Heme Drugs Flashcards
What is the mechanism of heparin?
Activator of antithrombin; Decr thrombin and factor Xa. Short half-life.
What is the clinical use of heparin? Is it safe during pregnancy? PTT or PT?
Immediate anticoagulation for pulmonary embolism (PE), acute coronary syndrome, MI, deep venous thrombosis (DVT). Safe in pregnancy. PTT.
What is HIT?
Heparin-induced thrombocytopenia (HIT)—development of IgG antibodies against heparinbound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets thrombosis and
thrombocytopenia.
What do LMWH such as apixaban and rivaroxaban more on?
More direct action against factor Xa.
What are the advantages to LMWH?
Better bioavail, 2-4times longer half=life, can be administered subQ, does not require lab monitoring.
What’s the big drawback to LMWH?
Not easily reversible.
How do you rapidly reverse heparin? How does it work?
For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).
What occurs w/ heparin toxicity?
Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions.
What are argatroban, dabigatran, and bivalarudin?
Bivalirudin is related to hirudin, the anticoagulant used by leeches; inhibit thrombin directly. Alternatives to heparin for anticoagulating patients with HIT.
What is the mechanism of action of warfarin?
Interferes with γ-carboxylation of vitamin K–
dependent clotting factors II, VII, IX, and X,
and proteins C and S by epoxide reductase.
What is its metabolism affected by?
Metabolism affected
by polymorphisms in the gene for vitamin
K epoxide reductase complex (VKORC1).
Which pathway and coagulation time is affected?
Extrinsic pathway, PT. (INR).
What are the clinical uses for warfarin? Is it safe in pregnancy?
Chronic anticoagulation (e.g., venous
thromboembolism prophylaxis, and prevention
of stroke in atrial fibrillation). Not safe in pregnancy, crosses the placenta (small molecule).
What are the first factors to drop when warfarin is started? What is done to offset this?
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.
What are the toxicities of warfarin?
Bleeding, teratogenic, skin/tissue necrosis
A , drug-drug interactions. Skin/tissue necrosis believed to be due to small
vessel microthromboses.
How to reverse warfarin?
For reversal of warfarin, give vitamin K.
For rapid reversal, give fresh frozen plasma.
How do alteplase, reteplase, streptokinase and tenecteplase work?
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.
What are the clinical uses for alteplase, reteplase, streptokinase and tenecteplase?
Early MI, early ischemic stroke, direct thrombolysis of severe PE.
What is the toxicity of alteplase, reteplase, streptokinase and tenecteplase?
Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent
surgery, known bleeding diatheses, or severe hypertension.
What treats toxicity of alteplase etc?
Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.
What is the mechanism of action of aspirin?
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.
What do the COX enzymes in platelets make and what does it do?
TXA2, which is a pro-aggregation factor for platelets.
What lab values will change with aspirin?
Incr bleeding time, Decr TXA2
and prostaglandins. No effect on PT or PTT.
What are the clinical uses for aspirin?
Antipyretic, analgesic, anti-inflammatory, antiplatelet ( aggregation).
What toxicities are associated with aspirin?
Gastric ulceration, tinnitus (CN VIII).
What can chronic use of aspirin lead to?
Chronic use can lead to acute renal failure, interstitial
nephritis, and upper GI bleeding. Reye syndrome in children with viral infection.
What metabolic changes does aspirin overdose cause?
Overdose initially causes hyperventilation and respiratory alkalosis, but transitions to mixed metabolic acidosis–respiratory alkalosis.
What is the mechanism of clopidogrel, prasugrel, ticagrelor, and ticlopidine?
Inhibit platelet aggregation by irreversibly blocking ADP receptors. Prevent expression of
glycoproteins IIb/IIIa on platelet surface. *Ticagrelor is reversible.
What are the clinical uses of clopidogrel, prasugrel, ticagrelor, and ticlopidine?
Acute coronary syndrome; coronary stenting. Decr incidence or recurrence of thrombotic stroke.
What is the toxicity associated with ticlopidine?
Neutropenia. TTP may be seen.
What is the mechanism of action of cilostazol and dipyridamole?
Phosphodiesterase III inhibitor; Incr cAMP in platelets, resulting in inhibition of platelet aggregation;
vasodilators.
What are the clinical uses of cilostazol and dipyridamole?
Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with
aspirin), angina prophylaxis.
What are the toxicities associated with cilostazol and dipyridamole?
Nausea, headache, facial flushing, hypotension, abdominal pain.
What is the mechanism of action of Abciximab, eptifibatide, tirofiban?
Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Abciximab
is made from monoclonal antibody Fab fragments.
What is the clinical use of Abciximab, eptifibatide, tirofiban?
Unstable angina, percutaneous transluminal coronary angiography.
What are the toxcities associated with Abciximab, eptifibatide, tirofiban?
bleeding, thrombocytopenia.
