what are pharmacokinetics based on?
absorption
distribution
metabolism
elimination
what does aging affect absorption?
- but peak serum concentration may be lower and delayed
what is the exception to aging and absorption?
drugs with extensive first pass effect - bioavailability may increase because less drug is extracted by the liver which is smaller with reduced blood flow
what are the factors that affect absorption?
what are the effects of aging on volume of distribution
what are the effects of aging on metabolism
metabolic clearance of a drug by the liver may be reduced because aging decreases liver blood flow, size and mass
phase I metabolic pathways
hydroxylation, oxidation, dealkylation and reduction
-convert drugs to metabolites with greater, less or the same effect as the parent compound
phase II metabolic pathways
convert drugs to inactive metabolites that do not accumulate
which metabolic pathway is preferred for older patients?
phase II (convert drugs to inactive metabolites that do not accumulate)
example of phase 1 pathway metabolism drug
benzodiazepine (causes old people to fall down)
examples of protein bound drugs
warfarin, barbiturates, phenytoin, carbamezapine
examples of water soluble drugs
digoxin and lithium
example of lipid-soluble drug
diazepam
list some drugs that require dose reduction with decreased creatinine clearance
aminoglycosides, fluoroquinolones, penicillins, procainamide, lithium, digoxin, metformin, biphosphonates, thiazides, atenolol, clofibrate, fluconazole, ACEi
what are some other factors other than aging that affect drug metabolism?
gender, hepatic congestion from heart failure, smoking (increases clearance of theophylline)
list some drugs that require hepatic metabolism
NSAIDs, aspirin, Ca channel blockers, acetaminophen, statins, cimetidine, ranitidine, proton pump inhibitors, beta blockers, ketoconazole, tricylic antidepressants, serotonin reuptake inhibitors, valproic acid, lidocaine, erythromycin, phenytoin
why is kidney function critical for elimination of a drug?
- reduced elimination causes drug accumulation and toxicity
what are the effects of aging on the kidney?
why does serum creatinine not reflect creatinine clearance?
lower lean body mass causes lower creatinine production AND there is a lower GFR causing serum creatinine to stay in normal range while masking change in creatinine clearance
what is the equation to calculate creatinine clearance?
cockroft and gault:
ideal weight in kg)(140-age) / (72)(serum creatinine in mg/dL) X (.85 if female
pharmacodynamics definition
time course and intensity of pharmacologic effect of a drug
impact of aging on pharmacodynamics
may change with aging:
which medications are most commonly involved in adverse drug events?
cardiovascular, CNS (esp anticholinergics), musculoskeletal medications, diphenhydramine (PM meds)
what are the risk factors for adverse drug events?