Drugs in Health and Disease 2 (Prescribing in elderly) Flashcards
85 yr old frail female admitted after a fall
DH: Warfarin, Perindopril, Diazepam, Ibuprofen, Furosemide, Sertraline, Amlodipine, Prochorperazine, Betahistine
What problem meds can you identify which may have contributed to the fall or cause problems because of the fall?
Warfarin/ibuprofen
- increase bleeding risk from fall
Ibuprofen/furosemide/perindopril
- Acute renal failure
Sertraline
- Low sodium, GI bleeding
Diazepam
- Sedation
Amlodipine
- antihypertensives increase risk of falls
Prochlorperazine
- Parkinsonism
What are pharmacodynamics and pharmacokinetics?
Pharmacodynamics- the effect a drug has on the body
Pharmacokinetics- the effect the body has on a drug. Factors: absorption, distribution, metabolism, excretion
How is drug absorption different in the elderly?
- Reduced saliva
- Reduced gastric acid
- Decreased GI motility
- Reduced surface area for absorption
- Reduced splanchnic blood flow
The overall effect is such that there is reduced absorption and it takes longer for a drug to reach a steady state
How does absorption changes affect levodopa and bisphosphonates?
- Levodopa competes with nutrients. Regimes should avoid meal times
- Bisphosphonates should be taken on an empty stomach, 30minutes before food
What is volume of distribution?
- Hypothetical volume obtained if all the drug entered blood
Vd= amount of drug in blood/ concentration in plasma
- if affects half life and duration of effect
How does muscle mass in elderly affect volume of distribution?
- Reduced muscle mass (lean) decreases Vd for drugs that distribute into muscles e.g. digoxin
- Results in higher plasma concentrations
What are the side effects of digoxin toxicity?
Cardiac
- heart block, bradycardia, junctional tachycardia
Psychiatric
- delirium, fatigue, malaise, confusion, dizziness
Visual
- blurred or yellow-green vision, halos, double vision, photophobia
GI
- nausea, vomiting, anorexia, diarrhoea, abdo pain
How does cardiotoxicity in digoxin toxicity vary?
- Patient with normal digoxin levels but renal insufficiency or severe hypokalaemia can have cardiotoxicity more serious than a patient with high levels and no renal/electrolyte disturbance
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How do you treat digoxin toxicity?
- Withdraw drug
- Correct electrolytes
- If severe: digoxin specific antibody fragment (Digibind)
How does fat mass in elderly affect volume of distribution?
- Increased body fat causes increase Vd for fat soluble drugs e.g. benzodiazepines, haloperidol
- This increases half life
- e.g. diazepam Vd doubles . This increases its t1/2 from 24 hours (in young patients) to 90 minutes in elderly
A 90 year old patient presents with drowsiness, confusion, ataxia. She has developed a dependence for Diazepam. How would you treat her?
- IV Flumazenil 200mcg
- Antagonises the effects of benzos
- It has a shorter half life than diazepam and so patient may become re-sedated
How does body water in elderly affect volume of distribution?
- Body water decreases
- Decreased Vd of water soluble drugs e.g. gentamicin
- This increases the plasma concentration of these drugs
How does albumin concentration in elderly affect volume of distribution?
Which drugs are affected?
- Albumin reduction up to 25%: further depressed by HF, renal disease, Rh arthritis, hepatic cirrhosis, malignancy
- Reduces drug binding capacity
- Increase free drug
Phenytoin, warfarin, propanolol, diazepam, levothyroxine, digoxin, furosemide
Symptoms of phenytoin toxicity
Why does it occur
Hypoalbuminaemia –> increase free drug in blood
- Nausea, vomiting
- Tremor, Ataxia
- Nystagmus
- Coarse facies
- Hepatitis
Describe the warfarin-aspirin interaction
- Warfarin is a highly bound to plasma albumin
- It has a narrow therapeutic window and a small Vd
- Aspirin can displace warfarin from plasma albumin
- Displacement of 1-2% of bound warfarin can x2/3 the concentration of free warfarin
- This increases the bleeding risk
What are the side effects of antiplatelets like aspirin?
How does this compare to anticoagulants such as warfarin/DOAC?
- PUD
- Bleeding tendency
- Fluid retention
- Renal failure
They also have bleeding tendency and they interact with other drugs
How is liver metabolism in the elderly different?
Give an example of a drug affected by this change
- The volume of the organ is less
- less hepatic blood flow
- FPHM decreases as a result of decreased blood flow
- Decreased enzyme activity (CP450) which decreased clearance of drugs –> increased t1/2
Antidepressants. antipsychotics, B-blockers, opiates, benzodiazepines, warfarin, phenytoin, NSAIDs, paracetamol, erythromycin
How does renal function change in elderly?
- Renal mass and renal blood flow decrease
- 30% nephron loss so function decreases
- GFR declines 1% per year after 40
How is renal excretion in the elderly different?
Give an example of a drug affected by this change
What are the therapetic indications?
- Reduction in renal function increases t1/2 of drugs and their serum levels
Drugs excreted primarily by kidneys
- digoxin, atenolol, sotalol, lithium, allopurinol, many antibiotics
Reduce dose in OD preparations, increase dosage interval in more frequently administered drugs
At which plasma level does lithium toxicity begin?
What are the signs of lithium toxicity?
Li >1.5mmol/l - tremor, agitation, twitching - lethargy >2mmol/l - coma, fits, arrhythmia, renal failure (haemodialysis may be needed)
A patient has been started on s/c morphine for pain management. She has been vomiting and feels drowsy
O/E: 110/50
Investigations: Low eGFR
What is this?
Why has this happened?
What other symptoms of this syndrome might you see?
How would you treat her
Morphine undergoes phase 2 metabolism by conjugation. The metabolite (morphine-6-glucoronide) is 40x more potent. It is the metabolite which is responsible for the analgesic effects.
Her renal impairment has caused an accumulation of the active metabolite –> morphine toxicity
- further exacerbated by the fact it was given sc (2x more potent that PO)
IV Naloxone 400mcg
State the effects of the following drugs which are increased in elderly
(1) Alcohol
(2) Benzodiazepines
(3) Warfarin
(4) Hypotensives
(5) NSAIDs
(6) Anticholinergerics
- Drowsiness, lateral sway
- enhanced sedation
- Anticoagulatory effects increased
- Effects increase, postural hypotension
- GI effects
- Central effects: delirium, confusion
State three effects that are decreased in the elderly
- The effect of B1 modulators in cardiac tissue
- Reduced and delayed bronchodilatory response to B-agonists
- Calcium channel blocking effect on PR interval
An elderly patient has difficulties swallowing her tablets
What advice can you give her?
What is she at risk at?
- Take medications with lots of fluid
- Sit in upright position
- Consider a liquid preparation for patient
If left in mouth, ulceration may occur
