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POLYPHARMACY Pio L. Oliverio, MD Fellow, Geriatrics SVCMC, Jamaica, NY
February 27, 2006
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Definition POLYPHARMACY
Use of several drugs or medicines together in the treatment of disease, suggesting indiscriminate, unscientific, or excessive prescription (Stedman’s Medical Dictionary)
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Definition POLYPHARMACY DRUG
The administration of many drugs at the same time DRUG is any substance that affects the physical and mental functioning of a living organism
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Epidemiology and Prevalence
2/3 of residents in long term care facilities receive 3 or more medications daily 7 different medications per patient per day Overall average per resident Older adults spend $3 billion annually on prescriptions
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Epidemiology and Prevalence
Direct correlation between age of the patient and the number of prescriptions they take daily 90% of older adults take at least one prescription daily most take two or more prescriptions daily
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Medication Underuse/Overuse
UNDERUSE – when available drugs are not used maximally for correct indication OVERUSE – when a particular medication is used excessively even if not properly indicated
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Polypharmacy Admission
3 and 10% - in two studies Result in several billions of dollars in yearly health care expenditures
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Commonly Prescribed Medications
Cardiovascular drugs Antihypertensives Analgesics Sedatives Anti-inflammatory GI preparations (laxatives)
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Definition PHARMACOKINETICS PHARMACODYNAMICS
management of the drug by the body PHARMACODYNAMICS target organ’s sensitivity to the drug
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Decreased drug absorption
Small bowel resection Malabsorption Multiple drugs Antacids Active transport - e.g. in nutrients and vitamins Passive transport – most common
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Antacids decrease absorption of
Cimetidine Digitalis Tetracycline Phenytoin Quinolones Ketoconazole Iron
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YOUNG ELDERLY Drug absorption Faster Slower/ decreased Metabolism Slower Excretion Fat: lean body mass Volume distribution
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Duration that a particular drug exerts its effort depends on:
Volume distribution (Vd) Metabolism of the drug The clearance of the drug All three factors change with age
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Volume distribution term used to relate the amount of drug in the body to the concentration of drug in the plasma Vd = Dose Cpo
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Vd is determined by Degree of plasma protein binding
The patient’s body composition Changes substantially with age Adipose tissue increases 18-36% in males 36-48% in females
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Elderly ↓ body water and lean body mass lower Vd ↑ drug concentration ↑ body fat large Vd prolongation of half life unless the clearance increases (unlikely in the elderly)
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The increase in adipose tissue larger Vd for lipid soluble drugs causing half life (T1/2) to be prolonged clinically important with the CNS drugs i.e. benzodiazepines and barbiturates
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Total body water composition decrease by 15%, consequently the Vd of water soluble drugs is decreased increased drug serum concentration
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↑ increased amt of free (active) drug in the body
Plasma protein concentration also ↓ with age ↑ increased amt of free (active) drug in the body Drugs have ↑ concentration due to ↓ plasma protein Digoxin Theophylline Phenytoin warfarin
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DRUG METABOLISM Phase 1 Cytochrome P – 450 enzyme system
Oxidation, reduction, hydrolysis Declines with increasing age Drugs involved Ketoconazole, erythromycin, SSRI
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DRUG METABOLISM Phase 2 Conjugation/ biotransformation Acetylation, glucoronidation, sulfation Usually not effected by age Not safe to assume efficient drug metabolism in geriatrics pt with normal liver function
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Effects Of Age On Renal Function
Wide inter-individual variation in the rate of decline in renal function with increasing age i.e. renal function declines by 40-50% between ages 20 and 90, - this is an average decline Can cause over or under dosing
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Effects Of Age On Renal Function
↓ muscle mass ↓ creatinine production Serum creatinine may be normal at a time when renal function is reduced. Serum creatinine does not reflect renal function accurately in the elderly
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Use creatinine clearance to determine renal function.
Formula to estimate renal function (Cockcroft & Gault) Creatinine clearance = (140 – age) X body weight in kg / 72 X serum creatinine (x 0.85 in females)
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Drugs given in reduced doses to elderly
Aminoglycosides Benzodiazepines Digoxin Haloperidol Metoclopramide Thyroxine Vitamin D
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Drugs with ↓ renal elimination
Aminoglycosides ACE-I Digoxin Diuretics Lithium H2 blockers
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Changes in the end-organ response to a drug due to
Pharmacodynamics The study of the effects of drugs at the receptor level Changes in the end-organ response to a drug due to Change in the receptor binding Decrease in receptor number Altered translation response to a receptor
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Pharmacodynamics Increase in receptor response is noted
Benzodiazepines Warfarin Opiates
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Adverse Drug Reactions
Primum non nocere “first do no harm” Applicable when drugs are prescribed for geriatric population Older adults are more at risk Can be reduced by decreasing number of medications
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Adverse Drug Reactions
Frequent symptoms Confusion (75%) Nausea Loss of balance Change in bowel pattern Sedation
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Adverse Reactions – Risk Factors
Advanced age Female Hepatic/ renal insufficiency Polypharmacy Lower body weight History of prior drug reaction
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Reasons for inappropriate medication ordering
Multiple problems and complaints may consult several health care professionals Use of multiple pharmacies OTC medication history Time limitations during office visits
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Consequences Non-adherence Adverse drug reactions
Drug-drug interactions Increased risk of hospitalizations Medication errors Increased costs from treatment of adverse events
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Strategies for Elderly Compliance
Make drug regimens and instruction as simple as possible Instruct relatives and care givers on the drug regimen Make sure patient can get to a pharmacist, can afford the prescription, and can open the container
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Strategies for Elderly Compliance
Enlist others (HHA, pharmacist) to help ensure compliance Use aids (special pill boxes and drug calendars) Keep updated medication record Review knowledge of and compliance with regimens regularly
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Factors not affecting compliance
Age Sex Education Disease severity
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Factors reducing compliance
Multiple medications Frequent dosing schedules Complicated dosing instruction Expensive medications
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Promote compliance Reducing the number of prescribed drugs
Simplifying dosage regime Evaluating patient’s functional ability to take medication
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Inability to self-medicate
Cognitive impairment Decreased dexterity Sensory/motor deficits Number of medications
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Measures of Compliance
Direct method drug concentration in the blood, urine, or saliva Indirect method Therapeutic response Self report Pill counts Pharmacy records
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Principles of Drug Prescribing
Make a diagnosis before drug therapy is initiated Carefully weigh the risks versus benefits Begin with low doses and slowly increase until effect is reached, monitor for reactions Inquire about the use of OTC and alternative medications
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Principles of Drug Prescribing
Periodically review the list of medications Simplify medication schedule Suspect a medication as the cause of any major medical or cognitive change Discuss the benefits of the medication and the consequences of non compliance Inform the patient about potential reactions
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Prescribing Practices
Basic elements… Reduction of polypharmacy Coordinated medication plan Clinicians, pharmacists, older person/ families Basic tenet… Non pharmacologic therapy is always initiated first whenever appropriate
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Summary Polypharmacy – epidemiology, prevalence, implications in terms of compliance Pharmacokinetics + pharmacodynamics Pharmacology of drugs Principles of appropriate prescribing Strategies to improve compliance in the elderly
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THANK YOU THANK YOU ANY QUESTIONS?
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