ANTICOAGULANTS

Question 1

antiCLOTTING drugs includes the following groups…

Answer 1

1. antiCOAGULANT drugs → effective in treatment of venous & arterial thrombosis
2. thrombolytics → effective in treatment of venous & arterial thrombosis
3. antiPLATELET drugs → used primarily for treatment of arterial disease

Question 2

ANTICOAGULANTS:

Answer 2

1. heparin
2. LMW fraction heparins
3. fondaparinux
4. vit. K antagonists
5. direct THROMBIN inhibitors
6. factor X inhibitors

Question 3

heparin → mechanism of action:

Answer 3

bind to antithrombin III (ATIII) → inactivates coagulation factors (esp. factor X = stuart factor) & thrombin

Question 4

heparin → pharmacokinetics:

Answer 4

1. IV administration → ass. with ACUTE states
2. SC administration → more long-term treatment
3. monitored with aPTT test
4. safe in PREGNANCY

Question 5

heparin → indications:

Answer 5

acute thromboembolic disorders:

1. peripheral and pulmonary embolism
2. venous thrombosis
3. coagulopathies (DIC)

prophylaxis:

1. arterial and heart surgery
2. blood transfusion
3. renal dialysis
4. prevent embolization in atrial fibrillation
5. prevent DVT & pulmonary embolism
6. heart attacks
7. alright to use during PREGNANCY (compared to warfarin which cross the placenta → may cause bleeding to the fetus)

Question 6

heparin → CONTRAindications:

Answer 6

1. hypersensitivity
2. bleeding disorders
3. alcoholism
4. recent surgery of brain, eye, spinal cord

Question 7

heparin → side effects:

Answer 7

1. most common = bleeding
2. two types of heparin-induced thrombocytopenias (HIT)
3. prolonged use → ass. with osteoporosis
4. hyperkalemia → suppression of aldosterone secretion
5. chills, fever
6. anaphylactic shock

Question 8

LMW heparins:

Answer 8

1. enoxaparin
2. dalteparin
3. tinzaparin
4. bemiparin
5. certoparin
6. nadroparin
7. parnaparin
8. reviparin

Question 9

LMW heparins → mechanism of action:

Answer 9

inactivates active factor X (Xa/stuart factor) → unlike heparin the LMW heparins cannot inactivate thrombin

Question 10

LMW heparins → pharmacokinetics:

Answer 10

• SC administration → 1-2/day

- monitoring in → obese, renal impairment & PREGNANCY

Question 11

LMW heparins → indications:

Answer 11

1. PREVENTION of thromboembolism ass. with abdominal surgery, knee or hip replacement
2. ischemic complications of unstable angina, acute coronary syndrome, angioplasty

Question 12

fondaparinux → mechanism of action:

Answer 12

1. even more selective factor Xa inhibitor
2. binds antithrombin → acc. inhibition of factor Xa
3. in contrast to heparin → fondaparinux does NOT inhibit thrombin

Question 13

fondaparinux → pharmacokinetics:

Answer 13

given SC once daily

Question 14

fondaparinux → indications:

Answer 14

1. treatment & prophylaxis of DVT

2. prevention of thromboembolism in hip fracture, hip or knee replacement surgery

Question 15

fondaparinux → side effects:

Answer 15

1. bleeding (no reversal treatment)

2. HIT less likely than with heparin

Question 16

VIT. K antagonists:

Answer 16

1. warfarin

2. coumarin derivatives

Question 17

VIT. K antagonists → mechanism of action:

Answer 17

1. inhibit synthesis of factor II, VII, IX & X in liver

2. inhibit synthesis of protein C & S → endogenous anticoagulants that inactivate V & VIII + promote fibrinolysis

Question 18

VIT. K antagonists → pharmacokinetics:

Answer 18

1. ORALLY
2. well absorbed from GIT → excreted in urine
3. max. effect after 3-5 days of treatment ≈ 1 week
4. INR test
5. CYP450 metabolism

Question 19

VIT. K antagonists → indications:

Answer 19

1. treatment & prevention of → DVT & PE
2. ischemic heart disease
3. rheumatic heart disease
4. pulmonary embolism
5. lifelong use in pat. with artificial heart valves (STROKE prevention)
6. protein C & S deficiency, antiphospholipid syndrome

Question 20

VIT. K antagonists → side effects:

Answer 20

1. hemorrhage
2. necrosis & skin lesions (rare)
3. purple toe syndrome (rare)
4. teratogenic → NOT safe in pregnancy!!

Question 21

direct THROMBIN inhibitors:

Answer 21

1. hirudin (not often used)
2. lepirudin
3. bivalirudin
4. argatroban
5. dabigatran (ORALLY)

Question 22

direct THROMBIN inhibitors → mechanism of action:

Answer 22

1. hirudin, lepirudin, bivalirudin → reversibly inhibit catalytic site of both free & clot-bound thrombin
2. argatroban → DIRECT thrombin inhibitor
3. dabigatran → potent, competitive, REVERSIBLE inhibitor of thrombin

Question 23

direct THROMBIN inhibitors → pharmacokinetics:

Answer 23

1. hirudin, lepirudin, bivalirudin → PARENTERAL / IV
2. argatroban:
   
   1. PARENTERAL/IV
   2. metabolized in the liver
   3. requires monitoring → aPTT etc.
3. dabigatran:
   
   1. ORALLY (= the FIRST orally active direct thrombin inhibitor!!)
   2. does NOT interact with food or most other drugs → therefore do NOT require monitoring

Question 24

direct THROMBIN inhibitors → indications:

Answer 24

1. hirudin, lepirudin, bivalirudin → alternative to heparin in pat. undergoing PCI who have/at risk for developing HIT (heparin-induced thrombocytopenia)
2. argatroban → prophylaxis or treatment of venous thromboembolism in pat. with HIT
3. dabigatran → reduce the risk of stroke & systemic embolism in pat. with non-valvular atrial fibrillation

Question 25

direct THROMBIN inhibitors → side effects:

Answer 25

1. hirudin, lepirudin, bivalirudin → bleeding
2. argatroban → bleeding
3. dabigatran:
   
   1. bleeding
   2. use with caution in renal impairment & pat. >75y
   3. dyspepsia, esophagitis, abdominal pain, GI bleeding

Question 26

factor X inhibitors:

Answer 26

1. rivaroxaban

2. apixaban

Question 27

factor X inhibitors → pharmacokinetics:

Answer 27

ORALLY

Question 28

factor X inhibitors → indications:

Answer 28

1. rivaroxaban → prevention of DVT, clots, PE after knee or hip surgery
2. apixaban:
   1. stroke prevention in atrial fibrillation
   2. prevention & treatment of DVT, prevention of CV events in MI

Question 29

factor X inhibitors → side effects:

Answer 29

1. bleeding

2. avoid abrupt discontinuation