The protein analogs of ___ bind simultaneously to the active site of thrombin and to thrombin substrates. binds solely to the thrombin-active site. also inhibits platelet activation.

- lepirudin - Argatroban - Bivalirudin

BLOOD_GOUT 2 Flashcards by Aserah Blank

DIRECT THROMBIN INHIBITORS
• Parenteral:
• Oral:

Parenteral: Lepirudin, desirudin, bivalirudin, argatroban

* Oral: Dabigatran

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these drugs inhibit both soluble thrombin and the thrombin enmeshed within developing clots.

DIRECT THROMBIN INHIBITORS

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The protein analogs of ___ bind simultaneously to the active site of thrombin and to thrombin substrates.
binds solely to the thrombin-active site.
also inhibits platelet activation.

lepirudin
Argatroban
Bivalirudin

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Direct thrombin inhibitors are used as alternatives to ___ primarily in patients with heparin-induced thrombocytopenia.

heparin

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Prolonged infusion of lepirudin can induce antibodies that form a complex with lepirudin and prolong its action, and it can induce

anaphylactic reactions

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These small molecules directly bind to and inhibit both free factor Xa and factor Xa bound in the clotting complex.

DIRECT ORAL FACTOR Xa INHIBITORS

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is approved for prevention of venous thromboembolism following hip or knee surgery and for prevention of stroke in patients with atrial fibrillation.

Rivaroxaban

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and other coumarins interfere with the normal post-translational modification of clotting factors in the liver, a process that depends on an adequate supply of reduced vitamin K.

Warfarin

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The vitamin K-dependent factors include

thrombin and
factors VII,
IX, and
X

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The effect of warfarin is monitored by the

prothrombin time (PT) test

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Used for chronic anticoagulation in all of the clinical situations described previously for heparin, except in

pregnant women

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Because warfarin has a ___, its involvement in drug interactions is of major concern.

narrow therapeutic window

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↑ warfarin’s clearance and↓ the anticoagulant effect of a given dose.

Cytochrome P450-inducing drugs (eg,

carbamazepine,
phenytoin,
rifampin,
barbiturates)

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↓ warfarin’s clearance and ↑ the anticoagulant effect of a given dose.

Cytochrome P450 inhibitors 
(eg, 
- amiodarone, 
- selective serotonin reuptake inhibitors, 
- cimetidine)

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The thrombolytic drugs used most commonly are either

forms of the endogenous tissue plasminogen activator (t-PA; eg, alteplase) or
- a protein synthesized by streptococci (streptokinase).

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is an endogenous fibrinolytic enzyme that degrades clots by splitting fibrin into fragments.

Plasmin

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is an enzyme that directly converts plasminogen to plasmin.

Tissue plasminogen activator (t-PA)

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is normal human plasminogen activator.

Alteplase

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forms a complex with endogenous plasminogen; the plasminogen in this complex undergoes a conformational change that allows it to rapidly convert free plasminogen into plasmin.
Unlike the forms of t-PA, it does not show selectivity for fibrin-bound plasminogen.

streptokinase

The major application of the thrombolytic agents is as an alternative to percutaneous coronary angioplasty in the

emergency treatment of coronary artery thrombosis.

MUST BE POSITIVELY RULED OUT BEFORE SUCH USE OF thrombolytic agents.

CEREBRAL HEMORRHAGE

Very prompt use (ie, within 3 h of the first symptoms) of t-PA in patients with ___ is associated with a significantly better clinical outcome.

ischemic stroke

is the most serious manifestation of thrombolytic agents.

Cerebral hemorrhage

CLASSIFICATION AND PROTOTYPES OF ANTIPLATELET DRUGS

(NSAIDs):
Glycoprotein IIb/IIIa receptor inhibitors:
Antagonists of ADP receptors:
Inhibitors of phosphodiesterase 3:

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
Glycoprotein IIb/IIIa receptor inhibitors: abciximab, tirofiban, and eptifibatide
Antagonists of ADP receptors: clopidogrel
Inhibitors of phosphodiesterase 3: dipyridamole and cilostazol

- Inhibit THROMBOXANE synthesis by blocking the enzyme cyclooxygenase. - is a potent stimulator of platelet aggregation.

- Aspirin and other NSAIDs | - Thromboxane A2

is a monoclonal antibody that reversibly inhibits the binding of fibrin and other ligands to the platelet glycoprotein IIb/IIIa receptor, a cell surface protein involved in platelet cross-linking.

Abciximab

is converted in the liver to active metabolites that IRREVERSIBLY inhibit the platelet ADP receptor and thereby prevent ADP-mediated platelet aggregation.

Clopidogrel

They prolong the platelet-inhibiting action of intracellular cAMP by inhibiting phosphodiesterase enzymes that degrade cyclic nucleotides, including cAMP, an inhibitor of platelet aggregation, and cyclic guanosine monophosphate (cGMP), a vasodilator.

- Dipyridamole | - the newer cilostazol

acts through platelet adenosine A2 receptors to increase platelet cAMP and inhibit aggregation.

Adenosine

is used to prevent further infarcts in persons who have had 1 or more myocardial infarcts and may also reduce the incidence of first infarcts. The drug is used extensively to prevent transient ischemic attacks (TIAs), ischemic stroke, and other thrombotic events.

Aspirin

prevent restenosis after coronary angioplasty and are used in acute coronary syndromes (eg, unstable angina and non-Q-wave acute myocardial infarction).

glycoprotein IIb/IIIa inhibitors

is effective in preventing TIAs and ischemic strokes, especially in patients who cannot tolerate aspirin. • is routinely used to prevent thrombosis in patients who have received a coronary artery stent.

Clopidogrel

is approved as an adjunct to warfarin in the prevention of thrombosis in those with cardiac valve replacement and has been used in combination with aspirin for secondary prevention of ischemic stroke.

Dipyridamole

is used to treat intermittent claudication, a manifestation of peripheral arterial disease.

Cilostazol

TOXICITY OF antiplatelet drugs. • Clopidogrel: • dipyridamole and cilostazol: • Cilostazol is CONTRAINDICATED in patients

* Clopidogrel is less hematotoxic. * The most common adverse effects of dipyridamole and cilostazol are headaches and palpitations. * Cilostazol is CONTRAINDICATED in patients with congestive heart failure because of evidence of reduced survival.

can be treated by administration of platelets or oprelvekin, the recombinant form of the megakaryocyte growth factor interleukin-11.

Thrombocytopenia

The Vit K deficiency is readily treated with oral or parenteral

phytonadione (vitamin K1)

Large doses of vitamin K1/phytonadione are used to reverse the anticoagulant effect of excess ___.

warfarin

The most important agents used to treat HEMOPHILIA are

- fresh plasma and - purified human blood clotting factors, especially factor VIII (for hemophilia A) and factor IX (for hemophilia B), which are either purified from blood products or produced by recombinant DNA technology.

increases the plasma concentration of von Willebrand factor and factor VIII. It is used to prepare patients with mild hemophilia A or von Willebrand disease for elective surgery.

vasopressin V2 receptor agonist desmopressin acetate

are orally active agents that inhibit fibrinolysis by inhibiting plasminogen activation.

- Aminocaproic acid | - tranexamic acid

Adverse effect of ANTIPLASMIN AGENTS

- thrombosis, - hypotension, - myopathy, and - diarrhea.

A 58-year-old business executive is brought to the emergency department 2 h after the onset of severe chest pain during a vigorous tennis game. She has a history of poorly controlled mild hypertension and elevated blood cholesterol but does not smoke. ECG changes confirm the diagnosis of myocardial infarction. The decision is made to attempt to open her occluded artery. ``` Which of the following drugs accelerates the conversion of plasminogen to plasmin? (A) Aminocaproic acid (B) Heparin (C) Lepirudin (D) Alteplase (E) Warfarin ```

Alteplase

If a fibrinolytic drug is used for treatment of this woman’s acute myocardial infarction, which of the following adverse drug effects is most likely to occur? (A) Acute renal failure (B) Development of antiplatelet antibodies (C) Encephalitis secondary to liver dysfunction (D) Hemorrhagic stroke (E) Neutropenia

Hemorrhagic stroke

A 65-year-old man is brought to the emergency department 30 min after the onset of right-sided weakness and aphasia (difficulty speaking). Imaging studies ruled out cerebral hemorrhage as the cause of his acute symptoms of stroke. ``` Prompt administration of which of the following drugs is most likely to improve this patient’s clinical outcome? (A) Abciximab (B) Alteplase (C) Factor VIII (D) Streptokinase (E) Vitamin K ```

Alteplase

A 65-year-old man is brought to the emergency department 30 min after the onset of right-sided weakness and aphasia (difficulty speaking). Imaging studies ruled out cerebral hemorrhage as the cause of his acute symptoms of stroke. Over the next 2 d, the patient’s symptoms resolved completely. To prevent a recurrence of this disease, the patient is most likely to be treated indefinitely with?

Aspirin