continue & the evening dose of olanzepine is increased to 7.5 mg
A Prescribing cascade The patient is noted by the nursing staff to be shaky and stiff, but no change is made in the olanzepine dose. She becomes increasingly lethargic. She is described as rigid and stooped over with ambulation and begins to have more difficulty with activities of daily living including bathing, dressing, toileting, and transferring. She begins to require a wheelchair.
A Prescribing cascade The patient s functional decline is attributed to Parkinson s Disease..
It is much easier to write upon a disease than upon a remedy. The former is in the hands of nature and a faithful observer with an eye of tolerable judgement cannot fail to delineate a likeness. The latter will ever be subject to the whim, the inaccuracies and blunder of mankind. William Withering 1741-1799
In the elderly, less medication is always better.
Drug used in the elderly 40% of all elderly use > 5 drugs/week 12% of elderly use > 10 drugs/week 3-25% of prescriptions to elderly classified as inappropriate. Sloane etal (2002 J. Am. Geriatr. Soc. 50,1001-1011) Spore etal,. (1997 J. public. Health87, 404-409)
ADRs in daily practice. SIZE OF THE PROBLEM 10% of patients visiting general practices showed one adverse drug event in the previous 6 months (AUST. Prscr 2011;34; 162-166) ADRs 1.5 million/year (Med.J Aust. 2006; 184-646) 190000 hospital admission/year (Asut. Prescr 2011,34;162-166)
Influence of poor communication 15% of patients will stop Rx vs. ADRs without advising their prescriber. 25% of patients report they did not receive info. about their Rx
Factors influencing Drug Effects & risk of ADE in Geriatrics. Multiple Co-existing illnesses. Polypharmacy :redundant effects & drug drug interactions. Adverse drug effects nonspecific. Pharmacologic changes with aging. Limited knowledge base. Medical errors issue of patient safety.
ALTERATIONS IN RESPONSE TO Rx WITH AGEING Pharmacokinetic Pharmacodynamic
Common problems of drug administration in the elderly Reduced homeostasis. Renal & hepatic functions. Target organ sensitivity. Polypharmacy. ADEs. Lack of available data fewer clinical trails. Non- compliance.
Pharmacokinetics changes with aging Absorption Distribution. Metabolism. Excretion.
Pharmacodynamics changes with ageing
Physiological changes in elderly patients affecting pharmacodynamics Target organ physiological changes Increased sensitivity to pharmcological agents. Decreased desirable effects of pharmacotherapy. Increased ADEs Homeostasis changes Decreased capacity to respond to physiological challenges & the adverse side effects of drug therapy
TWO MAIN SOURCES OF ADRs RISKS TO THE ELDERLY MISDIAGNOSIS & IMPROPER PRESCRIBING NATURE OF PHARMACOLOGICAL ACTIONS OF PRESCRIBED MEDICATIONS
Adverse Drug Reactions sensitivity to anticoagulants. vit. K dependent clotting factors deficiency. Pharmacokinetic changes. Narrow therapeutic window plasma protein. Drug interactions (e.g. phenytoin) Adverse effect s(excessive internal bleeding.)
Misdiagnosis & improper prescribing
The Prescribing cascade (metoclopramide) Drug 1 Extrapyramidal effects ADE L-Dopa Rx Drug 2 Proxy for ADE
ACE inhibitor ADRs e.g. postural hypertension Misdiagnosis Dizziness Prochlorperazine Worse postural hypotension Fall Hip fracture Rochon, P.A, Gurwitz JH. BMJ 1997;315 (1096-1099)
Medications involved in the prescribing Cascade 1 st medication ADR 2 nd medications Cholinesterase inhibitors Vasodilators ß blockers Ca+2 channel blockers NSAIDs Opiods analgesics Statins, Seductives ACE inhibitors Urinary incontinence Dizziness Anticholinergic (oxybutynin) Prochlorperazine
Medications involved in the prescribing Cascade 1 st medication ADR 2 nd medications NSAIDs BP Antihypertension Thiazide diuretics Metochlopramide ACE inhibitors uric acid (gout) Movement disorder Cough Allopurinol colchicine Levodopa Paroxetine, Haloperidal Tremor Levodopa - Carbidopa
Medications involved in the prescribing Cascade 1 st medication ADR 2 nd medications Erythromycin Arrhythmia Anti arrythmics Antiepileptic Rash Topical corticosteroids Antiepileptic Antipsychotic Nausea Extrapyramidal adverse effect Meoclopramide Domperidone Levodopa Anticholinergics
Medications involved in the prescribing Cascade 1 st medication ADR 2 nd medications Digoxin, Nitrates Loop diuretics Antiepileptics, Antibiotics ACE inhibitors Oral corticosteroids NSAIDs Opioid analgesics Theophylline Nausea Metoclopramide
Pharmacological actions of prescribed medications
ADR s NSAIDs Frequently prescribed in geriatrics. Pronounced GIT side effects. Effect on kidney & CNS.
ADRs Cardiovascular Agents CHF is a common age-related condition. Digoxin? effective dose is variable. versus cardiac symptoms Alternatives Beta adrenergic receptor blockers ACE inhibitors
THERAPEUTICS GUIDELINES BEER S LIST STOPP/START CRITERIA
Beers Drugs Criteria Originally compiled by Dr Mark Beers in 1991. First updated in 2003. - Rxs to be avoided (Dose & Duration) - Rxs to be avoided with certain diseases
The Beer s List (1991) Arch. Intl. Med 163,22 2716-2724 (1991) 2012 updated by the AGS. J.Am. Geriatr. Soc., 10, 1532 1541 List of harmful Rx to the elderly. List of inappropriate Rx (disease, risk factors) List with Rx need to be used with caution. Site www.americangeriatrics.org
Medications to avoid with concomitant diseases GIT Disorders - constipation - Ulcers Endocrine - Diabetes Cardiac Urologic Respiratory
commonly used medications best avoided in geriatrics- Beer s List Anticholinergic preparations. Diphenlydramine Amitriptyline doxepin Benzodiazepines with active metabolites. Diazepam (valium) Chloradiazepoxide (librium) Flurazepam (dalmene) Central acting CNS agents. Alpha methyldopa (Aldomet) Clonidine (catapres) Analgesics Propoxyphene (darvon) Pethidine indomethacin
STOPP/ START criteria STOPP (( Screening Tool of older person s potentially inappropriate prescriptions)) START (( Screening Tool to Alert doctors to the Right Treatment)) Mode of action P/K ADRs
STOPP criteria identifies (PIMs) CVS Loop diuretics as first line monotherapy for hypertension. Calcium channel blocker with chronic constipation. Aspirin at dose > 150 mg/day Aspirin with no history of coronary, cerebral or peripheral vascular systems or occlusive event.
STOPP criteria identifies PIM S Endocrine system: Glibenclamide or Chlorpropamide with type 2 DM Drugs that causes falls in predisposed elderly patients: Benzodiazepines. Neuroleptics.
STOPP criteria identifies (PIMs) CNS Long term ( > 1 month) neuroleptics as long term hypnotics or those with parkinsonism. Respiratory system: Nebulised ipratropium with glaucoma. Long term (i.e. > 1 month), long acting BZD s, long acting metabolite (diazepam).
STOPP criteria identifies (PIMs) Duplicate drugs: Concurrent NSAIDs Benzodiazepines.
STOPP/ START vs. BEER S STOPP & BEER S criteria detected similar % of PIM 50 60 % of Patients. STOPP criteria more sensitive to detect PIMs than Beers & more ADRs than Beers criteria
STOPP/ START criteria Cardiovascular system: STATINS with a documented history of coronary or cerebral or peripheral vascular disease. Respiratory system: Regular inhaled beta 2 agonist or anticholinergic agent for mild to moderate asthma or COPD CNS: L-DOPA in idiopathic Parkinson's disease with definite functional impairment. Antidepressant depressive illness moderate to severe lasting at least 3 months CVS omission of warfarin or aspirin in the presence of atrial fibrillation (AF).
Points to consider before prescribing to an elderly Is drug therapy required? Appropriate choice of drug & preparation. Dosage regimen vs physiology. Close monitoring & re-evalution. Clear & simple instructions
How to prevent a prescribing Cascade Begin new Rx at low doses & individualise the dose. Expect new symptoms (new Rx, dose change) Ask patient about new unusual symptoms (new Rx dose changed) Keep patients informed about possible ADRs & what to do if ADRs occur. Before prescribing a second Rx to treat ADRs of the first Rx the benefits of the first Rx must outweigh the risks of additional ADRs from the second Rx.
Summary Changes in physiology of the elderly dictate responses to drug therapy. P/K changes affect SDCs. P/D changes affect response. ADRs are more common in the elderly. Better primary care can decrease ADRs.
Useful guideline S.A.I.L Protocol
Thank you