10b: Coagulation Altering Medication

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What are the two main steps in hemostasis following blood vessel injury?

• Formation of a platelet plug.

• Fibrin activation to reinforce the plug.

What can be manipulated with anti-platelet medications in hemostasis?

Platelet plug formation.

What can be manipulated with anti-coagulant medications in hemostasis?

Fibrin activation.

How can thrombus/thrombosis be managed?

It can be manipulated mechanically.

What type of therapy is used to manage the physiologic breakdown of clots?

Fibrinolytic therapy.

What conditions fall under "Thrombosis" as an indication for coagulation therapy?

• AMI (Acute Myocardial Infarction)

• DVT (Deep Vein Thrombosis)

• PE (Pulmonary Embolism)

• CVA (Cerebrovascular Accident, thrombotic type)

What are two key aspects of "Hypercoagulability" that indicate coagulation therapy?

• Genetic component.

• Systemic embolism and/or prevention of recurrence.

List some "Risk for Thrombus" factors that may require coagulation therapy.

• Dysrhythmias

• MI (Myocardial Infarction)

• Carotid Disease

• Valvular Heart Disease

• Mechanical Heart Valves

What is the main function of anti-platelet medications?

To inhibit platelet aggregation.

Do anti-platelet medications dissolve clots?

No, they do not dissolve clots.

What type of thrombosis do anti-platelet medications primarily prevent?

They prevent thrombosis in arteries.

What is the primary action of anti-coagulant medications?

They disrupt the coagulation cascade, reducing the formation of fibrin.

Do anti-coagulants dissolve clots?

No, they do not dissolve clots.

Where do anti-coagulants primarily prevent thrombosis?

Primarily in veins, but also in arteries.

On which pathways do first-generation anti-coagulants act?

They can act on either the extrinsic or intrinsic pathways.

At what point do the extrinsic and intrinsic pathways converge?

They converge at Factor Xa.

What is the main action of fibrinolytic medications?

They dissolve clots by activating plasminogen into plasmin, which degrades the fibrin network.

In what setting are fibrinolytic medications typically used?

Only in hospital settings.

What is the primary use of anti-platelet medications?

They are used primarily in arterial thrombosis.

Do anti-platelet medications dissolve clots?

No, they do not dissolve clots.

What is an example of a cyclooxygenase inhibitor?

Acetylsalicylic acid (ASA), also known as aspirin.

Name three examples of P2Y12 inhibitors

Clopidogrel (Plavix), Prasugrel (Effient), and Ticagrelor (Brilinta).

Name two examples of IIB/IIIA inhibitors.

Eptifibatid (Integrilin) and Tirofiban (Aggrastat).

Name two other anti-platelet medications.

Dipyridamole (Persantine) and Cilostazol (Pletal).

What is the primary function of cyclooxygenase (COX) inhibitors?

They reduce inflammation and inhibit COX1.

What is an example of a cyclooxygenase inhibitor?

Aspirin (ASA), which is a first-generation NSAID.

Is aspirin a selective or non-selective COX inhibitor?

Aspirin is a non-selective COX inhibitor.

Why is aspirin given in acute angina or myocardial infarction (MI)?

Because of its short half-life (15-20 minutes), which allows for rapid onset of action.

How is aspirin administered and absorbed?

Aspirin is available in oral and PR (per rectum) forms, absorbed in the small intestine with rapid absorption, and binds extensively to plasma proteins.

How are aspirin metabolites excreted?

They are excreted renally.

What are two common adverse effects of aspirin?

Gastrointestinal (GI) bleed and gastric ulcer.

Why does aspirin increase bleeding risk?

Because inactive platelets increase the risk of bleeding.

What are the symptoms of salicylism (aspirin toxicity)?

Sweating, headache, dizziness, and tinnitus.

Why should aspirin not be given to children?

Due to the risk of Reye Syndrome.

What function should be monitored in patients taking aspirin?

Renal function.

Does a platelet count on a CBC indicate if platelets are functional?

No, a platelet count does not indicate platelet functionality.

Where is COX found in the body?

COX is found in all tissues, especially the stomach, platelets, kidneys, brain, and colon/rectum.

What is significant about aspirin (ASA) compared to other NSAIDs regarding cardiovascular risk?

Aspirin is the only NSAID that does not increase the risk of thrombotic cardiovascular (CV) events.

How does aspirin affect platelets?

Aspirin irreversibly binds to platelets, making them inactive for their lifespan.

What is the approximate lifespan of a platelet?

The lifespan of a platelet is approximately 7 days.

Why is aspirin held for 7 days before invasive procedures?

Because it irreversibly inactivates platelets, increasing bleeding risk, so it takes about 7 days to replenish functional platelets.

What can happen if aspirin is taken daily?

Daily aspirin use can increase the risk of bleeding.

What are some risks associated with even low doses (81 mg) of aspirin?

Low-dose aspirin can increase the risk of gastrointestinal bleeding (GIB) and hemorrhagic stroke.

Why should patients be cautious with over-the-counter headache treatments?

Many over-the-counter headache treatments, such as Goody’s powder, contain aspirin in their formulation.

What is the mechanism of action for Oral P2Y₁₂ ADP Receptor Blockers?

They block P2Y₁₂ receptors on the platelet surface, which prevents platelet aggregation.

What are examples of Oral P2Y₁₂ ADP Receptor Blockers?

Clopidogrel (Plavix), Prasugrel (Effient), and Ticagrelor (Brilinta).

How are Oral P2Y₁₂ ADP Receptor Blockers administered?

They are available orally.

How quickly do Oral P2Y₁₂ ADP Receptor Blockers take effect?

They are rapidly absorbed, with an effect within 2 hours.

When do Oral P2Y₁₂ ADP Receptor Blockers reach peak effect?

They reach peak effect 3-7 days after the first dose.

Do Oral P2Y₁₂ ADP Receptor Blockers need to be taken with food?

No, they can be taken with or without food.

What is a potential interaction that can impact the efficacy of Oral P2Y₁₂ ADP Receptor Blockers?

Proton pump inhibitors can impact their efficacy.

What are common side effects of Oral P2Y₁₂ ADP Receptor Blockers?

Rash and a risk of hemorrhagic events.

What are key contraindications or cautions for Oral P2Y₁₂ ADP Receptor Blockers?

They should not be used in patients with a history of hemorrhagic events or significant bleeding events while on dual antiplatelet therapy (DAPT).

What should be monitored when a patient is taking Oral P2Y₁₂ ADP Receptor Blockers?

Monitor for bleeding, dyspnea (especially with ticagrelor), and overall tolerance of the medication.

What do all P2Y₁₂ blocker medications have in their name?

All medications in this class have "grel" in their name.

What is unique about Clopidogrel's activation?

Clopidogrel is a prodrug metabolized hepatically by CYP2C19 and requires no dose adjustment for age or renal impairment.

Are Clopidogrel and Prasugrel reversible or irreversible?

Clopidogrel and Prasugrel are irreversible.

Which medication is considered superior for antiplatelet effect in DAPT for CVD?

Prasugrel is superior to Clopidogrel for antiplatelet effect with DAPT in cardiovascular disease (CVD).

What is a contraindication for Prasugrel?

Prasugrel is contraindicated in patients with a history of transient ischemic attack (TIA) or cerebrovascular accident (CVA), as indicated by a Black Box Warning.

Is Ticagrelor reversible or irreversible?

Ticagrelor is reversible.

What is a common side effect of Ticagrelor?

The most common side effect of Ticagrelor is dyspnea.

What is Cangrelor and how is it administered?

Cangrelor is an IV P2Y₁₂ inhibitor.

How is DAPT managed in patients with coronary artery disease (CAD)?

The choice of DAPT agents is patient-specific. If DAPT must be held for surgical procedures, continue ASA and resume DAPT as soon as possible.

When is DAPT used in carotid disease?

DAPT is used unless there is an indication for anticoagulation, such as in heart valve disease or atrial fibrillation (afib).

What is a special consideration for patients on DAPT?

Patients with comorbidities may require both an antiplatelet and an anticoagulant.

What are examples of IIB/IIIA Inhibitors?

Eptifibatid (Integrilin) and Tirofiban (Aggrastat).

What is the mechanism of action (MOA) for IIB/IIIA Inhibitors?

They inhibit binding of Factor VIII and fibrinogen to platelets, preventing platelet aggregation.

How are IIB/IIIA Inhibitors administered?

They are available in IV formulations only.

Where can IIB/IIIA Inhibitors be administered, and what is the onset of action?

They can be given intracoronary in the Cardiac Cath Lab with a rapid onset.

What are common side effects/adverse effects of IIB/IIIA Inhibitors?

Bleeding and thrombocytopenia.

What adjustments are needed for elderly and renal disease patients when using IIB/IIIA Inhibitors?

Dose adjustments are required in elderly and renal disease patients.

What are contraindications for using IIB/IIIA Inhibitors?

Major bleeding, history of ischemic stroke within 30 days, and platelet count less than 100,000/mm³.

What key parameters should be monitored with IIB/IIIA Inhibitors?

PT/aPTT, INR, dose adjustments in elderly and renal dysfunction patients, and concurrent use with anticoagulants.

What suffix do most IIB/IIIA inhibitors have in their name?

Most have "fiba" in the name.

For what indication are IIB/IIIA inhibitors primarily used?

They are indicated for patients undergoing percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome (ACS), including stable and unstable NSTEMI/STEMI.

How do IIB/IIIA inhibitors work as anti-platelets?

They cause reversible blockage of IIb/IIIa receptors, inhibiting the final step of platelet aggregation.

What is the intended duration of therapy for IIB/IIIA inhibitors?

They are intended for short-term therapy in ACS and/or PCI.

When should IIB/IIIA inhibitors not be given?

They should not be given if fibrinolytic therapy is administered.

What is the effect of combining IIB/IIIA inhibitors with ASA (aspirin) and heparin during PCI?

When combined with ASA and heparin peri-PCI, they reduce the incidence of myocardial infarction (MI) and cardiovascular (CV)-associated deaths.

What is the general mechanism of action (MOA) for other anti-platelet therapies like Dipyridamole and Cilostazol?

They suppress platelet aggregation, although the exact mechanism is not fully understood.

What is Dipyridamole (Persantine) FDA-approved for?

It is FDA-approved for thrombosis prevention following heart valve replacement and must be used in combination with warfarin.

What additional study is Dipyridamole being used for?

It is being studied for the reduction of recurrent stroke or TIA in combination with ASA (Aspirin), known as the ESPS-2 trial.

What is Cilostazol (Pletal) used for, and how does it work?

Cilostazol is a platelet inhibitor and vasodilator (inhibits PDE-3), indicated for peripheral artery disease (PAD) and intermittent claudication.

How long does it take for Cilostazol to have its full effect, and how quickly does it reverse?

Cilostazol may take up to 12 weeks for full effects and reverses quickly, within 48 hours.

What is the purpose of Dipyridamole/ASA (Aggrenox)?

It is indicated for stroke prophylaxis and the prevention of TIAs (transient ischemic attacks).

What is the pharmacokinetics characteristic of these anti-platelet therapies?

They undergo rapid hepatic metabolism.

What are the major side effects or contraindications for these therapies?

Side effects include bleeding, headache, dizziness, and GI issues such as dyspepsia, nausea/vomiting, abdominal pain, GI bleeding, and GI ulcers.

What are the main groups of anti-platelet medications?

• ASA (Aspirin)

• P2Y₁₂ ADP Receptor Blockers

• IIB/IIIA Inhibitors

• Other (Dipyridamole, Cilostazol)

What are the pros of using anti-platelet medications?

• Change how people clot

• Prevent strokes

• Improve cardiac outcomes in acute coronary syndromes (ACS)

What are the cons of using anti-platelet medications?

• Variable efficacy

• Narrow therapeutic index

• Potential for drug/food interactions

• Need for monitoring

• Bleed risk

• Issues with antidotes and reversibility

What are the main groups of anti-platelet medications?

• ASA (Aspirin)

• P2Y₁₂ ADP Receptor Blockers

• IIB/IIIA Inhibitors

• Other (Dipyridamole, Cilostazol)

What are the pros of using anti-platelet medications?

• Change how people clot

• Prevent strokes

• Improve cardiac outcomes in acute coronary syndromes (ACS)

What are the cons of using anti-platelet medications?

• Variable efficacy

• Narrow therapeutic index

• Potential for drug/food interactions

• Need for monitoring

• Bleed risk

• Issues with antidotes and reversibility

What is the main use of anti-platelet medications?

They are primarily used in arterial thrombosis and do not dissolve clots.

What is the function of Cyclooxygenase Inhibitors in anti-platelet therapy?

They inhibit the enzyme cyclooxygenase (COX), with Aspirin (ASA) being a primary example.

Which medications fall under P2Y₁₂ ADP Receptor Blockers?

• Clopidogrel (Plavix)

• Prasugrel (Effient)

• Ticagrelor (Brilinta)

• Cangrelor (Kengreal)

What are the IIB/IIIA inhibitors listed on the slide?

• Eptifibatide (Integrilin)

• Tirofiban (Aggrastat)

Name two other anti-platelet agents mentioned.

• Dipyridamole (Persantine)

• Cilostazol (Pletal)

What are the indications for anti-platelet therapy?

• Ischemic stroke or TIAs

• Chronic stable angina

• Coronary stents (bare-metal and drug-eluting stents)

• Acute or previous myocardial infarction (MI)

• Prevention of recurrent miscarriage

• Primary prevention of MI (when the risk of MI is greater than the risk of GI bleed)

What is the primary function of anti-coagulant medications?

They disrupt the coagulation cascade to reduce the formation of fibrin.