9. Safe drug use in the elderly Flashcards
Common drug problem
Warfarin/ibuprofen - bleeding Ibrupofen/diuretic/ramipril - ARF Sertraline - low Na+/GI bleeds Diazepam - sedation Antihypertensives amlodipine - falls Antipsychotics - parkinsonism
Drug reactions in older people
2-3 times more common in older people
patients over 65 are 13% of ppn but use 30-40% of meds
Pharmacodynamics vs pharmacokinetics
effect of drug on body vs way the body affects drug with time - absorpiton distribution metabolism excretion
Drug absorption in elderly
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
Drugs relevant with absorption in elderly
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
Volume of distribution
volume obtained if all drug was in the blood
vd affects halflife and duration of effect
Volume of distribution formula
amount of drug in body divided by concentration in plasma because v=n/c
Drug distribution in elderly - muscle
Decrease lean body mass
decreased vol of distribution for drugs that distribute into muscles e.g. digoxin
so increased plasma conc
Digoxin toxicity
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
Can normal levels of digoxin affect older patients?
Normal digoxin levels (1-2ng/ml) can have more serious cardiotoxicity than a pt with high digoxin levels and no renal or electrolyte disturbances.
How to treat digoxin toxicity?
withdrawing drug/correcting electrolytes
If severe - use digibind, which is a preparation of digoxin specific antibody fragments
Distribution in the elderly - fat
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
Benzodiazepine overdose in elderly
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
Drug distribution in elderly in relation to body water
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
Protein binding of drugs in the elderly
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
phenytoin toxicity
nausea, vomiting tremor ataxia nystagmus coarse facies hepatitis
Warfarin-aspirin interaction
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
metabolism
Phase 1 - activation, no change or inactivation (most)
through oxidation, reduciton and or hydrolysis.
Phase 2- synthesis or conjugation, almost all inactivated
Liver metabolism in elderly
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
kidneys in the elderly
renal blood flow affected, 20% less renal mass, 30% decrease in renal function (nephrons)
GFR decline 1% every year from age 40
Excretion in elderly
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
Lithium toxicity
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
Morphine
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
Morphine toxicity
Nausea, vomiting Constipation Drowsiness Resp depression Hypotension
Treat with IV naloxone 400mcg
