Cases in Geriatric Pharmacology (ARS) Flashcards
What is “always the answer on the boards” and the take home point of this talk?
Discontinue the amitriptyline
Which of the following changes least with age?
- absorption
- distribution
- metabolism
- elimination
- absorption
- amount absorbed (bioavailability) doesn’t change
- peak serum concentrations may be lower and delayed
Exceptions:
drugs with extensive first-pass effect (bioavailability may increase; serum concentrations may be higher because less drug is extracted by a smaller liver with reduced blood flow, e.g., nitrates)
Factors that affect drug absorption
- what is taken with the drug (ie food)
- comorbid illnesses (diabetic gastroparesis)
- enteral feedings interfere with absorption of some drugs (phenytoin)
- drugs that increase gastric pH or affect GI motility affect absorption (eg PPIs, iron)
An older woman is switched from atenolol to propranolol. What happens and why?
- bradycardia, confused, despondent
- Why? propranolol is more lipophilic (enters CNS)
Effects of aging on volume of distribution (VD)
- decreased body water– so lower VD for hydrophilic drugs
- decreased lean body mass– so lower VD for drugs binding muscle
- increased fat stores– so higher VD for lipophilic drugs and lipid soluble more likely to get into brain
- decreased plasma protein (albumin)– so higher percentage of drug that is unbound (active)
Most common site of drug metabolism
Liver
- metabolic clearance of a drug by the liver may be reduced because liver blood flow, size, and mass decreases
- individual hereditary differences in enzyme levels may be more important to explain inter-patient variation
Are drugs that undergo phase I or phase II metabolism preferred for older pts?
Phase II pathways are preferred in older pts.
(Phase I pathways convert drugs to metabolites with less than, equal, or greater pharm effect than parent compound. Hydrolysis, oxidation, reduction)
(Phase II: (e.g., conjugation) pathways convert drugs to inactive metabolites that do not accumulate)
Which factor accounts for most change in drug effects with age?
- absorption
- distribution
- metabolism
- elimination
ELIMINATION
Estimation of creatinine clearance with age
-With advancing age and lower body weight, serum creatine becomes a weaker estimator of creatinine clearance
- decrease in lean body mass leads to lower creatinine production AND less creatinine to clear
- so serum creatinine may stay in normal range despite decline in creatinine clearance
Cockroft-Gault Equation
[(Ideal weight in kg)(140-age)]/(72)(serum creatinine in mg/dL)
x(0.85 if female)
Pharmacokinetics vs pharmacodynamics
Pharmacokinetics - What the body does to the drug: Pharmacodynamics - What the drug does to the body
Why are elderly at greater risk for bleeding at any given INR (with warfarin)?
they are more like to have additional problems that increase that risk (e.g., friable stomach, more likely to fall & suffer head trauma, etc.)
What is the most common cause of adverse drug reactions in the elderly?
number of medications prescribed
Risk factors for ADR: 6 or more concurrent chronic conditions 12 or more doses of drugs/day 9 or more medications (potential drug interactions: 6% on 2 meds, 50% on 5 meds, approx. 100% on 8 meds) Prior adverse drug event Low body weight or low BMI Age 85 or older Estimated CrCl less than 50 mL/min
Beers Criteria
Comprehensive review and grading of drug-related problems and adverse drug events in older adults
-Examples: all “muscle relaxers”, tricyclic antidepressants
Other top drugs to avoid: Diphenhydramine, hydroxyzine, and first-generation antihistamines Clonidine Amiodarone, class 1 antiarrhythmic drugs Digoxin greater than 0.125 mg daily All benzodiazepines Glyburide, chlorprompramide Indomethacin, meperidine
Two types of errors to watch out for
prescription errors monitoring errors (ex: taking ACE-I, must monitor K+, serum creatinine)
Also be aware of OTC medications
When to be cautious about medication withdrawal
Amitriptyline: sudden cessation may cause a cholinergic rebound syndrome (agitation, borborygmi, diarrhea)
-Clonidine: sudden withdrawal may cause rebound HTN but less likely with dose less than 1 mg per day
What are some drugs that can cause bradycardia?
Digoxin, verapamil, and propranolol; slow cardiac conduction (note: Verapamil increases digoxin levels 50%-75%)
What are some drugs that can cause weight loss?
Theophylline and digoxin may cause nausea and dysgeusia (food tastes bad). Clonidine and amitriptyline cause dry mouth (harder to eat) and photophobia.
***Side effects beget more polypharmacy!
What are some drugs that cause drug-induced parkinsonism
can occur with medications not usually considered culprits (metoclopramide, valproic acid, prochlorperazine, etc.)
For drugs causing psychoactive SE, what is a commonality?
Most often psychoactive meds or those with anticholinergic side effects
Drugs impairing cognition:
Anticholinergics (eg, diphenhydramine, trihexyphenidyl, oxybutynin)
Anticonvulsants (phenytoin, gabapentin, valproate)
Muscle relaxers (carisoprodol [eg, Soma], cyclobenzaprine [eg, Flexeril])
Antiemetics (prochlorperazine, metoclopramide)
Digoxin, clonidine, amantadine, amiodarone
Benzodiazepines, antipsychotics
Patient with drug induced cognitive impairment = 3x more likely to fall
-most offending drugs taken for several years prior to dx
Medication reconciliation
- brown bag review is good snapshot
- assess nonadherence
- efficiency strategies: focus on highest risk and highest benefit medications; involve other health care providers
***Relative risk reduction
RRR= (incidence in control - incidence in treated)/incidence in control
***Absolute risk reduction
ARR= incidence in control-incidence in treated
***number needed to treat
1/ARR
What are the most useful calculations for deciding potential benefit of treatment for a patient?
ARR
NNT
(more beneficial than RRR)
Spironolactone and RALES trial and results
- RALES trial results: spironolactone (in addition to standard ACE-I and diuretic) reduces both morbidity and death among pts with severe heart failure
- Rates of spironolactone prescription after publication of RALES increased (avg age 78y, whereas trial focused more on 65y group)
- Resulted in increased hospitalization for hyperkalemia, no major change in hosp readmission for CHF (didn’t see expected benefit)
- Problem: prescribing for pts who would have likely been excluded from trial, and failing to account for impact of multiple chronic diseases on medication efficacy and safety
- Exclusions in trial based on 2.5 serum Cr, but remember in reality older people’s serum creatinine is not a good indicator of renal func
BP treatment and aging
Hard to reconcile multiple studies:
1. results from HYVET/SPRINT trials indicating that lower BP is better [these studies had very healthy participants with few comorbidities]
vs
2. results from other trials indicating that initiating BP presciption leads to increased fall risk; also older adults taking antihypertensive meds and having more rapid cognitive decline
Conclusion: many robust elderly have hypertension, so treat them.
However, frail older individuals with hypertension may deserve a more cautious approach
Risks of tight glycemic control in elderly
Patients avg age 62 with Hgb A1C 6.4% had increased mortality & no reduction in CV events compared to A1C 7.5% (3.5 yrs)
Hypoglycemia resulting in need for emergency room visit associated with increased risk of developing dementia; the more such episodes, the greater the risk
Role of ACE-inhibitors in diabetes
Time to see benefit in slowing progression of renal disease (decline in creatinine clearance) may be as little as one year
(Prescribing ACEI may be more important than tighter control of blood sugars)
What is the most important predictor of inappropriate prescribing and risk of adverse drug events in older patients?
the number of prescribed drugs
Deprescribing
Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes
Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies
Statins at the end of life
Randomized trial of stopping statins in patients with life expectancy less than 1 year had no effect on cardiovascular events but had modestly better quality of life
