antiplatelets, anticoagulants, and fibrinolytics Flashcards by Jasmin Maisuria

process of stopping bleeding, which involves:
* Vasoconstriction
* Platelet aggregation
* Coagulation cascade
* Fibrinolysis

hemostasis

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inhibit platelet aggregation to prevent
thrombus formation

anti platelet drugs

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Primarily for prevention of arterial thrombosis (e.g., stroke,
myocardial infarction) and for treatment of existing clot
o Mechanical heart valves
o Atrial fibrillation
o PAD
o Essential thrombocythemi

anti platelet drugs

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When injury results in activation of
factors, Von Willebrand Factor binds to________ to prevent degradation of
platelets

factor VIII

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TXA

platelet activation/recruit

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ADP

platelets change shape

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5-HT

activate aggregation

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Irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A2 production

aspirin

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(e.g., Clopidogrel, Ticagrelor)
Inhibit the P2Y12 receptor, blocking ADP-induced platelet aggregation

ADP or P2Y12 Inhibitors

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(e.g., Abciximab, Eptifibatide)
Block GPIIb/IIIa receptors, preventing platelet fibrinogen binding

GPIIb/IIIa Inhibitors

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Inhibits phosphodiesterase and adenosine uptake, increasing cyclic AMP, and preventing platelet activation

Dipyridamole & Cilostazol

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MOA: Irreversible inhibition of cyclooxygenase I and Thromboxane A2
Indications:
* Primary prevention of myocardial infarction
* Secondary prevention of vascular events (stroke, PAD, MI) in patients with a history of said events
Adverse Effects:
* Bleeding, gastric or duodenal ulcers, and hypersensitivity reactions
* Prolongs bleeding time for 5-7 days (preop)
Contraindications:
* Hypersensitivity to NSAIDs
* Reye’s Syndrome
* Signs: Serum glucose levels drop, liver swells and develop fatty deposits, brain may swell
* Symptoms: diarrhea, vomiting, lethargy, seizures
* Generally occurs in pediatric population ages 4-14 when given aspirin concurrently with viral infectio

aspirin

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S/S = Fever, tinnitus, vertigo, N/V/D, AMS, hyperventilating, arrhythmia
Labs = respiratory alkalosis, anion-gap metabolic acidosis (lactic acids and
ketoacids), hypokalemia, hypoglycemia
DX = salicylate level (>40mg/dL)

aspirin overdose

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aspirin overdose treatment

stabilize with ABCs, GI decon with activated charcoal, K+ if hypoK,
sodium bicarb to alkalinize plasma and urine, monitor renal level and
dialyze if renal + AMS, acidemia (pH <7.2), cerebral or pulmonary edema

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Your elderly patient complains of
bruising on ASA, what can you do?

give patient the aspirin every other day

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Indications: unstable angina, NSTEMI, STEMI, stroke, Peripheral Arterial Disease
Loading dose 600mg before PCI, reaches full antiplatelet action at 2 hours
Adverse events: Thrombotic thrombocytopenic purpura (form of allergy)
Blood clots in small blood vessels
Interactions: CYP 2C19 inhibitors
Remember Plavix is a prodrug, 50% absorbed, fraction activated in liver by CYP2C19
Caution if patient has CYP2C19 polymorphism
DI = Omeprazole (reduces active metabolite by 50%)
Caution: Thrombocytopenia (less than 150,000 platelets/microliter)
Clinical judgement
Contraindication: Active bleed (risk doubles if on aspirin

Adp OR P2y12 inhibitors
Clopidogrel (Plavix)

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if a patient has an allergy to aspirin, what can they use as an alternative

clopidogrel (plavix)

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More potent and faster blocker
Preferred in ACS and when strong antiplatelet action required
Prodrug = but complete absorption and activation
CYP2C19 SUBSTRATE = but watch for polymorphism still and limit or avoid Omeprazole
Indications: STEMI (shown to reduce death due to CVS causes than Plavix), superior in preventing
stent thrombosis
ADRs: None significant
Contraindications: History of TIA or stroke (evidence of harm via studies)
Caution in elderly (FDA approval for high risk only if DM or prior MI)
Low-weight patients <60kg need reduced dose

Adp OR P2y12 inhibitors
Prasugrel (Effient)

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Indication: Acute coronary syndromes in combination with aspirin
Maximum aspirin dose of 100 mg
MOA: Reversible inhibitor if P2Y12
Interactions: CYP3A inhibitors
Up to 5x increase of active metabolites with strong inhibitors (anti-fungal)
Can be given with moderate inhibitors (CCB)
Contraindications: History of intracranial hemorrhage

Adp OR P2y12 inhibitors
Ticagrelor (Brilinta)

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blocking aggregation. (no more sticky hands)

Gpiib/iiia receptor antagonists

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MOA: Bind to and reversibly inhibits GP IIb/IIIa receptor, blocking platelet aggregation
Indication: Percutaneous coronary intervention and acute coronary syndromes
* Not for long-term use (all are IV drugs)
Caution:
* Renal dysfunction (reduce dose)
Contraindications:
* Hypersensitivity to agent component
* Active internal bleeding or recent significant GI or GU bleed within past 6 months
* History of major bleeding within 30 days
* Severe uncontrolled hypertension
* Major surgery or trauma in last 6 months
* Brain: Stroke past 2 years, intracranial neoplasm, arteriovenous malformation, aneurysm, tumor

Gpiib/iiia receptor antagonists

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Gpiib/iiia receptor antagonists:
ADRs
Abciximab (Reopro):

Anaphylaxis
Thrombocytopenia

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Gpiib/iiia receptor antagonists:
ADRs
Eptifibatide (Integrillin) & Tirofiban (Aggrastat)

Anaphylaxis
Thrombocytopenia
Renal dysfunction

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MOA: Inhibits platelet function by inhibiting adenosine uptake and cGMP
phosphodiesterase activity (PDE3 inhibitor)
Indications: Often used with another agent
* Aspirin combo to prevent cerebrovascular ischemia
* Add to warfarin for primary prophylaxis against thromboembolism with prosthetic
heart valves
* May still see used in chemical stress tests (vasodilator)
* Data to come? There seems to be synergy with statins
Adverse Effects:
* Headaches, GI Distress, Dizziness

DIPYRIDAMOLE

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MOA: Inhibition of Phosphodiesterase III * Unlike other antiplatelet agents cilostazol not only inhibits platelet function but also improves endothelial cell function. Indication: Intermittent claudication * Pain in legs due to arterial obstruction (usually displayed during/after exercise) Adverse Reactions: Headache, GI Interactions: High-fat diet raises level, grapefruit (raises cilostazole level via CYP3A4) Contraindication: Heart failure

CILOSTAZOL (Pletal)

If blood vessel damage is so extensive that the platelet plug can not stop the bleeding, the coagulation phase begin. inhibit the coagulation cascade to prevent thrombus formation

anticoagulants

Use: Primarily for prevention of venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism), and stroke prevention in atrial fibrillation * Mechanism of action: Inhibit factors in the coagulation cascade

anticoagulants

virchow's triad The three factors that contribute to formation of blood clots:

* Endothelial injury * Hypercoagulability * Stasis (abnormal blood flow)

Inhibit vitamin K epoxide reductase, reducing synthesis of clotting factors II, VII, IX, and X

Vitamin K Antagonists (e.g., Warfarin

o Direct Factor Xa Inhibitors (e.g., Apixaban, Rivaroxaban) – inhibit factor Xa* o Direct Thrombin Inhibitors (e.g., Dabigatran) – inhibit thrombin*

Direct Oral Anticoagulants (DOACs

o Binds to antithrombin III, increasing its ability to inhibit thrombin and factor Xa o Low Molecular Weight Heparins (e.g., Enoxaparin) are preferred for outpatient use

Heparin

MOA: inhibits activation of vitamin K dependent clotting factors (S.N.T.T. (snot)) (VII, IX, X, II) * Also inhibits proteins C and S (anticoagulants) * Half-lives: Seven: 4-6 hours, Protein C: 8 hours, Nine: 24 hours, Protein S: 30 hours, Ten: 48- 72 hours, Two: 60 hours Indications: Prophylaxis and Treatment of DVT and PE complications from valvular and nonvalvular atrial fibrillation * Stroke prophylaxis in valvular and nonvalvular atrial fibrillation * During cardioversion * During rate control therapy * Adjunct to reduce risk of systemic embolism after MI * BOLD = Needs bridge with indirect thrombin inhibitor until reach therapeutic INR range

warfarin

* Adverse Effects: Bleeding, teratogenic, skin necrosis * Contraindications: Hemorrhagic tendencies, unsupervised/noncompliant patients, pregnancy/breastfeeding, alcoholism * Additional Concerns: o Diet changes o Hepatic impairment o Genetic polymorphisms (CYP2C9 and VKORC1

warfarin

Warfarin: monitoring

* INR = international normalized ratio * Goal 2-3 for most conditions

warfarin reversal agents

o Vitamin K = given when INR 4.5-10 or pre-surgery o FFP = fresh frozen plasma or clotting factors  Given if active bleeding when patient taking Warfarin

Warfarin interactions through cyp2c9 that increase INR

o Amiodarone*** o Fluoroquinolone antibiotics (ciprofloxacin) o Metronidazole o Azole antifungals (fluconazole) o Sulfamethoxazole/trimethoprim o Macrolide antibiotics (azithromycin) o Tamoxifen

Warfarin interactions through cyp2c9 that decrease INR

o Barbiturates o Rifampin o Cholestyramine

* MOA: Inhibition of Factor Xa * Binds selectively and reversibly to clotting factor Xa * Medications: Rivaroxaban (Xarelto), Apixaban (Eliquis) * Indications: Treatment and secondary prevention of DVT and PE * Primary prevention of DVT and PE in nonvalvular atrial fibrilation * Postoperative thromboprophylaxis  Post total knee and hip surgery

Direct oral anticoagulants (doacS): direct factor xA INHIBITORS

* Take with food for doses above 10 mg * Metabolized by CYP3A4 and P-glycoprotein * Avoid use in severe renal and hepatic impairment

Rivaroxaban (Xarelto) DoacS: DIRECT FACTOR XA INHIBITORS

* Metabolized by CYP3A4 and P-glycoprotein * Avoid use in severe renal and hepatic impairment * Think:  Age: Age 80 or greater  Body Mass: weight 60 kg or less  Creatinine: 1.5 mg/dL or greater ^^ Do not give if at least two of these situations apply

Apixaban (Eliquis) DoacS: DIRECT FACTOR XA INHIBITORS

DoacS: DIRECT FACTOR XA INHIBITORS considerations

* Avoid use in severe renal impairment * Abrupt discontinuation increases risk of thrombotic events * Epidural and spinal hematomas may occur in patients receiving neuraxial anesthesia or undergoing spinal puncture

DOACS: DIRECT THROMBIN INHIBITORS Parenteral

* Bivalirudin (Angiomax) * Percutaneous coronary intervention * Argatroban (Acova) * HIT (heparin-induced thrombocytopenia) * Percutaneous coronary intervention

DOACS: DIRECT THROMBIN INHIBITORS Oral

* Dabigatran (Pradaxa) * Reduction of stroke and systemic embolism risk in patients with nonvalvular afib * DVT and PE treatment and prevention * Postoperative thromboprophylaxis

DABIGATRAN (Pradaxa) * Advantages

* No routine monitoring * Doesn’t interact with CYP450 * Rapid onset and offset

DABIGATRAN (Pradaxa) * Disadvantages

* Renal Adjustments * Black Box Warnings: * Spinal and epidural hematomas * Abrupt discontinuation

Warfarin reversal agent

Oral or parenteral vitamin K (phytonadione), fresh-frozen plasma, clotting factors

DOAC reversal agent

Andexxa (coagulation factor Xa

Dabigatran reversal agent

Idarucizumab

Antidote, familiarity, can use in renal and hepatic impairment

warfarin pros

Narrow therapeutic window, affected by diet and other drugs, intensive monitoring

warfarin cons

Rapid onset and offset, no monitoring, fewer drug interactions

Newer Oral Anticoagulants (DOACs) pros

Noncompliance, hard to monitor, antidotes still pending

Newer Oral Anticoagulants (DOACs) cons

* Unfractionated heparin = Heparin * Low molecular weight heparins (LMWH) = Enoxaparin (Lovenox), Dalteparin (Fragmin), Tinzaparin * Synthetic heparin = Fondaparinux (Arixtra

Indirect thrombin inhibitors

* Heparin binds to the enzyme inhibitor antithrombin III (AT), and inactivates clotting factors IIa and Xa * It also inhibits the enzyme that acts on fibrin that causes clotting * It binds simultaneously to thrombin

Unfractionated Heparin Indirect thrombin inhibitors

* Binds to Antithrombin III but not fibrin * Makes dosing more predictable

Low Molecular weight and synthetic Heparin

* Prevention of clotting in arterial and cardiac surgery * Anticoagulant for extracorporeal circulation and dialysis procedures * Maintain patency of IV devices (heparin locks)

Unfractionated heparin

Prophylaxis and treatment of deep vein thrombosis and pulmonary embolism and thromboembolic complications associated with atrial fibrillation

Indirect thrombin inhibitors: indications (all of them)

* Acute coronary syndromes (unstable angina, NSTEMI, STEMI, arrhythmia) * Preferred in TOP: Trauma, Oncology, Pregnancy

Low molecular weight heparin (Enoxaparin, Dalteparin, Tinzaparin)

Indirect thrombin inhibitors: monitoring * Unfractionated Heparin:

activated partial thromboplastin time (aPTT or PTT) * aPTT for patients recently on Direct oral anticoagulants as they can falsely elevate PTT levels * Platelet levels and signs of bleeding * NO RENAL DOSING

Low-Molecular Weight Heparin monitoring

* Renal insufficiency, obese, pregnant, underweight monitor anti Xa units * For all other patients, monitor platelet count and signs of bleeding

Fondaparinux monitoring

Renal insufficiency, obese, pregnant, underweight monitor anti Xa units * Clinical signs of bleeding and platelet count

ADRs: * Bleeding * Heparin-Induced Thrombocytopenia (HIT) * Immune Response * Platelet factor 4-Heparin * 5-14 days after starting heparin therapy * Treatment * Stop Heparin agent * NO PLATELET TRANSPLANT * Change to Fondiparinux (does not bind to factor 4) Contraindications: patients who develop HIT (except Fondiparinux), have active bleeds, or hemophilia Reversal (used for bleed/pre-surgery): Protamine Sulfate

Indirect thrombin inhibitors

Clot busters MOA: Cause fibrinolysis by binding to fibrin in a clot and converting entrapped plasminogen to active plasmin

fibrinolytics

Alteplase, Reteplase, Tenecteplase Indications: * Acute ischemic stroke * Acute massive PE * ST-elevation myocardial infarction

fibrinolytics

TPA (tissue plasminogen activator) Indication: TIA, must be given within three hours of symptom onset (4.5 for MI sometimes) Contraindications: * Intracranial hemorrhage * Subarachnoid hemorrhage * Internal bleeding * Stroke within the last three months * Intracranial or intraspinal surgery within the last three months * Serious head trauma within the last three months * Intracranial neoplasms, arteriovenous malformations, or aneurysms * Conditions that increase the risk of bleeding * Currently severe uncontrolled hypertension

alteplase

TNK * Same indication, contraindications as Alteplase * Must be given within 3 hours of symptom onset * Better adverse drug reaction panel * Less bleeding * Better functional outcomes at 90 days (faster and more complete recovery) * It is cheaper than Alteplase

tenecteplase

MOA: * Antiplatelets:

 Aspirin: Inhibits COX-1, reducing thromboxane A2  P2Y12 inhibitors: Block ADP-induced platelet activation  GPIIb/IIIa inhibitors: Block fibrinogen binding

MOA: Anticoagulants:

 Warfarin: Inhibits vitamin K-dependent clotting factors  Heparin: Increases antithrombin activity  DOACs: Direct inhibition of factor Xa or thrombin

MOA Fibrinolytics:

tPA: Converts plasminogen to plasmin

if a patient is pregnant

low molecular weight heparin (lovenox)

If patient has a mechanical heart valve

warfarin

If patient has aspirin allergy

plavix

If patient needs to be on DVT preventative for 6 months

warfarin, Xarelto, Eliquis, Pradaxa

If patient needs to be on DVT preventative long-term

if patient has intermittent claudication

antiplatelets, anticoagulants, and fibrinolytics Flashcards

(75 cards)