[ ]
Latest News Updates
Showing posts with label Hematologic Drugs. Show all posts
Showing posts with label Hematologic Drugs. Show all posts
Thrombolytic drugs
By Piscean | Wednesday, April 6, 2011 | Posted in , | With 0 comments

Thrombolytic drugs
Thrombolytic drugs are used to dissolve a preexisting clot or thrombus, often in an acute or emergency situation. Some of the thrombolytic drugs currently used include alteplase, reteplase, streptokinase, tenecteplase, and urokinase.
Pharmacokinetics
After I.V. or intracoronary administration, thrombolytic drugs are distributed immediately throughout the circulation, quickly activating plasminogen (a precursor to plasmin, which dissolves fibrin clots).
Blood work
Alteplase, reteplase, tenecteplase, and urokinase are cleared rap-idly from circulating plasma, primarily by the liver. Streptokinase is removed rapidly from the circulation by antibodies and the reticuloendothelial system (a body system involved in defending against infection and disposing of products of cell breakdown). These agents don’t appear to cross the placental barrier.
Pharmacodynamics
Thrombolytic drugs convert plasminogen to plasmin, which lyses (dissolves) thrombi, fibrinogen, and other plasma proteins.

Pharmacotherapeutics
Thrombolytic drugs have a number of uses. They’re used to treat certain thromboembolic disorders (such as acute MI, acute ischemic stroke, and peripheral artery occlusion) and have also been used to dissolve thrombi in arteriovenous cannulas (used in dialysis) and I.V. catheters to reestablish blood flow.
Now I get it!
How alteplase helps restore circulation
When a thrombus forms in an artery, it obstructs the blood supply, causing ischemia and necrosis. Alteplase can dissolve a thrombus in either the coronary or pulmonary artery, restoring the blood supply to the area beyond the blockage.
Obstructed artery
A thrombus blocks blood flow through the artery, causing distal ischemia.
Inside the thrombus
Alteplase enters the thrombus, which consists of plasminogen bound to fibrin. Alteplase binds to the fibrin-plasminogen complex, converting the inactive plasminogen into active plasmin. This active plasmin digests the fibrin, dissolving the thrombus. As the thrombus dissolves, blood flow resumes.
Thrombolytic drugs
By Piscean | | Posted in , | With 0 comments
Thrombolytic drugs
Thrombolytic drugs are used to dissolve a preexisting clot or thrombus, often in an acute or emergency situation. Some of the thrombolytic drugs currently used include alteplase, reteplase, streptokinase, tenecteplase, and urokinase.
 
Pharmacokinetics
After I.V. or intracoronary administration, thrombolytic drugs are distributed immediately throughout the circulation, quickly activating plasminogen (a precursor to plasmin, which dissolves fibrin clots).
Blood work
 
Alteplase, reteplase, tenecteplase, and urokinase are cleared rap-idly from circulating plasma, primarily by the liver. Streptokinase is removed rapidly from the circulation by antibodies and the reticuloendothelial system (a body system involved in defending against infection and disposing of products of cell breakdown). These agents don’t appear to cross the placental barrier.
 
Pharmacodynamics
Thrombolytic drugs convert plasminogen to plasmin, which lyses (dissolves) thrombi, fibrinogen, and other plasma proteins.

Pharmacotherapeutics
Thrombolytic drugs have a number of uses. They’re used to treat certain thromboembolic disorders (such as acute MI, acute ischemic stroke, and peripheral artery occlusion) and have also been used to dissolve thrombi in arteriovenous cannulas (used in dialysis) and I.V. catheters to reestablish blood flow.
 
Now I get it!
How alteplase helps restore circulation
When a thrombus forms in an artery, it obstructs the blood supply, causing ischemia and necrosis. Alteplase can dissolve a thrombus in either the coronary or pulmonary artery, restoring the blood supply to the area beyond the blockage.
 
Obstructed artery
A thrombus blocks blood flow through the artery, causing distal ischemia.
Inside the thrombus
 
Alteplase enters the thrombus, which consists of plasminogen bound to fibrin. Alteplase binds to the fibrin-plasminogen complex, converting the inactive plasminogen into active plasmin. This active plasmin digests the fibrin, dissolving the thrombus. As the thrombus dissolves, blood flow resumes.
Thrombolytic drugs
By Piscean | | Posted in , | With 0 comments
Thrombolytic drugs
Thrombolytic drugs are used to dissolve a preexisting clot or thrombus, often in an acute or emergency situation. Some of the thrombolytic drugs currently used include alteplase, reteplase, streptokinase, tenecteplase, and urokinase.
 
Pharmacokinetics
After I.V. or intracoronary administration, thrombolytic drugs are distributed immediately throughout the circulation, quickly activating plasminogen (a precursor to plasmin, which dissolves fibrin clots).
Blood work
 
Alteplase, reteplase, tenecteplase, and urokinase are cleared rap-idly from circulating plasma, primarily by the liver. Streptokinase is removed rapidly from the circulation by antibodies and the reticuloendothelial system (a body system involved in defending against infection and disposing of products of cell breakdown). These agents don’t appear to cross the placental barrier.
 
Pharmacodynamics
Thrombolytic drugs convert plasminogen to plasmin, which lyses (dissolves) thrombi, fibrinogen, and other plasma proteins.

Pharmacotherapeutics
Thrombolytic drugs have a number of uses. They’re used to treat certain thromboembolic disorders (such as acute MI, acute ischemic stroke, and peripheral artery occlusion) and have also been used to dissolve thrombi in arteriovenous cannulas (used in dialysis) and I.V. catheters to reestablish blood flow.
 
Now I get it!
How alteplase helps restore circulation
When a thrombus forms in an artery, it obstructs the blood supply, causing ischemia and necrosis. Alteplase can dissolve a thrombus in either the coronary or pulmonary artery, restoring the blood supply to the area beyond the blockage.
 
Obstructed artery
A thrombus blocks blood flow through the artery, causing distal ischemia.
Inside the thrombus
 
Alteplase enters the thrombus, which consists of plasminogen bound to fibrin. Alteplase binds to the fibrin-plasminogen complex, converting the inactive plasminogen into active plasmin. This active plasmin digests the fibrin, dissolving the thrombus. As the thrombus dissolves, blood flow resumes.
Factor Xa inhibitor drugs
By Piscean | | Posted in , | With 0 comments

Factor Xa inhibitor drugs
Factor Xa inhibitor drugs are used to prevent DVT in patients undergoing total hip and knee replacement surgery or surgery to repair a hip fracture. The only factor Xa inhibitor drug used in the United States is fondaparinux.
Pharmacokinetics
Administered subQ, fondaparinux is absorbed rapidly and completely and is excreted primarily unchanged in urine. Its effects peak within 2 hours of administration and last for about 17 to 24 hours.
Pharmacodynamics
Fondaparinux binds to antithrombin III and greatly influences the neutralization of factor Xa by antithrombin III. Neutralization of factor Xa interrupts the coagulation cascade, thereby inhibiting clot formation.
Pharmacotherapeutics
Fondaparinux is used only to prevent the formation of blood clots.
Drug interactions
Avoid administering fondaparinux with another drug that may increase the risk of bleeding. 
Warning!
Adverse reactions to factor Xa inhibitors
Adverse reactions that can occur with factor Xa inhibitor therapy include:
  • bleeding
  • nausea
  • anemia
  • fever
  • rash
  • constipation
  • edema.
Factor Xa inhibitor drugs
By Piscean | | Posted in , | With 0 comments
Factor Xa inhibitor drugs
Factor Xa inhibitor drugs are used to prevent DVT in patients undergoing total hip and knee replacement surgery or surgery to repair a hip fracture. The only factor Xa inhibitor drug used in the United States is fondaparinux.
 
Pharmacokinetics
Administered subQ, fondaparinux is absorbed rapidly and completely and is excreted primarily unchanged in urine. Its effects peak within 2 hours of administration and last for about 17 to 24 hours.
 
Pharmacodynamics
Fondaparinux binds to antithrombin III and greatly influences the neutralization of factor Xa by antithrombin III. Neutralization of factor Xa interrupts the coagulation cascade, thereby inhibiting clot formation.
 
Pharmacotherapeutics
Fondaparinux is used only to prevent the formation of blood clots.
Drug interactions
Avoid administering fondaparinux with another drug that may increase the risk of bleeding. 
Warning!
Adverse reactions to factor Xa inhibitors
Adverse reactions that can occur with factor Xa inhibitor therapy include:
  • bleeding
  • nausea
  • anemia
  • fever
  • rash
  • constipation
  • edema.
Direct thrombin inhibitors
By Piscean | | Posted in , | With 0 comments

Direct thrombin inhibitors
Thrombin inhibitors, including argatroban, bivalirudin, and lepirudin, help prevent the formation of blood clots.
Pharmacokinetics
Direct thrombin inhibitors are typically administered by continuous I.V. infusion. They may also be given as an intra-coronary bolus during cardiac catheterization. In that case, the drug begins acting in 2 minutes, with a peak response of 15 minutes and a duration of 2 hours. After subQ injection, plasma levels peak in 2 hours; after I.V. administration, levels peak in less than 1 hour.
Effects on PTT become apparent within 4 to 5 hours of administration. In patients with heparin-induced thrombocytopenia, platelet count recovery becomes apparent within 3 days.
Argatroban is metabolized by the liver and excreted primarily in stool. Bivalirudin and lepirudin are metabolized by the liver and kidneys and excreted in urine
Pharmacodynamics
Direct thrombin inhibitors interfere with blood clotting by directly blocking all thrombin activity. These drugs offer several advantages over heparin: direct thrombin inhibitors act against soluble as well as clot-bound thrombin (thrombin in clots that have already formed); their anticoagulant effects are more predictable than those of heparin; and their actions aren’t inhibited by the platelet release reaction.The binding of the drug to thrombin is reversible.
Pharmacotherapeutics
Administered by I.V. infusion, argatroban and lepirudin are used to treat heparin-induced thrombocytopenia (HIT). Argatroban may also be given with aspirin to patients with HIT who are undergoing a cardiac procedure, such as PTCA, coronary stent placement, or atherectomy.

Bivalirudin has been approved for use in patients with unstable angina undergoing PTCA, and should be used in conjunction with aspirin therapy.
Patients with liver dysfunction may require a reduced dose of argatroban. Also, the dosage of bivalirudin and lepirudin may need to be reduced in patients with impaired renal function.
Use caution when administering a direct thrombin inhibitor to a patient who has an increased risk of bleeding. Patients at greatest risk for hemorrhage are those with severe hypertension, gastric ulcers, or hematologic disorders associated with increased bleeding. Patients receiving spinal anesthesia or those undergoing a lumbar puncture or having major surgery (especially surgery of the brain, spinal cord, or the eye) also have an increased risk for bleeding.
Drug interactions
  • Hemorrhage can occur as an adverse reaction to direct thrombin inhibitors, so avoid giving these drugs with another drug that may also increase the risk of bleeding.
  • Discontinue all parenteral anticoagulants before administering argatroban.
  • Administration of argatroban along with warfarin increases the INR.
  • If the patient has received heparin, allow time for heparin’s effect on PTT to decrease before administering argatroban.
Direct thrombin inhibitors
By Piscean | | Posted in , | With 0 comments
Direct thrombin inhibitors
Thrombin inhibitors, including argatroban, bivalirudin, and lepirudin, help prevent the formation of blood clots.
 
Pharmacokinetics
Direct thrombin inhibitors are typically administered by continuous I.V. infusion. They may also be given as an intra-coronary bolus during cardiac catheterization. In that case, the drug begins acting in 2 minutes, with a peak response of 15 minutes and a duration of 2 hours. After subQ injection, plasma levels peak in 2 hours; after I.V. administration, levels peak in less than 1 hour.
Effects on PTT become apparent within 4 to 5 hours of administration. In patients with heparin-induced thrombocytopenia, platelet count recovery becomes apparent within 3 days.
Argatroban is metabolized by the liver and excreted primarily in stool. Bivalirudin and lepirudin are metabolized by the liver and kidneys and excreted in urine
 
Pharmacodynamics
Direct thrombin inhibitors interfere with blood clotting by directly blocking all thrombin activity. These drugs offer several advantages over heparin: direct thrombin inhibitors act against soluble as well as clot-bound thrombin (thrombin in clots that have already formed); their anticoagulant effects are more predictable than those of heparin; and their actions aren’t inhibited by the platelet release reaction.The binding of the drug to thrombin is reversible.
 
Pharmacotherapeutics
Administered by I.V. infusion, argatroban and lepirudin are used to treat heparin-induced thrombocytopenia (HIT). Argatroban may also be given with aspirin to patients with HIT who are undergoing a cardiac procedure, such as PTCA, coronary stent placement, or atherectomy.

Bivalirudin has been approved for use in patients with unstable angina undergoing PTCA, and should be used in conjunction with aspirin therapy.
Patients with liver dysfunction may require a reduced dose of argatroban. Also, the dosage of bivalirudin and lepirudin may need to be reduced in patients with impaired renal function.
Use caution when administering a direct thrombin inhibitor to a patient who has an increased risk of bleeding. Patients at greatest risk for hemorrhage are those with severe hypertension, gastric ulcers, or hematologic disorders associated with increased bleeding. Patients receiving spinal anesthesia or those undergoing a lumbar puncture or having major surgery (especially surgery of the brain, spinal cord, or the eye) also have an increased risk for bleeding.
 
Drug interactions
  • Hemorrhage can occur as an adverse reaction to direct thrombin inhibitors, so avoid giving these drugs with another drug that may also increase the risk of bleeding.
  • Discontinue all parenteral anticoagulants before administering argatroban.
  • Administration of argatroban along with warfarin increases the INR.
  • If the patient has received heparin, allow time for heparin’s effect on PTT to decrease before administering argatroban.
Antiplatelet drugs
By Piscean | | Posted in , | With 0 comments

Antiplatelet drugs
Antiplatelet drugs are used to prevent arterial thromboembolism, particularly in patients at risk for MI, stroke, and arteriosclerosis (hardening of the arteries).
Aspirin, clopidogrel, dipyridamole, sulfinpyrazone, and ticlopidine are examples of oral antiplatelet drugs. Antiplatelet drugs administered I.V. include abciximab, eptifibatide, and tirofiban.
Pharmacokinetics
When taken orally, antiplatelet drugs are absorbed very quickly and reach peak concentration in 1 to 2 hours. Aspirin maintains its antiplatelet effect for about 10 days, or as long as platelets normally survive. The effects of clopidogrel last about 5 days. Sulfinpyrazone may require several days of administration before its antiplatelet effects occur.
After I.V. administration, antiplatelet drugs are quickly distributed throughout the body. They’re minimally metabolized and excreted unchanged in urine. The effects of these drugs occur within 15 to 20 minutes of administration and last about 6 to 8 hours.
Elderly patients and patients with renal failure may have decreased clearance of antiplatelet drugs, which would prolong the antiplatelet effect.
Pharmacodynamics
Antiplatelet drugs interfere with platelet activity in different drug-specific and dose-related ways.
  • Low doses of aspirin inhibit clot formation by blocking the synthesis of prostaglandin, which in turn prevents formation of the platelet-aggregating substance thromboxane A2.
  • Clopidogrel inhibits platelet aggregation by inhibiting platelet-fibrinogen binding.
  • I.V. antiplatelet drugs inhibit the glycoprotein IIa-IIIb receptor, which is the major receptor involved in platelet aggregation.
  • Dipyridamole may inhibit platelet aggregation because it increases adenosine, a coronary vasodilator and platelet aggregation inhibitor.
  • Ticlopidine inhibits the binding of fibrinogen to platelets during the first stage of the clotting cascade.
  • Sulfinpyrazone inhibits several platelet functions. It lengthens platelet survival and prolongs the patency of arteriovenous shunts used for hemodialysis. A single dose rapidly inhibits platelet aggregation.

Pharmacotherapeutics
Antiplatelet drugs have many different uses.
Managing MIs
Aspirin is used in patients who have had a previous MI or who have unstable angina to reduce the risk of death in patients at high risk for CAD. It’s also prescribed to reduce the risk of transient ischemic attacks (TIAs) (temporary reduction in circulation to the brain).
Clopidogrel is used to reduce the risk of stroke or vascular death in patients with a history of a recent MI, stroke, or established peripheral artery disease. Clopidogrel is also used to help treat acute coronary syndromes, especially in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft.
Eptifibatide may be used for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention (PCI). Abciximab may also be used in combination with PCI. Tirofiban may be used to treat acute coronary syndrome.
Salve for surgery
Dipyridamole is used with a coumarin compound to prevent thrombus formation after cardiac valve replacement. Dipyridamole may be administered with aspirin to prevent blood clots in patients who have had coronary artery bypass grafts (bypass surgery) or prosthetic (artificial) heart valves.
Warning!
Adverse reactions to antiplatelet drugs
Hypersensitivity reactions, particularly anaphylaxis, can occur. Bleeding is the most common adverse reaction when I.V. antiplatelet drugs are administered.
Aspirin
  • Stomach pain
  • Heartburn, nausea
  • Constipation
  • Blood in stool
  • Slight gastric blood loss
Clopidogrel
  • Headache
  • Skin ulceration
  • Joint pain
  • Flulike symptoms
  • Upper respiratory tract infection
Sulfinpyrazone
  • Abdominal discomfort
Ticlopidine
  • Diarrhea
  • Nausea
  • Dyspepsia
  • Rash
  • Elevated liver function test results
  • Neutropenia
Dipyridamole
  • Headache
  • Dizziness
  • Nausea
  • Flushing
  • Weakness
  • Fainting
  • Mild GI distress
Circumventing stroke
Ticlopidine is used to reduce the risk of thrombotic stroke in high-risk patients, such as those with a history of frequent TIAs or a previous thrombotic stroke.
Drug interactions
  • Antiplatelet medications taken with NSAIDs, heparin, oral anticoagulants, or another antiplatelet medication increase the risk of bleeding.
  • Sulfinpyrazone taken with aspirin and oral anticoagulants increases the risk of bleeding.
Tales of toxicity
  • Aspirin increases the risk of toxicity of methotrexate and valproic acid.
  • Aspirin and ticlopidine may reduce the effectiveness of sulfinpyrazone to relieve signs and symptoms of gout.
  • Antacids may reduce the plasma levels of ticlopidine.
  • Cimetidine increases the risk of ticlopidine toxicity and bleeding.
You just don’t know
Because guidelines haven’t been established for administrating ticlopidine with heparin, oral anticoagulants, aspirin, or fibrinolytic drugs, these drugs should be discontinued before ticlopidine therapy begins. 

Antiplatelet drugs
By Piscean | | Posted in , | With 0 comments
Antiplatelet drugs
Antiplatelet drugs are used to prevent arterial thromboembolism, particularly in patients at risk for MI, stroke, and arteriosclerosis (hardening of the arteries).
Aspirin, clopidogrel, dipyridamole, sulfinpyrazone, and ticlopidine are examples of oral antiplatelet drugs. Antiplatelet drugs administered I.V. include abciximab, eptifibatide, and tirofiban.
 
Pharmacokinetics
When taken orally, antiplatelet drugs are absorbed very quickly and reach peak concentration in 1 to 2 hours. Aspirin maintains its antiplatelet effect for about 10 days, or as long as platelets normally survive. The effects of clopidogrel last about 5 days. Sulfinpyrazone may require several days of administration before its antiplatelet effects occur.
After I.V. administration, antiplatelet drugs are quickly distributed throughout the body. They’re minimally metabolized and excreted unchanged in urine. The effects of these drugs occur within 15 to 20 minutes of administration and last about 6 to 8 hours.
Elderly patients and patients with renal failure may have decreased clearance of antiplatelet drugs, which would prolong the antiplatelet effect.
Pharmacodynamics
Antiplatelet drugs interfere with platelet activity in different drug-specific and dose-related ways.
  • Low doses of aspirin inhibit clot formation by blocking the synthesis of prostaglandin, which in turn prevents formation of the platelet-aggregating substance thromboxane A2.
  • Clopidogrel inhibits platelet aggregation by inhibiting platelet-fibrinogen binding.
  • I.V. antiplatelet drugs inhibit the glycoprotein IIa-IIIb receptor, which is the major receptor involved in platelet aggregation.
  • Dipyridamole may inhibit platelet aggregation because it increases adenosine, a coronary vasodilator and platelet aggregation inhibitor.
  • Ticlopidine inhibits the binding of fibrinogen to platelets during the first stage of the clotting cascade.
  • Sulfinpyrazone inhibits several platelet functions. It lengthens platelet survival and prolongs the patency of arteriovenous shunts used for hemodialysis. A single dose rapidly inhibits platelet aggregation.

Pharmacotherapeutics
Antiplatelet drugs have many different uses.
Managing MIs
Aspirin is used in patients who have had a previous MI or who have unstable angina to reduce the risk of death in patients at high risk for CAD. It’s also prescribed to reduce the risk of transient ischemic attacks (TIAs) (temporary reduction in circulation to the brain).
Clopidogrel is used to reduce the risk of stroke or vascular death in patients with a history of a recent MI, stroke, or established peripheral artery disease. Clopidogrel is also used to help treat acute coronary syndromes, especially in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft.
Eptifibatide may be used for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention (PCI). Abciximab may also be used in combination with PCI. Tirofiban may be used to treat acute coronary syndrome.
Salve for surgery
Dipyridamole is used with a coumarin compound to prevent thrombus formation after cardiac valve replacement. Dipyridamole may be administered with aspirin to prevent blood clots in patients who have had coronary artery bypass grafts (bypass surgery) or prosthetic (artificial) heart valves.
 
Warning!
Adverse reactions to antiplatelet drugs
Hypersensitivity reactions, particularly anaphylaxis, can occur. Bleeding is the most common adverse reaction when I.V. antiplatelet drugs are administered.
Aspirin
  • Stomach pain
  • Heartburn, nausea
  • Constipation
  • Blood in stool
  • Slight gastric blood loss
Clopidogrel
  • Headache
  • Skin ulceration
  • Joint pain
  • Flulike symptoms
  • Upper respiratory tract infection
Sulfinpyrazone
  • Abdominal discomfort
Ticlopidine
  • Diarrhea
  • Nausea
  • Dyspepsia
  • Rash
  • Elevated liver function test results
  • Neutropenia
Dipyridamole
  • Headache
  • Dizziness
  • Nausea
  • Flushing
  • Weakness
  • Fainting
  • Mild GI distress
Circumventing stroke
Ticlopidine is used to reduce the risk of thrombotic stroke in high-risk patients, such as those with a history of frequent TIAs or a previous thrombotic stroke.
Drug interactions
  • Antiplatelet medications taken with NSAIDs, heparin, oral anticoagulants, or another antiplatelet medication increase the risk of bleeding.
  • Sulfinpyrazone taken with aspirin and oral anticoagulants increases the risk of bleeding.
Tales of toxicity
  • Aspirin increases the risk of toxicity of methotrexate and valproic acid.
  • Aspirin and ticlopidine may reduce the effectiveness of sulfinpyrazone to relieve signs and symptoms of gout.
  • Antacids may reduce the plasma levels of ticlopidine.
  • Cimetidine increases the risk of ticlopidine toxicity and bleeding.
You just don’t know
Because guidelines haven’t been established for administrating ticlopidine with heparin, oral anticoagulants, aspirin, or fibrinolytic drugs, these drugs should be discontinued before ticlopidine therapy begins. 

Oral anticoagulants
By Piscean | Tuesday, April 5, 2011 | Posted in , | With 0 comments
Oral anticoagulants
The major oral anticoagulant used in the United States is the coumarin compound warfarin.



Pharmacokinetics
Warfarin is absorbed rapidly and almost completely when it’s taken orally. It binds extensively to plasma albumin and is metabolized in the liver and excreted in urine. Although warfarin is absorbed quickly, its effects don’t occur for about 48 hours, with the full effect taking 3 to 4 days.
Because warfarin is highly plasma-protein-bound and is metabolized by the liver, administration of warfarin with other medications may alter the amount of warfarin in the body. This may increase the risk of bleeding or clotting, depending upon the medications administered.

Pharmacodynamics
Oral anticoagulants alter the ability of the liver to synthesize vitamin K’dependent clotting factors, including prothrombin and factors VII, IX, and X. However, clotting factors already in the bloodstream continue to coagulate blood until they become depleted, so anticoagulation doesn’t begin immediately. 
Pharmacotherapeutics
Oral anticoagulants are prescribed to treat or prevent thromboembolism. Patients with this disorder begin taking the medication while still receiving heparin. However, outpatients at high risk for thromboembolism may begin oral anticoagulants without first receiving heparin.
Deep in the veins
Oral anticoagulants are also the drugs of choice to prevent DVT and for patients with prosthetic heart valves or diseased mitral valves. To decrease the risk of arterial clotting, oral anticoagulants are sometimes combined with an antiplatelet drug, such as aspirin, clopidogrel, or dipyridamole.
Monitoring warfarin levels
Patients taking warfarin need close monitoring of prothrombin time and International Normalized Ratios to make sure they are maintaining therapeutic levels of the drug. If laboratory results fall outside the accepted range, warfarin dosage should be adjusted.
Drug interactions
Many patients who take oral anticoagulants also receive other drugs, placing them at risk for serious 
drug interactions.
  • Many drugs, such as highly protein-bound medications, increase the effects of warfarin, resulting in an increased risk of bleeding. Examples include acetaminophen, allopurinol, amiodarone, cephalosporins, cimetidine, ciprofloxacin, clofibrate, danazol, diazoxide, disulfiram, erythromycin, fluoroquinolones, glucagon, heparin, ibuprofen, isoniazid, ketoprofen, methylthiouracil, metronidazole, miconazole, neomycin, propafenone, propylthiouracil,quinidine, streptokinase, sulfonamides, tamoxifen, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, and vitamin E.
  • Drugs metabolized by the liver may increase or decrease the effectiveness of warfarin. Examples include barbiturates, carbamazepine, corticosteroids, corticotropin, mercaptopurine, nafcillin, hormonal contraceptives containing estrogen, rifampin, spironolactone, sucralfate, and trazodone.
  • The risk of phenytoin toxicity increases when phenytoin is taken with warfarin, and phenytoin may increase or decrease the effects of warfarin.
Other interactions include the following:
  • A diet high in vitamin K reduces the effectiveness of warfarin.
  • Chronic alcohol abuse increases the patient’s risk of clotting while taking warfarin. Acute alcohol intoxication increases the risk of bleeding.
  • Vitamin K and fresh frozen plasma reduce the effects of warfarin. 
Warning!
Adverse reactions to oral anticoagulants
The primary adverse reaction to oral anticoagulant therapy is minor bleeding. Severe bleeding can occur, however, with the most common site being the GI tract. Bleeding into the brain may be fatal. Bruises and hematomas may form at arterial puncture sites (for example, after a blood gas sample is drawn). Necrosis or gangrene of the skin and other tissues can occur.
Quick fix
The effects of oral anticoagulants can be reversed with phytonadione (vitamin K1).
Anticoagulant drugs
By Piscean | | Posted in , | With 0 comments

Anticoagulant drugs
Anticoagulant drugs are used to reduce the ability of the blood to clot. Major categories of anticoagulants include:
  • heparin and its derivatives
  • oral anticoagulants
  • antiplatelet drugs
  • direct thrombin inhibitors
  • factor Xa inhibitor drugs.
Heparin
Heparin, prepared commercially from animal tissue, is an anti-thrombolytic agent used to treat and prevent clot formation. Because it doesn’t affect the synthesis of clotting factors, heparin can’t dissolve already-formed clots.

Weighty words
The two types of heparin are unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). LMWHs, such as dalteparin, enoxaparin, and tinzaparin, were developed to prevent deep vein thrombosis (DVT) (a blood clot in the deep veins, usually of the legs) in surgical patients.
Pharmacokinetics
Because heparin isn’t absorbed well from the GI tract, it must be administered parenterally. UFH is administered I.V. by continuous infusion or by subQ injection. LMWHs, because of their prolonged circulating half-life, can be administered once or twice daily by subQ injection.
After I.V. administration, the distribution of heparin is immediate; however, distribution isn’t as predictable following subQ injection.
I.M. is out
Heparin isn’t given I.M. because of the risk of localized bleeding. Heparin is metabolized in the liver, and its metabolites are excreted in urine.
Pharmacodynamics
Heparin prevents the formation of new thrombi. Here’s how it works:
  • Heparin inhibits the formation of thrombin and fibrin by activating antithrombin III.
  • Antithrombin III then inactivates factors IXa, Xa, XIa, and XIIa in the intrinsic and common pathways. The end result is prevention of a stable fibrin clot.
  • In low doses, heparin increases the activity of antithrombin III against factor Xa and thrombin and inhibits clot formation.
  • Much larger doses are necessary to inhibit fibrin formation after a clot has been formed. This relationship between dose and effect is the rationale for using low-dose heparin to prevent clotting.
  • Whole blood clotting time, thrombin time, and partial thromboplastin time (PTT) are prolonged during heparin therapy. However, these times may be only slightly prolonged with low or ultra-low preventive doses.

Pharmacotherapeutics
Heparin may be used in a number of clinical situations to prevent the formation of new clots or the extension of existing clots. These situations include:
  • preventing or treating venous thromboemboli, characterized by inappropriate or excessive intravascular activation of blood clotting

  • treating disseminated intravascular coagulation, a complication of other diseases, resulting in accelerated clotting
  • treating arterial clotting and preventing embolus formation in patients with atrial fibrillation, an arrhythmia in which ineffective atrial contractions cause blood to pool in the atria, increasing the risk of clot formation
  • preventing thrombus formation and promoting cardiac circulation in an acute myocardial infarction (MI) by preventing further clot formation at the site of the already formed clot.
Safe and sound
Monitoring PTT in heparin therapy
A patient receiving unfractionated heparin (UFH) therapy requires close monitoring of his partial thromboplastin time (PTT). Dosage adjustments, based on the test results, are typically necessary to ensure therapeutic effectiveness without increased risk of bleeding.
Low-molecular-weight heparin (LMWH) therapy doesn’t require PTT monitoring. Currently, no laboratory test exists to assess the effectiveness of LMWH therapy.
Heparin-induced thrombocytopenia
Platelet counts should be monitored in all patients receiving heparin therapy. A patient who develops heparin-induced thrombocytopenia (HIT) should be switched from anticoagulant therapy to argatroban, bivalirudin, or lepirudin. These drugs are direct thrombin inhibitors indicated for use in the patient who needs anticoagulation therapy but has HIT.
Circulate freely
Heparin can be used to prevent clotting whenever the patient’s blood must circulate outside the body through a machine, such as the cardiopulmonary bypass machine or hemodialysis machine, and during blood transfusions. 
You’re the one
Heparin is also useful for preventing clotting during intra-abdominal or orthopedic surgery. (These types of surgeries, in many cases, activate the coagulation mechanisms excessively.) In fact, heparin is the drug of choice for orthopedic surgery.



Warning!
Adverse reactions to heparin
One advantage of heparin is that it produces relatively few adverse reactions. Even so, these reactions can usually be prevented if the patient’s partial thromboplastin time is maintained within the therapeutic range
.
Bleeding, the most common adverse reaction, can be reversed easily by administering protamine sulfate, which binds to heparin to form a stable salt.
Other adverse reactions include bruising, hematoma formation, necrosis of skin or other tissue, and thrombocytopenia.

Drug interactions
  • Because heparin acts synergistically with all oral anticoagulants, the risk of bleeding increases when the patient takes both drugs together. The prothrombin time and International Normalized Ratio (INR), used to monitor the effects of oral anticoagulants, may also be prolonged.
  • The risk of bleeding increases when the patient takes nonsteroidal anti-inflammatory drugs (NSAIDs), iron dextran, cilostazol, or an antiplatelet drug, such as aspirin, clopidogrel, ticlopidine, or dipyridamole, while receiving heparin.
Another reason to quit
  • Drugs that antagonize or inactivate heparin include antihistamines, cephalosporins, digoxin, neomycin, nicotine, nitroglycerin, penicillins, phenothiazines, quinidine, and tetracycline.
  • Nicotine may inactivate heparin; nitroglycerin may inhibit the effects of heparin.
  • Administration of protamine sulfate and fresh frozen plasma counteract the effects of heparin. 

Anticoagulant drugs
By Piscean | | Posted in , | With 0 comments
Anticoagulant drugs
Anticoagulant drugs are used to reduce the ability of the blood to clot. Major categories of anticoagulants include:
  • heparin and its derivatives
  • oral anticoagulants
  • antiplatelet drugs
  • direct thrombin inhibitors
  • factor Xa inhibitor drugs.
Heparin
Heparin, prepared commercially from animal tissue, is an anti-thrombolytic agent used to treat and prevent clot formation. Because it doesn’t affect the synthesis of clotting factors, heparin can’t dissolve already-formed clots.

Weighty words
The two types of heparin are unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). LMWHs, such as dalteparin, enoxaparin, and tinzaparin, were developed to prevent deep vein thrombosis (DVT) (a blood clot in the deep veins, usually of the legs) in surgical patients.
 
Pharmacokinetics
Because heparin isn’t absorbed well from the GI tract, it must be administered parenterally. UFH is administered I.V. by continuous infusion or by subQ injection. LMWHs, because of their prolonged circulating half-life, can be administered once or twice daily by subQ injection.
After I.V. administration, the distribution of heparin is immediate; however, distribution isn’t as predictable following subQ injection.
I.M. is out
Heparin isn’t given I.M. because of the risk of localized bleeding. Heparin is metabolized in the liver, and its metabolites are excreted in urine.
 
Pharmacodynamics
Heparin prevents the formation of new thrombi. Here’s how it works:
  • Heparin inhibits the formation of thrombin and fibrin by activating antithrombin III.
  • Antithrombin III then inactivates factors IXa, Xa, XIa, and XIIa in the intrinsic and common pathways. The end result is prevention of a stable fibrin clot.
  • In low doses, heparin increases the activity of antithrombin III against factor Xa and thrombin and inhibits clot formation.
  • Much larger doses are necessary to inhibit fibrin formation after a clot has been formed. This relationship between dose and effect is the rationale for using low-dose heparin to prevent clotting.
  • Whole blood clotting time, thrombin time, and partial thromboplastin time (PTT) are prolonged during heparin therapy. However, these times may be only slightly prolonged with low or ultra-low preventive doses.

Pharmacotherapeutics
Heparin may be used in a number of clinical situations to prevent the formation of new clots or the extension of existing clots. These situations include:
  • preventing or treating venous thromboemboli, characterized by inappropriate or excessive intravascular activation of blood clotting

  • treating disseminated intravascular coagulation, a complication of other diseases, resulting in accelerated clotting
  • treating arterial clotting and preventing embolus formation in patients with atrial fibrillation, an arrhythmia in which ineffective atrial contractions cause blood to pool in the atria, increasing the risk of clot formation
  • preventing thrombus formation and promoting cardiac circulation in an acute myocardial infarction (MI) by preventing further clot formation at the site of the already formed clot.
Safe and sound
Monitoring PTT in heparin therapy
A patient receiving unfractionated heparin (UFH) therapy requires close monitoring of his partial thromboplastin time (PTT). Dosage adjustments, based on the test results, are typically necessary to ensure therapeutic effectiveness without increased risk of bleeding.
Low-molecular-weight heparin (LMWH) therapy doesn’t require PTT monitoring. Currently, no laboratory test exists to assess the effectiveness of LMWH therapy.
Heparin-induced thrombocytopenia
 
Platelet counts should be monitored in all patients receiving heparin therapy. A patient who develops heparin-induced thrombocytopenia (HIT) should be switched from anticoagulant therapy to argatroban, bivalirudin, or lepirudin. These drugs are direct thrombin inhibitors indicated for use in the patient who needs anticoagulation therapy but has HIT.
Circulate freely
 
Heparin can be used to prevent clotting whenever the patient’s blood must circulate outside the body through a machine, such as the cardiopulmonary bypass machine or hemodialysis machine, and during blood transfusions. 
You’re the one
Heparin is also useful for preventing clotting during intra-abdominal or orthopedic surgery. (These types of surgeries, in many cases, activate the coagulation mechanisms excessively.) In fact, heparin is the drug of choice for orthopedic surgery.


Warning!
Adverse reactions to heparin
One advantage of heparin is that it produces relatively few adverse reactions. Even so, these reactions can usually be prevented if the patient’s partial thromboplastin time is maintained within the therapeutic range
.
Bleeding, the most common adverse reaction, can be reversed easily by administering protamine sulfate, which binds to heparin to form a stable salt.
Other adverse reactions include bruising, hematoma formation, necrosis of skin or other tissue, and thrombocytopenia.
 

Drug interactions
  • Because heparin acts synergistically with all oral anticoagulants, the risk of bleeding increases when the patient takes both drugs together. The prothrombin time and International Normalized Ratio (INR), used to monitor the effects of oral anticoagulants, may also be prolonged.
  • The risk of bleeding increases when the patient takes nonsteroidal anti-inflammatory drugs (NSAIDs), iron dextran, cilostazol, or an antiplatelet drug, such as aspirin, clopidogrel, ticlopidine, or dipyridamole, while receiving heparin.
Another reason to quit
  • Drugs that antagonize or inactivate heparin include antihistamines, cephalosporins, digoxin, neomycin, nicotine, nitroglycerin, penicillins, phenothiazines, quinidine, and tetracycline.
  • Nicotine may inactivate heparin; nitroglycerin may inhibit the effects of heparin.
  • Administration of protamine sulfate and fresh frozen plasma counteract the effects of heparin. 

Oral anticoagulants
By Piscean | | Posted in , | With 0 comments
Oral anticoagulants
The major oral anticoagulant used in the United States is the coumarin compound warfarin.


Pharmacokinetics
Warfarin is absorbed rapidly and almost completely when it’s taken orally. It binds extensively to plasma albumin and is metabolized in the liver and excreted in urine. Although warfarin is absorbed quickly, its effects don’t occur for about 48 hours, with the full effect taking 3 to 4 days.
Because warfarin is highly plasma-protein-bound and is metabolized by the liver, administration of warfarin with other medications may alter the amount of warfarin in the body. This may increase the risk of bleeding or clotting, depending upon the medications administered.

Pharmacodynamics
Oral anticoagulants alter the ability of the liver to synthesize vitamin K’dependent clotting factors, including prothrombin and factors VII, IX, and X. However, clotting factors already in the bloodstream continue to coagulate blood until they become depleted, so anticoagulation doesn’t begin immediately. 
 
Pharmacotherapeutics
Oral anticoagulants are prescribed to treat or prevent thromboembolism. Patients with this disorder begin taking the medication while still receiving heparin. However, outpatients at high risk for thromboembolism may begin oral anticoagulants without first receiving heparin.
Deep in the veins
 
Oral anticoagulants are also the drugs of choice to prevent DVT and for patients with prosthetic heart valves or diseased mitral valves. To decrease the risk of arterial clotting, oral anticoagulants are sometimes combined with an antiplatelet drug, such as aspirin, clopidogrel, or dipyridamole.
Monitoring warfarin levels
 
Patients taking warfarin need close monitoring of prothrombin time and International Normalized Ratios to make sure they are maintaining therapeutic levels of the drug. If laboratory results fall outside the accepted range, warfarin dosage should be adjusted.
Drug interactions
Many patients who take oral anticoagulants also receive other drugs, placing them at risk for serious 
 
drug interactions.
  • Many drugs, such as highly protein-bound medications, increase the effects of warfarin, resulting in an increased risk of bleeding. Examples include acetaminophen, allopurinol, amiodarone, cephalosporins, cimetidine, ciprofloxacin, clofibrate, danazol, diazoxide, disulfiram, erythromycin, fluoroquinolones, glucagon, heparin, ibuprofen, isoniazid, ketoprofen, methylthiouracil, metronidazole, miconazole, neomycin, propafenone, propylthiouracil,quinidine, streptokinase, sulfonamides, tamoxifen, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, and vitamin E.
  • Drugs metabolized by the liver may increase or decrease the effectiveness of warfarin. Examples include barbiturates, carbamazepine, corticosteroids, corticotropin, mercaptopurine, nafcillin, hormonal contraceptives containing estrogen, rifampin, spironolactone, sucralfate, and trazodone.
  • The risk of phenytoin toxicity increases when phenytoin is taken with warfarin, and phenytoin may increase or decrease the effects of warfarin.
Other interactions include the following:
  • A diet high in vitamin K reduces the effectiveness of warfarin.
  • Chronic alcohol abuse increases the patient’s risk of clotting while taking warfarin. Acute alcohol intoxication increases the risk of bleeding.
  • Vitamin K and fresh frozen plasma reduce the effects of warfarin. 
Warning!
Adverse reactions to oral anticoagulants
The primary adverse reaction to oral anticoagulant therapy is minor bleeding. Severe bleeding can occur, however, with the most common site being the GI tract. Bleeding into the brain may be fatal. Bruises and hematomas may form at arterial puncture sites (for example, after a blood gas sample is drawn). Necrosis or gangrene of the skin and other tissues can occur.
Quick fix
The effects of oral anticoagulants can be reversed with phytonadione (vitamin K1).
Erythropoietin agents
By Piscean | Monday, March 28, 2011 | Posted in | With 0 comments
Erythropoietin agents
Epoetin alfa and darbepoetin alfa are glycoproteins that stimulate RBC production (erythropoiesis).
 
Pharmacokinetics
Epoetin alfa and darbepoetin alfa may be given subQ or I.V. After subQ administration, serum levels of epoetin alfa peak in 5 to 24 hours, while serum levels of darbepoetin alfa peak in 24 to 72 hours.
The circulating half-life of epoetin alfa is also shorter at 4 to 13 hours, compared to 49 hours for darbepoetin alfa. The therapeutic effect of these agents lasts for several days after administration.
 
Pharmacodynamics
Epoetin alfa and darbepoetin alfa boost the production of erythropoietin, thus stimulating RBC production in bone marrow. Normally, erythropoietin is formed in the kidneys in response to hypoxia (reduced oxygen) and anemia.

Patients with conditions that decrease production of erythropoietin typically develop normocytic anemia. This anemia can usually be corrected after 5 to 6 weeks of treatment with an erythropoietin agent.
 
Pharmacotherapeutics
Epoetin alfa is used to:
  • treat patients with anemia associated with chronic renal failure
  • treat anemia associated with zidovudine therapy in patients with human immunodeficiency virus infection
  • treat anemia in cancer patients receiving chemotherapy
  • reduce the need for allogenic blood transfusions in surgical patients.
Darbepoetin alfa is used to treat anemia associated with chronic renal failure.
 
Drug interactions
No known drug interactions exist with either drug, although they can cause some adverse reactions. 
Warning!
Adverse reactions to erythropoietin agents
Hypertension is the most common adverse reaction. Other adverse reactions may include:
  • headache
  • joint pain
  • nausea
  • edema
  • fatigue
  • diarrhea
  • vomiting
  • chest pain
  • skin reactions at the injection site
  • weakness
  • dizziness.
Erythropoietin agents
By Piscean | | Posted in | With 0 comments
Erythropoietin agents
Epoetin alfa and darbepoetin alfa are glycoproteins that stimulate RBC production (erythropoiesis).
 
Pharmacokinetics
Epoetin alfa and darbepoetin alfa may be given subQ or I.V. After subQ administration, serum levels of epoetin alfa peak in 5 to 24 hours, while serum levels of darbepoetin alfa peak in 24 to 72 hours.
The circulating half-life of epoetin alfa is also shorter at 4 to 13 hours, compared to 49 hours for darbepoetin alfa. The therapeutic effect of these agents lasts for several days after administration.
 
Pharmacodynamics
Epoetin alfa and darbepoetin alfa boost the production of erythropoietin, thus stimulating RBC production in bone marrow. Normally, erythropoietin is formed in the kidneys in response to hypoxia (reduced oxygen) and anemia.

Patients with conditions that decrease production of erythropoietin typically develop normocytic anemia. This anemia can usually be corrected after 5 to 6 weeks of treatment with an erythropoietin agent.
 
Pharmacotherapeutics
Epoetin alfa is used to:
  • treat patients with anemia associated with chronic renal failure
  • treat anemia associated with zidovudine therapy in patients with human immunodeficiency virus infection
  • treat anemia in cancer patients receiving chemotherapy
  • reduce the need for allogenic blood transfusions in surgical patients.
Darbepoetin alfa is used to treat anemia associated with chronic renal failure.
 
Drug interactions
No known drug interactions exist with either drug, although they can cause some adverse reactions. 
Warning!
Adverse reactions to erythropoietin agents
Hypertension is the most common adverse reaction. Other adverse reactions may include:
  • headache
  • joint pain
  • nausea
  • edema
  • fatigue
  • diarrhea
  • vomiting
  • chest pain
  • skin reactions at the injection site
  • weakness
  • dizziness.
Folic acid
By Piscean | | Posted in | With 0 comments
Folic acid
Folic acid is given to treat megaloblastic anemia due to folic acid deficiency. This type of anemia usually occurs in patients who have tropical or nontropical sprue, although it can also result from poor nutritional intake during pregnancy, infancy, or childhood.
 
Pharmacokinetics
Folic acid is absorbed rapidly in the first third of the small intestine, distributed into all body tissues, and metabolized in the liver. Excess folate is excreted unchanged in urine, and small amounts of folic acid are excreted in stool. Folic acid also appears in breast milk. Synthetic folic acid is readily absorbed, even in malabsorption syndromes.

Pharmacodynamics
Folic acid is an essential component for normal RBC production and growth. A deficiency in folic acid results in megaloblastic anemia and low serum and RBC folate levels.
 
Pharmacotherapeutics
Folic acid is used to treat folic acid deficiency. Patients who are pregnant or undergoing treatment for liver disease, hemolytic anemia, alcohol abuse, or skin or renal disorders typically need folic acid supplementation. Serum folic acid levels below 5 ng/ml indicate folic acid deficiency.
Leucovorin is a folic acid derivative used to treat folic acid deficiencies resulting from administration of methotrexate.
 
Drug interactions
  • Methotrexate, sulfasalazine, hormonal contraceptives, aspirin, triamterene, pentamidine, and trimethoprim reduce the effectiveness of folic acid.
  • In large doses, folic acid may counteract the effects of anticonvulsants, such as phenytoin, potentially leading to seizures. 
Warning!
Adverse reactions to folic acid
Adverse reactions to folic acid include:
  • erythema
  • itching
  • rash
  • anorexia and nausea
  • altered sleep patterns
  • difficulty concentrating
  • irritability
  • hyperactivity.

Folic acid
By Piscean | | Posted in | With 0 comments
Folic acid
Folic acid is given to treat megaloblastic anemia due to folic acid deficiency. This type of anemia usually occurs in patients who have tropical or nontropical sprue, although it can also result from poor nutritional intake during pregnancy, infancy, or childhood.
 
Pharmacokinetics
Folic acid is absorbed rapidly in the first third of the small intestine, distributed into all body tissues, and metabolized in the liver. Excess folate is excreted unchanged in urine, and small amounts of folic acid are excreted in stool. Folic acid also appears in breast milk. Synthetic folic acid is readily absorbed, even in malabsorption syndromes.

Pharmacodynamics
Folic acid is an essential component for normal RBC production and growth. A deficiency in folic acid results in megaloblastic anemia and low serum and RBC folate levels.
 
Pharmacotherapeutics
Folic acid is used to treat folic acid deficiency. Patients who are pregnant or undergoing treatment for liver disease, hemolytic anemia, alcohol abuse, or skin or renal disorders typically need folic acid supplementation. Serum folic acid levels below 5 ng/ml indicate folic acid deficiency.
Leucovorin is a folic acid derivative used to treat folic acid deficiencies resulting from administration of methotrexate.
 
Drug interactions
  • Methotrexate, sulfasalazine, hormonal contraceptives, aspirin, triamterene, pentamidine, and trimethoprim reduce the effectiveness of folic acid.
  • In large doses, folic acid may counteract the effects of anticonvulsants, such as phenytoin, potentially leading to seizures. 
Warning!
Adverse reactions to folic acid
Adverse reactions to folic acid include:
  • erythema
  • itching
  • rash
  • anorexia and nausea
  • altered sleep patterns
  • difficulty concentrating
  • irritability
  • hyperactivity.

Vitamin B12
By Piscean | | Posted in | With 0 comments
Vitamin B12
Vitamin B12 preparations are used to treat pernicious anemia. Common vitamin B12 preparations include cyanocobalamin and hydroxocobalamin.
 
Pharmacokinetics
Vitamin B12 is available in parenteral, oral, and intranasal forms. For the body to absorb oral forms of vitamin B12, the gastric mucosa must secrete a substance called intrinsic factor. People who have a deficiency of intrinsic factor develop a special type of anemia known as vitamin B12-deficiency pernicious anemia.

Parenteral possibilities
When cyanocobalamin is injected by the I.M. or subcutaneous (subQ) route, it’s absorbed and bound to transcobalamin II for transport to the tissues. It then travels via the bloodstream to the liver, where 90% of the body’s supply of vitamin B12 is stored.
 
Although hydroxocobalamin is absorbed more slowly from the injection site, its uptake in the liver may be greater than that of cyanocobalamin. Hydroxocobalamin is only administered I.M.
Most gets lost
 
With either drug, the liver slowly releases vitamin B12 as needed by the body. About 3 to 8 mcg of vitamin B12 are excreted in bile each day and then reabsorbed in the ileum. It’s also secreted in breast milk during lactation.
 
Within 48 hours after a vitamin B12 injection, 50% to 95% of the dose is excreted unchanged in urine.
Pharmacodynamics
 
When vitamin B12 is administered, it replaces vitamin B12 that the body would normally absorb from the diet. This vitamin is essential for cell growth and replication and for the maintenance of myelin (nerve coverings) throughout the nervous system. Vitamin B12 may also be involved in lipid and carbohydrate metabolism.
 
Pharmacotherapeutics
Cyanocobalamin and hydroxocobalamin are used to treat pernicious anemia, a megaloblastic anemia characterized by decreased gastric production of hydrochloric acid and intrinsic factor deficiency. Intrinsic factor, a substance normally secreted by the parietal cells of the gastric mucosa, is essential for vitamin B12 absorption. Intrinsic factor deficiencies are common in patients who have had total or partial gastrectomies or total ileal resection. Oral vitamin B12 preparations are used to supplement nutritional deficiencies of the vitamin. The parenteral and intranasal formulations are used to treat patients with pernicious anemia.
 
Warning!
Adverse reactions to vitamin B12 therapy
No dose-related adverse reactions occur with vitamin B12 therapy. However, some rare reactions may occur when vitamin B12 is administered parenterally.
Parenteral problems
Adverse reactions to parenteral administration can include hypersensitivity reactions that could result in anaphylaxis and death, pulmonary edema, heart failure, peripheral vascular thrombosis, polycythemia vera, hypokalemia, itching, transient rash, hives, and mild diarrhea.
Drug interactions
Alcohol, aspirin, neomycin, chloramphenicol, and colchicine may decrease the absorption of oral cyanocobalamin. 
Vitamin B12
By Piscean | | Posted in | With 0 comments
Vitamin B12
Vitamin B12 preparations are used to treat pernicious anemia. Common vitamin B12 preparations include cyanocobalamin and hydroxocobalamin.
 
Pharmacokinetics
Vitamin B12 is available in parenteral, oral, and intranasal forms. For the body to absorb oral forms of vitamin B12, the gastric mucosa must secrete a substance called intrinsic factor. People who have a deficiency of intrinsic factor develop a special type of anemia known as vitamin B12-deficiency pernicious anemia.

Parenteral possibilities
When cyanocobalamin is injected by the I.M. or subcutaneous (subQ) route, it’s absorbed and bound to transcobalamin II for transport to the tissues. It then travels via the bloodstream to the liver, where 90% of the body’s supply of vitamin B12 is stored.
 
Although hydroxocobalamin is absorbed more slowly from the injection site, its uptake in the liver may be greater than that of cyanocobalamin. Hydroxocobalamin is only administered I.M.
Most gets lost
 
With either drug, the liver slowly releases vitamin B12 as needed by the body. About 3 to 8 mcg of vitamin B12 are excreted in bile each day and then reabsorbed in the ileum. It’s also secreted in breast milk during lactation.
 
Within 48 hours after a vitamin B12 injection, 50% to 95% of the dose is excreted unchanged in urine.
Pharmacodynamics
 
When vitamin B12 is administered, it replaces vitamin B12 that the body would normally absorb from the diet. This vitamin is essential for cell growth and replication and for the maintenance of myelin (nerve coverings) throughout the nervous system. Vitamin B12 may also be involved in lipid and carbohydrate metabolism.
 
Pharmacotherapeutics
Cyanocobalamin and hydroxocobalamin are used to treat pernicious anemia, a megaloblastic anemia characterized by decreased gastric production of hydrochloric acid and intrinsic factor deficiency. Intrinsic factor, a substance normally secreted by the parietal cells of the gastric mucosa, is essential for vitamin B12 absorption. Intrinsic factor deficiencies are common in patients who have had total or partial gastrectomies or total ileal resection. Oral vitamin B12 preparations are used to supplement nutritional deficiencies of the vitamin. The parenteral and intranasal formulations are used to treat patients with pernicious anemia.
 
Warning!
Adverse reactions to vitamin B12 therapy
No dose-related adverse reactions occur with vitamin B12 therapy. However, some rare reactions may occur when vitamin B12 is administered parenterally.
Parenteral problems
Adverse reactions to parenteral administration can include hypersensitivity reactions that could result in anaphylaxis and death, pulmonary edema, heart failure, peripheral vascular thrombosis, polycythemia vera, hypokalemia, itching, transient rash, hives, and mild diarrhea.
Drug interactions
Alcohol, aspirin, neomycin, chloramphenicol, and colchicine may decrease the absorption of oral cyanocobalamin. 
Drugs and the hematologic system
By Piscean | | Posted in | With 0 comments
Drugs and the hematologic system
The hematologic system includes plasma (the liquid component of blood) and blood cells, such as red blood cells (RBCs), white blood cells, and platelets. Types of drugs used to treat disorders of the hematologic system include:
  • hematinic
  • anticoagulant
  • thrombolytic.
Hematinic drugs
Hematinic drugs provide essential building blocks for RBC production. They do so by increasing hemoglobin, the necessary element for oxygen transportation.

Iron, vitamin B12, folic acid
This section discusses hematinic drugs used to treat microcytic and macrocytic anemia’iron, vitamin B12, and folic acid.
It also describes the use of erythropoietin agents to treat normocytic anemia.

Iron
Iron preparations are used to treat the most common form of anemia’iron deficiency anemia. Iron preparations discussed in this section include ferrous fumarate, ferrous gluconate, ferrous sulfate, iron dextran, and sodium ferric gluconate complex.
 
Pharmacokinetics (how drugs circulate)
Iron is absorbed primarily from the duodenum and upper jejunum of the intestine. Different iron formulations don’t vary in absorption, but they do vary in the amount of elemental iron supplied.
 
Low iron increases absorption
The amount of iron absorbed depends partially on the body’s stores of iron. When body stores are low or RBC production is accelerated, iron absorption may increase by 20% to 30%. On the other hand, when total iron stores are large, the body absorbs only about 5% to 10% of the iron available.
Enteric-coated preparations decrease iron absorption because, in that form, iron isn’t released until after it leaves the duodenum. The lymphatic system absorbs the parenteral form after I.M. injections.
Hemoglobin has it
 
Iron is transported by the blood and bound to transferrin, its carrier plasma protein. About 30% of the iron is stored primarily as hemosiderin or ferritin in the reticuloendothelial cells of the liver, spleen, and bone marrow. About 66% of the total body iron is contained in hemoglobin. Excess iron is excreted in urine, stool, sweat, and through intestinal cell-sloughing. It appears in breast milk and crosses the placenta.

Pharmacodynamics (how drugs act)
Although iron has other roles, its most important role is the production of hemoglobin. About 80% of iron in the plasma goes to the bone marrow, where it’s used for erythropoiesis (production of RBCs).
 
Pharmacotherapeutics (how drugs are used)
Oral iron therapy is the preferred route for preventing or treating iron deficiency anemia. It’s used to prevent anemias in children ages 6 months to 2 years because this is a period of rapid growth and development. Pregnant women may need iron supplements to replace the iron used by the developing fetus.


Warning!
Adverse reactions to iron therapy
The most common adverse reactions to iron therapy are gastric irritation and constipation. Iron preparations also darken stool, and liquid preparations can stain the teeth.
The most serious reaction is anaphylaxis, which may occur after administration of parenteral iron. To guard against such a reaction, administer an initial test dose before giving a full-dose infusion.
Ironclad options
 
Parenteral iron therapy is used for patients who can’t absorb oral preparations, aren’t compliant with oral therapy, or have bowel disorders (such as ulcerative colitis or Crohn’s disease). Patients with end-stage renal disease who are receiving hemodialysis may also receive parenteral iron therapy at the end of their dialysis session. While parenteral iron therapy corrects the iron store deficiency quickly, it doesn’t correct the anemia any faster than oral preparations would.
Iron preparations available for parenteral administration are iron dextran (given by I.M. injection or slow, continuous I.V. infusion) and iron sucrose. Iron sucrose is used for patients on hemodialysis. 
 
Drug interactions
Iron absorption is reduced by antacids as well as by such foods as coffee, tea, eggs, and milk. Other drug interactions involving iron include:
  • Absorption of tetracyclines (demeclocycline, doxycycline, minocycline, oxytetracycline, and tetracycline), methyldopa, quinolones (ciprofloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, and sparfloxacin), levothyroxine, and penicillamine may be reduced when taken with oral iron preparations.
  • Cholestyramine, cimetidine, proton-pump inhibitors, and colestipol may reduce iron absorption in the GI tract
Safe and sound
Testing for parenteral iron sensitivity
Parenteral iron can cause acute hypersensitivity reactions, including anaphylaxis, dyspnea, urticaria, other rashes, pruritus, arthralgia, myalgia, fever, sweating, and allergic purpura. To test for drug sensitivity and prevent serious reactions, always give a test dose of iron dextran before beginning therapy.
 
Carefully assess the patient’s response to the test dose. If no adverse reactions occur within 1 hour, give the total dose. If adverse reactions occur, notify the prescriber immediately. To treat anaphylaxis, keep epinephrine and standard emergency equipment readily available.