Flashcards in Pharm elderly pharm Deck (30)
what are pharmacokinetics based on?
what does aging affect absorption?
-amount absorbed (bioavailability) is not changed
-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?
-route of administration (enteral feedings interfere with absorption of some drugs)
-what is taken with the drug (divalent cations - ca, mg, fe - can affect absorption of many fluoroquinolones; drugs)
-comorbid illnesses (increased gastric pH may increase/decrease absorption)
what are the effects of aging on volume of distribution
-lower body water (lower VD for hydrophilic drug)
-lower lean body mass (lower VD for drugs that bind muscle)
-higher fat stores (higher VD for lipophilic drugs)
-lower plasma protein (albumin) - higher percentage of drug that is unbound (active)
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
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?
-most drugs exit via kidney
-reduced elimination causes drug accumulation and toxicity
what are the effects of aging on the kidney?
-reduced kidney size
-reduced renal blood flow
-reduced number of functioning nephrons
-reduced renal tubular secretion
--> lower GFR
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)
time course and intensity of pharmacologic effect of a drug
impact of aging on pharmacodynamics
may change with aging:
-benzos cause more sedation and poorer psychomotor performance in older adults (d/t reduced clearance of drug)
-older patients may experience higher levels of morphine with longer pain relief
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?
1. 6 or more concurrent chronic conditions
2. 12+ doses of drugs/day
3. 9+ meds
4. prior adverse drug reaction
5. low body weight or BMI
6. age 85+
7. estimated CrCl less than 50
most common adverse effects of drug-drug interactions
2. cognitive impairment
3. arterial hypotension (esp when standing)
4. acute renal failure
risk with combination of ACE inhibitor + diuretic
risk with combination of antiarrhythmic + diuretic
electrolyte imbalance, arrhythmias
risk with combination of calcium channel blocker + diuretic or nitrate
principles of prescribing for older patients
start low and go slow!
titrate upward slowly and avoid starting 2 drugs at teh same time