Podcast Beta
Questions and Answers
What is primarily responsible for the process of hemostasis?
Which term describes the process of breaking down a clot after bleeding has ceased?
What condition is characterized by excessive clotting due to a deficiency in the ADAMTS13 enzyme?
Which type of blood thinner works by inhibiting platelet activity?
Signup and view all the answers
What could potentially result from a hemostasis process impairment?
Signup and view all the answers
What is the main indication for the use of Aggrenox?
Signup and view all the answers
Which of the following mechanisms of action is associated with Cilostazol?
Signup and view all the answers
What is a recommended action regarding theophylline administration prior to stress testing with dipyridamole?
Signup and view all the answers
Which symptom is the primary indication for Cilostazol treatment?
Signup and view all the answers
What is the combination of ingredients in Aggrenox?
Signup and view all the answers
What is a potential consequence of fetal COX-2 inhibition during pregnancy?
Signup and view all the answers
Which statement correctly explains why COX inhibitors should be discontinued before elective surgery?
Signup and view all the answers
What can chronic use of COX inhibitors lead to in terms of renal health?
Signup and view all the answers
How do COX inhibitors affect asthma conditions?
Signup and view all the answers
Which of the following is a potential adverse effect of salicylate toxicity?
Signup and view all the answers
What is Reye syndrome and when should COX inhibitors be avoided?
Signup and view all the answers
Which of the following is NOT a potential outcome of using COX inhibitors?
Signup and view all the answers
What effect do COX inhibitors have on sodium levels in the body?
Signup and view all the answers
What primarily binds platelets to collagen during the hemostatic process?
Signup and view all the answers
What substance is released by activated platelets to promote further platelet aggregation?
Signup and view all the answers
What stabilizes the platelet plug during secondary hemostasis?
Signup and view all the answers
What initiates the extrinsic pathway of the coagulation cascade?
Signup and view all the answers
Which of the following best describes the role of COX-1 in platelet function?
Signup and view all the answers
Which class of medication is primarily used to inhibit platelet aggregation?
Signup and view all the answers
What is the loading dose of Ticagrelor before PCI for maximal effect?
Signup and view all the answers
What is the mechanism of action of aspirin regarding platelet aggregation?
Signup and view all the answers
Which condition is associated with a patent foramen ovale?
Signup and view all the answers
During tertiary hemostasis, what is the role of plasmin?
Signup and view all the answers
Which of the following substances inhibits platelet aggregation and promotes vasodilation?
Signup and view all the answers
What is a common adverse effect of Ticagrelor?
Signup and view all the answers
What is the typical daily dose range of aspirin for prophylactic use?
Signup and view all the answers
What is the main mechanism of action for GPIIb/IIIa receptor inhibitors?
Signup and view all the answers
What is the primary adverse effect associated with the inhibition of PGE2 by aspirin?
Signup and view all the answers
What is the recommended maintenance dose of Ticagrelor?
Signup and view all the answers
Which components are involved in the formation of a stable fibrin clot?
Signup and view all the answers
Which drug is indicated to reduce thrombotic cardiovascular events during PCI?
Signup and view all the answers
What correct action does COX-1 inhibition by aspirin have on platelet function?
Signup and view all the answers
What effect do strong CYP 3A4 inhibitors have on Ticagrelor?
Signup and view all the answers
Which of the following is NOT a component of tertiary hemostasis?
Signup and view all the answers
Which of the following is NOT a contraindication for Pragugrel?
Signup and view all the answers
What is the primary adverse effect associated with GPIIb/IIIa receptor inhibitors?
Signup and view all the answers
What is the initial infusion rate for Aggrastat when dosing?
Signup and view all the answers
How long after stopping Aggrastat does platelet function typically restore to baseline?
Signup and view all the answers
What is the maintenance dose for Prasugrel when combined with aspirin?
Signup and view all the answers
Study Notes
Blood Thinners and Anticoagulants
- Not all blood thinners are anticoagulants.
- Three primary ways of thinning blood:
- Anti-platelets: Destroy the activity of platelets.
- Anti-coagulants: Inhibit the coagulation factors involved in clot formation.
- Thrombolytics: Break down existing clots.
Hemostasis
- The process of stopping bleeding, primarily in response to injury.
- Involves a complex interplay of the vascular system, platelets, and blood proteins/factors.
- Hemostasis prevents and stops bleeding, or hemorrhaging.
- After bleeding stops, the clot is removed through fibrinolysis.
- Crucial for maintaining blood volume and pressure.
- Deficiencies or disorders in hemostasis lead to bleeding disorders or thrombosis (excessive clotting).
Thrombotic Thrombocytopenic Purpura (TTP)
- A disorder characterized by excessive clotting, which consumes platelets.
- Caused by a deficiency in the enzyme ADAMTS13.
- ADAMTS13 controls blood clot formation.
- Without enough ADAMTS13, the body produces too many clots.
Primary Hemostasis: Temporary Clot Formation
- Involves vasoconstriction to reduce blood flow.
- Platelets adhere to exposed subendothelial collagen via glycoprotein Ib (GpIb) binding to von Willebrand factor (vWF).
- Adhered platelets become activated, changing shape and releasing substances (ADP, thromboxane A2, and serotonin) that attract more platelets.
- Platelet aggregation occurs, forming a temporary "plug" at the injury site.
Secondary Hemostasis: Stable Clot Formation
- Involves the coagulation cascade, leading to the formation of a stable fibrin clot.
- Inactive clotting factors, produced in the liver, are activated in a cascade fashion at the injury site.
- The coagulation cascade has two pathways:
- Intrinsic pathway: Initiated by damage to the blood vessel itself, involving factors XII, XI, IX, and VIII.
- Extrinsic pathway: Initiated by tissue factor (TF) released from damaged tissue, involving Factor VII and Factor X.
- Both pathways converge into the common pathway, culminating in the conversion of prothrombin (Factor II) to thrombin (Factor IIa).
- Thrombin converts fibrinogen (Factor I) into fibrin (Factor Ia), forming a mesh that strengthens the platelet plug.
Tertiary Hemostasis: Clot Dissolution
- The process of dissolving the fibrin clot as the vessel heals.
- Dependent on plasminogen activation.
- Key components include: plasminogen, plasminogen activators, plasmin, fibrin, fibrin degradation products (FDP), and inhibitors of plasminogen activators & plasmin.
Activators of Fibrinolysis
- Intrinsic activators: Factor XIIa, XIa, kallikrein.
- Extrinsic activators: Tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA).
- Exogenous activators: Streptokinase (derived from beta strep bacteria).
Antiplatelets
- Used both prophylactically and acutely to inhibit platelet activation and aggregation.
- Main classes:
-
Cyclooxygenase (COX-1) inhibitors:
- Acetylsalicylic acid (aspirin) is the prototype and only COX-1 inhibitor used.
- MOA: Irreversibly blocks COX-1 activity by acetylating the enzyme.
- Prevents the conversion of arachidonic acid to TXA2 in platelets, blocking platelet aggregation and vasoconstriction.
- Platelet-induced TXA2 synthesis is blocked for the lifespan of the platelet (7-10 days).
- COX-1 inhibition also prevents the formation of PGI2 in vascular endothelium, leading to a net reduction of platelet aggregation.
-
Dipyridamole/ASA combination (Aggrenox):
- Approved for stroke reduction in patients with TIA or history of thrombotic stroke.
-
Cilostazol (Pletal):
- Quinolinone derivative used for peripheral artery disease (PAD).
- MOA: Inhibits phosphodiesterase III, leading to increased cAMP levels, which causes vasodilation and inhibits platelet aggregation.
- Clinical use: Reduces the symptoms of intermittent claudication.
-
Cyclooxygenase (COX-1) inhibitors:
Adverse Effects of Aspirin
- Dose-dependent adverse effects due to PGE2 and TX inhibition.
- GI effects: Abdominal pain, heartburn, nausea, ulcers, and bleeding.
- Bleeding: Potential for excessive bleeding, particularly during surgeries or procedures.
- Renal dysfunction: Progressive dysfunction with chronic use due to vasoconstriction of renal arteries.
- Asthma exacerbation: Increased leukotriene synthesis and risk of bronchospasms.
- Other adverse effects: Tinnitus, headache, dizziness, confusion, vision changes, metabolic acidosis, hypersensitivity reactions, Reye’s syndrome.
- Contraindications: Avoid in children under 16 with viral infections (risk of Reye’s syndrome).
- Interactions: Patients on theophylline require higher doses of dipyridamole during stress testing.
Ticagrelor
- Ticagrelor is a reversible ADP receptor antagonist, meaning it inhibits platelet aggregation.
- Ticagrelor's effect on platelet aggregation takes 24-48 hours to develop, but loading doses can be used to accelerate this process.
- Different dosages and durations of Ticagrelor result in different times to reach maximum platelet inhibition.
- 75mg PO QD takes 7 days for maximal effect
- 300mg PO X1 before PCI takes 6-10 hours for maximal effect.
- 600mg PO X1 before PCI takes 2 hours for maximal effect.
- Ticagrelor's maintenance dose is 75mg PO QD.
- Ticagrelor can cause GI upset, diarrhea, and rash.
- Ticagrelor's effectiveness can be decreased by CYP2C19 inhibitors.
- Ticagrelor is contraindicated in cases of known hypersensitivity and active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
Prasugrel
- Prasugrel is an irreversible ADP receptor antagonist.
- The FDA indicates Prasugrel reduces the rate of thrombotic cardiovascular events in patients with unstable angina, non-ST-segment elevation MI, or ST-elevation MI managed with percutaneous coronary intervention (PCI).
- Prasugrel's loading dose is 60mg, and its maintenance dose is 10mg in combination with aspirin.
- Prasugrel's adverse effects are similar to other ADP antagonists, but it carries a higher risk of bleeding in certain patient populations.
- Prasugrel is contraindicated in cases of peptic ulcer disease, intracranial hemorrhage, TIA, or Stroke.
Ticagrelor
- Ticagrelor is a highly effective and preferred medication for patients with ACS, including patients with ST-elevation myocardial infarction (STEMI), patients who are candidates for PCI, and patients who are unstable and not candidates for PCI.
- Ticagrelor's FDA indication is to reduce the risk of CV death, MI, stroke, and stent thrombosis in patients with ACS in combination with aspirin.
- Ticagrelor's loading dose is 180mg, and its maintenance dose is 90mg BID in combination with aspirin 81mg/day.
- Using higher doses of aspirin will reduce Ticagrelor's effectiveness.
- Ticagrelor should be avoided in patients taking strong CYP3A4 inhibitors.
- Ticagrelor's most common adverse effect is bleeding.
- Other adverse effects of Ticagrelor include bradycardia, dyspnea, and gynecomastia in men.
- Ticagrelor is contraindicated in cases of peptic ulcer disease, intracranial hemorrhage, and severe hepatic impairment.
GPIIb/IIIa Receptor inhibitors
- These agents include Tirofiban (Aggrastat) and Eptifibatide (Integrilin); they inhibit platelet aggregation by antagonizing the GPIIb/IIIa receptor.
- These agents have potent antithrombotic effects and have been shown to decrease mortality and reinfarction.
- GPIIb/IIIa receptor inhibitors are indicated for use in acute coronary syndromes, including patients managed medically, those undergoing PCI.
- Integrilin has broader indications compared to Aggrastat, including elective, urgent, or emergency PCI.
- Aggrastat is used in combination with aspirin and heparin.
- Integrilin is used in combination with aspirin and heparin.
- Both Aggrastat and Integrilin have a high incidence of bleeding and thrombocytopenia.
Abciximab (Reopro)
- Abciximab binds to the GPIIb/IIIa receptor, inhibiting platelet aggregation.
- Abciximab is indicated to prevent acute cardiac ischemic complications and abrupt closure of the treated coronary vessel during percutaneous transluminal angioplasty (PCTA).
- Abciximab can be used in patients with UA/NSTEMI not responding to medical therapy when PCI is planned within 24 hours.
- Abciximab use in patients with UA/NSTEMI not undergoing PCI shows no significant benefit.
- Abciximab is a low margin of safety drug due to its long half-life, which affects platelet function for 12-24 hours after infusion.
- Abciximab is used in combination with aspirin and heparin.
- Abciximab’s usual dose is 0.25mg/kg via IV bolus.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on blood thinners, anticoagulants, and the complex process of hemostasis. Dive into the mechanisms of how blood thinners work and understand conditions like Thrombotic Thrombocytopenic Purpura (TTP). This quiz covers essential concepts related to blood coagulation and disorders.
