Drugs Acting on the Hematologic System PDF

Module 4 Drugs Acting on the Hematologic System MONECELLE JOY D. PESINABLE Instructor Lesson 1 Hematinic Drugs MONECELLE JOY D. PESINABLE Instructor Hematinic Drugs provide essential building blocks for RBC production by increasing the hemoglobin necessary for oxygen transportation Anemia...

Module 4 Drugs Acting on the Hematologic System MONECELLE JOY D. PESINABLE Instructor Lesson 1 Hematinic Drugs MONECELLE JOY D. PESINABLE Instructor Hematinic Drugs provide essential building blocks for RBC production by increasing the hemoglobin necessary for oxygen transportation Anemia a clinical condition that results from an insufficient supply of healthy RBCs, the volume of packed RBC and/or the quantity of hemoglobin Iron used to treat Iron Deficiency Anemia (IDA) ferrous sulfate, ferrous gluconate, ferrous sulfate and iron dextran Pharmacokinetics absorbed primarily form the duodenum and upper jejunum of the intestine Pharmacodynamics production of hemoglobin; 80% of iron in the plasma goes to the bone marrow where they are used for erythropoiesis Iron Pharmacotherapeutics oral iron therapy is used to prevent IDA pregnant women may need supplements to replace the iron used by the developing fetus parenteral iron therapy (iron dextran)*: used for patients who can’t absorb oral preparations, aren’t compliant with oral therapy or with bowel disorders Iron Drug Interactions and Adverse Reactions absorption is reduced by antacid and food (coffee, tea, eggs, and milk) tetracycline, oxytetracycline, methacycline, doxycycline, methyldopa, ciprofloxacin, ofloxacin, chloramphenicol, and penicillin absorption may be reduced when taken with oral iron preparations cimetidine and other H2 receptor antagonists may decrease GI absorption of iron most common adverse reaction: gastric irritation darkens the stool and liquid ones can stain the teeth Vitamin B12 used to treat pernicious anemia* cyanocobalamin and hydroxocobalamin available in oral and injectable forms Pharmacodynamics replaces Vitamin B12** Folic Acid treats folic acid* deficiency absorbed rapidly in the first third of the small intestine and distributed into all body tissues metabolized in the liver excess folate is excreted unchanged in the urine and small in the stool, also in the breast milk preventive folic acid therapy: pregnancy, undergoing treatment for liver disease, hemolytic anemia, alcohol abuse, skin disease and renal failure Epoetin Alfa stimulates RBC production peak serum levels for SQ occur within 5-24 hours; IV unknown distribution, metabolism and excretion boosts the production of erythropoietin* decreased erythropoietin can lead to chronic normocytic anemia, necessitating epoetin alfa administration Epoetin Alfa Pharmacotherapeutics normocytic anemia* caused by chronic renal failure anemia associated with zidovudine** therapy in patients with HIV infection to decrease the need for transfusion in patients with certain types of leukemia*** Adverse Reactions Most common is hypertension; others include headache, joint pain, nausea, edema, fatigue, diarrhea, vomiting, chest pain, skin reactions at the administration site, weakness and dizziness Lesson 2 Anticoagulant Drugs MONECELLE JOY D. PESINABLE Instructor Heparin prepared commercially from animal tissue prevents blood clot formation cannot dissolve already formed clots dalteparin sodium and enoxaparin sodium* were developed to prevent deep vein thrombosis** in surgical patients absorbed parenterally* IV and SQ** metabolized in the liver and metabolites are excreted in the urine Heparin Pharmacodynamics prevents formation of new thrombi inhibits the formation of thrombin and fibrin by activating antithrombin III antithrombin III inactivates factors IX, X, XI and XII in the intrinsic and common pathways end result: prevention of stable fibrin clot low dose: increases the activity of antithrombin III against factor X and thrombin and inhibits clot formation Heparin Pharmacodynamics large doses: inhibit fibrin formation after a clot has been formed* heparin therapy: prolongs blood clotting time, thrombin time and partial thromboplastin time Heparin Pharmacotherapeutics Prevention and treatment of venous thromboembolism characterized by inappropriate or excessive intravascular activation of blood clotting Treatment of disseminated intravascular coagulation*, a complication of other diseases resulting in accelerated clotting Treatment of arterial clotting and preventing embolus formation in patients with atrial fibrillation** Prevention of thrombus formation and promotion of cardiac circulation in an acute MI by preventing further at the site of the already formed clot Useful for preventing clotting during orthopedic surgery (DOC)*** Heparin Drug Interactions acts synergistically when taken with oral anticoagulants risk of bleeding increases when taken with NSAIDs, iron dextran or an antiplatelet drug Adverse Reaction most common is bleeding – can be revered by administering protamine sulfate* Oral Anticoagulants major anticoagulants: coumarin compounds warfarin sodium and dicumarol* Pharmacokinetics absorbed rapidly and almost completely when given orally** warfarin and dicumarol are both bound extensively to plasma albumin, metabolized in the liver and excreted in the urine Oral Anticoagulants Pharmacodynamics Oral drugs alter the ability of the liver to synthesize vitamin K dependent clotting factors including prothrombin and factors VII, IX and X Pharmacotherapeutics treat thromboembolism* drugs of choice to prevent deep vein thrombosis Side Effect primary SE is minor bleeding** Antiplatelet Drugs used to prevent arterial thromboembolism, particularly in patients at risk for MI, stroke and arteriosclerosis aspirin, dipyridamole, sulfinpyrazone, and ticlopidine Pharmacokinetics all are taken orally, absorbed very quickly and reach peak concentration between 1 and 2 hours after administration aspirin maintains its antiplatelet effect approximately 10 days or as long as platelets normally survive sulfinpyrazone may require several days of administration Antiplatelet Drugs Pharmacodynamics 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*, thus preventing the formation of the platelet-aggregating substance thromboxane A2** dipyridamole inhibits platelet aggregation sulfinpyrazone inhibits several platelet functions ticlopidine inhibits the binding of fibrinogen to platelets during the first stage of the clotting cascade Antiplatelet Drugs Pharmacotherapeutics aspirin: previous MI or unstable angina to reduce the risk of death and in men to reduce risk of TIA* sulfinpyrazone: after MI to decrease the risk of sudden cardiac death Drug Interactions aspirin + heparin, oral anticoagulants and dipyridamole = increased risk of bleeding sulfinpyrazone + aspirin and oral anticoagulants = increased risk of bleeding Lesson 3 Thrombolytic Drugs MONECELLE JOY D. PESINABLE Instructor Thrombolytic Drugs Pharmacokinetics IV and intracoronary administration: distributed immediately throughout the circulation, quickly activating plasminogen* alteplase is cleared rapidly from circulating plasma, primarily by the liver anistreplase is metabolized in the plasma streptokinase is removed rapidly from the circulation by the antibodies and the reticuloendothelial system** Thrombolytic Drugs Pharmacodynamics convert plasminogen to plasmin which dissolves thrombi, fibrinogen, and other plasma proteins Pharmacotherapeutics used to treat certain thromboembolic disorders and have also been used to dissolve thrombi in arteriovenous cannulas and IV catheters to reestablish blood flow Thrombolytic Drugs Pharmacotherapeutics drugs of choice to break down newly formed thrombi alteplase: acute MI, pulmonary embolism, acute ischemic stroke anistreplase: acute MI streptokinase: acute MI, pulmonary embolus, DVT, arterial thrombosis, arterial embolism and thrombosis Thrombolytic Drugs Drug Interactions interact with heparin, oral anticoagulants, antiplatelet drugs, and NSAIDs thus increasing the patient’s risk for bleeding aminocaproic acid* inhibits streptokinase and can be used to reverse its fibrinolytic effects Adverse Reactions bleeding and allergic responses, especially with streptokinase and anistreplase Lesson 4 Antilipemic Drugs MONECELLE JOY D. PESINABLE Instructor Bile-Sequestering Drugs cholestyramine and colestipol hydrochloride* Pharmacokinetics are not absorbed from the GIT; they remain in the intestine where they combine with bile acids for about 5 hours; excreted in the stool Pharmacodynamics lower blood levels of LDL combine with bile acids in the intestines to form an insoluble compound that is then excreted in the stool** Bile-Sequestering Drugs Pharmacotherapeutics type IIa hyperlipoproteinemia in patients who are not able to lower LDL levels through dietary changes patients whose blood cholesterol levels indicate a severe risk of coronary artery disease are most likely to require one of these drugs to supplement the diet Drug Interactions May bind with acidic drugs in the GIT, decreasing their absorption and effectiveness* Reduce the absorption of lipid-soluble vitamins such as vitamins A,D,E and K** Absorption of many other drugs that normally are absorbed from the GIT – including tetracyclines – also may be decreased Fibric Acid Derivatives produced by several fungi clofibrate and gemfibrozil* Pharmacokinetics absorbed readily from the GIT and are highly protein bound clofibrate is hydrolyzed, and gemfibrozil undergoes extensive metabolism in the liver both are excreted in the urine Pharmacodynamics** reduce cholesterol production early in its formation; mobilize cholesterol from the tissues; increase cholesterol excretion; decrease synthesis and secretion of lipoproteins; decrease synthesis of triglycerides gemfibrozil produces other 2 effects: increases HDL levels in the blood and the serum’s capacity to dissolve additional cholesterol Fibric Acid Derivatives Pharmacotherapeutics used primarily to reduce triglyceride levels, especially very low-density triglycerides, and secondarily to reduce blood cholesterol levels useful in treating patients with types II, III, IV, and mild type V hypoproteinemia* Drug Interactions may displace acidic drugs such as barbiturates, phenytoin, thyroid derivatives, and digitalis glycosides risk of bleeding increases when taken with oral anticoagulants clofibrate may increase the hypoglycemic effect of oral antidiabetic drugs can lead to adverse GI effects Cholesterol Synthesis Inhibitors also known as statins lower lipid levels by interfering with cholesterol synthesis lovastatin, pravastatin sodium, simvastatin Pharmacokinetics after oral administration, lovastatin is absorbed incompletely and much of the drug dose is lost due to extensive first-pass metabolism in the liver; food may increase the drug’s systemic absorption pravastatin is absorbed rapidly but incompletely after being taken orally; undergoes extensive first-pass metabolism in the liver simvastatin is absorbed incompletely and undergoes extensive first-pass metabolism in the liver; both simvastatin and its major metabolite are highly protein bound Pharmacodynamics reduce cholesterol levels by inhibiting enzyme activity* Cholesterol Synthesis Inhibitors Pharmacotherapeutics used to treat elevated total cholesterol and LDL levels in patients with primary hypercholesterolemia (types IIa and IIb)** Drug Interactions when any of these drugs are administered with an immunosuppressant*, gemfibrozil, erythromycin, or niacin, the interaction may increase the risk of myopathy** or rhabdomyolysis* pravastatin and simvastatin may increase the risk of bleeding when administered with warfarin cholestyramine and colestipol may decrease the effectiveness of pravastatin Adverse Reactions The most common adverse reactions to lovastatin include GI disturbances and headache; increased liver enzyme levels may occur in patient receiving long term lovastatin therapy