Pharmacology

Question 1

Reversing warfarin in the context of emergency surgery: guidelines about timing & corresponding agent?

Answer 1

• If surgery can wait for 6-8 hours - give 5 mg vitamin K IV

- If surgery can’t wait - 25-50 units/kg four-factor prothrombin complex

Question 2

Warfarin: class of medication, MOA & Indications?

Answer 2

• Warfarin is an oral anticoagulant
• MOA: vitamin K antagonist that inhibits the vitamin K-dependent coagulation factors (II, VII, IX and X) (mnemonic = 1972) and protein C.

-Indications:
1-venous thromboembolism:
target INR = 2.5, if recurrent 3.5

2-atrial fibrillation, target INR = 2.5

3-mechanical heart valves, target INR depends on the valve type and location.

4-Mitral valves generally require a higher INR than aortic valves.

Question 3

Warfarin: how are patients monitored?

Factors that potentiate the effects of Warfarin?

SE?

Answer 3

Monitoring:

1-INR (international normalised ratio): Ratio of the prothrombin time for the patient over the normal prothrombin time.

Warfarin has a long half-life and achieving a stable INR may take several days. There a variety of loading regimes and computer software is now often used to alter the dose.

Factors that may potentiate warfarin:
liver disease
P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
cranberry juice
drugs which displace warfarin from plasma albumin, e.g. NSAIDs
inhibit platelet function: NSAIDs

Side-effects:
haemorrhage
teratogenic, although can be used in breastfeeding mothers
skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis
purple toes

Question 4

ACE-Inhibitors: Indications, MOA, SE?

Answer 4

Indications:
-first-line treatment in younger patients (non-black) with hypertension, heart failure, diabetic nephropathy & secondary prevention of IHD.

MOA:
inhibit the conversion angiotensin I to angiotensin II
ACE inhibitors are activated by phase 1 metabolism in the liver

Side-effects:
1-cough
occurs in around 15% of patients and may occur up to a year after starting treatment
thought to be due to increased bradykinin levels
2-angioedema: may occur up to a year after starting treatment
3-hyperkalaemia
4-first-dose hypotension: more common in patients taking diuretics

Question 5

ACE-i: CI, Interactions, Monitoring?

Answer 5

Cautions and contraindications:

1-pregnancy and breastfeeding - avoid
2-renovascular disease - may result in renal impairment
3-aortic stenosis - may result in hypotension
4-hereditary of idiopathic angioedema
5-specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L

Interactions:
patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day)= significantly increases the risk of hypotension

Monitoring:
urea and electrolytes should be checked before treatment is initiated and after increasing the dose
a rise in the creatinine and potassium may be expected after starting ACE inhibitors
acceptable changes are an increase in serum creatinine, up to 30% from baseline and an increase in potassium up to 5.5 mmol/l.
significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis