Pitfalls in Pharmacotherapy of Geriatrics DR Ali M. Alyami (M Pharm., PhD)

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 < ADRsMultiple 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 PROBLEM10% 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 RxWITH 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 RISKSTO THE ELDERLY

MISDIAGNOSIS & IMPROPER PRESCRIBING

NATURE OF PHARMACOLOGICAL ACTIONS OFPRESCRIBED 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

Rochon, P.A, Gurwitz JH. BMJ 1997;315 (1096-1099)

Prochlorperazine

Worse postural hypotension

Fall Hip fracture

Misdiagnosis Dizziness

Medications involved in the prescribing Cascade

1st medication ADR 2nd medications

Cholinesterase inhibitors Urinary incontinence

Anticholinergic (oxybutynin)

Vasodilatorsß – blockers

Ca+2 channel blockersNSAIDs

Opiods analgesicsStatins, Seductives

ACE inhibitors

Dizziness Prochlorperazine

Medications involved in the prescribing Cascade

1st medication ADR 2nd medications

NSAIDs ↑BP Antihypertension

Thiazide diuretics ↑uric acid (gout)

Allopurinol colchicine

Metochlopramide Movement disorder Levodopa

ACE inhibitors Cough

Paroxetine, Haloperidal Tremor Levodopa - Carbidopa

Medications involved in the prescribing Cascade

1st medication ADR 2nd medications

Erythromycin Arrhythmia Anti – arrythmics

Antiepileptic Rash Topical corticosteroids

Antiepileptic Nausea MeoclopramideDomperidone

Antipsychotic Extrapyramidal adverse effect

Levodopa Anticholinergics

Medications involved in the prescribing Cascade

1st medication ADR 2nd medications

Digoxin, NitratesLoop diureticsAntiepileptics,

AntibioticsACE inhibitors

Oral corticosteroidsNSAIDs

Opioid analgesicsTheophylline

Nausea Metoclopramide

Pharmacological actions of prescribed medications

ADR’s…

NSAIDs

• Frequently prescribed in geriatrics.• Pronounced GIT side effects.• Effect on kidney & CNS.

ADRsCardiovascular 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 LISTSTOPP/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 actionP/KADRs

STOPP criteria identifies (PIMs)

CVSLoop diuretics as first line monotherapy for hypertension.

Calcium channel blocker with chronic constipation.

Aspirin at dose > 150 mg/dayAspirin 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 DMDrugs that causes falls in predisposed elderly patients:Benzodiazepines.Neuroleptics.

STOPP criteria identifies (PIMs)

CNSLong 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 NSAIDsBenzodiazepines.

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 COPDCNS:

L-DOPA in idiopathic Parkinson's disease with definite functional impairment.

Antidepressant → depressive illness moderate to severe lasting at least 3 monthsCVS → 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