Anticoagulants (Lentz)

Question 1

what injectable drug was the first comercially available anticoagulant (1940s)? what was the first oral anticoagulant?

Answer 1

heparin; warfarin

Question 2

this drug works by interacting with thrombin and antithrombin via a template mechanism, which ultimately enhances the inhibition of clotting factors

Answer 2

heparin

Question 3

Which of the following statements is FALSE?

A. Unfractionated heparin (UFH) works by binding both thrombin and antithrombin (AT) and bringing them into contact, ultimately leading to the inactivation of thrombin and other clotting factors.

B. LMWH is better at binding thrombin than UFH

C. LMWH binding to AT is a strong mechanism for inhibition of factor XA

D. Heparin is isolated from pig intestines

E. Heparin indirectly inactivates Factor XA by its association with AT

Answer 3

B. LMWH is not a large enough molecule to bind both thrombin and antithrombin, so it is weaker in regards to this mechanism.

Question 4

Which of the following characteristics of unfractionated heparin (UFH) is FALSE?

A. It must be given parenterally, either by IV or SC administration.

B. It has a rapid onset of action and a short half life 1-2 hours).

C. It can be used safely during pregnancy.

D. It enhances the ability of AT, a serine protease inhibitor, to inhibit thrombin, factor Xa, and other clotting factors.

E. It is cleared by the kidneys and is contraindicated in patients with impaired renal function.

Answer 4

E. This is a characteristic of low molecular weight heparin.

Question 5

What drug is used to reverse the effects of heparin quickly?

Answer 5

protamine

Question 6

Which of the following characteristics of low molecular weight heparin (LMWH) is FALSE?

A. It is usually given by subcutaneous (SC) administration

B. It enhances the ability of AT to to inhibit factor Xa

C. It can be used safely during pregnancy.

D. It has unpredictable bioavailability and requires frequent monitoring of the activated PTT.

E. It has a relatively short half life of 6-12 hours and can be partially reversed by protamine.

Answer 6

D. This is true of UFH. LMWH has more predictable biovailability and does not require continuous monitoring. It is monitored via a heparin level assay, not APTT.

Question 7

Name 3 adverse effects associated with use of heparin.

Answer 7

1. bleeding
2. osteoporosis
3. heparin induced thrombocytopenia

Question 8

condition that results from IgG antibodies that bind to platelet factor 4 (PF4) when it is bound to heparin, most often UFH, leading to thrombocytpenia and thrombosis

Answer 8

heparin-induced thrombocytopenia (HIT)

Question 9

treatment of HIT includes stopping treatment with heparin, as well as using a synthetic LMWH analogue like _____ or a direct thrombin inhibitor like ______.

Answer 9

fondaparinux; argatroban or lepirudin

Question 10

drug that inhibits the glutamate carboxylation of vitamin-K dependent clotting factors, resulting in impaired synthesis of active procoagulant factors

Answer 10

warfarin

Question 11

Which of the following characteristics of warfarin is FALSE?

A. Its action is reversed with vitamin K.

B. Warfarin therapy is monitored using the APTT.

C. It is metabolized by both the liver and kidneys.

D. It has a slow onset of action (days) and recovery requires synthesis of new clotting factors.

E. It is administered orally but requires monitoring because of its many drug and dietary pharmacogenetic interactions.

Answer 11

B. Warfarin therapy is monitored using the INR (international normalized ratio) and the PT (prothrombin time).

Question 12

What is the enzyme target of warfarin?

Answer 12

vitamin K epoxide reductase

Question 13

this drug, approved for treatment of HIT:

• is a direct thrombin inhibitor
• is administered by IV infusion
• has a short half life and rapid onset
• is metabolized in the liver
• is monitored using APTT

Answer 13

argatroban

Question 14

these two drugs, approved for treatment of HIT and derived from from the medicinal leach:

• are a direct thrombin inhibitor
• are administered by IV infusion
• have a short half life and rapid onset
• are metabolized by the kidneys
• are monitored using APTT

Answer 14

lepirudin and bivalirudin

Question 15

What are 3 advantages of new oral anticoagulants (e.g., dabigatran, rivaroxaban, apixaban) over warfarin? What is currently their 1 major drawback?

Answer 15

1. wider therapeutic window - monitoring not needed
2. faster onset
3. shorter half life than warfarin, but not too short (can be given once or twice a day)
   drawback: no antidote

Question 16

clopidogrel, ticlopidine, prasugrel and ticagrelor all belong to what class of anti-platelet drugs?

Answer 16

P2Y12 receptor antagonists

Question 17

abciximab, tirofibran, and eptifibitide all belong to what class of anti-platelet drugs that inhibit fibrinogen binding?

Answer 17

glycoprotein IIb/IIIa antagonists

Question 18

this drug is often combine with aspirin (aggrenox)

Answer 18

dypiridamole

Question 19

____ works by irreverisbly inhibiting the COX enzymes, decreasing platelet synthesis and inhibiting their function for the life of the platelet

Answer 19

aspirin

Question 20

_____ work by activating plasmin to degrade clots, producing D-dimers and fibrogen degradation products

Answer 20

fibrinolytics (e.g., streptokinase, urokinase, tPA)

Question 21

fibrinolytic that works by binding and allosterically activating plasminogen to produce plasmin; adverse effects include allergic reactions and hypotension

Answer 21

streptokinase

Question 22

drug isolated from urine or kidney cells that directly cleaves both plasminogen and fibrinogen and is non-antigenic

Answer 22

urokinase

Question 23

advantages of this drug include localized speficifity (only cleaves plasminogen), as well as a short half life and non-antigenic properties; given in conjunction with heparin

Answer 23

tissue plasminogen activator (tPA)

Question 24

What is the standard treatment of venous thromboembolism?

Answer 24

Intial: LMWH (Sub Q) or UFH (IV), monitoring with APTT

long-term: warfarin, monitoring with INR

Question 25

a new but promising treatment for unprovoked VTE includes all oral therapy with a drug such as _____, which studies have shown reduces risk of recurrence in the first year after embolism as well as reduces risk of major bleeding.

Answer 25

apixaban; most effective at low dose from 6 months on after VTE.