9. Safe drug use in the elderly

Question 1

Common drug problem

Answer 1

Warfarin/ibuprofen - bleeding
Ibrupofen/diuretic/ramipril - ARF
Sertraline - low Na+/GI bleeds
Diazepam - sedation
Antihypertensives amlodipine - falls
Antipsychotics - parkinsonism

Question 2

Drug reactions in older people

Answer 2

2-3 times more common in older people

patients over 65 are 13% of ppn but use 30-40% of meds

Question 3

Pharmacodynamics vs pharmacokinetics

Answer 3

effect of drug on body vs way the body affects drug with time - absorpiton distribution metabolism excretion

Question 4

Drug absorption in elderly

Answer 4

Reduced saliva, reduced gastric acid, decreased GI motility
reduced surface area for absorption
Reduced splanchnic blood flow
= reduced rate of absorption and increased time to steady state

Question 5

Drugs relevant with absorption in elderly

Answer 5

levodopa - competes with nutrients so need to plan dosing regimes to avoid meal times

bisphosphonates - take on empty stomach, sitting up, 30 mins before food

Question 6

Volume of distribution

Answer 6

volume obtained if all drug was in the blood

vd affects halflife and duration of effect

Question 7

Volume of distribution formula

Answer 7

amount of drug in body divided by concentration in plasma because v=n/c

Question 8

Drug distribution in elderly - muscle

Answer 8

Decrease lean body mass

decreased vol of distribution for drugs that distribute into muscles e.g. digoxin

so increased plasma conc

Question 9

Digoxin toxicity

Answer 9

Cardiac - heart block, bradycardia, junctional tachycardia

psych - delirium fatigue, malaise, confusion, dizziness

Visual - blurred or yellow-green vision, halos, double vision, photophobia

GI - nausea, vomiting, anorexia, diarrhoea, abdo pain

Effects can vary depending on pt’s comorbidities e.g. pt with renal insufficiency or hypokalemia can have more serious cardiotoxicity than

Question 10

Can normal levels of digoxin affect older patients?

Answer 10

Normal digoxin levels (1-2ng/ml) can have more serious cardiotoxicity than a pt with high digoxin levels and no renal or electrolyte disturbances.

Question 11

How to treat digoxin toxicity?

Answer 11

withdrawing drug/correcting electrolytes

If severe - use digibind, which is a preparation of digoxin specific antibody fragments

Question 12

Distribution in the elderly - fat

Answer 12

increased body fat so increased vol of distribution for fat soluble drugs so longer half-times

e. g. benzodiazepines, haloperidol
e. g. diazepam has twice as much vol of distribution in elderly and halflife is 24 hours in young patients to 90hrs in elderly

Question 13

Benzodiazepine overdose in elderly

Answer 13

drowsiness, confusion, ataxia, dependence

treat IV flumaxenil 200mcg. This is an antagonist w a shorter half-life than diazepam and so patient can become re-sedated

Question 14

Drug distribution in elderly in relation to body water

Answer 14

Decrease in body water so decreased vol of distribution of water sol drugs like gentamicin

so water soluble drugs have higher plasma conc
and loading doses are lower

Question 15

Protein binding of drugs in the elderly

Answer 15

12-25% decrease in albumin - more in heart failure, renal disease, RA, hepatic cirrhosis and some malignancies

So drug binding capacity decreased by 12-25%

So more free drugs

Examples: phenytoin, warfarin, propanalol, diazepam, levothyroxine, digoxin, furosemide

Question 16

phenytoin toxicity

Answer 16

nausea, vomiting
tremor
ataxia
nystagmus
coarse facies
hepatitis

Question 17

Warfarin-aspirin interaction

Answer 17

Warfarin is 99% bound to plasma albumin, has narrow therapeutic index and a small volume of distribution

aspirin can displace warfarin from albumin

displacing 1-2% of bound warfarin can double or triple concentrations of free warfarin and so massively increases bleeding

Question 18

metabolism

Answer 18

Phase 1 - activation, no change or inactivation (most)
through oxidation, reduciton and or hydrolysis.
Phase 2- synthesis or conjugation, almost all inactivated

Question 19

Liver metabolism in elderly

Answer 19

up to 30% reduction in liver volume
12-40% decreased blood flow to liver
so decreased first pass metabolism

decreased enzyme activity of CP450 in frail elderly, so decreased drug clearance and increased halflife

e.g. antidepressants, antipsychotics, beta blockers, opiates, benzodiazepines, calcium channel blockers, theophylline, warfarin, phenytoin, NSAIDs, paracetamol, erythromycin

Question 20

kidneys in the elderly

Answer 20

renal blood flow affected, 20% less renal mass, 30% decrease in renal function (nephrons)
GFR decline 1% every year from age 40

Question 21

Excretion in elderly

Answer 21

drugs which are more than 60% excreted by kidneys are affected by renal function reduction

increased halflife and increased serum levels

Drugs excreted mainly by kidneys include digoxin, atenolol, sotalol, lithium, allopurinol and many Abx

So dose needs to be reduced in daily preps, and dosage interval needs to be increased in more frequently administered drugs

Question 22

Lithium toxicity

Answer 22

12 hour post dose o.4-0.8 mmol/l

Early toxicity above 1mmol/l (~1.5) - tremor, agitation, twitching

intermediate - lethargy

late Li>2mmol/l - coma, fits, arrhythmia, renal failure - haemodialysis may be needed

Question 23

Morphine

Answer 23

undergoes phase 2 metabolism by conjugation to
Morphine-6-glucuronide which is 40x more potent and provides 80% of analgesic action

Renal impairment results in accumulation of metabolite, prolonged effect, and increased toxicity

S/C morphine is 2x potent po

Question 24

Morphine toxicity

Answer 24

Nausea, vomiting
Constipation
Drowsiness
Resp depression
Hypotension

Treat with IV naloxone 400mcg

Question 25

Ageing and pharmacodynamics

Answer 25

decline in homeostatic mechanisms due to receptor affinity or number, alterations in second messenger function or in cellular and nuclear responses

Question 26

Increased pharmacodynamic effects in ageing

Answer 26

alcohol causes increased drowsiness and lateral sway than in younger ppl

benzos - enhanced sedation

warfarin - more bleeding

hypotensives - postural hypotension

GI effects of NSAIDs

central effects of anticholinergics

Question 27

Decreased pharmacodynamic effects in ageing

Answer 27

Beta1 modulators in cardiac tissue downregulated by a third, so reduced and delayed bronchodilatory response to beta agonists

Decreased calcium channel blocking effect on PR interval

Question 28

Antihypertensive meds side effects

Answer 28

Ace-Is e.g. ramipril - hypotension, K+ sparing, renal failure, cough

Beta blockers e.g. atenolol - hypotension, confusion, bradycardia, lethargy, impotence

CCBs e.g. amlodipine -negatively inotropic, fluid retention

Diuretics loop/thiazide e.g. furosemide, bedfrolumethazide - hypotension, hypokalaemia, hyponatraemia, confusion, dehydration

Question 29

Traditional antipsychotics side effects

Answer 29

confusion
sedation
parkinsonism
tardive dyskinesia
neuroleptic malignant syndrome

Question 30

How to prescribe

Answer 30

Consider risk/benefit ratio
pharmacokinetic/dynamic facrtors
start low go slow
review the effect
communicate w patient, relative other healthcare professionals
use BNF

Question 31

what to do about compliance?

Answer 31

consider cognitive problems - carer to prompt pt with medications
simplify regimes as much as poss to once or twice daily
dossit boxes
consider manual dexterity and vision of pt
check inhaler techniques
syrups if dysphagia for large tablets

Question 32

Adverse drug reactions

Answer 32

prevalence increases w age in hospital, length of stay, number of meds

15.3% of admissions are due to adverse drug reactions

Question 33

Steroids adverse reactions

Answer 33

osteoporosis
gastric irritation/ulcers
hyperglycaemia

Question 34

TCA adverse effects

Answer 34

cardiac arrhythmias
drowsiness
dry mouth
constipation
urinary retention

Question 35

NSAIDs

Answer 35

renal failure
gastric irritation
fluid retention

Question 36

Alpha blockers

Answer 36

tamulosin, doxazosin

selective alpha blockers - urinary retention - relax smooth muscle in BPH