Anticoagulants, Antiplatelets, Thrombolytic agents Flashcards
Drug: Heparin
MOA:
Clinical Use/Monitoring Tests/administration route:
Toxicity (AE - 2 subtypes- and Tx for Tox, allergy risks for Tox Tx?)/Interactions/Contraindications (2)/safe for pregnant women?:
ANTICOAGULANTS
Prevent blood clotting
-natural product derived from mast cells; MW 5-30,000daltons
MOA: Accelerates (1000 fold) inactivation of 2 (thrombin), 9 and 10 (via AT-III - coag factors irreversibly bind this) by reversibly binding (via specific pentasaccharide site with a 3-O-sulfated glucosamine residue… needs minimum of 18 monosaccharide units to bind?) to Antithrombin III (AT-III) -> accelerates action of AT-III (suicide substrate) which prevents fibrin generation)
Clinical Use/Monitoring Tests: - can use to prevent blood coag in VITRO - i.e. when take a sample of blood
-Tx for venous thromboembo
-Patency of IV cannulas and in angioplasty (do a hepatin IV flush!)
- Monitor via aPTT and platelet count if long-term;give via SubQ or IV (IM -> hematoma)
Toxicity/Interactions/Contraindications: OK for preggos but d/c 24h prior to labor
AE = Bleeding -> thrombocytopenia: HIT-type 1 = non-immune, within 2 d of therapy, d/t platelet-heparin interaxn
HIT-type 2 = more severe; immune mediated; after 5-10 days -heparin(acting as hapten to)-platelet factor 4 complex causes autoAb binding to platelet surface and aggregation
Tx of toxicity(excess hemorrhage) =
-Protamine sulfate: Heparin-protamine complex cannot bind to AT-III - BUT NOT in ppl with fish allergy nor in diabetics who take NP(rotamine)H insulin b/c allergy risk
- plasma
- whole blood
Contraindications
-Bleeding disorder
-Pre-existing bleeding sites
Drug: LMW-HePARIN (EnoxaPARIN; DaltePARIN; TinzaPARIN)
MOA:
Clinical Use/Monitoring Tests/ administration route:
Toxicity/Interactions/Contraindications - ok in preggo?:
ANTICOAGULANTS
Prevent blood clotting
-fractionated from standard heparin
MW = 4500 daltons; 15 monosach units so too small to bind AT-III and Thrombin at same time
MOA: specifically enhance AT-III’s inactivation of factor 10 ONLY -LOW affinity for thrombin
Clinical Use:
- in VITRO to prevent clotting in test tubes
-PPx and Tx of DVT and PE
- unstable angina or NON-Q-wave MI for thrombus Ppx
Admin route: subQ only – NO IV; 1x/day dose - longer 1/2 life- … likely what you got
Monitoring Tests: don’t have to monitor but can with: anti-Xa activity (bc so specific)
Toxicity: safer and more effective than regular heparin
Interactions:
Contraindications: OK for PREGGO**
**lower incidence of thrombocytopenia - can use as outpatient!
Drug: Warfarin
MOA: (2)
Clinical Use/Monitoring Tests(2); therapeutic goals (2 ranges):
Toxicity/Interactions/Contraindications - ok for preggo?:
Tx for OD (2)?
ANTICOAGULANTS
Prevent blood clotting
** #1 ORAL anticoag in UNITED STATES *
MOA:
- 1. Inhibits hepatic synthesis of biologically active Vitamin K-dependent clotting factors **(2,7-shortest 1/2 life,9,10-longest 1/2 life) and Protein C and S
-2. also prevents gamma carbox (b/c Warfarin inhibits conversion of Vitamin K epoxide to hydroquinone) so cannot bind Ca++ anymore and thus remain INACTIVE
Delayed therapeutic effect, initial effect occurs in 24 hr and maximal effect takes 5- 7 days - b/c needs time to inhibit TXN/TLN… i.e. hepatic protein synthesis
Clinical Use:
- cannot use in test tubes -in VITRO- bc gets +ed in liver (epoxide via vit K)
-PPx & Tx of DVT and PE
- TE Ppx in pts with Prosthetic Heart Valves
- Arterial thromboembolism Ppx in atrial fibrillation
Monitoring Tests:
INR values which are standardized PT values (prothrombin time) use (pts’s PT/mean normal PT)^ISI = INR need this b/c of thromboplastin reactivity
therapeutic goals for INR:
Goal for INR is 2.0-3.0
prophylactic for heart valves INR 2.5-3.0
Toxicity/AE - Hemorrhage (bleeding)
AE more likely in: issues with vit K, coag factor synth(shitty hepatic fn), change in fibrin degradation, change in platelet fn or #
Genetic predisposition to AE
1) Genetic variants of CYP2C9 and VKORC1 genes use less warfarin?????
Interactions/ - different card
Contraindications:
- patients with bleeding disorder or existing bleeding site -NO PREGGO!!!!(Pregnancy Category X)
->congenital abnormalities occur if fetus exposed first, second or third trimester -greater incidence of neonatal and fetal hemorrhage
Tx for OD:
a. Administer whole blood or plasma
b. Administer Vitamin K1– (phytonadione)takes 24 hrs
Drug: Fondaparinux
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications - ok for preggo?:
ANTICOAGULANTS Prevent blood clotting **even smaller than LMW heparins** MOA: Synthetic pentasaccharide binds to ATII to accelerate only Factor Xa inactivation Clinical Use: - in VITRO to prevent clotting in test tubes -Ppx and DVT Tx Admin route: IV, SC administration Monitoring Tests: Toxicity - Adverse effect BLEEDING Interactions Contraindications: ***ok for preggo*** -active bleeding -severe renal impairment (
Drug: Argatroban
MOA:
Clinical Use/Administration route/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTICOAGULANTS
Prevent blood clotting
MOA: Direct thrombin inhibitor, blocks active site of thrombin; Active on free and fibrin bound thrombin: Action independent of ATIII
Administration route: **IV administration
Clinical Use: Tx and Ppx in thrombosis with HIT
Monitoring Tests: aPTT
Toxicity/Interactions/Contraindications:
Drug: Dabigatran
MOA:
Clinical Use/Admin route/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTICOAGULANTS
Prevent blood clotting
MOA: Direct thrombin inhibitor, blocks active site of thrombin; Active on free and fibrin bound thrombin: Action independent of ATIII **Prodrug **converted by esterases to Dabigatran (active)
-Converted to 4 Different Glucuronide metabolites (active)
Administration route: **-Oral administration
Clinical Use/ - Ppx for thrombotic stroke
-Ppx for TE and CVA d/t AFib
Monitoring Tests:
Toxicity/ - bleeding
- no way to reverse if OD; can just give plasma
Interactions/ not a p450 substrate so less interaxns
Contraindications: - caution in pts with renal insufficiency
Drug: Aspirin (ASA)
MOA: (3)
Clinical Use/Monitoring Tests:
Toxicity/AEs
ANTIPLATELET Inhibit platelet function MOA:a. Inhibit platelet aggregation b. Irreversible inhibitor of cyclo-oxygenase (acetylates the enzyme) c. Platelet prostaglandin formation (TXA2) inhibited by 160 mg/day aspirin Clinical Use/ 1) transient ischemic attacks; 2) unstable angina 3) ****history of Myocardial infarction (Ppx for 2nd MI) Toxicity - AEs = a. GI bleeding, pain and peptic ulcer b. Bleeding
Drug: Dipyridamole
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTIPLATELET
Inhibit platelet function
MOA: -Inhibits phosphodiesterase (↑ platelet cAMP)
Clinical Use:
Given with Warfarin for Ppx of TE in patients with prosthetic heart valves (little benefit alone)
Drug: Clopridogrel
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTIPLATELET
Inhibit platelet function
MOA: block ADP binding at the purinergic P2Y12 receptor which inhibits IIb/IIIa complex needed for AGGREGATION (no TXA2 release, increase PI hydrolysis and a rise in intracellular Ca)
PRODRUG
Thiol Metabolite is an irreversible inhibitor of P2Y12 receptor.
must make new platelets to reverse effect **
Clinical Use/-
*acute coronary syndrome
Reduce Thrombotic events following MI, stroke, unstable angina or peripheral areterial
disease
Monitoring Tests: Must monitor WBC and platelets
Toxicity
a) Bleeding due to diminished platelet function
b) Thrombocytopenia purpura /Interactions/Contraindications: **preferred over ticlopidine d/t less side effects
Drug: Ticlopidine
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTIPLATELET
Inhibit platelet function
MOA: block ADP binding at the purinergic P2Y12 receptor which inhibits IIb/IIIa complex needed for AGGREGATION (no TXA2 release, increase PI hydrolysis and a rise in intracellular Ca)
PRODRUG
Thiol Metabolite is an irreversible (disulfide bridges)
inhibitor of P2Y12 receptor.
**must make new platelets to reverse effect *
Clinical Use/
- Reduce Thrombotic events following a stroke
- Second line, due to side effects, used only if response fails to aspirin (or pt aspirin intolerant)
Monitoring Tests: Must monitor WBC and platelets
Toxicity/ - this has longer 1/2 life than clopidogrel
a) Bleeding due to diminished platelet function
b) Thrombocytopenia purpura (higher risk)
c) **can cause life threatening agranulocytosis AKA TTP?
Interactions/Contraindications:
Drug: Abciximab
MOA: (4 parts)
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTIPLATELET Inhibit platelet function MOA:-Platelet Glycoprotein IIb/IIIa Receptor Antagonists -Competitive reversible inhibitor -Inhibit platelet crosslinking with fibrinogen ( no vWF ineraxn) -Monoclonal antibody Fab fragment Clinical Use/ -Acute coronary syndrome (unstable angina) -Prevent acute Adjunct with Angioplasty -Administered IV (bolus plus infusion)***lasts 24 - 48 hrs after stop IV*** ***more effective than Efab...tide*** Monitoring Tests: Toxicity/ AE = high incidence of -Bleeding -Increased bruising Contraindications: -History of hemorrhagic stroke -Active internal bleeding or GI/genitourinary bleeding in past 6 weeks -Thrombocytopenia -Major surgery or trauma in past 6 weeks -Cannot use concurrent with warfarin
Drug: Eptifibatide
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
ANTIPLATELET Inhibit platelet function MOA: PEPTIDE derivative -Platelet Glycoprotein IIb/IIIa Receptor Antagonist -Competitive reversible inhibitor - of interaxn w/ vWF and fibrinogen with IIb/IIIa Receptor -Inhibit platelet crosslinking with fibrinogen Clinical Use/ -Acute coronary syndrome (unstable angina) -Prevent acute Adjunct with Angioplasty -Administered IV (bolus plus infusion) ***lasts 4-6 hrs after stop IV*** but less effective than abciximab Toxicity/ AE = high incidence of -Bleeding -Increased bruising Interactions/ Contraindications: -History of hemorrhagic stroke -Active internal bleeding or GI/genitourinary bleeding in past 6 weeks -Thrombocytopenia -Major surgery or trauma in past 6 weeks -Cannot use concurrent with warfarin
Drug: Streptokinase
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
THROMBOLYTICS
Dissolve formed clots
. Protein derived from beta-hemolytic streptococci; antigenic
MOA: a. Complexes stoichiometrically (1:1) with plasminogen
b. Conformational change of plasminogen exposes catalytic site for conversion of a second
plasminogen molecule to plasmin
c. Acts on fibrin bound and circulating plasminogen; lytic state may occur
Lytic state: excessive bleeding: circulating plasmin exceeds capacity of α2-antiplasmin
Clinical Use/ Reperfusion of occluded coronaries following acute MI b. Pulmonary emoblism
c. Arterial thrombosis
Toxicity/a. High antigenic activity; fever occurs in 33% of patients b. Bleeding : *drug-induced fever (secondary to having had a strep inFXn before)
Interactions/
Contraindications
a. Surgery or trauma in past 10 days
b. Pre-existing bleeding disorder or episode c. Intracranial trauma
d. Diastolic blood pressure >110
Drug: AlTePlAse aka ___?
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
AKA t-PA (rt-PA) THROMBOLYTICS Dissolve formed clots MOA: Directly Activates fibrin bound plasminogen more selectively than circulating plasminogen Clinical Use/ -reperfusion of coronary arteries post-MI -pulmonary embolism -thrombotic stroke (use within 3 hours)
Toxicity/**Lytic state is less marked than observed with streptokinase and anistreplase
Drug: Anistreplase
MOA:
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications:
THROMBOLYTICS
Dissolve formed clots
MOA: combo of streptokinase and plasminogen with catalytic site acylated (acyl -ed by plasma enzymes)
more specific fibrin binding* Designed to provide more specific binding to thrombi
Clinical Use/Monitoring Tests:
Toxicity/Interactions/Contraindications: *drug-induced fever (secondary to having had a strep inFXn before) but LESS LYTIC state!
