How does chloral hydrate effect warfarin?
- displaces it from albumin
- enhances effect of Warfarin
Which drugs decrease metabolism of Warfarin by inhibiting p450 enzymes?
How do abx effect Warfarin?
- decrease gut bacteria
- decrease in vitamin K availability in GI tract
- enhance effect of Warfarin
How do anabolic steroids (like testosterone) effect Warfarin?
- inhibit synthesis
- increase coagulation degradation factors
What coagulation factors are affected by Warfarin and what is their half-life?
- VII: 4-6 hrs
- IX: 24 hrs
- X: 48 hrs
- II: 60 hrs
Main CYP450 enzyme used to metabolize Warfarin.
How does cholestyramine effect Warfarin?
inhibits GI absorption (reduces effect)
Which drugs increase metabolism of Warfarin by inducing P450 enzymes (esp 2C9)?
- (all reduce effects of Warfarin)
How does vitamin K effect Warfarin?
- bypasses its inhibition of epoxide reductase;
- reduces effect
Warfarin will inhibit _____ before inhibiting ______.
- protein C
- Factors II, VII, IX, X
Major AEs of Warfarin.
- Purple Toe (sm cholesterol deposit breaks off & travels to feet)
- Osteoporosis (b/c of decreased vitamin K intake & inhibition of vitamin K-mediated bone function)
- Skin Necrosis (Microvascular thrombosis via inhibition of Proteins C & S)
Goal of INR with Warfarin.
2-3 or 2.5-3.5
What are Enoxaparin, dalteparin, & tinzaparin? How are they eliminated?
What does heparin bind to?
- *ATIII by itself will not inactivate coagulation factors*
Coagulation factors effected by heparin.
- IIa (Thrombin)
- *LMWH more selective for Xa than IIa 3:1)
What is a type 1 HIT reaction?
- (heparin-induced thrombocytopenia)
- Ab-coated platelets are targeted for removal from circulation
- 50-75% reduction in platelet counts after 5 days
Which HIT reaction is transient and rapidly reversible?
What is a type 2 HIT reaction?
- platelets are targeted for destruction, AND
- the ab cause plt activation and aggregation
Which HIT rxn causes FATAL thrombosis? How?
- type 2
- ab cause platelet activation and aggregation
What is the antidote for heparin? What is it ineffective against?
- fondaparinux, a selective factor Xa inhibitor
What is a sign of HIT reaction?
decreased platelet count (20,000 - 30,000) in just a few days
Rivaroxaban (Xarelto) & apixaban (Eliquis)—oral
Selective Factor Xa Inhibitors
Lepirudin, hirudin, desirudin, bivalirudin, argatroban, dabigatran.
Direct Thrombin Inhibitors.
Many _______ are for HIT to prevent further reduction of platelet count while preventing thrombosis
direct thrombin inhibitors
Oral direct thrombin inhibitor.
Which direct thrombin inhibitor is a prodrug?
Advantage and disadvantage of Dabigatran (Pradaxa) over Warfarin.
- advantage: no frequent monitoring
- disadvantage: no direct reversal agent
How does tPA work?
- Converts plasminogen to plasmin;
- Plasmin degrades fibrin, which is required for formation of stable clot.
Three tPA fibrinolytics.
- Alteplase (recombinant)
- Tenecteplase (genetically engineered)
- Reteplase (genetically engineered)
Two thrombolytics (not tPAs)
Cause lysis of EXISTING clots.
How do Thrombolytics/Fibrinolytics prevent distal tissue necrosis?
- Restore patency of an obstructed tissue
- cause lysis of existing clots
Clinical indications for thrombolytics.
- Acute MI
- Acute ischemic stroke
- Massive PE
- Central IV line occlusion
What to administer with acute ischemic stroke?
Alteplase w/in 3 hours
Most potent statin.
Atorvastatin, simvastatin, & lovastatin are metabolized by _____.
How do HMG CoA Reductase Inhibitors work?
- Reduce body’s natural production of LDL, which
- causes upregulation of LDL receptors, which
- increases uptake of plasma LDL into hepatocytes
- (takes it out of systemic circulation)
Pharm classes of lipid-lowering agents.
- HMG CoA reductase inhibitors (statins)
- Bile acid sequestrants
- Cholesterol absorption inhibitors
- Omega-3 fatty acids
Which HMG CoA Reductase Inhibitors are not metabolized by 3A4?
What is Ezetimibe?
A cholesterol absorption inhibitor that is usually combined with a statin
How are Cholesterol Absorption Inhibitors metabolized? Why is this significant?
- less drug interactions
Fibrates bind to ______.
- peroxisome proliferator-activated receptors (PPAR)
- PPARs play a role in metabolism of macronutrients
How do fibrates work?
increase plasma HDL & decrease triglyceride synthesis
How do fibrates effect Warfarin?
displace warfarin from albumin binding sites --- increases free warfarin concentrations
Fibrates increase _____ clearance
Niacin releases _____ and _____ within the skin
AE of Niacin.
- Impaired insulin sensitivity
- Myopathy (rare)