Antianemia drugs
| Drug: Epoetin alpha (erythropoietin, Epo) (Epogen, Procrit ®) |
| Drug Class: Drug Used in Anemia (normocytic) |
| Mechanism of Action: a glycoprotein which stimulates red blood cell production. Epoetin alfa is a 165 amino acid glycoprotein manufactured by recombinant DNA technology, and has the same biological effects as endogenous erythropoietin. |
| Indications: treatment of anemia in: 1) chronic renal failure patients, 2) zidovudine-treated HIV-infected patients, 3) cancer patients on chemotherapy; and 4) reduction of allogeneic blood transfusion in surgery patients. Erythropoietin deficiency can result from compromised renal function (it's primary site of production). Erythropoietin deficiency results in a normocytic anemia. |
| Contraindications: Uncontrolled hypertension or known hypersensitivity to either mammalian cell-derived products or to human albumin. |
| Pharmacokinetics: given i.v. or s.c. Half llife of 4-13 hrs in patients with chronic renal failure. It is measured in international units (IU). |
| Side Effects: a rapid increase in hematocrit & hemoglobin may cause hypertension & thrombotic complications. These can be minimized by raising the hematocrit slowly and treating the hypertension. |
Notes: Epo is one of the drugs banned by the International Olympic Committee. Darbopoetin alpha (Aranesp ®) is a glycosylated form of erythropoietin that differs only in having a 2-3 fold longer half-life. Hypoxia is the primary physiological stimulus for erythropoietin production in the body. |
| References: www.rxlist.com & Katzung's text |
| Drug: Ferrous Sulfate (generic) |
| Drug Class: Drug Used in Anemia (microcytic) |
| Mechanism of Action: Iron combines with porphyrin and globin chains to form hemoglobin, which is critical for oxygen delivery from the lungs to other tissues. Iron defeciency causes a microcytic anemia due to the formation of small erythrocytes with insufficient hemoglobin. |
| Indications: iron deficiency anemia, blood loss related to pregnancy or GI bleeding (NSAIDs), hookworm infestation, or excess coffee |
| Contraindications: patients with hemochromatosis, hemosiderosis or hemolytic anemia |
| Pharmacokinetics: An oral (absorbable) iron formulation. |
| Side Effects: very mild - nausea, upper abdominal paoin, constipation or diarrhea. Iron overdose (1-2 g) can lead to circulatory collapse and death. Iron overdose can be treated by gastric lavage with a phosphate solution and deferoxamine (iron chelator). |
| Major drug interactions: it may decrease the absorption of other medications |
Notes: Primary hemochromatosis is a hereditary disease in which there is increased accumulation of iron. |
| References: Katzung's text |
| Drug: Deferoxamine (Desferal ®) |
| Drug Class: Iron Chelator |
| Mechanism of Action: binds iron avidly, but poorly binds other essential trace metals. It competes in binding loosely bound iron, but fails to bind iorn that is biologically chelated, such as in microsomal and mitrochondrial cytochromes and hemoproteins. |
| Indications: iron poisoning. Used for treating both acute iron intoxication and in patients with secondary iron overload from multiple transfusions. Deferoxamine plus hemodialysis may also be useful in treatment of aluminum toxicity in renal failure. (It is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for removing excess iron in this disorder.) |
| Contraindications: in patients with severe renal disease or anuria, since the drug and the iron chelate are excreted primarily by the kidney |
| Pharmacokinetics: given parentally (i.m., s.c. or i.v.). It is poorly absorbed if taken orally, and may actually increase iron absorption if given orally. Iron-chelator complexes are excreted in the urine, often turning the urine an orange-red color. |
| Side Effects: rapid i.v. administration may cause hypotension. Idiosyncratic responses such as flushing, rash, abdominal discomfort may occur. |
| References: www.rxlist.com & Katzung's text |
| Drug: Folic acid (Folvite ®) |
| Drug Class: Drug used in anemia (megaloblastic) |
| Mechanism of Action: essential cofactor for synthesis of amino acids, purines and DNA. |
| Indications: 1) folic acid is effective in the treatment of megaloblastic anemias due to a deficiency of folic acid as may be seen in tropical or non-tropical sprue, in anemias of nutritional origin, pregnancy, infancy, or childhood. 2) a reduced form of folic acid known as Citrovorum Factor (Leukovorin ®) is given to replenish endogenous folic acid in patients on methotrexate (which inhibits dihydrofolate reductase). Citrovorin is better absorbed compared to folic acid. |
| Contraindications: folic acid should not be given alone in patients with pernicioius anemia without knowing whether they also have a Vit B12 deficiency. The danger is that folic acid supplements can mask the signs of Vit B 12 deficiency, yet not prevent the development of irreversible neurological disease due to Vit B12 deficiency. The Shilling test can be used to test for abnormalities in Vit B12 absorption. |
| Pharmacokinetics: a dose of 1 mg of folic acid orally daily is typically sufficient to reverse megaloblastic anemia & restore normal folate levels. |
| Side Effects: allergic sensitization |
Notes: Folate deficiency (in pregnant women) is implicated as a cause of congenital malformations in newborns. Folate may also play a beneficial role in preventing the development vascular disease such as ischemic heart disease & stroke (see Katzung pg 536, 9th ed.) However, folic acid supplements may mask the signs of Vit B 12 deficiency, which can produce neurological disease if undetected. Folic acid deficiency is also known as Will's disease. |
| References: www.rxlist.com & Katzung's text |
| Drug: Vitamine B12 (generic cyanocobalamin or hydroxocobalamin) |
| Drug Class: Vitamin |
| Mechanism of Action: a cofactor for several essential biochemical reactions. |
| Indications: used to treat or prevent deficiency of Vit B12. The most common causes of Vit B12 deficiency are pernicious anema, fish tapeworm infection, partial or total gastrectomy & various intestinal disorders that impair absorption of Vit B12. (Pernicious anema results from defective secretion of intrinsic factor by the gastric mucosal cells) |
| Pharmacokinetics: different formulations can be administered orally, or by parenteral injection. |
Notes: Vit B12 deficiency leads to megaloblastic anemia, GI symptoms & neurological abnormalities including degeneration of myelin sheaths in axons of the spinal cord & peripheral nerves. Symptoms include: paresthesias & weakness in peripheral nerves, progressing to spasticity, ataxia & other CNS dysfunctions. Vit B12 deficiency in elderly patients due to abnormal absorption of dietary Vit B12 is relatively common and easily treated. |
| References: www.rxlist.com & Katzung's text |
| Drug: Iron Dextran (INFeD ®) |
| Drug Class: Parental Iron Preparation |
| Mechanism of Action: same as ferrous sulfate |
| Indications: treatment of patients with documented iron deficiency in whom oral administration is unsatisfactory or impossible (e.g. malabsorption syndrome, prolonged salicylate therapy, dialysis patients). |
| Pharmacokinetics: given by deep i.m. injection or i.v. Most adults with iron deficiency require 1-2 g of replacement iron, or 20-40 ml. The favored route of administration is i.v. infusion in several hundred mls of normal saline over 1-2 hrs. |
| Side Effects: local pain & tissue staining (brown discoloration), headache, light-headedness, fever, nausea, flushing, urticaria, bronchospasm, and rarely anaphylaxis & death. |
Notes: a small test dose should be given before the full dose, to test for the risk of hypersensitivity. Patients with a strong history of allergy or who have previously received parenteral iron are more likely to have hypersensitivity reactions. |
| References: www.rxlist.com |
Anticoagulants
| Drug: Warfarin (generic, Coumadin ®) |
| Drug Class: anticoagulant |
| Mechanism of Action: blocks the carboxylation of several glutamate residues in prothrombin & factors VII, IX and X as well as the endogenous anticoagulant proteins C and S. The blockade results in incomplete molecules that are biologically inactive in coagulation. The protein carboxylation is physiologically coupled with the oxidative deactivation of vitamin K. Warfarin prevents the reductive metabolism of the inactive form of vitamin K back to its active form by vitamin K epoxide reductase. Mutational change of this enzyme results in genetic resistance to warfarin in a subset of the human population. |
| Indications: 1) prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. 2) prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. 3) to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction |
| Contraindications: pregnancy (warfarin can cross the placenta & cause a hemorrhagic disorder in the fetus). |
| Side Effects: fatal or non-fatal bleeding from any tissue or organ, necrosis of skin & other tissues. Hemorrhagic complications may present as paralysis; paresthesia; headache, chest, abdomen, joint, muscule, or other pain; dizziness, shortness of breath, difficult breathing or swallowing; unexplained swelling; weakness; hypotension; or unexplained shock. |
| Pharmacokinetics: has 100% bioavailability & 99% becomes bound to plasma albumin, resulting in a small apparent volume of distribution (the albumin space). It's half-life is 36 hrs. There is an 8-12 hour delay in the action of warfarin due to the time it takes for degredation of clotting factors within the circulation. |
| Major drug interactions: there are significant interactions between warfarin and other drugs and disease states. These can be divided into pharmacodynamic & pharmacokinetic effects. Pharmacokinetic interactions can occur from enzyme induction, enzyme inhibition or reduced plasma protein binding. Pharmacodynamic mechanisms for interactions are synergism (reduced clotting factor synthesis - as in hepatic disease), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K (hereditary resistance to warfarin). The most serious interactions are those that increase warfarins anticoagulant effect & risk of bleeding. Drugs that do this (increase prothrombin time) by pharmacokinetic interactions include amiodarone, cimetidine & numerous other drugs. In contrast, barbiturates & rifampin produce a marked decrease of the anticoagulant effect of warfarin by induction of cytochrome P450 enzymes that metabolize warfarin. |
| Drug: Heparin (generic, Liquaemin ®) |
| Drug Class: Anticoagulant |
Mechanism of Action: a heterogeneous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans having anticoagulant properties. Heparin acts at multiple sites in the normal coagulation system. Heparin interacts with antithrombin (heparin cofactor) to change its conformation and enhance its ability to inhibit thrombosis by inactivating clotting factor proteases, especially thrombin (IIa), IXa and Xa by forming equimolar complexes with them. |
Indications: The agent of choice for short term anticoagulant thereapy which includes:
|
| Contraindications: patients with uncontrolled bleeding or severe thrombocytopenia (e.g. hemophelia, GI ulcers), severe hypertension, advanced hepatic or kidney disease. |
| Pharmacokinetics: Heparin sodium is not effective by oral administration and should be given by intermittent intravenous injection, intravenous infusion or deep subcutaneous injection (intrafat, i.e., above the iliac crest or abdominal fat layer) . The intramuscular route of administration should be avoided because of the frequent occurrence of hematoma at the injection site. The dosage of heparin sodium should be adjusted according to the patient's coagulation test results. Heparin is metabolized by the liver. |
| Side Effects: Hemorrhage. Nosebleeds, blood in urine or tarry stools may be noted as the first sign of bleeding. Easy bruising or petechial formations may precede frank bleeding. Bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect, such as: a) adrenal hemorrhage, with resultant acute adrenal insufficiency; b) ovarian (corpus luteum) hemorrhage (potentially fatal); c) retroperitoneal hemorrhage. Heparin causes a transient thrombocytopenia in 25% or more of patients, and a severe thrombocytopenia in 5%. Platelet counts should be performed frequently in patients receiving heparin. |
| Major drug interactions: aspirin, warfarin (enhanced bleeding if given concomitantly). Protamine sulfate can be given i.v. to neutralize the action of heparin. |
Notes: Heparine occurs naturally in the body & is found with histamine in tissue mast cells. Commercially purified from porcine intestinal mucosa. Bleeding time is usually unaffected by heparin sodium. Clotting time is prolonged by full therapeutic doses of heparin sodium; in most cases it is not measurably affected by low doses of heparin. |
| References: www.rxlist.com |
| Drug: Enoxaparin (LMW heparin, Lovenox ®) |
| Drug Class: anticoagulant |
| Mechanism of Action: inhibits clotting factors IIa (prothrombin) and Xa |
Indications: 1) for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, such as in patients:
2) Lovenox Injection is indicated for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. |
| Pharmacokinetics: better bioavailability & longer half life than unfractionated heparin. Its clinical use requires less testing of clotting times compared to heparin. Typically given by s.c. injection. |
| References: www.rxlist.com & Katzung's text |
Drugs used to Treat Anticoagulant Overdose
| Drug: Vitamin K1 (Phytonadione) (generic, Mephyton, AquaMephyton ®) |
| Drug Class: Vitamin |
| Mechanism of Action: Vitamin required for the synthesis of four different clotting factors, including prothrombin & factors VII, IX & X, as well as the endogenous anticoagulant proteins C and S. |
Indications:
|
| Contraindications: known hypersensitivity |
| Pharmacokinetics: Whenever possible, Vitamin K1 Injection (Phytonadione Injection, USP) should be given by the subcutaneous or intramuscular route. When intravenous administration is considered unavoidable, the drug should be injected very slowly, not exceeding 1 mg per minute (see side effects). |
| Side Effects: severe reactions including hypersensitivity, anaphylaxis and fatalities have occured when it is given i.v.. The i.v. route of administration should therefore be restricted to those situations where other routes are not feasible and the serious risk involved is considered justified. |
| Major drug interactions: Temporary resistance to prothrombin-depressing anticoagulants |
| References: www.rxlist.com & Katzung's text |
| Drug: Protamine Sulfate (generic) |
| Drug Class: Anti-Heparin agent |
| Mechanism of Action: When administered alone, protamine has an anticoagulant effect due to an interaction with platelets and with many proteins including fibrinogen. However, when it is given in the presence of heparin (which is strongly acidic), a stable salt is formed and the anticoagulant activity of both drugs is lost. |
| Indications: the treatment of heparin overdosage |
| Pharmacokinetics: Protamine sulfate has a rapid onset of action. Neutralization of heparin occurs within 5 minutes. |
| Side Effects: i.v. administration may cause a sudden fall in blood pressure and bradycardia. Other reactions include transitory flushing and feeling of warmth, dyspnea, nausea, vomiting, and lassitude. Anaphylaxis has also been reported. |
| Major drug interactions: incompatible with certain antibiotics, including several of the cephalosporins and penicillins |
Notes: Protamines are simple proteins of low molecular weight that are rich in arginine and strongly basic. They occur in the sperm of salmon and certain other species of fish. |
| References: www.rxlist.com |
Antiplatelet Drugs
| Drug: Aspirin (Acetylsalicylic acid, ASA) (generic) |
| Drug Class: NSAID / Antiplatelet |
| Mechanism of Action: Aspirin irreversibly inhibits both isoforms of COX (by irreversible acetylation) and thereby reduces the formation of thromboxane A2, an arachidonate product that causes plateletes to change shape, to release their granules, and to aggregate. This effect of aspirin serves to inhibit platelet aggregation. Aspirin also interferes with the chemical mediators of the kallikrein system, thus inhibiting granulocyte adherence to damaged vasculature, stabilizing lysosomes, and inhibiting the chemotaxis of PMN leukocytes and macrophages. |
Indications: 1) Antiplatelet Effects due to irreversible inhibition of platelet COX, so that aspirin's antiplatelet effect lasts 8-10 days (the life of the platelet). 2) Anti-inflammatory Effects. Aspirin's antiinflammatory effects are believed to contribute to aspirin's beneficial effects in patients having atherosclerotic disease, since inflammatory reactions within atherosclerotic plaques can result in plaque rupture. 3) MI Prophylaxis: Aspirin is indicated to reduce the risk of death and/or nonfatal myocardial infarction in patients with a previous infarction or unstable angina pectoris. 4) Transient Ischemic Attacks: Aspirin is indicated for reducing the risk of recurrent transient ischemic attacks (TIAs) or stroke in men who have transient ischemia of the brain due to fibrin emboli. There is currently no evidence that aspirin is effective in reducing TIAs in women, or is of benefit in the treatment of completed strokes in men or women. Other thereapeutically beneficial effects (covered elsewhere): 5) Analgesia, 6) Antipyretic. . |
Reference: www.rxlist.com & Katzung's text |
| Drug: Clopidogrel (Plavix ®) |
| Drug Class: Antiplatelet |
| Mechanism of Action: irreversibly blocks the ADP receptor on platelets, thereby reducing platalet aggregation. Has no effect on prostaglandin metabolism (unlike aspirin). |
| Indications: given to patients undergoing placement of a coronary stent (a standard practice) |
| References: Katzung's text |
First Generation Fibrinolytics
| Drug: Urokinase (Abbokinase ®) & Streptokinase (Streptase ®) |
| Drug Class: Fibrinolytics |
| Mechanism of Action: Streptokinase is a protein (not an enzyme) synthesized by streptococci that combines with plasminogen and increases its conversion to active plasmin. Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin formed inside a thrombus by these activators allows them to lyse a thrombus from within. |
| Indications: Urokinase is no longer commonly used. Streptokinase is still available for use. Clinical trials have shown that coronary catherization reduces mortality significantly better than the use of thrombolytics in patients suffering from a myocardial infarction caused by coronary artery disease. Thrombolytics are still very important for treatment of coronary occlusion in situations where coronary catherization is not readily available. |
| References: Katzung's text & rxlist.com |
2nd Generation Tissue-type plasminogen activators
| Drug: t-PA (aletplase recombinant or Activase ®) |
| Drug Class: Plasminogen activator |
| Mechanism of Action: t-PA binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis (i.e. acts selectively on thrombi). |
| Indications: 1) the management of acute myocardial infarction in adults for the improvement of ventricular function following acute myocardial infarction (see notes); 2) management of acute massive pulmonary embolism; 3) management of acute ischemic stroke in adults for improving neurological recovery and reducing the incidenceof disability (see notes); 4) treatment of central deep venous thrombosis. |
| Pharmacokinetics: given as an i.v. infusion |
| Side Effects: bleeding |
Notes: when used to treat stroke - therapy should only be initiated within 3 hours after the onset of stroke symptoms, and after exclusion of intracranial hemorrhage by a cranial computerized tomography (CT) scan or other diagnostic imaging method sensitive for the presence of hemorrhage. Coronary occlusion due to a thrombus is present in the infarct-related coronary artery in approximately 80% of patients experiencing a transmural myocardial infarction evaluated within 4 hours of onset of symptoms. |
| References: www.rxlist.com & Katzung's text |
| Drug: Reteplase (Retavase ®) |
| Drug Class: Plasminogen activator |
| Mechanism of Action: a recombinant t-PA |
Notes: Reteplase is a recombinant human t-PA from which several amino acids have been deleted. Because it lacks the major fibrin-binding domain, it is less fibrin-specific than t-PA. It is less expensive to produce than t-PA. |
| References: www.rxlist.com & Katzung's text |
| Drug: Tenecteplase (TNKase ®) |
| Drug Class: Plasminogen activator |
| Mechanism of Action: a mutant form of t-PA |
| Pharmacokinetics: longer half life. Can be given as a single i.v. bolus. |
Notes: Slightly more fibrin-specific than t-PA. |
| References: www.rxlist.com & Katzung's text |
Platelet GP IIA/IIIA Receptor Blockers
GP IIb/IIIa receptors
| Background: The platelet glycoprotein IIb/IIIa receptor complex functions as a receptor for fibrinogen and other macromolecules. Activation of this receptor complex is the "final common pathway" for platelet aggregation. There are approximately 50,000 copies of this complex on the platelet surface. |
| Drug: Abciximab (Reopro ®) |
| Drug Class: Antiplatelet |
| Mechanism of Action: a humanized monoclonal antibody directed against the IIb/IIIa complex. It binds to the receptor complex on platelets and thereby prevents platelet aggregation. |
| Indications: percutaneous coronary intervention (e.g. angioplasty, placement of coronary stints) & in acute coronary syndromes. Commonly used concomittantly with aspirin & heparin. |
| Pharmacokinetics: given parenterally; not orally effective |
| References: www.rxlist.com & Katzung's text |
| Drug: Eptifibatide (Integrilin ®) and Tirofiban (Aggrastat ®) |
| Drug Class: Antiplatelet |
| Mechanism of Action: Eptifibatide is an analog of the fibrinogen sequence that binds to the GP IIb/IIIa receptor & prevents platelet aggregation. Tirofiban is a smaller molecule with similar properties. |
| Indications: same as abciximab (above) |
| Pharmacokinetics: given parenterally; not orally effective |
| References: www.rxlist.com (eptifibatide & tirofiban) Katzung's text |
| Drug: Chloroquine (generic, Aralen ®) |
| Drug Class: Antimalarial, antiprotozoal |
| Mechanism of Action: the mechanism of plasmodicidal action of chloroquine is not completely certain. It probably acts by concentrating in parasite food vacuoles, preventing the polymerization of the hemeoglobin product, heme, into hemozoin and thus eliciting parasite toxicity due to the build up of heme. It is not active against liver stage parasites (and primaquine must be added for the radical cure of these species). |
| Clinical Indications: for malaria and extraintestinal amebiasis. Effective against nonfalciparum and sensitive falciparum malaria. Resistance to chloroquine is now very common against strains of P. falciparum, and uncommon but increasing for P vivax. |
| Contraindications: patients with psoriasis or porphyria, in whom chloroquine may precipitate attacks of these diseases.Avoid use in patients with retinal or visual field abnormalities or myopathy. |
| Side Effects: Usually well tolerated. Side effects such as nausea, vomiting, etc. may be reduced by dosing after meals. Pruritis is common, primarily in Africans. |
| Pharmacokinetics: Typically given orally. Chloroquine is rapidly and almost completely absorbed fromthe gastrointestinal tract. Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Slightly more than half of the urinary drug products can be accounted for as unchanged chloroquine. Large i.m. injections or rapid i.v. infusions of chloroquine can result in severe hypotension & respiratory & cardiac arrest. Parenteral administration is best avoided. |
| Major drug Interactions: antidiarrheal agents (kaolin) & calcium- and magnesium-containing antacids interefere with chloroquin absorption. |
| Notes: Chloroquine does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Quinine ( generic ®) |
| Drug Class: Antimalarial (P. falciparum) |
| Mechanism of Action: Unknown. Quinine is effective as a malarial suppressant and in control of overt clinical attacks. Its primary action is schizontocidal, no lethal effect is exerted on sporozoites or preerythrocitic tissue forms. |
| Clinical Indications: a first line therapy (along with its stereoisomer quinidine) for falciparum malaria - especially severe disease. Resistance to quinine is uncommon but increasing. It is not effective against liver stage parasites. Quinidine is the standard therapy for parenteral treatment of severe falciparum malaria (parenteral quinine is not available in the USA). |
| Contraindications: if signs of severe cinchonism, hemolysis or hypersensitivity occur. |
| Side Effects: cinchonism: tinnitus, headache, headache, nausea, dizziness, visual disturbances. |
| Pharmacokinetics: Rapidly absorbed after oral administration. Primarily metabolized by the liver & excreted in the urine. Parenteral quinine is not available in the USA, although quinidine is available. Because of it's potential for causing cardiotoxicity & unpredictable pharmacokinetics, i.v. quinidine should be administered with cardiac monitoring. Therapy should be changed to oral quinine as soon as the patient has improved & can tolerate oral medications. Dosage should be reduced in renal insuficiency. |
| Major drug Interactions: do not give to a patient taking mefloquine, and used with caution in patients who have previously received mefloquin therapy. Quinine can raise plasma levels of warfarin & digoxin. Aluminum containing antacids interfere with absorption. |
| Note: Quinine is gametocidal against P. vivax and P. ovale but not P. falciparum. Chloroquine is more effective and less toxic than quinine against non-falciparum malarias. Hence quinine is not a drug of choice for non-falciparum malaria. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Primaquine (generic) |
| Drug Class: Antimalarial (P. vivax & P. ovale) |
| Mechanism of Action: Mechanism of action not known, but the drug binds to and may alter the properties of DNA leading to decreased protein synthesis. Active against the hepatic stages of all human malarial parasites. Some gametocytes are destroyed while others cannot undergo maturation division in the gut of the mosquito. |
| Clinical Indications: For therapy of acute vivax and ovale malaria, it is given as a 14 day drug regimen to eradicate liver hypnozoites following acute therapy with chloroquine (which eradicates erythrocytic forms). Also used as a single dose to render falciparum gametocytes noninfective to mosquitoes (to disrupt transmission of malaria). |
| Contraindications: Concomitant use with quinacrine. In clients with rheumatoid arthritis or lupus erythematosus who are acutely ill or who have a tendency to develop granulocytopenia or methemoglobenemia. Concomitant use with other bone marrow depressants (e.g. quinidine) or hemolytic drugs. Patients should be evaluated for normal G6PD levels before giving primaquine. Avoid in pregnancy (because the fetus is relatively G6PD defecient and therefore at risk of hemolysis.) |
| Side Effects: Usually well tolerated. Side effects such as nausea, vomiting, etc. may be reduced by dosing after meals. May cause hemolysis or methemoglobinemia (cyanosis), especially in patients with G6PD deficiency or other hereditary metabolic defects. |
| Pharmacokinetics: Well absorbed from GI tract. t1/2 elimination: 4 hr. Rapidly metabolized. Never given parentally because of marked hypotension. |
| Major drug Interactions: myelosuppresant drugs, quinidine |
| Reference: www.healthdigest.org/drugs/ & Katzung's text |
| Drug: Mefloquine (generic, Lariam ®) |
| Drug Class: Antimalarial |
| Mechanism of Action: Unknown, chemically related to quinidine. Has strong bllod schizonticidal activity against P. falciparum and P. vivax, but not against hepatic stages or gametocytes. |
| Clinical Indications: the drug of choice for chemoprophylaxis against chloroquine-resistant strains of malaria. Recommended by the CDC for chemoprophylaxis in all malarious areas except those with no chloroquine resistance (where chloroquine is prefered) and some rural areas of SE Asia with a high prevalence of mefloquine resistance. As with chloroquine, eradication of P. vivax and P. ovale requires a course of primaquine. |
| Contraindications: history of epilepsy, psychiatric disorders, arrhythmia or drug sensitivity. Should not be given with quinidine, quinine, or halofantrine and caution is required when using these drugs after mefloquine chemoprophylaxis. |
| Side Effects: nausea, vomiting, dizziness, and infrequently seizures & psychosis. |
| Pharmacokinetics: Orally administration only (parenteral use causes severe local irritation). Well absorbed & eliminated slowly (half-life of 20 days). Can be given once a week for chemoprophylaxis. The parent drug and metabolites are slowly excreted, mainly in the feces. |
| Major drug Interactions: quinidine, quinine or halofantrine |
| Notes: Mefloquine is not appropriate for treating severe or complicated malaria since quinine and quinidine are more rapidly active and drug resistance is less likely with those agents. |
| Reference: www.rxlist.com & Katzung's text |
Inhibitors of folate synthesis
| Drug: Pyrimethamine + Sulfadoxine (Fansidar ®) |
| Drug Class: Antimalarial |
| Mechanism of Action: Folic acid antagonists. The rationale for there combination is a synergistic effect to inhibit folic acid synthesis, and a differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine is chemically related to trimethoprim. It acts slowly against erythrocytic forms of susceptible strains of all four human malaria species. It is not adequately gametocidal or effective against liver stages. |
| Clinical Indications: Fansidar is commonly used to treat uncomplicated falciparum malaria. Also considered appropriate therapy after chloroquine treatment failure. Used as a presumptive therapy for travelers who develop fever while traveling in malaria-endemic regions & are unable to obtain medical evaluation. |
| Contraindications: Use with caution in patients with renal or hepatic dysfunction. Must give folate supplements in patients that are pregnant. |
| Side Effects: GI symptoms, skin rashes, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. Fatalaties have occured, and fansidar should be discontinued at the first signs of skin rash. |
| Pharmacokinetics: Slowly but adequately absorbed from the GI tract. |
| Notes: In many areas resistance to folate antagonists and sulfonamides is common of P. falciparum and less common for P. vivax. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Trimetrexate (Neutrexin ®) |
| Drug Class: Treatment of Pneumonia in AIDS |
| Mechanism of Action: a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. |
| Clinical Indications: trimetrexate glucuronate for injection with concurrent leucovorin administration (leucovorin protection) is indicated as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS), who are intolerant of, or are refractory to, trimethoprim-sulfamethoxazole therapy or for whom trimethoprim-sulfamethoxazole is contraindicated |
| Contraindications: patients with clinically significant sensitivity to trimetrexate, leucovorin, or methotrexate. It can cause fetal harm when administered to a pregnant women |
| Side Effects: severe hematologic, hepatic, renal, and gastrointestinal toxicities. |
| Drug Interactions: trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug-drug interactions that may alter trimetrexate plasma concentrations. Agents that might be coadministered with trimetrexate in AIDS patients for other indications that could elicit this activity include erythromycin, rifampin, rifabutin, ketoconazole, and fluconazole. Cimetidine reduces trimetrexate metabolism. |
| WARNING: NEUTREXIN (TRIMETREXATE GLUCURONATE FOR INJECTION) MUST BE USED WITH CONCURRENT LEUCOVORIN (LEUCOVORIN PROTECTION) TO AVOID POTENTIALLY SERIOUS OR LIFE-THREATENING TOXICITIES |
| Reference: www.rxlist.com |