Polypharmacy Study Resources

Polypharmacy      Use of 5 or more drugs. o Including prescribed, over the counter and complementary medicines. “Excessive polypharmacy” if use ≥10 drugs. >65 years old using (Data from USA and Sweden): o One medication = 90%. o ≥5 = 40%. o ≥10 = 12%. Associated with: o Multiple co-morbidities. o Inappropriate prescribing (i.e. over-prescribing). o Under-prescribing (if a patient needs a drug, but physician feels that it’s too much). o Gender: F > M. o Low level of self-rated health. o Multiple doctors. o Depression. o Recent hospitalisation. o Low educational level. However, it is not an independent marker of quality of prescribing. o Many benefit from multiple medications for which there may be significant evidence base. Adverse drug reactions  The number of meds correlates with incidence: o ≥2 meds = 13%. o ≥5 meds = 58%. o ≥7 meds = 82%.  Prescribing cascade: the side effect of one medication causes the need to use another one in conjunction.  Prevalence of ADRs increases with age.  In one study: o 35% of older outpatients experienced ADR. o 29% requiring medical care for ADR.  Two-thirds of nursing home residents over 4 year periods seen to have ADR.  One-seventh of ADRs require hospitalisation.  May be more severe with increasing age.  NSAIDs: o Bleeding. o Renal impairment. o Antihypertensive therapy.  H2-receptor antagonist: o Nephritis/hepatitis.  Warfarin: o Increased risk of haemorrhage.  Anti-psychotics. o Commonly used for treatment of agitation in dementia. o Frequently used in aged care facilities. o Atypical vs. typical. o Side-effect profile: extra-pyramidal motor symptoms, sedation, tardive dyskinesia, metabolic syndrome, increased risk of stroke. o Possible association with increased mortality. o Therefore, would not rush into using anti-psychotics; must be aware of side effects before commencing treatment. Falls  Hip fractures associated with: o Barbiturates. o Benzodiazepines. o TCA. o Antipsychotics. o SSRI’s.  Benzodiazepines: o 50 – 110% increase in risk of hip fracture. o May account for 10% of all hip fractures. Confusion  Delirium may be drug induced in 11 – 30% of cases.  Benzodiazpines: o Reduced MMSE.  Anticholinergic drugs: o Reduced MMSE. o Mild cognitive impairment. o Delirium. Drug burden index  TDB = BAC + BS + BNW. o AC = anticholinergic. o S = sedating. o NW = total number of drugs.  Associated with changes in physical function score and cognitive tests. Beers’ criteria  JAGS 2012 evidence based guidelines.     53 medications or medication classes described as potentially inappropriate. 34 potentially inappropriate medications and classes to avoid in older adults. Other described as potentially inappropriate in older adults with certain diseases and syndromes. 14 classified as ‘use with caution’. Benzodiazepines  Increased sensitivity due to three factors: o Reduced clearance. o Changes in distribution. o Increased pharmacodynamics sensitivity in the brain (animal models).  Compare increased sensitivity to opioids: o Probably not related to pharmacokinetic changes. o Changes at receptor level (pharmacodynamics). Clinical trials  Pre-clinical.  Phase I: o Undertaken in healthy volunteers to determine tolerability, major toxicities, pharmacokinetics. o Usually 12 – 20 young male volunteers with dose escalation and monitoring.  Phase II: o Smaller trials; lower doses; placebo controlled. o Proof of concept.  Phase III: o Randomised control trial – usually younger cohorts. o Looking at real patient outcomes. o Traditionally had upper age limits.  Phase IV: o Licence and release of drug. o Observational studies. o Essentially post-marketing surveillance.  Therefore, the limitation of the effects of medication on the elderly is that clinical trials aim to test younger populations. Beta-blockers  Hospitalisation and death more likely to be mutli-factorial in the elderly.  With age, there is decreasing responsiveness of beta-adrenergic receptors due to changes in Ca2+ channels.  This contributes to an increasing risk of diastolic heart failure (thickened and unable to relax, as opposed to inability to contract). Hypertension treatment in >80  There was controversy of the correlation between anti-hypertensive treatment and mortality.  Study showed that conservative treatment of hypertension reduced mortality, and risk of stroke.  However, should note that it was a “conservative treatment”; don’t treat hypertension too aggressively in elderly patients. Warfarin  Benefits of Warfarin well established in the management of atrial fibrillation.  Average risk of stroke 5% per year; higher in the elderly.  Physicians may be wary when prescribing warfarin: o >75 greater risk of major haemorrhage with Warfarin. o Aspirin often used in the elderly.  However, Warfarin reduces the risk of stroke more: o Warfarin = 62% reduction. o Aspirin = 22% reduction.  May not use Warfarin in the cases approaching palliative care settings. General principles of prescribing to geriatric patients  Comprehensive geriatric assessment.  Multidisciplinary management plans.  Broad functional outcomes.  Paucity of clinical trials relevant to the elderly.  Few guidelines.  Determine the evidence for efficacy in older subjects.  Determine the likelihood of adverse drug events in older subjects.  Discuss the harm:benefit analysis with the patient and family.  Decide on the dose regimen.  Monitor the patient very carefully. Compliance  Non-compliance rates up to 50%.  May not change with age.  Barriers include: o Chronicity of conditions. o ADRs. o Polypharmacy. o o o o o Complexity of regimens. Financial costs. Cognition. Visual impairment. Hand coordination and swallowing problems.