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Transcript
GERONTOLOGICAL PHARMACOLOGY UPDATE Thomas W. Barkley, Jr., DSN, ACNP-BC, FAANP Professor of Nursing CONSIDERATIONS Drug use in the older population Polypharmacy and inappropriate prescribing y Senior health considerations y Drugs for common indications y Drug dosing in the older patient y y Ń Drugs most prone to cause adverse drug reactions Ń Dosage reduction of commonly prescribed drugs Director of Nurse Practitioner Programs California State University, Los Angeles and President y Drug of abuse Barkley & Associates Pharmacotherapeutics in the Geriatric Patient Older adults (age>65) are the fastest growing segment of the population. y Most Americans will suffer from at least 3 chronic illnesses. y Adults over 65 consume over 30% of all prescription meds; 86% have a chronic health problem requiring meds. y Elderly also consume the greatest number of over-the-counter meds. y Pharmacotherapeutics in the Older Patient Male Medicare patients are prescribed over 13 medications/year. y Female Medicare patients are prescribed over 16 medications/year. y Pharmacotherapeutics in the Older Patient Over 20% of hospitalizations in adults over 65 are due to effects of prescription drugs. y Polypharmacy and inappropriate prescribing are major contributors to these hospitalizations. y WHAT PREDISPOSES THE OLDER PATIENT TO ADVERSE DRUG REACTIONS? Facts About Adverse Drug Effects in the Elderly Predisposing Factors for Drug Toxicity in the Older Patient Elderly have more ADEs than any other group due to greater number of medications and concurrent disease states. y ADEs rank 5th after congestive heart failure, breast cancer, hypertension, and pneumonia among leading preventable threats to health of older Americans. y Increased number and potency of drugs contributes. y Elderly population is increasing. y ENVIRONMENTAL FACTORS COMPLICATING THE PROBLEM Predisposing Factors for Drug Toxicity in the Older Patient Gastrointestinal tract: Altered gastric pH (more alkaline) and altered GI transit time due to the use of stimulant laxatives. y Dietary factors: Such as grapefruit juice, vitamins, alcohol use. y Smoking: Affects the metabolism of tricyclic antidepressants, propranolol, neuroleptics, theophylline and warfarin. y y y Metabolism and Polypharmacy Use of medications that interfere with drug metabolism at the same cytochrome P450 enzyme also elevates risk of cognitive adverse effects (e.g. CYP3A inhibitor, fluoxetine with alprazolam can increase risk of oversedation). y Consider pharmacogenetics as well. y Increased prevalence of chronic disease(s). Adverse drug effects may go unnoticed or unreported. y Decreased drug absorption with increasing age. y Physiological changes which affect drug metabolism and excretion Ń Decreased hepatic blood flow Ń Decreased liver enzyme activity and synthesis Ń Decreased renal blood flow x Use creatinine clearance, not serum creatinine, as a measure. Ń Decreased renal excretion of drugs x ALL OF THESE TEND TO INCREASE THE DURATION OF THE DRUG IN THE BODY. Gerontological Pharmacology: Implications For All Prescribers Effects of Aging on Pharmacokinetics Absorption Distribution y Elimination y y EFFECTS OF AGING ON PHARMACOKINETICS: DRUG ABSORPTION Photo by rubberpaw Effects of Aging on Pharmacokinetics: Drug Absorption y Effects of Aging on Pharmacokinetics: Drug Absorption y Elderly may have: Ń Decreased gastrointestinal motility Ń Decreased blood flow Ń Increased gastric pH • These changes are expected to decrease gastrointestinal blood absorption, but decreased motility results in a longer drug absorption time. • As a result, alternate administration routes for drugs should be considered. Effects of Aging on Pharmacokinetics: Drug Distribution y Volume distribution Ń Not an actual physiological measurement but important nonetheless Ń Volume of distribution (Vd) = Amount of Drug in the Body Concentration of Drug in the Blood or Plasma per Kilogram of Body Weight Gastrointestinal conditions may further complicate drug absorption • Little information regarding absorption of: – – – – Delayed release formulation Transdermal administration Transbuccal administration Transbronchial administration Effects of Aging on Pharmacokinetics: Drug Distribution y The volume of distribution determines the loading dose of a drug Ń Loading dose (mg/kg) = Desired Blood Concentration (mg/L) Volume of distribution (L/kg) Effects of Aging on Pharmacokinetics: Drug Distribution y Aged have lean body mass and body water, thus decreasing Vd Ń Decreased Vd will cause drugs that distribute into body water or muscle will have higher initial plasma concentration following administration. Ń Water soluble drugs distributed less effectively in elderly patients x Cardiovascular (CV) disease can further complicate this distribution Ń Ethanol is thought to be affected by reduced Vd, causing a higher blood concentration for any quantity Cw4 of ethanol consumed Effects of Aging on Pharmacokinetics: Drug Distribution More adipose tissue in elderly person increases the Vd of lipophilic drugs because fat is a depot for these agents y The effect and duration of action of some drugs are increased as both liver size and hepatic blood flow decrease along with subsequent hepatic inactivation. y Renal function in the aged is also decreased, resulting in higher plasma levels of free drug. y Ń More free drug concentration = more potent effect Photo by Biggishben Effects of Aging on Pharmacokinetics: Drug Distribution y Orosomucoid or alpha-1 glycoprotein binding is not altered with aging Ń Neutral pH, basic drugs not affected, as these typically bind to orosomucoid y However, most drugs are acidic and bound by serum albumin Ń Serum albumin and, subsequently, the drug-binding capacity of most drugs are decreased approximately 12% in the aged, thereby increasing free drug concentration. Effects of Aging on Pharmacokinetics: Drug Distribution Drug-drug interactions can increase in free drug concentration when one drug displaces another from albumin. y Notable drug-drug interaction occur only if: y Ń Drug is highly bound to plasma albumin Ń The free drug has a narrow concentration range between therapeutic and toxic concentration Ń Drug has small Vd y One such example of drug-drug interaction is between warfarin and acetylsalicylic acid. Warfarin Effects of Aging on Pharmacokinetics: Drug Distribution y Conditions in which drug-drug interactions can occur include: Ń Ń Ń Ń Ń Ń Inhibition of drug absorption Decreased Hepatic blood flow Inhibition of renal excretion Inhibition or stimulation of drug metabolism Displacement from albumin binding Pharmacodynamic effects of drugs on tissue Acetylsalicylic acid Effects of Aging on Pharmacokinetics: Drug Distribution y Narcotic analgesics also affected by decreased protein binding Ń Meperidine study indicated a correlation between aged patients and higher free drug fractions y Renal disease Ń Frequent acidosis also results and further decreases binding