Elderly - Drugs and Polypharmacy - Part 2 Flashcards
Clinical pharmacology of old age - what is the therapeutic range?
how is absorption affected in old age?
- Physiological changes occur that effect the rate but generally not the extent of absorption from the GI tract - May lead to a delay in onset of action
- Examples - A reduction in saliva production may result in a reduction in the rate of absorption of buccally administered drugs e.g. glyceryl trinitrate (GTN) – coronary vasodilator
______ of absorption not affected by age but ____ is
Drugs take _______ to work
Extent
rate
longer
Distribution:
what body composition changes happen in old age that affect distribution?
Reduced muscle mass
Increased adipose tissue:
•Fat soluble drugs: ↑ Vd, ↑ T1/2, ↑ duration of action e.g. diazepam
Reduced body water:
•Water soluble drugs: ↓Vd, ↑ serum levels e.g. digoxin
Drugs are either fat or water soluble
Increased fat and decreased water as we get older
Distribution:
what body protein binding changes happen in old age that affect distribution?
Decreased albumin:
•↓ binding, ↑ serum levels acidic drugs e.g. furosemide
Many drugs that are bound to protein/albumin and when drugs are bound they are inactive but this decreased in older age as the liver makes less albumin
So lower dose in older person
Distribution:
•___________ permeability across the blood-brain barrier (in old age)
Increased
An increase in permeability across the blood brain barrier allows drugs to be more readily distributed in the CNS
The two most important factors that affect drug distribution in the elderly are changes in ____ _____________ and _______ _______
body composition
protein binding
For fat soluble drugs, in the elderly the Vd is __________ owing to the increase in body fat. E.g. Diazepam, haloperidol, The adipose tissue acts as a reservoir for these drugs and an enhanced t1/2 is also seen, resulting in a ___________ duration of action
increased
prolonged
Water soluble drugs tend to experience a ________ in Vd, resulting in _______ serum levels. This can be found in the case of theophylline, atenolol, propranolol and hydrochlorthiazide.
reduction
higher
Digoxin, although water-soluble has a high Vd. This is due to widespread distrubution into the muscle. The reduction in muscle mass in older people means there is a significant _________ digoxins Vd. The clinical consequence of this is that the loading dose has to be substantially _______ in the elderly.
Drugs with a low Vd such as warfarin is ___ widely distributed. Those with _____ Vd e.g. digoxin, amiodarone are extensively distributed.
reduction
reduced
not
large
metabolism:
•Hepatic metabolism is affected by what in old age?
- Decreased liver mass
- Decreased liver blood flow
•Hepatic metabolism is affected by:
- Decreased liver mass
- Decreased liver blood flow
what are the consequences?
- Toxicity due to reduced metabolism/excretion
- Reduced first pass metabolism
- ↑ in bioavailability with some drugs e.g. propranolol
- Can cause ↓ bioavailability of pro-drugs e.g. enalapril
Lower doses lead to higher doses within the plasma
Prodrugs = have to pass through the liver and be metabolized into an active form
how is excreiton affected by old age?
- Renal function decreases with age
- Reduces clearance and increases half-life of many drugs leading to toxicity
Creatinine clearance ( CrCl ) is an estimate of Glomerular Filtration Rate ( GFR )
Drug accumulates until it reaches a toxic level
Pharmaokinetics is what the ?????
Pharmacodynamics – what the ?????
body does to the drug and how it handles it
drug does to the body
Pharmacodynamics in old age:
__________ sensitivity to particular medicines
Increased
Pharmacodynamics:
•Increased sensitivity to particular medicines
what is this due to?
- change in receptor binding,
- decrease in receptor number, (most receptors are proteins and are synthesized less as we get older)
- altered translation of a receptor initiated cellular response into a biochemical reaction
•Examples: diazepam (↑ sedation), warfarin (↑ anti-coagulation) - So give less warfarin as liver is making less clotting factors
Principles of prescribing for older people:
- Where possible, be clear about the ________ to avoid prescribing a drug to manage an ________ effect (Make sure there is a disease and it is the problem)
- Consider whether ____ therapy is the best therapeutic action
- _____ doses (or reduced frequency of administration) are generally ______
diagnosis
adverse
drug
Lower
needed
Principles of prescribing for older people:
- Think about whether the drug causes particular ________ in elderly patients
- Check whether a _____ dose is recommended in the elderly: start at the lowest dose and ______ up slowly (‘start low, go slow’)
- ______ the new drug and check whether it is achieving its ___
problems
lower
titrate
Review
aim
Principles of prescribing for older people:
- Review all _________ regularly and stop any _________ that are not beneficial
- Try to keep regimens as ______ as possible
- Consider ________ issues which elderly patients in particular may experience
prescriptions
medicines
simple
compliance
Principles of prescribing for older people:
- Elderly patients should not be ______ proven ________ medicines on the basis of age
- But bear in mind that clinical trials are often performed in a ________ population which may mean that _______ do not translate to an older age group
Prescribing needs a bit more thought and care
denied
beneficial
younger
benefits
what are some Prescribing Tools and Guides?
Beers’ criteria:
- List of ‘inappropriate’ drugs for older people
- Updated occasionally but many weaknesses (it’s a US list)
START-STOPP criteria (O’Mahony et al):
- Advice on medical optimisation
- A lot to remember, so mostly research tool
NHS Scotland Polypharmacy Guidance
Gives a framework on how to deal with people based on 7 questions
Relies on a lot of knowledge on clinical pharmacology and the patient themselves
Page from within the polypharmacy guidance
NNT for certain conditions
The effect of drugs is vastly over estimated by doctor and even more so by patients
describe what is shown here?
17 people adversely affected by it and 1 that has a serious effect causing hospitalisation
Most it does nothing
Only helps 7 people, and that benefit is an extra 25 minutes of sleep per night and wake up once less often every 2 nights
So quite harmful
Do have a role in people affected by insomnia
Number needed to treat is only half the equation but you also need to consider the number needed to harm
