CHAPTER 21: ANTICOAGULANTS

Question 1

Blood Coagulation: formation of fibrin

Answer 1

• cascade of enzymatic rxns transform plasma factors to their active/enzymatic forms

factor Xa–> converts factor II (prothrombin) to factor IIa (thrombin)
thrombin then converts fibrinogen into fibrin

Question 2

intrinsic vs extrinsic pathways

Answer 2

intrinsic starts at XII and extrinsic starts at VII
- they converge at 10 and 10a (X)

Question 3

thrombin role

Answer 3

coagulation, responsible for generating fibrin (forms mesh-like matrix of blood clot)

Question 4

inhibition of coagulation

Answer 4

• coag restricted to local site of vascular injury
• protein C, S, antithrombin III, ad tissue factor pathway inhibitor all inhib coag factors (all endogenous)

Question 5

Anticoagulant Drugs
- names
- MOAs (2)

Answer 5

• heparin or warfarin
• LMWH: enoxaparin, dalteparin
• either inhibit action of coag factors, or interfere with synth of coag factors

Question 6

Heparin: intro

Answer 6

injectable, rapid-acting to interfere formation of thrombi

• macromolecule complexed w histamine in mast cells
• unfractioned heparin: mix of straight chain glycosaminoglycans
  (range of MWs)
• low MW forms also work as anticoags (enoxaparin, dalteparin)

Question 7

Heparin: MOA

Answer 7

• bind to antithrombin III–> rapid inactivation of coag factors

antithrombin III–> inhibit thrombin (factor IIa) and factor Xa

Question 8

Low MW Heparin MOA

Answer 8

form complex w antithrombin III and inactive factor Xa but DONT bind as well to thrombin

• pentasaccharide seq permits binding to antithromb III

Question 9

Heparin: therapeutic use

Answer 9

• acute venour thromboembolism (DVT or PE)
• prophylaxis postop venous thrombosis in PT doing surgery and w acute MI
• pregnant women (bc doesn’t cross placenta)

LMWHs don’t need as intense monitoring

Question 10

Heparin: Pharmacokinetics

Answer 10

Route adminisitration: SC, IV
SC only for LMWHs

• inactive metabolites, undergo renal excretion
• renal insufficiency prolongs half life of LMWH, dose should be reduced

Question 11

Heparin: Adverse Effects

Answer 11

• bleeding (protamine sulfate for excessive bleed, 1:1)
• allergic rxns (chills, fever, anaphylactic shock)
• heparin-induced thrombocytopenia (HIT)—> circ blood contains low # platelets, risk of venous and arterial embolism
• osteoporosis for long term use

Question 12

Warfarin: MOA

Answer 12

• factors II, VII, IX, and X need vit K as cofactor for synth by liver
• glutamic acid residues carbox to form gama carboxyglutamic residues which bind Ca ions

vit K regen by vit K epoxide reductase, its INHIBITED BY WARFARIN

Question 13

Warfarin: therapeutic use

Answer 13

• prevent/treat DVT and PE
• prevent stroke, Afib
• protein C and S deficiency
• antiphospholipid syndrome
• prevent venous thromboembo following ortho surgery

Question 14

Warfarin: pharmacokinetics

Answer 14

• rapid absorb, PO
• high plasma albumin binding–> can displace anticoag and lead to transient, elevated activity
• CROSSES PLACENTA
• drug-drug interactions

Question 15

Warfarin: adverse effects

Answer 15

common:
- bleeding –>oral vit K for minor bleed, IV vit K for severe

rare:
- skin lesions, necrosis
- purple toe syndrome (caused by cholesterol emboli from plaques)

TERATOGENIC

Question 16

Drugs for Treating Bleeding: Protamine sulfate

Answer 16

• antag anticoag effects of heparin
• protamine interacts w heparin forming stable complex

AE: hypersensitivity, dyspnea, bradycardia, hypotension

Question 17

Drugs for Treating Bleeding: Vitamin K

Answer 17

• inc supply of active vit K1, inhibit warfarin effect
  ROUTES: PO, SC, IV (slowly)
• slow response, needs 24 hrs to reduce INR (synth new coag factors)