Heme Drugs

Question 1

What is the mechanism of heparin?

Answer 1

Activator of antithrombin;  Decr thrombin and  factor Xa. Short half-life.

Question 2

What is the clinical use of heparin? Is it safe during pregnancy? PTT or PT?

Answer 2

Immediate anticoagulation for pulmonary embolism (PE), acute coronary syndrome, MI, deep venous thrombosis (DVT). Safe in pregnancy. PTT.

Question 3

What is HIT?

Answer 3

Heparin-induced thrombocytopenia (HIT)—development of IgG antibodies against heparinbound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets Ž thrombosis and
thrombocytopenia.

Question 4

What do LMWH such as apixaban and rivaroxaban more on?

Answer 4

More direct action against factor Xa.

Question 5

What are the advantages to LMWH?

Answer 5

Better bioavail, 2-4times longer half=life, can be administered subQ, does not require lab monitoring.

Question 6

What’s the big drawback to LMWH?

Answer 6

Not easily reversible.

Question 7

How do you rapidly reverse heparin? How does it work?

Answer 7

For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).

Question 8

What occurs w/ heparin toxicity?

Answer 8

Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions.

Question 9

What are argatroban, dabigatran, and bivalarudin?

Answer 9

Bivalirudin is related to hirudin, the anticoagulant used by leeches; inhibit thrombin directly. Alternatives to heparin for anticoagulating patients with HIT.

Question 10

What is the mechanism of action of warfarin?

Answer 10

Interferes with γ-carboxylation of vitamin K–
dependent clotting factors II, VII, IX, and X,
and proteins C and S by epoxide reductase.

Question 11

What is its metabolism affected by?

Answer 11

Metabolism affected
by polymorphisms in the gene for vitamin
K epoxide reductase complex (VKORC1).

Question 12

Which pathway and coagulation time is affected?

Answer 12

Extrinsic pathway, PT. (INR).

Question 13

What are the clinical uses for warfarin? Is it safe in pregnancy?

Answer 13

Chronic anticoagulation (e.g., venous
thromboembolism prophylaxis, and prevention
of stroke in atrial fibrillation). Not safe in pregnancy, crosses the placenta (small molecule).

Question 14

What are the first factors to drop when warfarin is started? What is done to offset this?

Answer 14

Proteins C and S
have shorter half-lives than clotting factors
II, VI, IX, and X, resulting in early transient
hypercoagulability with warfarin use. Bridge w/ heparin.

Question 15

What are the toxicities of warfarin?

Answer 15

Bleeding, teratogenic, skin/tissue necrosis
A , drug-drug interactions. Skin/tissue necrosis believed to be due to small
vessel microthromboses.

Question 16

How to reverse warfarin?

Answer 16

For reversal of warfarin, give vitamin K.

For rapid reversal, give fresh frozen plasma.

Question 17

How do alteplase, reteplase, streptokinase and tenecteplase work?

Answer 17

Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots.  Incr in PT and PTT, no change in platelet count.

Question 18

What are the clinical uses for alteplase, reteplase, streptokinase and tenecteplase?

Answer 18

Early MI, early ischemic stroke, direct thrombolysis of severe PE.

Question 19

What is the toxicity of alteplase, reteplase, streptokinase and tenecteplase?

Answer 19

Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent
surgery, known bleeding diatheses, or severe hypertension.

Question 20

What treats toxicity of alteplase etc?

Answer 20

Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.

Question 21

What is the mechanism of action of aspirin?

Answer 21

Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation.
Platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced.

Question 22

What do the COX enzymes in platelets make and what does it do?

Answer 22

TXA2, which is a pro-aggregation factor for platelets.

Question 23

What lab values will change with aspirin?

Answer 23

Incr bleeding time,  Decr TXA2

and prostaglandins. No effect on PT or PTT.

Question 24

What are the clinical uses for aspirin?

Answer 24

Antipyretic, analgesic, anti-inflammatory, antiplatelet ( aggregation).

Question 25

What toxicities are associated with aspirin?

Answer 25

Gastric ulceration, tinnitus (CN VIII).

Question 26

What can chronic use of aspirin lead to?

Answer 26

Chronic use can lead to acute renal failure, interstitial

nephritis, and upper GI bleeding. Reye syndrome in children with viral infection.

Question 27

What metabolic changes does aspirin overdose cause?

Answer 27

Overdose initially causes hyperventilation and respiratory alkalosis, but transitions to mixed metabolic acidosis–respiratory alkalosis.

Question 28

What is the mechanism of clopidogrel, prasugrel, ticagrelor, and ticlopidine?

Answer 28

Inhibit platelet aggregation by irreversibly blocking ADP receptors. Prevent expression of
glycoproteins IIb/IIIa on platelet surface. *Ticagrelor is reversible.

Question 29

What are the clinical uses of clopidogrel, prasugrel, ticagrelor, and ticlopidine?

Answer 29

Acute coronary syndrome; coronary stenting.  Decr incidence or recurrence of thrombotic stroke.

Question 30

What is the toxicity associated with ticlopidine?

Answer 30

Neutropenia. TTP may be seen.

Question 31

What is the mechanism of action of cilostazol and dipyridamole?

Answer 31

Phosphodiesterase III inhibitor;  Incr cAMP in platelets, resulting in inhibition of platelet aggregation;
vasodilators.

Question 32

What are the clinical uses of cilostazol and dipyridamole?

Answer 32

Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with
aspirin), angina prophylaxis.

Question 33

What are the toxicities associated with cilostazol and dipyridamole?

Answer 33

Nausea, headache, facial flushing, hypotension, abdominal pain.

Question 34

What is the mechanism of action of Abciximab, eptifibatide, tirofiban?

Answer 34

Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Abciximab
is made from monoclonal antibody Fab fragments.

Question 35

What is the clinical use of Abciximab, eptifibatide, tirofiban?

Answer 35

Unstable angina, percutaneous transluminal coronary angiography.

Question 36

What are the toxcities associated with Abciximab, eptifibatide, tirofiban?

Answer 36

bleeding, thrombocytopenia.