11/4- Pharmacology for the Elderly Flashcards
What percentage of the US population is over 65?
How does this compare to the percentage of medication they consume?
Elderly (>65) make up:
- 15% of the US population
- 30% of the consumers of prescribed drugs
- 50% of the consumers of over-the-counter drugs
- Don’t forget “health food meds/nutritional supplements” and over the counter meds
- Injudicious use of meds can be dangerous and expensive
- BUT don’t withhold an indicated drug b/c pt is on a lot of other meds
What population has the most adverse drug events (ADEs)
- Responsible for __% of hospital admissions
- Examples of ADEs
Elderly
- 5-15% of all hospital admission of older people are due to ADEs (28% of admissions from nursing homes)
- Nursing homes spend $1.33 on ADEs for every $1 spent on medications
- Typical ADEs include: falls, anorexia, fatigue, delirium, urinary incontinence
- Any new symptom or sign, think about the drugs
What are risk factors for ADEs?
- 6+ concurrent chronic conditions
- 12+ doses of drugs/day
- 9+ medications
- Prior adverse drug reaction
- Low body weight or BMI
- Age 85+
- Estimated CrCl under 50 mL/min
Why are ADEs so common in the elderly?
- Inadequate pre-clinical information
- Old people are not in drug studies
- Pharmocokinetics
- Pharmacodynamics
- Homeostenosis
Why are old people not in drug studies?
- Concomitant drug use is frequently an exclusion in trials of new agents
- Physically or cognitively frail persons are excluded from almost all randomized drug trials
Problem, because much of pharmacology practice is based on extrapolation from study of younger/healthier persons
What is pharmacokinetics?
- What does it include?
“What the body does to the drug”
- Absorption
- Distribution
- Metabolism
- Excretion
What are the age effects on absorption from the GIT?
- Decreased rate of gut transport
- May increase absorption of sustained release drugs (theophylline)
- Increased metabolism in gut (sometimes by flora; e.g. levodopa, digoxin)
- Increased gastric pH (decreased acid)
- Decreased absorptive surface
- Peak serum concentration may be lower and delayed
- Overall aging changes in the GIT seem to be of minor clinical significance because motility and absorptive area changes cancel out
What are factors that affect absorption from the GIT?
- Divalent cations (Ca, Mg, Fe) can affect absorption of fluoroquinolones (e.g. ciprofloxacin; Fe + thyroxine)
- Enteral (tube) feedings interfere with absorption of some drugs (e.g. phenytoin)
- Drugs that affect GI motility can affect absorption
- Increased gastric pH may increase or decrease absorption of some drugs
How does drug absorption from the skin compare to other methods of administration
- What factors affect absorption
- What meds can be given this way
- Unpredictable rate of absorption of topical agents
- Thin skin favors absorption (seen in elderly)
- Decreased perfusion of skin delays absorption
- Nitroglycerin, estrogens, pain meds, BP meds, Alzheimer’s meds…
What are changes in distribution of mass/composition in the elderly?
- Decrease in lean body mass and total body water; higher concentrations of water soluble or muscle protein bound drugs
- Increased fat increases volume distribution for lipophilic drugs, such as sedatives that penetrate CNS (remember your brain is just a hunk of fat)
How does age change protein binding?
- How does this affect pharmacokinetics
- Increased free fraction of some highly bound acidic drugs
- Albumin may drop rapidly with illness (increasing free concentration of highly bound drugs)
- Alpha-1-acid glycoprotein increases with age and will go up further with illness (binds antidepressent drugs)
- Protein binding changes are of modest significance for must drugs, especially at steady-state because clearance also increases
- Only free proportion is active, blood levels usually give total (free + bound)
Albumin decreases in response to ___, but not ___
Albumin decreases in response to illness, but not aging!
T/F: Albumin has multiple drug binding sites
True
What protein increases with healthy aging?
How does it change with illness?
Alpha-1-glycoprotein increases with healthy aging
- Greatly increases in illness
How do Dilantin (Phenytoin) concentrations change in the elderly?
- In young people, Dilantin (Phenytoin) is 99% bound to have 0.1-0.2 free and a total of 10-20
- In elderly, 98% is bound so 0.1-0.2 is free with a total of only 5-10 THUS, it is OKAY to have lower concentrations in the elderly
- So if older person is seizure-free with total phenytoin of 7, that is satisfactory. Do NOT increase their dose unless they are seizing
- You can always check a free phenytoin level (but expensive, and a hassle)
Since many drugs compete for albumin binding sites, what is the effect of adding a new drug?
- Addition of a new drug will modify the dynamic situation such that some bound drug may be released increasing its free concentration (and effect)
- The more drugs, the harder to anticipate the dynamics
Describe drug metabolism in aging
- First pass metabolism
- Phase I
- Phase II
- Enzyme effect
- Overall decline in metabolic capacity due to decreased liver mass and hepatic blood flow
- Metabolic capcity is highly variable; no good estimation algorithm exists
- Decreased first pass metabolism in old
- Phase I (P450 system -> oxidation, reduction, hydrolysis) is more likely to decrease with advancing age
- Phase II (conjugation) usually unchanged
- Induction decreased for some enzymes
What are the effects of aging on Cytochrome P450 and drug interactions?
- Effects of aging and clinical implications are still being reserached
- CYP3A(4) is involve din > 50% of drugs on the market
- Induced by: rifampin, phenyotin, carbamazepine
- Inhibited by: macrolide Abx, nefazodone, itraconazole, ketoconazole, and grapefruit juice
