Download gerontological pharmacology update considerations

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