Day 4 Cardiology Flashcards
(24 cards)
What is unfractured heparin’s MOA?
What factors does unfractured heparin inhibit?
Pharmacokinetics of unfractured heparin?
Only 1/3 molecules have ability to bind to AT3. Potentiates action of AT3(1000 fold) and inactivates thrombin(as well as factors 9-12 and plasmin). Does NOT break down existing clots. Prevents conversion of fibrinogen to fibrin.
Xa and IIa.
IV or subq. Immediate onset for IV(20-30 mins for subq). Can be used in pregnancy but may increase maternal hemmorhage in 3rd trimester.
How do you monitor UFH?
A/E’s of UFH?
Benefits and limitations of UFH?
aPTT, should be 1.5-2 times normal, check every 6 hours until normal and then daily. Can also check ACT(for high doses and cardiac surgeries) and Anti Xa.
Bleeding, Osteoporosis, thrombocytopenia, Overdose.
Benefit: cheap, effective, easily reversible and can be used in pregnancy and kids. Limitations: high monitoring, variable anticoagulant response, continuous IV drip, risk of HIT, BID-TID dosing for Px.
HIT diagnosis? Scoring?
What are the low molecular weight heparins?
What are the LMWH’s moa?
Thrombocytopenia, Timing, Thrombosis, Othercauses. 0-3 low probability of HIT, 4-5 intermediate, 6+ high probability.
Enoxaparin, Dalteparin, Tinazaparin.
potentiates action of AT3, Inhibits factor Xa mainly and some 2a(thrombin), Does not break down existing clots.
Do all LMWH molecules have the unique pentasacchride unit? How many have the 18 sacchride unit?
Pharmacokinetics of LMWH?
Monitoring of LMWH?
YES. 25-50%.
IV or Subq,(onset immediate IV, 1-5 hours subq). Duration is 12-24 hours, metabolized in liver and excreted through urine.
None, treatment doses are weight based. Can use Anti-Xa when needed.
A/E’s of LMWH?
Benefits and limitations of LMWH?
Factor Xa inhibitors?
Bleeding, HIT.(less incidence than UFH)
Long half life, no monitoring, less chance of major bleed, HIT, osteoporosis, increased subq bioavailability, drug of choice in pregnancy, Limitations: Long half life(if need surgery this is bad, not completely reversible, cost, renally excreted.
Fondaparinux, Rivaroxaban, Apixaban, Edoxaban
Factor Xa MOA?
Fondaparinux indications, dosing, warnings?
Fondaparinux Availability, mechanism, excretion?
inhibits factor Xa only, does not break down existing clots! Fondaparinux binds directly to AT3.
DVT in hip or knee surgery patients,VTE treatment, off label ACS treatment. 2.5 mg subq daily, weight based >100 kg is 10 mg, 50-100 is 7.5 mg, <50 is 5 mg. CI’d in CrCl<30 mL/min.
Sub q 100% bio available. Half life 17-21 hours, hepatic,. Excreted through urine.
What drug was featured in the EINSTEIN trial? Rivaroxaban’s indications? Rivaroxaban dosing? Rivaroxaban warnings?
A/M/E of Rivaroxaban(xarelto)?
Which drug was featured in the ARISTOTLE trial? Indications and dosing for this drug?
Rivaroxaban, Stroke patients in NVAF, DVT in knee or hip patients, VTE treatment. 20 mg in evening with meal or 10 mg daily with or without food or 15 mg po BID for 3 weeks then 20 mg po daily. Hemmorhage in pregnancy use, Avoid in hepatic impairment, Renal dosing, significant drug interaction with CYP3A4 drugs.
A- 80-100% bioavailable,M- 5-9 hour HL with hepatic metabolism, E- Urine and feces.
Apixaban. Indications- same as Rivaroxaban. Dosing- 2.5-5 mg po BID or 10 mg PO BID for 7 days then 5 MG BID for 6 months.
Edoxaban’s trial? Indications, Dosing, Warnings for Edoxaban?
CrCl cut offs for Xa inhibitors?
Xa inhibitors monitoring?
Engage trial. Indications-Stroke Px in NVAF, VTE treatment. Dosing- 60 mg PO Qday or must start 5-10 days of parenteral treatment then >60 kg: 60 mg PO qday, <60 kg: 30 m g PO qday. Warnings- Do not use in NVAF patients with better CrCl than 95/min, Renal Dosing required.
Fondaparinux= CrCl<30. Rivaroxaban= VTE patients CrCl<30, NVAF patients CrCl<15. Apixaban= Reduce dosing for SCr>1.5, Edoxaban= CrCl<15.
No lab monitoring necessary, Can use Anti Xa in obesity, pregnancy, poor renal function.
A/E’s of Xa inhibitors?
Benefits and Limitations of Xa inhibitors?
Are the direct thrombin inhibitors all IV? Do they all have reversal agents?
Bleeding- less incidence of similar to LMWH and/or warfarin, HIT(1 case for fondaparinux), Rivaroxaban increases LFT’s, muscle cramps and spasms.
Benefits- Long half life, Almost no incidence of HIT, Less/similar incidence of bleeding and no lab monitoring. Limitations- Not fully reversible, Cost, Most are CI’d in renal dysfunction.
Yes except Dabigatran. None do except dabigatran.
What are the direct thrombin inhibitors?
Direct thrombin inhibitors MOA?
What is dabigatrans renal dosing?
Bivalrudin, Argatroban, Dabigatran, Lepirudin(discontinued May 2012).
Binds directly to thrombin, no AT3 action. CAN get to clot bound thrombin, does NOT break down exisiting clots.
15-30 CrCl is 75 mg po BID, CrCl<15 is no recommendation.
Dabigatrans indications? Dabigatran dosing?
Dabigatrans warnings?
A/M/E of dabigatran? Drug interactions?
Normal 3(stroke in NVAF, DVT for knee and hip, VTE). 150 mg PO BID, 110 mg PO BID for 1 dose then 220 mg PO qday, Must start 5-10 days of parenteral then 150 mg PO BID.
Highest rate of GI upset, increased incidence of MI, no reversal agent and CI’d in patients with mechanical heart valves.
75% when capsule opened, 3-7% oral normally. M- Prodrug, half life is 12-17 hours. E- Urine. P-gp drugs(Rifampin, Amiodarone, Verapamil. Ketoconazole).
Monitoring for DTI’s?
A/Es of DTI’s?
Which DTI has hepatic clearance? Shortest and longest half life? Irreversable binding?
No lab monitoring, ACT used for bivalrudin, aPTT used for lapirudin, argatroban, INR- dabigatran, lapirudin, argatroban will increase this but not used for monitoring.
Bleeding, MI(dabigatran).
Argatroban. Bivalrudin(25 minutes), Dabigatran(12-17 hours). Lepuridin.
Warfarin MOA?
Which clotting factor is eliminated early in warfarin treatment? Warfarin onset?
Warfarin availability? Warfarin Distribution? Metabolism and excretion?
Vitamin K antagonist, so inhibits clotting factors 2,7,9,10, also lowers Protein C and S, does not break down existing clots.
Protein C(paradoxial coagulation, may see skin necrosis early in treatment, hypercoaguable state). Anti coagulant state seen in 2-5 days, full effect may take 8-16 days.
Oral(also Iv, Subq, rectal). Highly protein bound and can cross the placenta. Metabolized hepatically 2-5 days, s isomer more potent and is CYP 2C9. Excreted through Urine.
Warfarin monitoring?
What to do if patients has single INR dose out of range?
How to dose warfarin?
Prothrombin Time, INR–> 2-3 is normal, higher is increased anticoagulation and bleed risk, frequency of monitoring is daily upon initiation then q2-3 days then weekly until stable, monthly until therapeutic INR’s are achieved then q12 weeks.
continue current dose and retest in 1-2 weeks.
Directly proportional to weight and indirectly proportion to age(men>women). Most patients start with 5 mg daily, 2.5 mg used in elderly, interacting medications, elevated INR, liver dysfunction, 10 mg daily for 2 days may be given to healthy outpatients.
A/Es of Warfarin?
Warfarin dietary counseling points?
Warfarin reversal agent?
Bleeding, Skin necrosis, minor GI irritation.
Vitamin K inhibits effect, consistent vitamin k diet, cigarette smoke increases warfarin metabolism, Chronic alcohol use may require higher doses, binge drinking requires lower doses.
Vitamin K!(Phytonadione).
Vitamin K availability?
How does warfarin resistance happen?
INR vitamin K recommendations? Fastest reversal agent?
Oral-safest but 6-10 hour onset, IV- severe anaphylactic reactions 1-2 hour onset, IM- avoid due to risk of hematoma, SubQ- CHEST guidelines do NOT recommend this route.
Liver store Vit K and spits it out.
4.5-10 no use, >10 oral use, Any INR increase with major bleeding–> Rapid reversal four factor PCC, Prolonged effect Vitamin K 5-10 mg by slow IV in addition to PCC. PCC! Also helps with rivaroxaban.
Benefits and limitations to warfarin?
Aspirin MOA? Aspirin dosing?
Aspirin A/E’s?
Benefits- Oral dosing, medication is inexpensive but consider lab costs. Limitations- Frequent monitoring, NTI, Drug and dietary interactions, Can’t be used in pregnancy, inter-patient variability.
inhibits COX and decreases thromboxane A2, and prostaglandin production. 80-320 mg/day, higher doses need for pain relief and anti inflammatory effect, higher doses is increased GI bleed.
Bleeding, GI dose related.
Benefits/Limitations of aspirin?
ADP receptor antagonists?
ADP receptor antagonist use?
Benefits–> Cheap, low dose is well tolerated. Limitations–> GI bleed, anti-platelet effects last for life of platelet which is problem of surgery need arises.
Ticlopidine(severe neutropenia causes limited use),Clopodigrel, Prasugrel, Ticagrelor, Cangrelor(IV).
4-7 days to steady state for oral so loading doses often given. Used in combination with aspirin or instead of aspirin in allergy.
Clopodigrel pharmacodynamics?
Prasugrel stuff to know?
Prodrug activated by cyp3A4,5,Cyp2c19. Binds irreversibly to P2Y12 receptor, Advantages- years of data, more indications, generic, once daily dosing. Disadvantages- Drug interactions/resistance and irreversible binding.
prodrug used for patients undergoing PCI for ACS. Advantages- once daily dosing, more rapid onset 10x more potent, less variability in respone(0-3%). Disadvantages- irreversibly bound, CI’d in any stroke or TIA, active or recent bleeding, fewer indications, high cost, renal adjustment.
Ticagrelor stuff to know?
Cangrelor stuff to know?
ADP receptor antagonist A/E’s?
Stent thrombosis and PCI for ACS use. Advantages- Superiority over clopodigrel and no increased bleed risk. Disadvantages- BBW of lower aspiring dose to <100 mg and can only uses 325 dose right at first. fewer indications, BID dosing, costs.
PCI use. Advantage- reversible binding with short half life, suppresses platelets within 2 minutes. Disadvantage- IV dosing only, interferes with oral binding, high cost.
Bleeding,Discomfort, Elevated LFT’s, Dyspnea(Tica and cangrelor).
Benefits and limitations of ADP’s?
Glycoprotein inhibitors?
A/E’s of GPI? CI’s?
Benefits- Oral dosing, Clopodigrel can be used in ASA allergies,PTC have fast onset. Limitations-Cost! Clopodigrel slow onset, more adverse reactions than aspirin, neutropenia in ticlopidine.
Abciximab,Tirofiban,Eptifibatide. Pt’s undergoing PCI, All are IV drugs.
Bleeding, Thrombocytopenia, Antibody formation(Abciximab only). Bleeding risk factors, uncontrolled hypertenstion that’s severe, recent surgery or head trauma.
Benefits and limitations to GPI’s?
What are the fibrinolytics?
A/E’s of fibrinolytics?
Benefits- fast acting. Limitations-Cost, IV has to run for 12-24 hours, surgery indications, only use is ACS. Eptifibatide is CI’d in dialysis.
Alteplase, Reteplase, Streptokinase, Tenecteplase. Used to dissolve clots in patients having a stroke, ACS , or VTE.
Bleeding, thrombocytopenia, antibody formation(streptokinase).
Fibrinolytics CI’s?
How to manage bleeding?
What does protamine reverse?
same as GPI’s, pregnacy, prolonged CPR, Active PUD.
stop the agent, give blood, administer reversal agent.
UFH and LMWH to some extent,
Fibrinolytic reversal agent?
Dabigatran reversal agent?
HIT treatment?
Aminocaproic Acid mainly used during cardiac bypass surgery
Idarucizumab.
Discontinue heparin–> direct thrombin inhibitor(argatroban preferred)–>Warfarin(overlap with DTI for 5 days, start once platelet count is >150.
