Drugs in health and disease 2

Question 1

Drug absorption in the elderly

Answer 1

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

Question 2

Volume of distribution

Answer 2

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

Question 3

Muscle

Answer 3

Decreased lean body mass

Decreased volume of distribution for drugs that distribute into muscles e.g. digoxin

Leads to increase in plasma concentration

Question 4

Digoxin cardiac toxicity

Answer 4

Heart block

Bradycardia

Junctional tachycardia

Question 5

Digoxin psychiatric toxicity

Answer 5

Delirium

Fatigue

Malaise

Confusion

Dizziness

Question 6

Digoxin visual toxicity

Answer 6

Blurred or yellow- green vision

Halos

Double vision

Photophobia

Question 7

Digoxin GI toxicity

Answer 7

Nausea

Vomiting

Anorexia

Diarrhoea

Abdominal pain

Question 8

Body fat

Answer 8

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

Question 9

Benzodiazepines

Answer 9

Drowsiness

Confusion

Ataxia

Dependence

Treat IV flumazenil 200mcg

• antagonist
• shorter half life than diazepam and so patient may become re-sedated

Question 10

Drug distribution in the elderly

Answer 10

Decrease body in water

Decreased volume of distribution of water soluble drugs e.g. gentamicin

= increased plasma concentration

Loading doses are lower

Question 11

Serum albumin

Answer 11

Decreased 12-25%- further depressed by HF, renal disease, rheumatoid arthritis, hepatic cirrhosis

Drug binding capacity decreased 12-25%

Increased free drug

Question 12

Phenytoin toxicity

Answer 12

Nausea, vomiting

Tremor

Ataxia

Nystagmus

Coarse facies

Hepatitis

Question 13

Warfarin- aspirin interaction

Answer 13

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

Question 14

Antiplatelet agents

Answer 14

e.g. aspirin

Peptic ulcer disease

Bleeding tendency

Fluid retention

Renal failure

Question 15

Anticoagulants

Answer 15

Bleeding tendency

Interaction with other drugs

Question 16

Liver metabolism in the elderly

Answer 16

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

Question 17

Excretion in the elderly

Answer 17

Renal blood flow

Decreased renal mass

Decreased renal function

GFR declines by 1% per year from age 40

Question 18

Drugs excreted primarily by the kidneys

Answer 18

Digoxin

Atenolol

Sotalol

Lithium

Allopurinol

Many antibiotics

Question 19

Excretion- therapeutic implications

Answer 19

Reduce dose in once daily preps

Increase dosage interval in more frequently administered drugs

Question 20

Lithium

Answer 20

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

Question 21

Morphine

Answer 21

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

Question 22

Morphine toxicity

Answer 22

Nausea, vomiting

Constipation

Drowsiness

Respiratory depression

Hypotension

Treatment naloxone IV 400mcg

Question 23

Pharmacodynamics

Answer 23

Effects of ageing on biochemical and physiological effects of drugs and their mechanisms of action are not clearly known

Progressive decline in homeostatic mechanisms

Question 24

Some drug effects increased

Answer 24

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

Question 25

Some drug effects decreased

Answer 25

B1 modulators in cardiac tissue- down regulated by 1/3

Reduced and delayed bronchodilatory response to B-agonsits

Calcium channel blocking effect on PR interval decreased

Question 26

Frail patients and tablets

Answer 26

Difficulty swallowing tablets

If left in mouth ulceration may develop

Encourage with enough fluid, upright position, consider liquid preparation

Question 27

ACE inhibitor side effects

Answer 27

Hypotension

Potassium sparing

Renal failure

Cough

Question 28

Beta blocker side effects

Answer 28

Hypotension

Confusion

Bradycardia

Lethargy

Impotence

Better with cardio selective B blockers e.g. bisoprolol

Question 29

Calcium channel blockers side effects

Answer 29

Hypotension

Negatively inotropic

Fluid retention

Question 30

Diuretic side effects

Answer 30

Hypotension

Hypokalaemia

Hyponatraemia

Confusion

Dehydration

Question 31

Side effects of haloperidol

Answer 31

Typical antipsychotic

Confusion

Sedation

Parkinsonism

Tardive dyskinesia

Neuroleptic malignant syndrome

Question 32

Steroid side effects

Answer 32

Osteoporosis

Gastric irritation/ ulcers

Hyperglycaemia

Question 33

Tricyclic antidepressants side effects

Answer 33

Cardiac arrhythmias

Drowsiness

Dry mouth

Constipation

Urinary retention

Question 34

NSAIDs side effects

Answer 34

Renal failure

Gastric irritation

Fluid retention

Question 35

Alpha blocker side effects

Answer 35

e.g. tamsulosin, doxazosin

Drowsiness

Hypotension

Syncope