Polypharmacy

Question 1

How does metformin work?

Answer 1

Reduces hepatic glucose production and increases peripheral glucose utilisation.

Question 2

Lactic acidosis is a potential but rare risk of metformin. Which patients are at increased risk?

Answer 2

Lactic acidosis is a rare complication which is usually predictable and caused by metformin accumulation when contraindications overlooked (e.g. renal or hepatic impairment, moderate-severe cardiac failure, major illness, surgery, IV radiographic contrast given in renal impairment).

Question 3

What is the maximum dose of metformin?

Answer 3

1g three times daily

Question 4

Metformin is contraindicated in patients with an eGFR of …?

Answer 4

= 30

Question 5

When is digoxin used in patients with heart failure

Answer 5

Digoxin is a second-line drug for patients with heart failure. It is usually used if atrial fibrillation is also present.

Question 6

What are toxicity effects of digoxin

Answer 6

Significant toxicity (nausea, vomiting, arrhythmias, AV block, confusion).

Question 7

Digoxin is available in two strength tablets - what are they?

Answer 7

62.5microg and 250microg

Question 8

How long does it take for a steady state of digoxin to be achieved after initiation or dose change?

Answer 8

When commencing treatment or changing dose it is necessary to wait for 4-5 half lives (5-7 days) for steady state to be reached. Blood should be taken at least 6 hours after the last dose to allow for redistribution.

Question 9

What electrolyte disturbance is common with ACE inhibitors?

Answer 9

Hyperkalemia

Question 10

What are potential side effects of sulphonylureas?

Answer 10

Weight gain, hypoglycaemia

Question 11

What sulphonyureas are preferred in elderly and those with renal impairment?

Answer 11

In the elderly and those with renal impairment short acting (glipizide) and intermediate (gliclazide) sulphonylureas are preferable. Long acting drugs are more likely to cause hypoglycaemia, especially in patients with renal impairment (eg the elderly) because of accumulation of active metabolites.

Question 12

What percentage of patients taking ACE inhibitors develop cough?

Answer 12

~10%

Question 13

Renal failure can occur in patients commenced on ACE inhibitors who have ischaemic kidneys. Give some examples of such scenarios.

Answer 13

• Renal artery stenosis
• Hypovolaemia
• Left ventricular failure

Question 14

What are potential teratogenic effects of ACE inhibitors?

Answer 14

• Intrauterine growth retardation
• Foetal limb contracture
• Craniofacial deformity
• Patent ductus arteriosus
• Hypoplastic lungs
• Renal tubular dysgenesis
• Renal failure
• Oligohydramnios
• Death

Question 15

What is the annual cost of ACE inhibitor therapy?

Answer 15

$400/yr

Question 16

Why is captopril rarely used in the long-term management of hypertension?

Answer 16

Short half-life and the need for multiple daily dosing

Question 17

When may the use of captopril be useful for the management of hypertension?

Answer 17

It may be used to commence patients on an ACE-I if the patient is particularly susceptible to the adverse effects of an ACE-I e.g. underlying renal impairment, on high dose diuretic, aortic stenosis. In these circumstances, they are no less likely to develop these adverse reactions with captopril, but should they occur, it is not going to last as long as with an ACE-I with a longer half life.

Question 18

Is enalapril better for heart failure or hypertension?

Answer 18

Enalapril has extensive evidence particularly in heart failure, but is not favoured in hypertension as it really should be given twice daily. It is renally cleared.

Question 19

What is the main disadvantage of perindopril?

Answer 19

The main disadvantage of perindopril is that it comes in 2 different formulations with 2 different sets of doses, which are bioequivalent. To make matters worse you can get the arginine formulation as brand name Coversyl in doses of 2.5, 5 and 10 mg, but if you want to combine it with a thiazide diuretic, (Coversyl Plus) it is only available as the erbumine salt (perindopril 4 mg/indapamide 1.25 mg).

Question 20

Why is ramipril preferred by some clinicians for treatment of hypertension?

Answer 20

Ramipril is preferred by some clinicians as it has a long half life, and has been proven in a number of different clinical trials. Unfortunately, currently there is a patient premium associated with its use because of its higher price.

Question 21

What is the duration of action of loop diuretics?

Answer 21

Short duration of action (4 to 6 hours). Hence, they should usually be taken twice a day to maintain naturesis.

Question 22

What are potential adverse effects of loop diuretics?

Answer 22

• Dehydration
• Hypokalaemia
• Hyponatraemia
• Hyperuricaemia

Question 23

What are potential adverse effects of NSAIDs?

Answer 23

• Peptic ulcer / GI bleeds
• Renal failure
• Fluid retention
• Cardiovascular complications

Question 24

How are calcium channel blockers categorised?

Answer 24

Ca channel-blockers are best divided into the more centrally acting verapamil & diltiazem, and the more peripherally acting dihydropyridines (nifedipine, felodipine, lercarnidipine and amlodipine).

Question 25

In which conditions may calcium channel blockers be useful?

Answer 25

1. Angina
2. Atrial fibrillation (ventricular rate control)
3. Supraventricular tachycardia (verapamil, diltiazem)
4. Raynaud’s syndrome

Question 26

What are potential side effects of calcium channel blockers?

Answer 26

1. Negative inotropic effect (best avoided in heart failure)
2. Oedema
3. Flushing
4. Headache
5. Palpitations (especially with dihydropyridines)
6. Gynaecomastia

Uncommonly:

• Rash
• Gingival hyperplasia
• Cholestatic hepatitis
• Malaise

Dihydropyridine Ca channel blockers can cause secondary tachycardia, especially shorter acting preparations.