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
Give an example of where receptor binding is interfered with in older age
salbutamol less effective due to calcification of blood vessels, calcification changes the beta-adrenoceptor receptor itself and post-receptor effects
Name some drugs which are have a particularly high anticholinergic burden
Antidepressants: Amitryptilline
Antipsychotics: clozapine
(ALL) Opioids: codeine, morphine, fentanyl
blAdder drugs - oxybutinin
Name some anticholinergic side effects
a. Brain: Hallucinations, cognitive impairment, delirium
b. Heart: tachycardia, orthostatic hypotension
c. Eyes: dry eyes, light sensitivity
d. Mouth: dry mouth, difficulty swallowing
e. Skin: decreased sweating, dry skin
f. Bladder/bowel: difficulty starting urination, urinary retention, constipation
Why are anticholinergic side effects problematic for older patients and what does this mean for their use?
Older adults are particularly sensitive to anticholinergic effects
Older adults with cognitive impairment are more likely to get CNS effects from anticholinergics
older adults should avoid drugs with anticholinergic effects if possible
What medications apart from anticholinergics also cause problems in older people?
sedatives
What are the geriatric giants (in terms of Is)?
- Incontinence
- Intellectual impairment
- Iatrogenesis
- Instability (falls)
- immobility
What is the significance of cognitive impairment as a result of being on anticholinergics?
pts may be referred to the memory clinic when it is actually a side effect of a medication they are on
What scale can be used to measure anticholinergic burden?
the anticholinergic burden scale
What are the common causative drugs for adverse drug reactions?
- Cardiovascular drugs
- Diuretics
- Digoxin
- Antihypertensives - CNS drugs
- Hypnotics
- Antipsychotics
- Antidepressants - Opioids
- NSAIDs
When looking at someone’s medications, how can you decide which are the most important and therefore not to deprescribe?
- Drugs providing immediate relief of distressing symptoms
eg pain relief, antiemetics, antianginals esp in end of life care - Modify an acute condition that is life-threatening or will soon result in distressing symptoms if untreated
eg antibiotics for pneumonia or sepsis, diuretics for heart failure, Parkinson’s drugs, antiepileptics - Modify a chronic condition that may progress to become life-threatening or cause significant symptoms if not treated
eg methotrexate for RA
When looking at someone’s medications, how can you decide which are the least important and therefore consider deprescribing?
- Can prevent serious disease without symptomatic benefit
eg antiplatelets, antihypertensives, statins - Unlikely to be useful in short or long-term eg fish oil
- Where non-pharmacological therapy is just as good eg physio
- drugs that address a problem that is no longer present
What is it important to remeber before deprescribing drusg?
Consult with the patient and have a clear discussion about your reasoning nad explore their preferences
Some drugs can only be deprescribed by a specialsit
eg antiepileptic meds, antiparkinsons drugs
What tools are there to aid in deprescribing?
STOPP START Toolkit
Beer criteria
STOPP FRAIL
NO TEARS – designed to be used in a 10 minute primary care consultations
List some barriers to deprescribing
Doctor factors:
Concern from clinicians to discontinue medications started by someone else
Fear of losing dr-pt relationship
Fear of drug-withdrawal side effects
Time and resource constraints – eg explaining to pt why you are doing this or resources such as mental health support vs antidepressants
Research studies often do not include older people or only include pts with a single disease
Patient factors:
Resistance from pts or family
