Stroke Rx

Question 1

what is the first line of therapy for an ischemic stroke?

Answer 1

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

Question 2

what are the antiplatelet drugs?

Answer 2

aspirin
ADP receptor blocks
glycoprotein IIb/IIIa inhibitors
phosphodiesterase-3 inhibitors

Question 3

what are the anticoagulants?

Answer 3

unfractionated heparin
warfarin
Direct Thrombin Inhibitors

Question 4

what are the direct thrombin inhibitors? when are they used?

Answer 4

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

Question 5

what is the mode of action of heparin?

Answer 5

potentiates antithrombin III - most important being IIa and Xa

safe in pregnancy

Question 6

what are the risks of heparin?

Answer 6

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

Question 7

what are the variation of heparin?

Answer 7

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

Question 8

warfarin - mode of action? Uses?

Answer 8

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

Question 9

what is meant by heparin ‘overlap’?

Answer 9

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

Question 10

what are the antihypertensives?

Answer 10

calcium channel blockers

dihydropyridine (nifedipine), labetalol, statins

Question 11

what type of ca++ channels do calcium channel blockers work on?

Answer 11

L-type receptors

effect - relax arterioles, TPR and lowers BP, makes heart work less for systole

Question 12

Nifedipine

Answer 12

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

Question 13

labetalol - uses and toxicities

Answer 13

targets - alpha and beta antagonists

uses - hypertensive crisis, CHD, cocaine withdrawal

toxicity - bronchoconstirction, it can mask hypoglycemia and cause othrostasis (falls)

Question 14

mode of action for statins, toxicity

Answer 14

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

Question 15

ADP receptor blockers

Answer 15

mostly prodrugs

clopidogrel - alt to aspirin
ticlopidine - neutropenia
prasugrel
ticagrelor - direct active

irreversible, stops expression of GPIIb/IIa

Question 16

what are the GpIIb/IIIa inhibitors?

Answer 16

abciximab
eptifibatide
tirofiban

Question 17

what are the phosphodiesterase inhibitors?

Answer 17

dipyridamole - compine with aspirin for stroke or TIA prevention
cilostasol - stroke, peripheral vascular diseas e

Question 18

Clopidogrel

Answer 18

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

Question 19

Ticlopidine

Answer 19

ADP Receptor Inhibitor

Alternative to Aspirin, causes neutropenia and anemia

Useful for angioplasties and stents, CAD, acute coronary syndrome, stroke, atheroscleosis.

Question 20

Prasugrel

Answer 20

ADP receptor inhibitor

Alternative aspirin, has a faster onset and is metabolized by CYP3A4 and CYP2B6

Used for angioplasty, stroke, stent etc..

Question 21

Ticagrelor

Answer 21

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

Question 22

Abciximab

Answer 22

monoclonal antibody that inhibits glycoprotein IIb and IIIa — long lasting

Causes bleeding

Used for angioplasty, stroke, CAD or stents

Question 23

Epifibatide/Tirofiban.

Answer 23

Glycoprotein IIb and IIIa, short acting — reversible

Used for angioplasty, stents, CAD and stroke

Causes bleeding

Question 24

Aspirin.

Answer 24

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

Question 25

Dipyridamole

Answer 25

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

Question 26

Cilostasol

Answer 26

Phosphodiesterase inhibitor - inc cAMP

Claudication, thrombosis in peripheral vascular disease and for preventing stroke

Causes vascular headache and stroke.

Question 27

Streptokinase

Answer 27

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

Question 28

Alteplase - name the other ‘plases’, use, MOA and toxicities

Answer 28

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

Question 29

Toxicities and uses of DTI

Answer 29

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

Question 30

Warfarin - uses

Answer 30

Anticoagulent benefits after 4-5 days

Hypercoagulopathy

Vascular necrosis

Causes Protein C def which can be controlled with heparin

Question 31

Toxicities and uses of DTI

Answer 31

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