Drugs in health and disease 2 Flashcards
What percentage of the population are over 65s?
13%
What percentage of prescriptions are for over 65s?
30-40%
How many times more common are drug reactions in the elderly?
2-3
What does an increased number of drugs cause?
Increased reactions
Increased adverse effects
Decreased adherence
Define pharmacodynamics
The effect the drug has on the body
Describe pharmacokinetics
The way the body affects the drug over time
List some concepts involved in pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Describe drug absorption in the elderly
Reduced saliva Reduced gastric acid Decreased GI motility Reduced surface area for absorption Reduced splanchnic blood flow
Overall effect:↓ rate of absorption & ↑ time to steady state
When should levodopa be taken and why?
Not at mealtimes
Competes with nutrients
Describe how bisphosphonates should be taken
On an empty stomach
Sitting up
30 mins before food
What is the volume of distribution?
Hypothetical volume obtained if all the drug was in the blood
What is the equation for the volume of distribution?
Vd = Amount of drug in body / Concentration in plasma
What does Vd affect?
Half life and duration of action
Describe how drug distribution is affected in the elderly
Decreased lean body mass (muscle), Decreased volume of distribution for drugs that distribute into muscles, Increased plasma concentration of drugs that distribute into muscles
Increased body fat, increased volume of distribution for fat soluble drugs, increased half life
Decreased body water, decreased volume of distribution of water soluble drugs, increased plasma concentration
Albumin decreased by 15-25% so drug binding capacity is reduced which increases the free drug
Describe the presentation of digoxin toxicity
Cardiac - heart block, bradycardia, junctional tachycardia
Psychiatric - delirium, fatigue, malaise, confusion and dizziness
Visual - blurred or yellow green vision, halos, double vision, photophobia
Gastrointestinal - anorexia, vomiting, nausea, diarrhea, abdominal pain
What are normal digoxin values?
1-2ng/ml
Which patient has the more serious cardiotoxicity?
a) Normal dioxin levels 6hrs post dose with renal insufficiency and severe hypokalemia
b) high digoxin levels and no renal or electrolyte disturbance?
A
How is digoxin toxicity treated?
Correction of electrolytes
Withdrawal of drug
If severe - use digoxin specific antibody fragments
List some fat soluble drugs
Benzodiazepines
Haloperidol
Give some symptoms of benzodiazepine toxicity
Confusion
Drowsiness
Ataxia
Dependence
How is benzodiazepine toxicity treated?
IV flumazenil 200mcg
Antagonist
Shorter half life than diazepam so the patient may become resedated
Name a water soluble drug
Gentamicin
Name some drugs which bind to albumin
Phenytoin Warfarin Propranolol Diazepam Levothyroxine Digoxin Furosemide
What conditions depress albumin?
Old age Heart failure renal disease RA hepatic cirrhosis Malignancy
List the sins of phenytoin toxicity
Nausea, vomiting Tremor Ataxia Nystagmus Coarse facies Hepatitis
What is warfarin highly bound to?
Plasma albumin
What properties does warfarin have?
Narrow therapeutic index
Small volume of distribution
Describe the interaction between aspirin and warfarin
Aspirin can displace warfarin from plasma albumin
Displacement of 1-2% bound warfarin doubles or triples the concentration of warfarin and so increases the risk of bleeding.
Give the adverse effects of antiplatelet drugs
Peptic ulcer disease
Increased bleeding risk
Fluid retention
Renal failure
Give the adverse effects of anticoagulants
Bleeding tendency
Interaction with other drugs
Describe liver metabolism in the elderly
Decreased liver size - (30%)
Decreased liver blood flow (12-40%) - decreased first pass metabolism
Decreased enzymatic activity of CP450 - decreased clearance of drugs and increased half life
Which drugs are metabolised by the liver?
Benzodiazepines, phenytoin, antidepressants, antipsychotics, beta blockers, calcium channel blockers, warfarin, theophylline, NSAIDS, erythromycin
Describe renal excretion in the elderly
Decreased renal size (20%), decreased renal blood flow, decreased renal function
What happens to eGFR with age?
Decreases by 1% each year from the age of 40
The excretion of which drugs is affected by renal function
Any drug which is greater than 60% excreted by the kidneys
Digoxin Atenolol Sotalol Lithium Allopurinol Antibiotics
How does impaired excretion affect the elderly?
Increased half life and serum plasma
What are the implications for problems in excretion of drugs in the elderly?
Reduce the dose in once daily preparations
Increase the dosage interval between more frequently administered drugs
What is the normal 12 hour post dose lithium level?
0.4-0.8 mmol/L
Give some signs of early lithium toxicity?
Tremor, twitching and agitation
Give some intermediate sin of lithium toxicity
Lethargy
Give some signs of late lithium toxicity
Coma, fits, arrhythmia, renal failure
What level of lithium does late lithium toxicity occur at?
> 2 mmol/L
What level does early lithium toxicity occur at?
> 1.5mmol/L
What is a treatment of late lithium toxicity?
Haemodialysis
How many times more potent is SC morphine than PO?
2 times
Describe the metabolism of morphine in elderly
Phase 2 conjugation reaction
Morphine 6 glucuronide 40X more potent
Approximately 80% analgesic action derived from morphine 6 glucuronide
Renal impairment results in accumulation of metabolite
Prolonged effect increases the toxicity
Give the signs of morphine toxicity
Nausea Vomiting Constipation Drowsiness Respiratory depression Hypotension
How do you treat morphine toxicity?
IV naloxone 400 micrograms
How does ageing affect pharmacodynamics do we think?
Decreased number and affinity of receptors
Alterations in 2nd messenger function
Alterations in cellular and nuclear responses
Which drug effects are increased in the elderly?
Alcohol - sedation and lateral sway Hypotensives - postural hypotension Anticholinergics - central effects increased Warfarin - increased bleeding Increased GI effects of NSAIDs Benzodiazepines - increased sedation
Which drug effects are decreased in the elderly?
B1 modulators in cardiac tissue
Reduced and delayed bronchodilatory response to beta agonists
Calcium channel blocker effect on PR interval decreased
How should elderly patients take their medications?
Upright position with plenty of fluid
Describe how frailty affects ability to take oral medications?
Unable to swallow
Tablets may cause ulceration in the mouth
List the side effects of ACE inhibitors
Dry cough
Hypotension
Renal failure
Potassium sparing
List the side effects of beta blockers
Hypotension Confusion Bradycardia Impotence Lethargy
List the side effects of calcium channel blockers
Hypotension
Negatively inotropic
Fluid retention
List the side effects of diuretics
Hypotension Hypokalaemia Hyponatraemia Confusion Dehydration
List the side effects of traditional antipsychotics
Confusion Sedation Parkinsonism Tardive dyskinesia Neuroleptic malignant syndrome
Name a traditional antipsychotic
Haloperidol
What can you do to increase compliance of the elderly
Consider cognitive problems – carer to prompt patient with medications
Simplify regimes as much as possible to once or twice daily
Dossit boxes
Consider manual dexterity and vision of the patient
Check inhaler techniques
Syrups if dysphagia for large tablets
What percentage of hospital admissions are due to adverse drug reactions
15.3%
