Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
103 Cards in this Set
- Front
- Back
|
Which enantiomer of warfarin is more active? |
S-warfarin |
|
|
What enzyme does warfarin block? |
Vitamin K epoxide reductase |
|
|
What process/reaction does warfarin block? |
The conversion of oxidized vitamin K epoxide to its reduced form, vitamin K hydroquinone |
|
|
What factors are vitamin K dependent? |
Factors II, VII, IX, and X |
|
|
What enzyme is reduced vitamin K a cofactor for? |
gamma-Glutamyl carboxylase |
|
|
What does gamma-glutamyl carboxylase? |
Catalyzes carboxylation and conversion of prozymogens to zymogens capable of binding Ca+2 |
|
|
Why is gamma-carboxylation important? |
Allows zymogens to bind Ca+2 which lets them interact with the anionic phospholipid surfaces |
|
|
What metabolizes S-warfarin? |
CYP2CP |
|
|
Prophylaxis/treatment of venous thrombosis and pulmonary embolism Prophylaxis/treatment of thromboembolic complications of atrial fibrillation and/or cardiac valve replacement Reduce risk of death, recurrent MI, and thromboembolic events after a MI |
Indications for warfarin |
|
|
Given orally for long-term therapy Initial dose 2-5 mg/day; can change to 1-10 mg/day |
Warfarin |
|
|
Requires monitoring and adjustments based on PT and INR |
Warfarin |
|
|
Almost complete absorption with peak concentrations in 2-8 hours Metabolized by liver; half-life of ~40 hrs |
Warfarin |
|
|
This drug is highly bound to proteins in the plasma, creating a large reserve |
Warfarin |
|
|
This drug has a substantial delay in onset and termination of action; Causes prolonged PT after 8-12 hrs but maximal effect can take 3-5 days |
Warfarin |
|
|
What is the cause of the delay in onset and maximal effect of warfarin? |
The coagulation factors it affects all have different half-lives so it can take several days for it to lower the concentrations of some factors |
|
|
Fatal or non-fatal bleeding from tissue or organs Necrosis of skin or other tissues Teratogenic |
Adverse effects of warfarin |
|
|
What causes necrosis of skin in patients given warfarin? |
Rapid loss of protein C results in early hypercoagulability and increased clot formation Especially a problem if they are protein C deficient |
|
|
What reverses the effects of warfarin? How quickly does it work? |
IV or oral vitamin K
|
|
|
What are specific contraidications to warfarin? |
Warfarin hypersensitivity Pregnancy Caution in patients with hepatic, renal impairment |
|
|
This is the drug of choice for rapid, short-term anticoagulant therapy? |
Unfractionated Heparin (UFH) |
|
|
Prophylaxis/treatment of venous thrombosis, pulmonary embolism, and peripheral arterial embolism Prevent post-op DVT and pulmonary embolism Atrial fibrillation with embolization Prevent clotting in arterial and cardiac surgery Anticoag in blood transfusions, extracorporeal circulation, dialysis, and in some blood samples for lab purposes |
Indications for unfractionated heparin |
|
|
What is the mechanism of unfractionated heparin? |
Enhances antithrombin-mediated inhibition of thrombin and factor Xa (also IXa and XIIa)
Does not inhibit fibrin-bound thrombin |
|
|
How is unfractionated heparin given? |
Parenterally for direct and immediate effects IV, deep SC, but not IM |
|
|
How long is the duration of unfractionated heparin? |
30-90 min This is variable and dose-dependent |
|
|
How is unfractionated heparin eliminated? |
Reticuloendothelial system |
|
|
How is unfractionated heparin monitored? |
aPTT time |
|
|
What is the most common adverse effects of unfractionated heparin? |
Bleeding and bruising |
|
|
What is HIT? |
Heparin-induced thrombocytopenia Results of antibody produced against heparin-Platelet Factor 4 complex |
|
|
What is HITT? |
Heparin-induced thrombocytopenia and thrombosis |
|
|
What is sometimes seen with prolonged use of unfractionated heparin? |
Osteoporosis |
|
|
What rapidly neutralizes heparin? |
Protamine sulfate forms a complex with heparin |
|
|
What is the mechanism of action of low molecular weight heparin? |
Enhances antithrombin-mediated inhibition of factor Xa and thrombin Has enhanced inhibition of factor Xa and reduced inhibition of thrombin |
|
|
Has similar indications to unfractionated heparin Also can be used in DIC when there are no signs of bleeding |
LMW Heparin |
|
|
How is LMW heparin administered? |
SubQ |
|
|
How is LMW heparin eliminated? |
Primarily renal |
|
|
What is the half-life of LMW heparin? |
~4 hrs |
|
|
Protamine is only partially effective in neutralizing this drug |
LMW Heparin |
|
|
What is the mechanism of action of synthetic pentasaccharides? |
Bind antithrombin and selectively inhibits factor Xa |
|
|
How are synthetic pentasaccharides administered? |
SubQ |
|
|
How long is the half-life of synthetic pentasaccharide? |
15 hrs; allows once daily dosing |
|
|
This heparinoid does not bind HIT antibody is most patients and is used in patients with HIT? |
Synthetic pentasaccharide |
|
|
Bleeding Thrombocytopenia Increased serum aminotransaminase levels |
Adverse effects of synthetic pentasaccharides |
|
|
What is used to neutralize/reverse effects of synthetic pentasaccharides? |
Trick question, there is no antidote |
|
|
What is the mechanism of direct factor Xa inhibitors? |
Directly bind and inhibit factor Xa |
|
|
What is the half-life of a direct factor Xa inhibitor? |
5-9 hrs; given orally once or twice daily |
|
|
What are contraindications for direct factor Xa inhibitors? |
Active pathological bleeding Hypersensitivity Hepatic impairment > or = to moderate |
|
|
GI bleeding Discontinuing use has increased risk of stroke/MI Risk of spinal/epidural hematoma in patients receiving neuraxial anesthesia or spinal puncture |
Adverse effects of direct factor Xa inhibitors |
|
|
How is the mechanism of direct thrombin inhibitors? |
Directly bind and inhibit thrombin |
|
|
What kind of drug is dabigatran? |
Direct thrombin inhibitor |
|
|
What are uses of dabigatran? |
Reduce stroke and embolism in non-valvular atrial fibrillation Used for DVT after knee/hip surgery or recurrent VTE |
|
|
How is dabigatran given? |
It is an oral prodrug |
|
|
What is the half-life of dabigatran? |
12-17 hrs |
|
|
How does dabigatran work? |
Binds and inhibits free and fibrin-bound thrombin May inhibit thrombin-induced platelet activation |
|
|
What does dabigatran interact with? |
Antibiotics |
|
|
How is dabigatran eliminated? |
Renal elimination |
|
|
Active pathological bleeding Hypersensitivity Mechanical prosthetic heart valve |
Contraindications to dabigatran |
|
|
Discontinuation increases risk of thrombotic events Gastritis and increased risk of GI bleed |
Adverse effects of dabigatran |
|
|
What reverses dabigatran? |
Idarucizumab |
|
|
What is idarucizumab? |
Fab fragment that target dabigatran to reverse its effects |
|
|
What kind of drug is argatroban? |
Direct thrombin inhibitor |
|
|
What is argatroban used for? |
Administered IV for HIT |
|
|
How is argatroban eliminated? |
Cleared by the liver (used in patients with renal dysfunction) |
|
|
What is the adverse effect of argatroban? |
Risk of increased bleeding |
|
|
How is argatroban reversed? |
No specific reversal agents |
|
|
How are direct factor Xa inhibitors reversed? |
No specific agents Partially reversed by clotting factor concentrates |
|
|
Irreversible inhibitor of cyclooxygenases; prefers COX1 over COX2 Effects seen for 10 days after stopping |
Aspirin |
|
|
What is the half-life of aspirin? |
20 min |
|
|
What are therapuetic uses of aspirin? |
Prevent MI, ischemic stroke, and other acute coronary syndromes Decrease cardiovascular events in high risk patients |
|
|
What is aspirin resistance? |
Insufficient inhibition of platelet function Mechanisms unclear |
|
|
History of GI ulcer Hypersensitivity Thrombocytopenia Bleeding disorder <16 yrs old Concurrent oral coagulant therapy |
Contraindications for aspirins |
|
|
Increased risk of GI ulcer Hemorrhage Hypersensitivity Skin rashes |
Adverse effects of aspirin |
|
|
What is mechanism of dypyridamole? |
Inhibits phosphodiesterase activity in platelets leading to increased cAMP Short-acting |
|
|
What are therapeutic uses of dypyridamole? |
Primarily with aspirin in secondary prevention of stroke |
|
|
What has similar contraindications and adverse effects to aspirin? |
Dypyridamole |
|
|
What is mechanism of clopidogrel? |
Irreversible antagonist of platelet ADP receptors (P2Y12) |
|
|
What are uses of clopidogrel? |
Similar to aspirin Used with aspirin and in patients who can't tolerate aspirin |
|
|
Bleeding Reduced effectiveness in those with low CYP2C19 Avoid use with proton pump inhibitors |
Contraindications to clopidogrel |
|
|
Increased risk of serious bleeding Rare incidence of thrombotic thrombocytopenic purpura Bone marrow suppression with ticlopidine |
Adverse effects of clopidogrel |
|
|
What is the mechanism of ticagrelor? |
Reversible inhibitor of platelet ADP receptors (P2Y12) Nucleoside analog that is an allosteric inhibitor |
|
|
What is ticagrelor used for? |
Similar to aspirin; used with aspirin |
|
|
History of intracranial hemorrhage Active bleeding Severe hepatic impairment |
Contraindications to ticagrelor |
|
|
Increased risk of bleeding Shortness of breath |
Adverse effects of ticagrelor |
|
|
What is mechanism of abciximab/tirofiban? |
Blocks platelet aggregation by antagonizing fibrinogen binding to GP2b/3a receptors, inhibiting final step in platelet aggregation |
|
|
What is abciximab/tirofiban used for? |
Acute coronary syndromes Prevent restenosis following percutaneous coronary interventions |
|
|
How is abciximab given? What kind of molecule is it? |
Given IV; it is an antibody |
|
|
Hypersensitivity Thrombocytopenia Bleeding disorder or increased risk of bleeding |
Contraindications to abciximab/tirofiban |
|
|
Bleeding Hypotension Hypersensitivity |
Adverse effects of abciximab/tirofiban |
|
|
What is the mechanism of vorapaxar? |
Reversible antagonist of PAR-1 (thrombin receptor) Long half-life makes it effectively irreversible |
|
|
How long is the half life of vorapaxar? |
5-13 days |
|
|
What is vorapaxar used for? |
Reduce thrombotic cardiovascular events in those with history of MI or with established peripheral arterial disease |
|
|
How is vorapaxar administered? |
Orally |
|
|
How is vorapaxar cleared? |
Metabolized by the liver; CYP3A4 |
|
|
What is the adverse effect of vorapaxar? |
Higher incidence of severe bleeding |
|
|
Contraindicated in those with history of stroke, intracranial hemorrhage, TIA, or active bleeding |
Vorapaxar |
|
|
What is the mechanism of plasminogen activators? |
Increase conversion of plasminogen to plasmin which degrades fibrin |
|
|
What are indications for plasminogen activators? |
Limit clot formation or remove existing clots Acute MI; acute ischemic stroke; acute pulmonary embolism |
|
|
When should plasminogen activators be given for stroke? For MI? |
Within 3 hours for stroke Within 4-6 hours for MI |
|
|
Recent history of intracranial bleeding Recent trauma or surgery Low platelet count |
Contraindications for plasminogen activators |
|
|
What are the adverse effects of plasminogen activators? |
Bleeding |
|
|
This plasminogen activator can bind fibrin which makes it the drug of choice for treating an MI |
Recombinant tissue plasminogen activator |
|
|
This plasminogen activator is fibrin specific |
Alteplase |
|
|
This plasminogen activator is a truncated form of tissue plasminogen activator Less specific for fibrin than t-PA |
Reteplase |
|
|
This plasminogen activator is a mutated form of tissue plasminogen activator Longer has half-life More fibrin specific than t-PA |
Tenecteplase |
