Drugs in health and disease 2 Flashcards
Drug absorption in the elderly
Reduced saliva
Reduced gastric acid
Decreased GI motility
Reduced surface area for absorption
Reduced splanchnic blood flow
Overall effect: decreased rate of absorption and increased time to steady state
Volume of distribution
Hypothetical volume obtained if all drug was in the blood
= amount of drug in body/ concentration in plasma
Affects half life and duration of effect
Muscle
Decreased lean body mass
Decreased volume of distribution for drugs that distribute into muscles e.g. digoxin
Leads to increase in plasma concentration
Digoxin cardiac toxicity
Heart block
Bradycardia
Junctional tachycardia
Digoxin psychiatric toxicity
Delirium
Fatigue
Malaise
Confusion
Dizziness
Digoxin visual toxicity
Blurred or yellow- green vision
Halos
Double vision
Photophobia
Digoxin GI toxicity
Nausea
Vomiting
Anorexia
Diarrhoea
Abdominal pain
Body fat
Increased body fat
Increased volume of distribution for fat soluble drugs e.g. benzodiazepines, haloperidol
= increased half life
e.g. diazepam- volume of distribution increased x2 in elderly
Benzodiazepines
Drowsiness
Confusion
Ataxia
Dependence
Treat IV flumazenil 200mcg
- antagonist
- shorter half life than diazepam and so patient may become re-sedated
Drug distribution in the elderly
Decrease body in water
Decreased volume of distribution of water soluble drugs e.g. gentamicin
= increased plasma concentration
Loading doses are lower
Serum albumin
Decreased 12-25%- further depressed by HF, renal disease, rheumatoid arthritis, hepatic cirrhosis
Drug binding capacity decreased 12-25%
Increased free drug
Phenytoin toxicity
Nausea, vomiting
Tremor
Ataxia
Nystagmus
Coarse facies
Hepatitis
Warfarin- aspirin interaction
Warfarin is highly bound to plasma albumin
Warfarin has narrow therapeutic index
Warfarin has small volume of distribution
Aspirin can displace warfarin from plasma albumin
Displacement of 1-2% of bound warfarin doubles or triples concentration of free warfarin
Increased bleeding
Antiplatelet agents
e.g. aspirin
Peptic ulcer disease
Bleeding tendency
Fluid retention
Renal failure
Anticoagulants
Bleeding tendency
Interaction with other drugs
Liver metabolism in the elderly
Decreased liver volume- up to 30% reduction
Decreased liver blood flow 12-40%
Decreased first pass metabolism due to decreased blood flow
Decreased enzyme activity CP450
Excretion in the elderly
Renal blood flow
Decreased renal mass
Decreased renal function
GFR declines by 1% per year from age 40
Drugs excreted primarily by the kidneys
Digoxin
Atenolol
Sotalol
Lithium
Allopurinol
Many antibiotics
Excretion- therapeutic implications
Reduce dose in once daily preps
Increase dosage interval in more frequently administered drugs
Lithium
12 hour post dose 0.4-0.8mmol/l
Early toxicity Li 1.5mmol/l- tremor, agitation, twitching
Intermediate- lethargy
Late Li >2mmol/- coma, fits, arrhythmia, renal failure- haemodialysis may be needed
Morphine
Undergoes phase II metabolism by conjugation
Morphine-6-glucuronide 40X more potent
Approx 80% analgesic action derives from morphine-6-glucuronide
Renal impairment results in accumulation of metabolite
Prolonged effect, increased toxicity
Morphine toxicity
Nausea, vomiting
Constipation
Drowsiness
Respiratory depression
Hypotension
Treatment naloxone IV 400mcg
Pharmacodynamics
Effects of ageing on biochemical and physiological effects of drugs and their mechanisms of action are not clearly known
Progressive decline in homeostatic mechanisms
Some drug effects increased
Alcohol causes increased drowsiness and lateral sway in older people than younger people at same serum levels
Benzodiazepines- enhanced sedation
Warfarin
Hypotensives- postural hypotension
NSAIDs- GI effects
Anticholinergics- central effects
