Anticoagulants & Thrombolytics Flashcards
purified Fab fragments of monoclonal antibody that prevent GP IIb/IIIa receptors from binding to fibrinogen
abciximab
indication for GP IIb/IIIa inhibitor to limit/prevent ischemia (3 words)
acute coronary syndromes
indication for alteplase, especially when within 3-6 hrs and option of percutaneous coronary intervention is unavailable (3 words)
acute myocardial infarction
platelet derived ligand for autocrine/paracrine stimulation of P2Y12 receptors
ADP
glycoprotein produced via recombinant DNA technology that is identical in aa sequence to human tissue plasminogen activator
alteplase
a treatment for bleeding, it prevents activation of plasminogen and directly inhibits plasmin (2 words)
aminocaproic acid
no reliable way to monitor the degree of this for either dabigatran or rivaroxaban
anticoagulation
recombinant human form purified from goat’s milk is available for those with deficiency, but it is expensive
antithrombin
contraindication for alteplase (2 words)
aortic dissection
laboratory test used to monitor the anticoagulant activity of heparin; ideally kept at 1.5-2 but can be a challenge since heparin has highly variable plasma levels due a short half-life and multiple sites of nonspecific binding, some of which can hasten its clearance
aPTT
hirudin analog administered IV for the prophylaxis and treatment of thrombosis in patients with or at great risk for developing heparin-induced thrombocytopenia
argatroban
irreversibly blocks the synthesis of thromboxane A2 by platelets, one of the agents that promotes the activation and aggregation of platelets; taking this at low-doses for cardiovascular prophylaxis is now (as of March 2019) no longer recommended for anyone without clinical signs of heart disease or stroke
aspirin
a synthetic peptide similar to leech anticoagulant hirudin, it is a direct inhibitor of thrombin, but class as a whole has had limited use since must be administered intravenously and much more expensive than heparin
bivalirudin
risk of this can be reduced during alteplase administration by minimizing physical manipulation of the patient, avoiding subQ and IM injections, and minimizing concurrent use of anticoagulants and antiplatelet drugs
bleeding
obvious and effective treatment for bleeding (2 words)
blood replacement
type 3 phosphodiesterase inhibitor used to suppress platelet aggregation, indicated for intermittent claudication
cilostazol
among the best selling drugs in the world, it suppresses platelet aggregation by irreversibly blocking P2Y12 receptors
clopidogrel
depending on risk for this, a daily dose of aspirin may be indicated (3 words)
coronary heart disease
blocking stenosis here is an indication for clopidogrel (2 words)
coronary stents
enzyme thought to be responsible for synthesis of platelet inhibitor PGI2 by endothelial cells; its selective sparing by low doses of aspirin is thought to explain the cardiovascular benefits of aspirin and the adverse effects associated with withdrawn drug rofecoxib
COX2
needed by clopidogrel for activation and inhibited by proton pump inhibitors; reason Prilosec media mention Plavix and vice versa
CYP2C19
orally active and reversible direct inhibitor of thrombin
dabigatran
low-molecular weight heparins are now the dugs of first choice for the treatment and prevention of this (3 words)
deep venous thrombosis
dabigatran is unstable and must be stored in this type of bottle, also avoiding excess heat or cold
desiccator
a vasopressin V2 analog that can be useful for treating VWD and hemophilia, it promotes release of vWF and factor VII
desmopressin
abbr. for condition treated with heparin
DIC
suppresses platelet aggregation via uncertain mechanism (PDE inhibitor?), synergizes with aspirin and used in combination to prevent recurrent ischemic stroke in patients with TIA or past stroke
dipyridamole
warfarin has a multitude of these that can influence its activity and mandates regular testing and additional testing whenever changes are made to the daily treatment regimen (2 words)
drug interactions
example of a low-molecular weight heparin made by depolymerizing heparin; with its shorter chain length, its binding to antithrombin inhibits factor Xa but is generally unable to form the ternary complex with thrombin needed for its inhibition
enoxaparin
small peptide inhibitor of GP IIb/IIIa receptor approved for use during acute coronary syndromes and percutaneous coronary intervention
eptifibatide
substrate for plasmin
fibrin
bridging molecule between activated gp IIb/IIIa receptors on platelets
fibrinogen
synthetic pentasaccharide, the minimum sequence needed to bind to antithrombin and inhibit factor Xa; sequence is too short to form the ternary complex with thrombin that is needed to inhibit thrombin activity
fondaparinux
platelet receptors that allow the platelets to link together (aggregate), drugs that block these receptors block the final common pathway of platelet aggregation and are therefore the most effective antiplatelet drugs
GPIIb/IIIa
sequence of letters in a generic drug name that suggests blockade of P2Y12 receptors
grel
the use of heparin increases the risk for one of these forming and damaging the brain or spinal cord
hematoma
a mixture of long highly negatively charged polysaccharide chains isolated from bovine lung or porcine intestine, a pentasaccharide sequence randomly distributed along its length binds to antithrombin to facilitate its inhibition of factor Xa and thrombin
heparin
when severe and uncontrolled, a relative contraindication for alteplase
hypertension
lower than 2 and the risk for thromboembolism increases in patients treated with warfarin while higher than 3 and risk of intracranial hemorrhage increases
INR
not required for dabigatran or rivaroxaban (2 words)
INR monitoring
contraindication for alteplase and most serious concern with its use (2 words)
intracranial hemorrhage
contraindication for alteplase unless has occurred within past 3 hrs, when it is an indication (2 words)
ischemic stroke
duration of clopidogrel and aspirin effects on platelets
lifetime
dabigatran was found to be inferior to warfarin at inhibiting thromboembolism in these (3 words)
mechanical heart valves
warfarin has the potential to cause this in skin, occurs when rapid fall in protein C leads to a hypercoagulable state
necrosis
indication for rivaroxaban or dabigatran (3 words)
nonvalvular atrial fibrillation
seeing this sequence of letters in a generic drug name suggests product is some sort of heparin analog
parin
procedure (abbr.) that is indication for a GP IIb/IIIa inhibitor, which is used to prevent rapid re-occlusion
PCI
because predictable for both fondaparinux and low-molecular weight heparins, these agents can be self-administered at home
pharmacokinetics
generic ending of name for drugs that function as tissue plasminogen activators
plase
when clot-bound, converted by alteplase to enzyme responsible for clot breakdown
plasminogen
breaks down a blood clot when bound to it, when circulating it breaks down various clotting factors unless bound by alpha2-antiplasmin
plasmin
a P2Y12 inhibitor similar to clopidogrel and competing for market share
prasugrel
platelet Fc receptors bind an IgG bound to heparin and this in heparin-induced thrmobocytopenia, leads to platelet activation/thrombosis and platelet removal by splenic macrophages
platelet factor 4
reason for selecting heparin (i.e., due to its inability to cross membrane barriers) as anticoagulant rather than warfarin
pregnancy
vitamin K-dependent anti-clotting factor with shorter half-life than several other factors, its disappearance is reason warfarin adminstration can cause a pro-coagulant phase
protein C
antidote for “oops, too much heparin”
protamine
aspirin has this for ischemic strokes, transient ischemic attacks, stable and unstable angina and myocardial infarction among others (2 words)
proven efficacy
indication for alteplase if acute and massive (2 words)
pulmonary embolism
advantage of dabigatran and rivaroxaban in comparison to warfarin (2 words)
rapid onset
ticagrelor differs from clopidogrel by causing this type of P2Y12 receptor block
reversible
a direct inhibitor of activated factor X, it therefore rapidly inhibits the generation of thrombin from prothrombin
rivaroxaban
characteristic of both onset and offset of warfarin’s anticoagulant effects
slow
doing this near eye, brain or spinal cord is a contraindication for anticoagulants
surgery
potent activator of platelets; it exerts these effects by cleaving a peptide from protease activated receptors (PAR1, PAR4) on the platelet surface, thereby allowing the ligand tethered to the GPCR to activate the receptor
thrombin
can be induced by unfractionated heparin and low-molecular weight heparin; fondaparinux will not induce but should not be used as a replacement anticoagulant as it can exacerbate the situation
thrombocytopenia
useful for diagnosing heparin-induced thrmbocytopenia, expect onset between days 5-14 after heparin exposure
timing
prevention of this and its potential adverse consequences is a common reason for taking warfarin (2 words)
venous thrombosis
required for synthesis of biologically active clotting factors II, VII, IX, X, protein C and protein S among others, and antidote for warfarin (2 words)
vitamin K
newly approved (5/2014) reversible (but long half-life) PAR1 antagonist indicated for reduction of thrombotic cardiovascular events in patients with history of myocardial infaction or with peripheral arterial disease; life-threatening/fatal bleeding is a side effect that will limit its use
vorapaxar
exerts its slow onset anticoagulation effects by blocking the conversion of vitamin K epoxide to its active reduced form; depletion of biologically active vitamin K results in an inability to post-translationally carboxylate specific glutamate residues and results in enzyme proteins with a non-functional active site
warfarin
type of bleeding seen primarily at platelet counts below 10,000/microL
spontaneous
comparative color of arterial clots
white
type of bleeding common with platelet defects (along with rapid/greater bleeding from cuts)
mucocutaneous
common with platelet defects, uncommon with clotting factor defects
petechiae
bleeds here (e.g., hematomas) are a common manifestation of clotting factor deficiencies
deep tissue
leading to decreased levels of VKORC1 (vitamin K epoxide reducatase complex subunit 1), this is found in ~90% of asians and is why they are more sensitive to warfarin than blacks (~14% incidence)
genetic variability
metabolizes the more potent S-warfarin to 7-OH-warfarin; there are numerous polymorphisms in this gene and those decreasing its activity against warfarin are more common (10-20%) in caucasians, increasing warfarin potency 3-5X
CYP2C9
a challenge for both heparin and warfarin, reason that frequent coagulation tests are required
dosing
humanized antibody recently available to neutralize/serve as an antidote for dabigatran
idarucizumab
recently approved as a reversal agent for factor Xa inhibitors rivaroxaban and apixaban
andexanet alfa
second physiological activator of plasminogen activator to degrade clotting factors, acts in fluid phase/extravascular compartment; was withdrawn from market but now back for treatment of pulmonary embolism needing a clot buster
urokinase
