Polypharmacy Flashcards
Define pharmacokinetics and explain in simple terms
the bodily absorption, distribution, metabolism, and excretion of drugs (DAME)
What the body does the to the drug
Define pharmacodynamics and explain in simple terms
the biochemical and physiological effects of drugs
what the Drug does to the body (pharmacoDynamics)
Define polypharmacy
taking more than 4 medications, or the concurrent use of multiple medications by one person
What is appropriate polypharmacy?
Optimisation of medication for patients with complex conditions or comorbidities
What is inappropriate/problematic polypharmacy?
When multiple medications are prescribed inappropriately, increasing risk of side effects
Why do we have problematic prescribing?
- Multimorbidity – as clinical trials only include single-disease pts
- Incremental prescribing/prescribing cascade – where medications are given as a result of side effects of others – iatrogenic
- End of life – pts staying on meds beyond the point at which they get benefit from them
Give an example of inappropriate prescribing?
Patient on several antihypertensives leading to postural hypotension
What are the risk factors for polypharmacy?
- chronic disease
- comorbidity
- cognitive impairment/dementia
- renal or liver impairment
- end of life
- past or current non-adherence
Why might older patients find it hard to take many medications?
Cognitive impairment - Pts may not understand instructions
Visual impairment - unable to read instructions
Lack of treatment supervision leads to non-adherance
What is a drug-disease interaction and give an example?
When a medication makes management of a disease more difficult
NSAIDs making hypertension worse
What about a drugs pharmacokinetics mean that older people more sensitive to the adverse effects of polypharmacy?
Distribution
- Increase in body fat and decrease in body water
- Increased permeability of the blood brain barrier
- Malnutrition
Absorption
- increased gastric pH
Metabolism
- reduced hepatic perfusion
- changes in CYP450
Elimination
- reduced renal perfusion
How does an increase in body fat and decrease in body water affect the pharmacokinetics of a drug?
lipophilic drugs eg Benzodiazepines eg Diazepam and Chlordiazepoxide accumulate due to increased volume of distribution, so still have an effect after the medication has been stopped – takes longer to be eliminated (increased elimination half life) so more likely to have drowsiness and confusion for longer and increased risk of side effects if given multiple doses.
Volume of distribution of water-soluble drugs decreases eg Digoxin, so need a lower loading dose
Define volume of distribution
the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma (smaller volume of distribution, means need less drug)
How does increased permeability of the blood brain barrier affect the pharmacokinetics of a drug?
causes cognitive affects, as drugs can pass through thre BBB
eg older patients get confused and sleepy for longer with buprenorphine patches than younger pts even after you take it off
How does malnutrition affect the pharmacokinetics of a drug?
Serum concentrations of unbound (free) drug increase, due to reduced serum albumin. this enhances drug effects and toxicity
eg Phenytoin and warfarin
Why are older patients more likely to have an increased gastric pH (ie more alkaline)?
due to PPIs and atrophic gastritis
How does increased gastric pH affect the pharmacokinetics of a drug?
medications that are meant to be absorbed in acidic conditions don’t get absorbed as well
eg calcium carbonate reduced so may need a higher dose of calcium replacement or use a capsule
and enteric coated tablets may be released early in the stomach, causing GI adverse effects eg enteric coated aspirin or erythromycin
How does reduced hepatic perfusion affect the pharmacokinetics of a drug?
reduced clearance
eg amitriptyline, propranolol and nifedipine (a CCB for angina and hypertension)
BUT may also result in reduced first-pass metabolism in the liver, which occurs before a drug reaches systemic circulation also decreases
How are CYP450 enzymes affected in older patients?
More likely to be taking CYP450 inducers or inhibitors which increases the chance of drug-drug interactions
AND
Hepatic metabolism of many drugs through the CYP450 enzyme decreases with age, which causes a decrease in hepatic clearance by 40%
Name 3 CYP450 inducers
SCRAP GP - a few are:
- Rifampicin
- alcohol (chronic)
- Carbamazepine
- phenytoin
Name 3 CYP450 inibitors
SICKFACES.COM - a few are:
- sodium valproate
- alcohol (acute)
- Erythromycin
- omeprazole
How does reduced renal perfusion affect the pharmacokinetics of a drug?
reduced eGFR, so water soluble drugs (to be cleared in the urine) are cleared slower
eg diuretics, digoxin and NSAIDs - digoxin may accumulate in renal failure to cause toxicity
What are the signs of digoxin toxicity?
o N+V
o Abdo pain
o Yellow discolouration of vision
o Arrythmias
What pharmakoDynamic changes occur in older patients?
- changes in receptor binding
- post-receptor effects
- pathological changes in organs