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Questions and Answers
Which characteristic distinguishes anticoagulant drugs from antiplatelet drugs?
Which characteristic distinguishes anticoagulant drugs from antiplatelet drugs?
- Anticoagulants enhance blood coagulation, while antiplatelets inhibit coagulation factors.
- Anticoagulants block platelet activation, while antiplatelets degrade thrombi.
- Anticoagulants degrade thrombi, while antiplatelets prevent the occurrence of a thrombus.
- Anticoagulants impede blood coagulation, while antiplatelets block platelet activation and aggregation. (correct)
Which of the following drugs inhibits vitamin K reductase?
Which of the following drugs inhibits vitamin K reductase?
- Warfarin (correct)
- Apixaban
- Heparin
- Aspirin
The anticoagulant effect of warfarin is primarily due to its interference with which of the following?
The anticoagulant effect of warfarin is primarily due to its interference with which of the following?
- Activation of plasminogen.
- Inhibition of platelet aggregation.
- Synthesis of vitamin K-dependent clotting factors. (correct)
- Direct thrombin inhibition.
Why is heparin often used in conjunction with warfarin at the start of anticoagulant therapy?
Why is heparin often used in conjunction with warfarin at the start of anticoagulant therapy?
Why is warfarin contraindicated during pregnancy?
Why is warfarin contraindicated during pregnancy?
What is the primary mechanism of action for unfractionated heparin (UFH)?
What is the primary mechanism of action for unfractionated heparin (UFH)?
Why can't heparin be administered orally effectively?
Why can't heparin be administered orally effectively?
Heparin-induced thrombocytopenia (HIT) is caused by what?
Heparin-induced thrombocytopenia (HIT) is caused by what?
Which of the following adverse effects is specifically associated with long-term use of heparin?
Which of the following adverse effects is specifically associated with long-term use of heparin?
Argatroban's mechanism of action involves?
Argatroban's mechanism of action involves?
Which statement is true regarding argatroban's elimination from the body?
Which statement is true regarding argatroban's elimination from the body?
What is the primary concern when administering argatroban to a patient?
What is the primary concern when administering argatroban to a patient?
What is the mechanism of action of apixaban?
What is the mechanism of action of apixaban?
What percentage of apixaban is typically absorbed after oral administration?
What percentage of apixaban is typically absorbed after oral administration?
A patient taking apixaban is also prescribed atorvastatin. What is a potential drug interaction that needs to be monitored?
A patient taking apixaban is also prescribed atorvastatin. What is a potential drug interaction that needs to be monitored?
What is the mechanism of action for aspirin as an antiplatelet drug?
What is the mechanism of action for aspirin as an antiplatelet drug?
How long does the antiplatelet effect of aspirin typically last, and why?
How long does the antiplatelet effect of aspirin typically last, and why?
What is a potential interaction between aspirin and warfarin?
What is a potential interaction between aspirin and warfarin?
Which of the following describes the mechanism of action of abciximab?
Which of the following describes the mechanism of action of abciximab?
A patient is prescribed abciximab. What other medication should be used with caution due to increased bleeding risk?
A patient is prescribed abciximab. What other medication should be used with caution due to increased bleeding risk?
Clopidogrel's antiplatelet effects are a result of what action?
Clopidogrel's antiplatelet effects are a result of what action?
What is a common adverse effect associated with clopidogrel?
What is a common adverse effect associated with clopidogrel?
What is the mechanism of action of dipyridamole?
What is the mechanism of action of dipyridamole?
Dipyridamole is contraindicated with what drug?
Dipyridamole is contraindicated with what drug?
What is the primary mechanism of action of alteplase?
What is the primary mechanism of action of alteplase?
What should be used with caution when using Alteplase due to an increased bleeding risk?
What should be used with caution when using Alteplase due to an increased bleeding risk?
A patient is on warfarin therapy and has an INR value of 8. Which action should be taken?
A patient is on warfarin therapy and has an INR value of 8. Which action should be taken?
What is the target of Warfarin?
What is the target of Warfarin?
What is the half life of Apixaban?
What is the half life of Apixaban?
What is the target of abciximab?
What is the target of abciximab?
Clopidogrel is a direct inhibitor of what?
Clopidogrel is a direct inhibitor of what?
Which drug inhibits both ADP receptor and prevents aggregation of platelets and cross-linking?
Which drug inhibits both ADP receptor and prevents aggregation of platelets and cross-linking?
P2Y purinoceptor 12 is a target of:
P2Y purinoceptor 12 is a target of:
What agents are considered being fibrinolytic drugs?
What agents are considered being fibrinolytic drugs?
What drug target both adenosine deaminase and phosphodiesterase?
What drug target both adenosine deaminase and phosphodiesterase?
What is the most common adverse effect of taking Argatroban?
What is the most common adverse effect of taking Argatroban?
What is the half life of Heparin?
What is the half life of Heparin?
Which of the following drugs is a direct factor Xa inhibitor?
Which of the following drugs is a direct factor Xa inhibitor?
A patient on warfarin therapy requires an immediate surgical procedure. Which of the following medications would most rapidly reverse the anticoagulant effects of warfarin?
A patient on warfarin therapy requires an immediate surgical procedure. Which of the following medications would most rapidly reverse the anticoagulant effects of warfarin?
A patient with a history of heparin-induced thrombocytopenia (HIT) requires anticoagulation. Which of the following would be the MOST appropriate choice?
A patient with a history of heparin-induced thrombocytopenia (HIT) requires anticoagulation. Which of the following would be the MOST appropriate choice?
A patient is prescribed apixaban for atrial fibrillation but also takes atorvastatin for hyperlipidemia. How does atorvastatin affect apixaban?
A patient is prescribed apixaban for atrial fibrillation but also takes atorvastatin for hyperlipidemia. How does atorvastatin affect apixaban?
A patient on aspirin therapy is scheduled for a minor surgical procedure. Which of the following is the most appropriate approach to manage their aspirin therapy?
A patient on aspirin therapy is scheduled for a minor surgical procedure. Which of the following is the most appropriate approach to manage their aspirin therapy?
A patient receiving alteplase for acute ischemic stroke begins to show signs of bleeding. What is the most appropriate immediate action?
A patient receiving alteplase for acute ischemic stroke begins to show signs of bleeding. What is the most appropriate immediate action?
Flashcards
Anticoagulants
Anticoagulants
Drugs that impede blood coagulation and prevent thrombus formation.
Antiplatelet drugs
Antiplatelet drugs
Drugs that block platelet activation and aggregation.
Fibrinolytic/Thrombolytic drugs
Fibrinolytic/Thrombolytic drugs
Drugs that degrade thrombi (blood clots).
Warfarin's Mechanism
Warfarin's Mechanism
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Warfarin's target
Warfarin's target
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Warfarin Protein Binding
Warfarin Protein Binding
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Warfarin Adverse Effects
Warfarin Adverse Effects
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UFH or LMW Heparin with Warfarin
UFH or LMW Heparin with Warfarin
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Heparin Mechanism of Action
Heparin Mechanism of Action
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Heparin Targets
Heparin Targets
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Heparin Absorption
Heparin Absorption
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Heparin Adverse Effects
Heparin Adverse Effects
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Argatroban's Mechanism
Argatroban's Mechanism
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Apixaban's Mechanism
Apixaban's Mechanism
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Apixaban Metabolism
Apixaban Metabolism
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Aspirin's Mechanism
Aspirin's Mechanism
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Aspirin's duration of effect
Aspirin's duration of effect
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Abciximab Mechanism
Abciximab Mechanism
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Clopidogrel's Mechanism
Clopidogrel's Mechanism
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Dipyridamole's Mechanism
Dipyridamole's Mechanism
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Alteplase's Mechanism
Alteplase's Mechanism
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Anticoagulants
Anticoagulants
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Antiplatelet drugs
Antiplatelet drugs
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Fibrinolytic drugs
Fibrinolytic drugs
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Study Notes
Anticoagulants, Antithrombotics and Antiplatelets Agents
- Anticoagulants prevent blood coagulation and the occurance of thrombus
- Antiplatelet drugs block platelet activation and aggregation
- Fibrinolytic or thrombolytic drugs degrade thrombi
Anticoagulant Drugs
- Vitamin K antagonists include: Warfarin, Acenocoumarol, Phenprocoumaron, Phenindione and Fluindione
- Heparin and related drugs include: UFH or HMWH, LMWH (Enoxaparin, dalteparin, tinzaparin) and Fondaparinux (synthetic pentasacharide)
- Direct thrombin inhibitors include: Hirudin and Lepirudin, Bivalirudin, Dabigatran, Argatroban and Melagatran
- fXa inhibitors includes: Rivaroxaban, Apixaban and Edoxaban
Antiplatelet Drugs
- Antiplatelet drugs include Aspirin, Prasugrel, Ticagrelor and Ticlopidine
- GPIIb/IIIa receptor inhibitors include: Abciximab, Eptifibatide and Tirofiban
- P2Y12 adenosine disphosphate receptor inhibitors includes Clopidogrel
- Inhibitors of both adenosine deaminase and phosphodiesterase includes Dipyridamole
- Fibrinolitic drugs include Alteplase and Reteplase
- Other agents include Aminocaproic acid, Tranexamic acid, Phytonadione and Protamine sulfate
Warfarin
- Inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2).
- Limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins.
- Factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited
- Targets Vitamin K epoxide reductase complex subunit 1
- Rapidly absorbed following oral administration, but absorption is also percutaneous
- 99% bound primarily to albumin
- Metabolised by hepatic microsomal enzymes
- Almost entirely removed through metabolism
- Very little is excreted unchanged in urine
- Metabolites are principally excreted into the urine, and to a lesser extent into the bile.
- Half life: R-warfarin 37-89 hours, S-warfarin 21-43 hours
- Transient hypercoagulable state can occur due to residual activity of the longer half-life procoagulants in the face of protein C depletion, overlapping therapy is generally 5-7 days.
- UFH or LMW heparin is used to achieve immediate anticoagulation until adequate warfarin-induced depletion of the procoagulant clotting factors is achieved.
- Should never be administered during pregnancy
- Can cause cutaneous necrosis
Warfarin Drug Interactions
- Increased Prothrombin Time drugs include: Amiodarone, Cimetidine, Disulfiram, Fluconazole, Metronidazole, Phenylbutazone, Sulfinpyrazone and Trimethoprim-sulfamethoxazole
- Decreased Prothrombin Time drugs include: Barbiturates, Cholestyramine and Rifampin
Heparin (UFH)
- Unfractionated heparin (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da
- Binds reversibly to ATIII, leading to inactivation of factors lla and Xa; the heparin-ATIII complex can also inactivate factors IX, XI, XII and plasmin
- Action is ATIII-dependent
- Acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin
- Targets include: Antithrombin-III potentiator, coagulation factor X inhibitor and P-selectin inhibitor
- Must be given parenterally as it is not absorbed through the gastrointestinal mucosa, usually given by iv infusion or deep sc injection
- Onset of action is immediate after iv injection but can be delayed 20 to 60 minutes following sc injection
- Protein binding: Very high, mostly to low-density lipoproteins
- Also extensively bound by globulins and fibrinogens
- Sites of biotransformation includes the liver and reticulo-endothelial system
- Appears to be removed mainly by the reticuloendothelial system
- A small fraction excreted in urine and cannot be eliminated by hemodialysis.
- Half life: 1.5 h
Adverse Effects of Heparin (UFH)
- Heparin-induced thrombocytopenia (HIT syndrome)
- Platelet counts usually do not fall until between days 5 and 12 of heparin therapy.
- HIT is caused by an immunological reaction, platelets form clots within the blood vessels, using up coagulation factors
- Can progress to thrombotic complications like arterial thrombosis, gangrene, stroke, myocardial infarction and disseminated intravascular coagulation
- Therapeutic doses for at least 4 months link to osteoporosis and spontaneous vertebral fractures
Heparin Drug Interactions
- Aliskiren and amiodarone increases risk or severity of hyperkalemia
- Omega-3 fatty acids increases the anticoagulant activities
- NSAIDs increases the risk or severity of hyperkalemia
Argatroban
- Action: Inhibits thrombin-catalyzed or -induced reactions, including fibrin formation, activation of coagulation factors V, VIII, and XIII, protein C, and platelet aggregation
- Is a prothrombin inhibitor
- Absorption is 100% intravenous
- 54% Protein binding
- Metabolized by liver via hydroxylation and aromatization of the 3-methyltetrahydroquinoline ring
- Age and gender do not substantially affect the pharmacodynamic or pharmacokinetic profile
- Primarily excreted in the feces (65%) through biliary secretion; 22% is eliminated via urine
- Half life: 39-51 minutes
- Causes excess of bleeding
- The risk or severity of bleeding can increase when combined with Acetylsalicylic acid
- The metabolism can be decreased when combined with Atorvastatin
Apixaban
- An oral, direct, and highly selective factor Xa (FXa) inhibitor (of both free and prothrombinase-bound FXa independently of antithrombin III)
- Action: Directly inhibits (in a reversible manner), free and clot-bound factor Xa to inhibit coagulation
- Targets coagulation factor X
- Absorbs in the stomach and small intestine, bioavailability is about 50%
- Oral administration absorption is not affected by food
- 87% plasma proteins
- Metabolism: Hepatic by o-demethylation and hydroxylation to metabolites (CYP3A4)
- 25% of the administered dose is eliminated in the feces and urine
- Eliminated in the feces, excreted by the intestine and bile
- Half life: 12 hours
- Causes major bleeding
Apixaban Drug Interactions
- The serum concentration of Apixaban can be increased when it is combined with Acetaminophen.
- Can increase the anticoagulant activities of Acetylsalicylic acid.
- Atorvastatin metabolism can be decreased
- The risk or severity of bleeding and hemorrhage can be increased when Sulindac is combined
Aspirin
- Directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid
- Irreversible acetylation renders cyclooxygenase inactive, preventing the formation of the aggregating agent thromboxane A2 in platelets
- Platelets lack the ability to synthesize new proteins, so effects persist for the life of the exposed platelets (7-10 days)
- Inhibit production of prostacyclin (prostaglandin 12), by blood vessel endothelial cells
- Targets prostaglandin G/H synthase 1 & 2
- Absorption is generally rapid and complete following oral administration with varying effects following specific salicylate used, dosage form, and gastric or intraluminal pH
- 99.5% binds to albumin
- Hydrolyzed primarily in the liver to salicylic acid, conjugated with glycine, forming salicyluric acid and glucuronic acid and excreted largely in the urine
- Plasma half-life is approximately 15 minutes, which is lengthened depending on the dose.
- 300 to 650 mg have a half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is increased to 5 hours and with 2 grams it is increased to about 9 hours
Aspirin Adverse Effects and Drug Interactions
- Adverse Effects include: tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma, and death
- Warfarin: The risk or severity of bleeding can increase when Acetylsalicylic acid is combined with (R)-warfarin
- Statins: Serum concentration of Acetylsalicylic acid can increase when combined with Atorvastatin
- Fibrates: The metabolism of Acetylsalicylic acid can be decreased when combined with Gemfibrozil
Abciximab
- A Fab fragment of the chimeric human-murine monoclonal antibody 7E3.
- Action: binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. Block access of large molecules to the receptor (but not by direct interaction) with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa.
- Targets integrin beta-3, integrin alpha-IIb and vitronectin
- Metabolism: Most likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production and is excreted renally.
- Following intravenous bolus administration, concentrations decrease rapidly half-life of less than 10 minutes
- Second phase half-life of about 30 minutes, related to rapid binding to the platelet GPIIb/IIIa receptors.
- The risk or severity of bleeding can be increased when combined with Acetylsalicylic acid or Indometacin
- Omega-3 fatty acids may increase the antiplatelet activities
Clopidogrel
- Action: Specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor. Importnat in aggregation of platelets and cross-linking by the protein fibrin. Prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex.
- Targets P2Y purinoceptor 12
- Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites
- Bioavailability isn't affected by food
- 98% protein binding
- Hepatic, extensive and rapid, by hydrolysis to the main circulating metabolite, a carboxylic acid derivative, which accounts for appx 85% of the circulating drug-related compounds.
- Appx 50% of total radioactivity is excreted in urine and approximately 46% in feces over the 5 days post-dosing.
- Half life: 11 days
- Adverse effects include vomiting, breathing difficulty, hemorrhage, and prostration
- The metabolism of (S)-Warfarin can be decreased when combined
- Increased risk/severity of adverse effects when combined with Aminosalicylic Acid.
- Atorvastatin metabolism can be decreased when combined
Dipyridamole
- A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells.
- Action: Inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, inhibits platelet function. Elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity.
- Targets: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A and adenosine deaminase
- 70% absorption, 99% protein binding, hepatic metabolism
- Metabolized in the liver to the glucuronic acid conjugate and excreted with the bile, half life 40 min
- Possible adverse effect of hypotension. Vasopressor drug may be used if necessary
- The risk/severity of bleeding can increase when Dipyridamole in combined with (R)-warfarin
- Can increase the bradycardic activities of Metoprolol while also increasing antihypertensive activities of Captopril
Alteplase
- Binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain.
- The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin.
- Plasmin degrades the fibrin matrix of the thrombus, exerting its thrombolytic action.
- Targets plasminogen and fibrinogen alpha chain
- Clopidogrel can increase the anticoagulant activities
- The risk or severity of bleeding can increase when combined with Acetylsalicylic acid or with Heparin
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