Anticoagulant, Antiplatelet, thromboltic agents 1 Flashcards
Heparin MOA
binds reversibly to Antithrombin-III
accelerates inactivation by AT-III of intrinsic and common pathway
Thrombin, IXa, Xa bind irreversibly to Arg-Ser site on AT-III
what drug has anticoagulant activity both in vitro and in vivo
heparin
heparin has what clinical uses
venous thrombosis
pulmonary embolism
patency of IV cannulas
what anticoagulant can be used in pregnancy
Heparin and low molecular weight heparin (discontinue use 24 hour prior to induction of labor)
what method of administration is contraindicated for heparin use and why
intramuscular
induces painful hematoma
what effect other than anticoagulant does heparin have
lipid clearing effect by activating lipoprotein lipase (cleave TG from VLDL)
how does one monitor heparin
activated partial thromboplastin time (PTT)
this monitors the common and intrinsic pathway
what are the adverse effects associated with heparin use
bleeding- Heparin Induced Thrombocytopenia (type 1 non immune mediated and type 2 immune mediated)
osteoporosis (if given for more than 6 months)
treatment of excess hemorrhage due to heparin can be done how
protamine sulfate- the heparin-protamine complex cannot bind to AT-III
administer plasma or blood containing coagulation factors
what is protamine sulfate
heparin-protamine complex cannot bind to AT-III
Heparin use is contraindicated for use in what
bleeding disorder
pre-existing bleeding sites
Enoxaparin, dalteparin, and tinzaparin are examples of what
low molecular weight heparin
low molecular weight heparin have what MOA
higher specificity for enhanced antithrombin III inactivation of Xa
low molecular weight heparin is used for what
prophylaxis and acute deep vain thrombosis, pulmonary embolism, orthopedic abdominal surgery
unstable angina or non-Q-wave MI
how is low molecular heparin administered
sub-cutaneous
how does one monitor low molecular weight heparin
anti-Xa activity
LMW heparin is better than unfractioned heparin why
longer half life
can be used outpatient
lower incidence of thrombocytopenia (less binding to platelet proteins)
predicable response
what does one need to monitor in long term use of unfractioned heparin
platelet count
Fondaparinux MOA
synthetic pentasaccharide binds to ATIII to accelerate only factor Xa inactivation
Fondaparinux is used for what
DVT acute and postoperative
PE
can be used in pregnancy (stope 24 hours b4 labor)
adverse effects of Fondaparinux
bleeding
contraindications of Fondaparinux
active bleeding
severe renal impairment
warfarin MOA
inhibits conversion of vitamin K epoxide reductase
inhibits hepatic synthesis of biologically active vitamin K-dependent clotting factors, protein C and S
biological activity of warfarin requires what
gamma-carboxyglutamyl residues on clotting factors
warfarin is the drug of choice for what
oral anticoagulant
warfarin is used for what
anticoagulant
venous thromboembolism
PE
prothetic heart valves
warfarin only works as an anticoagulant when administered how
in vivo
how is warfarin monitored
INR laboratory standardized quick one-stage prothrombin time
warfarin monitors what coagulation cascade pathway
extrinsic via prothrombin time
the goal for INR is what normally and what in prophylactic for heart valves
normal- 2.0-3.0
prophylactic for heart valves- 2.5-3.0
what adverse reactions are there to warfarin
hemorrhage (more likely to occur if changes in absorption or metabolism of warfarin or vitamin K, alteration occurs in synthesis or catabolism of coagulation factors)
genetic predisposition to warfarin are in what genes
CYP2C9
VKORC1
what drugs or conditions increase warfarin response
vitamin K deficiency hepatic disease thyroid hormones cimetidine Aspirin Erythromycin cephalosporins ketoconazole
what drugs or conditions decrease warfarin response
cholestyramine
oral contraceptives
rifampin
excess vitamin K
warfarin use in contraindicated in what patients
those with bleeding disorders or existing bleeding site
pregnant woman
what is used to treat warfarin overdose
whole blood or plasma vitamin K (phyonadione)
Direct Thrombin inhibitor are
Argatroban and dabigatran etexilate
direct thrombin inhibitors MOA
block active site of thrombin
active (free or fibrin bound thrombin)
argatroban is administered how
IV
argatroban is used for what
treatmetn and prophylaxis in thrombosis with heparin induced thromboytopenis
argatroban is monitored how
PTT
dabigatran is administed how
oral
dabigatran given how
a produg covered by esterase’s to dabigatran
what drug is a substrate for p-glycoprotein transport
dabigatran
what is dabigatran used for
venous thrombosis prophylaxis
prevent stroke
caution must be used in what patients when administering dabigatran
diminished renal excretion
what are the side effects of dabigatran
bleedings
what is the goal of anti platelet drugs
diminish platelet function
antiplately drugs are used to treat what
arterial thrombotic diseases (TIA, unstable angina, history of MI)
Aspirin MOA
irreversible inhibitor COX, decreases TXA2 platelet aggregation
Adverse effects of aspirin
GI bleeding, pain and peptic ulcer
bleeding
Dipyridamole MOA
inhibits phosphodiesterase (increase platelet cAMP)
Dipyridamole use
given with warfarin for prevention of thromboembolism in patients with prosthetic heart valves
Clopidogrel, Ticlopidine, and cangelor are examples of what
P2Y12 receptor inhibitor
Clopidogrel, Ticlopidine, and cangelor MOA
ticlopidine and clopidogrel block ADP binding at the purinergic P2Y12 receptor
what P2Y12 receptor inhibitors are prodrugs
ticlopidine and clopidogrel
Clopidrogel metabolite and ticlopidine thiol metablolite work how
irreversible inhibitors of P2Y12 receptor
Cangrelor works how
reversible inhibitor
IV administration
ticlopidine and clopidogrel are used for what and which is preferred
reduced risk of thrombotic events in predisposed individuals
clopidogrel is preferred
Clopidogrel is used for what
reduce thrombotic events following MI, stroke, unstable angina, or peripheral arterial disease
major adverse effects of P2Y12 receptor inhibitors are
bleeding due to diminished platelet function
thrombocytopenia purport
ticlopidine can cause life threatening agranulocytosis
Abciximab and eptifibatide are examples
glycoprotein IIB/IIIA inhibitors
Abciximab and eptifibatide MOA
platelet glycoprotein IIb/IIIa receptor antagonists
competitive reversible inhibitor
inhibit platelet cross linking with fibrinogen
monoclonal antibody Fab fragment
Abciximab and eptifibatide are used for what
acute coronary syndrome (unstable angina)
prevent acute adjunct with angioplasty
administered IV
Abciximab and eptifibatide adverse effects
bleeding
increased bruising
Abciximab and eptifibatide contraindications
history of hemorrhagic stroke
active internal bleeding or GI/genitourinary bleeding in the past 6 weeks
thrombocytopenia
major surgery or trauma in past 6 weeks
glycoprotein IIb/IIIa inhibitors can’t be used with what
warfarin
t-PA is inactivated by what
plasminogen activator inhibitor 1 (PAI-1)
alpha-2 antiplasmin does what
binds covalently to plasmin at a lysine rich binding site causing inactivation occurs only with circulating plasmin
streptokinase MOA
complexes with plasminogen promoting conformational change of plasminogen exposes catalytic site for conversion of a second plasminogen molecule to plasmin
streptokinase on what
fibrin bound and circulation plasminogen
therapeutic use of streptokinase
repercussion of occluded coronaries following acute MI
PE
arterial thrombosis
adverse effects of streptokinase
high antigenic activity
bleeding
contraindications of streptokinase
surgery or trauma in the past 10 days
pre-exisiting bleeding disorder or episode
intracranial trauma
antistreplase is what
streptokinase complexed with human lys-plasminogen: the active catalytic center is blocked by an acyl group (acyl group removed by plasma enzymes)
alteplase is what type of drug
tissue-type plasminogen activator (rt-PA)
alteplace is used for what
repercussion of coronary arteries in acute MI
PE
thrombotic stroke
tenecteplace is what type of drug
genetically engineered derivative of alteplace
tenecteplace is approved for
MI
tenecteplace is better than alteplace why
longer half-life
greater fibrin specificity
slower inactivation by PAI-1
minocaproic acid is what type of drug
inhibitor of plasminogen activation
lysine analog, compete for lysine binding site on plasminogen and plasmin
