Stroke Rx Flashcards
what is the first line of therapy for an ischemic stroke?
fibrinolytics - alteplase
within 3 hours
others - reteplase, tenecteplase, streptokinase, and anistreplase
promotes the activation of plasmin
antidote is aminocaproic acid or tranzemic - blocks plasmin and fibrin interaction
what are the antiplatelet drugs?
aspirin
ADP receptor blocks
glycoprotein IIb/IIIa inhibitors
phosphodiesterase-3 inhibitors
what are the anticoagulants?
unfractionated heparin
warfarin
Direct Thrombin Inhibitors
what are the direct thrombin inhibitors? when are they used?
they bind directly to the active site of thrombin -
Bivalirudin and Argatroban
dabigatran - rapid onset, co CYP or dietary interactions
use when patient responds to heparin with type II heparin-induced thrombocytopenia
what is the mode of action of heparin?
potentiates antithrombin III - most important being IIa and Xa
safe in pregnancy
what are the risks of heparin?
hypersensitvity, osteoporosis, and hyperkalemia
Bleeding or thrombocytopenia
heparin-induced thrombocytopenia: two types, type 1 reverses itself and type 2 is immune mediated and carries risk of re-thrombosis - treat with DTI’s
what are the variation of heparin?
low molecular weight - enoxaparin, dalteparin, and tinzaparin - inactivated Xa only
subcutaneous injections
fondaparinux - inactivates Xa, long half-life and once daily dosing, no cross-reacition causing HIT
warfarin - mode of action? Uses?
inhibits recycling of vitamin K - vitamine K epoxide reductase
taken orally
Uses - delay of 4 to 5 days for effective anticoagulant benefit, hypercoagulopathy, vascular necrosis, protein C deficiency (controlled by heparin)
Warfarin crosses the placenta
Toxicities - bleeding: administure vitamin K or replace clotting factors and also drug interactions
what is meant by heparin ‘overlap’?
clotting factor II has a long half life, and warfarin works slowly, so in order to avoid thromus formation you start patient on herparin and then wafarin, you can discontinue heparin and release patient when PT levels are met
what are the antihypertensives?
calcium channel blockers
dihydropyridine (nifedipine), labetalol, statins
what type of ca++ channels do calcium channel blockers work on?
L-type receptors
effect - relax arterioles, TPR and lowers BP, makes heart work less for systole
Nifedipine
Calcium Channel Blocker
acts only on arterioles
decreases total peripheral resistance and BP
can cause SANS reflex and tachycardia
SANS reflex can cause angina or MI in CHD patients
labetalol - uses and toxicities
targets - alpha and beta antagonists
uses - hypertensive crisis, CHD, cocaine withdrawal
toxicity - bronchoconstirction, it can mask hypoglycemia and cause othrostasis (falls)
mode of action for statins, toxicity
HMG CoA reductase Inhibitors, competitive - increases numbers of LDL receptors.
toxicity - causes hepatic toxicity, not for use in alcoholics or people with liver dysfunction, interacts with enzyme inhibitors,
myopathy, rhapdomyolosis
toxicity can increase with Red Yeast Rice
ADP receptor blockers
mostly prodrugs
clopidogrel - alt to aspirin
ticlopidine - neutropenia
prasugrel
ticagrelor - direct active
irreversible, stops expression of GPIIb/IIa
what are the GpIIb/IIIa inhibitors?
abciximab
eptifibatide
tirofiban
what are the phosphodiesterase inhibitors?
dipyridamole - compine with aspirin for stroke or TIA prevention
cilostasol - stroke, peripheral vascular diseas e
Clopidogrel
ADP Receptor inhibitor
Requires an enzyme to activate, some people have a mutation in this enzyme.
Alternative to aspirin, however patients are at risk for MI stroke and death
used for angioplasty, putting in a stint, CAD, stroke - vascular ischemia with atherosclerosis, and acute coronary syndrome
Ticlopidine
ADP Receptor Inhibitor
Alternative to Aspirin, causes neutropenia and anemia
Useful for angioplasties and stents, CAD, acute coronary syndrome, stroke, atheroscleosis.
Prasugrel
ADP receptor inhibitor
Alternative aspirin, has a faster onset and is metabolized by CYP3A4 and CYP2B6
Used for angioplasty, stroke, stent etc..
Ticagrelor
Reversible ADP Receptor Inhibitor
Direct inhibitor that doesnt need to be activated
Inhibits CYP3A4 — as a consequence increase the concentrations of drugs that are metabolized by CYP3A4
Abciximab
monoclonal antibody that inhibits glycoprotein IIb and IIIa — long lasting
Causes bleeding
Used for angioplasty, stroke, CAD or stents
Epifibatide/Tirofiban.
Glycoprotein IIb and IIIa, short acting — reversible
Used for angioplasty, stents, CAD and stroke
Causes bleeding
Aspirin.
Blocks formation of thrombaxane (Txa2) and blocks COX
Contraindication in patients with gastrointestinal issues, some pts have allergic rxns (because of the shunted leukotriene pathway), bleeding.
Used as an analgesic, antipyretic, anti-inflammatory, and a low-dose antiplatelet
Dipyridamole
phosphodiesterase inhibitor
increase cAMP, cGMP, NO, PGI2 (another vasodilator). inhibits synthesis of Txa2
typically combined with aspirin to prevents TIA’s and strokes.
causes bleeding, hypotension and vasodilation
Cilostasol
Phosphodiesterase inhibitor - inc cAMP
Claudication, thrombosis in peripheral vascular disease and for preventing stroke
Causes vascular headache and stroke.
Streptokinase
Replaced by Alteplase because of allergic rxns (it’s a bacterial protein)
Natural tissue plasminogen - targets to plasmin
Same toxicities and contraindications as the other fibrinolytics
Alteplase - name the other ‘plases’, use, MOA and toxicities
Human recombinant tissue plasinogen - infused into thrombosed vessels to lyse clots
Anistreplase - streptokinase with plasmonige, same uses as above
Reteplase, tenecteplase (longer half life) - faster onset, used for MI, acute ischemic stroke, pulmonary embolism and central venous catherization
Toxicities - bleeding; contraindicated in patients with prior intracranial hemorrhage and malignant intracranial neoplasm
Toxicities and uses of DTI
Toxicities - bleeding with antidote - idarucizumab, dosing adjustments are necessary for patients with renal impairment
Uses - alternative to heparin when a patient has a HIT type II response, angioplasty and stents
Dibigatron specifically is used for stroke prevention in patients with nonvalvular atrial fibrillation
Warfarin - uses
Anticoagulent benefits after 4-5 days
Hypercoagulopathy
Vascular necrosis
Causes Protein C def which can be controlled with heparin
Toxicities and uses of DTI
Toxicities - bleeding with antidote - idarucizumab, dosing adjustments are necessary for patients with renal impairment
Uses - alternative to heparin when a patient has a HIT type II response, angioplasty and stents
Dibigatron specifically is used for stroke prevention in patients with nonvalvular atrial fibrillation
