Katzung 12th ed - Chapter 34 - Anticoagulants (1)

Question 1

In basic terms, describe the pharmacodynamics of Low Molecular Weight Heparin

Answer 1

LMWH binds to Antithrombin III, and enhances its inactivation of factor Xa.

Question 2

In basic terms, describe the pharmacodynamics of Unfractionated Heparin.

Answer 2

Unfractionated Heparin binds to Antithrombin III, and enhances its activity 1000-fold. This activity is to inactivate factor Xa, factor IXa, and thrombin.

Question 3

In basic terms, what is HIT?

Answer 3

Heparin Induced Thrombocytopaenia is a hypercoagulable state that can occur in patients treated with unfractionated heparin.

Question 4

How common is HIT? Which patients are at higher risk of developing HIT and which are at lower risk?

Answer 4

HIT occurs in 1-4% of patients receiving UFH for a minimum of 7 days. It is more common in surgical patients, and less common in paediatric and pregnant patients.

Question 5

Name a specific antidote to heparin, used in cases of excessive dosing. By which route is it given, and what is the dose?

Answer 5

Protamine sulphate. Give 1mg IV for every 100 units of heparin remaining in the patient.

Question 6

What is the basic pharmocodynamics of rivaroxaban?

Answer 6

Rivaroxaban inhibits factor Xa.

Question 7

What is the half-life of rivaroxaban?

Answer 7

10 hours.

Question 8

Apart from rivaroxaban, name another drug that inhibits factor Xa?

Answer 8

Apixaban (Eliquis).

Question 9

What is the basic pharmacodynamics of dabigatran?

Answer 9

Dabigatran is a direct thrombin inhibitor.

Question 10

Dabigatran: bioavailability?

Answer 10

3-7%

Question 11

Dabigatran: half-life?

Answer 11

12-17 hours

Question 12

Dabigatran: what if the patient has renal impairment?

Answer 12

Dose adjustment required: halve the dose.

Question 13

Dabigatran puts patients at greater risk of ________ than warfarin does.

Answer 13

GI bleeding.

Question 14

Warfarin: describe the basic pharmacodynamics.

Answer 14

Warfarin prevents the activation of vitamin K, which means that there is impaired synthesis of factors II (prothrombin), VII, IX, X (the vitamin-K-dependent clotting factors).

Question 15

Warfarin: Bioavailability?

Answer 15

100%

Question 16

Warfarin: how much is protein-bound?

Answer 16

99%

Question 17

Warfarin: half-life?

Answer 17

36 hours

Question 18

How is the INR calculated?

Answer 18

This is the patient’s prothrombin time divided by the international mean prothrombin time (which is designated as 1).

Question 19

Which drugs reduce the effect of warfarin by increasing its metabolism?

Answer 19

Barbiturates, Rifampicin. These drugs induce hepatic enzymes.
Cholestyramine binds warfarin in the intestine.

Question 20

Which drugs (and conditions) reduce the effect of warfarin by interacting with or enhancing the synthesis of clotting factors?

Answer 20

Vitamin K, loop diuretics, hypothyroidism (decreased turnover of clotting factors), hereditary resistance to clotting factors.

Question 21

Which drugs (and conditions) increase the effect of warfarin by interacting with or inhibiting the synthesis of clotting factors?

Answer 21

3rd gen cephalosporins (kill bacteria that produce vitamin K), Heparin, Hyperthyroidism (increased turnover of clotting factors), Aspirin in high doses (increased turnover of clotting factors)

Question 22

Which drugs increase the effect of warfarin by affecting warfarin’s pharmacokinetics? (e.g. by decreasing warfarin’s metabolism?)

Answer 22

Amiodarone, Cimetidine, Disulfuram, Metronidazole, Fluconazole, Phenylbutazone, Sulfinpyrazone, Bactrim.