Altered pharmacokinetics and pharmacodynamics with high polypharmacy risk
Mnemonic
START and STOPP, the two halves of the same tool:
- STOPP - Screening Tool of Older People’s Prescriptions, listing drugs to stop
- START - Screening Tool to Alert to Right Treatment, listing drugs wrongly omitted
“The elderly are underprescribed as often as they are overprescribed”, which is why the tool has two halves.
The anticholinergic burden is the single most useful concept: many drugs contribute a little (amitriptyline, oxybutynin, antihistamines, antipsychotics, some antiemetics), and the total predicts confusion, falls, retention and mortality.
Physiological changes that drive the risk:
- Reduced renal clearance, though creatinine may be normal because of low muscle mass
- Reduced hepatic first pass metabolism
- Increased fat and reduced water, prolonging lipid soluble drug half lives
- Increased sensitivity to sedatives, opioids and anticoagulants
“Start low, go slow, and review”, and every new symptom in an older person should be considered a drug side effect until proven otherwise.
Expansion
Pharmacokinetic changes
- Reduced renal clearance, even with a normal creatinine, since muscle mass falls in parallel
- Reduced hepatic mass and first pass metabolism
- Increased body fat prolongs the half-life of lipid soluble drugs such as diazepam
- Reduced body water raises levels of water soluble drugs such as digoxin
- Reduced albumin raises the free fraction of highly bound drugs
Pharmacodynamic changes: increased sensitivity to benzodiazepines, opioids, anticholinergics and antihypertensives, with blunted baroreflex and thermoregulation.
High risk drug groups: benzodiazepines and Z drugs, anticholinergics, opioids, NSAIDs, antipsychotics, and drugs causing postural hypotension. The cumulative anticholinergic burden correlates with falls, delirium and cognitive decline.
Principles
- Start low, go slow, one change at a time
- Use STOPP/START criteria to identify inappropriate prescriptions and omissions
- Conduct structured medication review, deprescribing where benefit no longer outweighs harm
- Consider the time to benefit against life expectancy, particularly for preventive drugs such as statins and bisphosphonates