Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Section VII λ Drugs Used in Blood Disorders

λClinical features:

–Overriding factor in effectiveness is early administration, e.g., >60% decrease in mortality post-MI if used within 3 hours

–ASA, beta blockers, and nitrates further ↓ mortality, and adenosine ↓ infarct size

–Complications include bleeding, possible intracerebral hemorrhage

–Streptokinase may cause hypersensitivity reactions and hypotension

–Antifibrinolysins (aminocaproic and tranexamic acids)—possible antidotes in excessive bleeding

Chapter Summary

λThrombolytics (also referred to as fibrinolytics) are of clinical value in the early treatment of fibrin-clot–induced ischemia (e.g., >60% decrease in post-MI mortality if used within 3 hours).

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Section VII λ Drugs Used in Blood Disorders

λClopidogrel, prasugrel, ticagrelor, and ticlopidine

–Block ADP receptors on platelets → ↓ activation

–Alternatives to ASA in TIAs, post-MI, and unstable angina

–Aspirin + ADP receptor blockers are used in patients with non-ST elevation ACS

–Hemorrhage, leukopenia, and thrombocytopenic purpura

λAbciximab, eptifibatide, and tirofiban

–Antagonists that bind to glycoprotein IIb/IIIa receptors → ↓ aggregation by preventing the cross-linking reaction

–Used mainly in acute coronary syndromes and postangioplasty

Chapter Summary

λPlatelets adhere to sites of vascular injury, where they are activated by various factors to express a glycoprotein to which fibrinogen binds, resulting in platelet aggregation and formation of a platelet plug. Antiplatelet drugs inhibit this process, thus reducing the chances of thrombi formation. The major drugs are aspirin, ticlopidine, clopidogrel, abciximab, eptifibatide, and tirofiban.

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Anticoagulants

λHeparin

λWarfarin

λArgatroban

λBivalirudin

λDabigatran

λRivaroxaban

Thrombolytics

λAlteplase (tPA)

λStreptokinase

Antiplatelet

λAspirin

λTiclopidine

λClopidogrel

λAbciximab

λPrasugrel

λTicagrelor

Review Questions

1.Which of the following compounds is most likely to block ADP receptors and prevent platelet aggregation?

A.Clopidogrel

B.Aspirin

C.Prostacyclin

D.Abciximab

E.Montelukast

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Section VII λ Drugs Used in Blood Disorders

2.A woman who has a mechanical heart valve and who is taking warfarin informs you that she hopes to get pregnant in the near future. What advice should she receive regarding her antithrombotic medication during the anticipated pregnancy?

A.Warfarin should be continued until the third trimester.

B.Warfarin should be replaced with aspirin at analgesic doses.

C.All medications that affect the blood should be discontinued.

D.Warfarin should be replaced with heparin.

E.Warfarin should be discontinued, and supplementary vitamin K taken throughout the pregnancy.

3.The primary advantage of enoxaparin over heparin is that it

A.is unlikely to cause bleeding

B.more effectively Inhibits the synthesis of clotting factors

C.has a more rapid onset

D.does not case thrombocytopenia

E.has a longer half-life

4.Which of the following statements regarding warfarin is true?

A.It is a prodrug converted to its active metabolite spontaneously in the blood.

B.It has low lipophilicity and does not cross the placental barrier.

C.It causes a depletion in protein C before it decreases prothrombin.

D.It inhibits release of vitamin K–dependent clotting factors from hepatocytes.

E.It is inactivated by protamine.

5.Which of the following statements is true regarding the parenteral administration of alteplase?

A.It increases the formation of plasminogen.

B.It is less effective than streptokinase when given after a myocardial infarction.

C.It causes a high incidence of thrombocytopenia.

D.It may cause bleeding reversible by aminocaproic acid.

E.It activates free plasminogen.

6.Following a myocardial infarction, a patient is stabilized on warfarin, the dose being adjusted to give a prothrombin time of 22 seconds. Which of the following statements regarding potential drug interactions in this patient is accurate?

A.Cholestyramine will increase prothrombin time.

B.Cimetidine is likely to decrease prothrombin time.

C.Antibacterial sulfonamides may enhance the effects of warfarin.

D.Vitamin K would restore prothrombin time to normal within 30 minutes.

E.If this patient takes half an aspirin tablet daily, the dose of warfarin will need to be increased.

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