Elderly - Drugs and Polypharmacy - Part 2

Question 1

Clinical pharmacology of old age - what is the therapeutic range?

Answer 1

Question 2

how is absorption affected in old age?

Answer 2

• 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

Question 3

______ of absorption not affected by age but ____ is

Drugs take _______ to work

Answer 3

Extent

rate

longer

Question 4

Distribution:

what body composition changes happen in old age that affect distribution?

Answer 4

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

Question 5

Distribution:

what body protein binding changes happen in old age that affect distribution?

Answer 5

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

Question 6

Distribution:

•___________ permeability across the blood-brain barrier (in old age)

Answer 6

Increased

An increase in permeability across the blood brain barrier allows drugs to be more readily distributed in the CNS

Question 7

The two most important factors that affect drug distribution in the elderly are changes in ____ _____________ and _______ _______

Answer 7

body composition

protein binding

Question 8

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

Answer 8

increased

prolonged

Question 9

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.

Answer 9

reduction

higher

Question 10

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.

Answer 10

reduction

reduced

not

large

Question 11

metabolism:

•Hepatic metabolism is affected by what in old age?

Answer 11

• Decreased liver mass
• Decreased liver blood flow

Question 12

•Hepatic metabolism is affected by:

• Decreased liver mass
• Decreased liver blood flow

what are the consequences?

Answer 12

• 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

Question 13

how is excreiton affected by old age?

Answer 13

• 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

Question 14

Pharmaokinetics is what the ?????

Pharmacodynamics – what the ?????

Answer 14

body does to the drug and how it handles it

drug does to the body

Question 15

Pharmacodynamics in old age:

__________ sensitivity to particular medicines

Answer 15

Increased

Question 16

Pharmacodynamics:

•Increased sensitivity to particular medicines

what is this due to?

Answer 16

• 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

Question 17

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 ______

Answer 17

diagnosis

adverse

drug

Lower

needed

Question 18

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 ___

Answer 18

problems

lower

titrate

Review

aim

Question 19

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

Answer 19

prescriptions

medicines

simple

compliance

Question 20

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

Answer 20

denied

beneficial

younger

benefits

Question 21

what are some Prescribing Tools and Guides?

Answer 21

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

Question 22

Gives a framework on how to deal with people based on 7 questions

Answer 22

Relies on a lot of knowledge on clinical pharmacology and the patient themselves

Question 23

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

Question 24

describe what is shown here?

Answer 24

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