Protozoal infections drugs

The mechanism of inhibition of these protozoal infections by the most active drugs, puromycin and the aminonucleoside, is not known. Puromycin and nucleocidin both interfere with protein synthesis, but the aminonucleoside does not. It is known to be demethylated to 3 -amino-3-deoxyadenosine, which is phosphorylated and interferes with nucleic acid metabolism (see above). Whether puromycin must be converted to the aminonucleoside before it can inhibit protozoa has not been established. Some purine analogues known to interfere with nucleic acid metabolism, however, are less effective as antiprotozoal agents, even in vitro, perhaps because their effects are primarily on the de novo pathway which many, if not all, protozoa do not use [406]. 

Other protozoal infection is giardiasis which is caused by Giardia lamblia and the drug of choice in its treatment are imidazole derivatives. 

The primary drugs used to treat African trypanosomiasis are set forth in Table 52-6, and those for other protozoal infections are listed in Table 52-7. Important drugs that are not covered elsewhere in this or other chapters are discussed below. 

One relatively common disease caused by protozoal infection is malaria. Malaria is caused by several species of a protozoan parasite known as plasmodia. Although this disease has been virtually eliminated in North America and Europe, malaria continues to be a primary health problem throughout many other parts of the world.44 Individuals who live in these areas, as well as those traveling to parts of the world where malaria is prevalent, must often undergo antimalarial chemotherapy. Hence, drugs that prevent and treat malaria are extremely important. 

The primary agents used to treat protozoal infections are listed in Tables 35-3 and 35-4, and each agent is described subsequently. Drugs that are primarily used to treat and prevent malaria are grouped together, followed by drugs that are used to treat other types of protozoal infections (intestinal and extraintestinal infections). 

Chloroquine is also used for the treatment of treat infections in the liver and pericardium. As discus-conditions other than malaria. This drug is effective sed in Chapter 16, chloroquine is effective in rheuma-against other types of protozoal infections such as ame- toid disease and is used in the treatment of conditions biasis and may be used with iodoquinol or emetine to such as rheumatoid arthritis and systemic lupus erythe- ... 

Pyrimethamine may also be combined with other antimalarials such as artemisinin derivatives, but these regimens should only be used if the malarial parasites are not resistant to the specific drugs in the regimen.13 Pyrimethamine can also be combined with a sulfonamide drug such as dapsone, sulfadiazine, or sulfamethoxazole to treat protozoal infections that cause toxoplasmosis, or fungal infections that cause Pneumocystis pneumonia.These agents are administered orally. 

Drugs Used to Treat Protozoal Infections in the Intestines and Other Tissues... 

Clinical Use. Emetine and dehydroemetine (Mebadin) are used primarily to treat protozoal infections in the intestinal tract and extraintestinal sites such as the lungs and liver. These drugs are powerful amebicides and are generally reserved for severe, acute cases of intestinal amebiasis (dysentery).51 Because of the potential for adverse effects, these drugs are no longer marketed in the United States, and safer agents like metronidazole are often used in their place. Emetine and dehydroemetine are typically administered by deep subcutaneous injection or intramuscular injection. 

Clinical Use. lodoquinol (Diquinol, Yodoxin, other names) is used primarily to treat protozoal infections within the intestinal tract,51 and it is often combined with a second tissue amebicide, which kills protozoa at extraintestinal sites. For instance, iodoqui-nol may be combined with metronidazole to ensure the destruction of parasites throughout the body, lodoquinol is usually administered orally. Because iodoquinol is relatively toxic, the routine use of this drug has been replaced somewhat by other agents such as paromomycin, which may be somewhat safer. 

Clinical Use. Paromomycin (Humatin) is an aminoglycoside antibacterial (see Chapter 33) that is used primarily to treat mild to moderate intestinal infections (amebiasis).51 This drug may also be used as an adjunct to other amebicides during the treatment of more severe protozoal infections. Paromomycin is also effective against some bacteria and tapeworms, and may be used as a secondary agent in certain bacterial or helminthic infections. This drug is administered orally. 

Quinine is a cinchona alkaloid that acts rapidly against all four species of Plasmodium. It is used to treat protozoal infections and leg cramps, and as a bitter and flavoring agent. However, the drug is not used prophylactically for malaria. Quinines are contraindicated in patients with a history of hypersensitivity to quinine or quinidine. They should not be used in the presence of hemolysis and should be used with caution in patients with atrial fibrillation, cardiac conduction defects, or heart block. Quinine administration in myasthenia gravis may aggravate the disease, hence it should be avoided. Quinine can be used in pregnancy.37 Intravenous infusion of quinine should be slow, and the patient should be monitored for cardiotoxicity.38 Cinchonism, which is characterized by tinnitus, GI disturbances, and impaired vision may occur with therapeutic doses of quinine.39... 

Protozoal infections. Malaria is the major transmissible parasitic disease in the world. The life cycle of the plasmodium that is relevant to prophylaxis and therapy is described. Drug resistance is an increasing problem and differs with geographical location, and species of plasmodium. 

The drug treatment of other protozoal infections is summarised in Table 14.4. 

The broad-spectrum anthelmintic nitazoxanide has been undergoing efficacy trials in the USA for the treatment of EPM (Vatistas et al 1999). This drug is currently used to combat intestinal parasites of humans in developing countries and in patients with the acquired immimodeficiency syndrome complicated by secondary protozoal infections. Nitazoxanide is administered daily for 28 days as an oral paste. The side-effects of this drug are more serious than with other medications because it kills other parasites in addition to S. neurona. This has led to recommendations for deworming with another anthelmintic prior to starting this treatment (McClure Palma 1999). Nitazoxanide may also cause colic in treated horses. 

ANTIMICROBIAL with ANTIBACTERIAL and ANTIPROTOZOAL actions. It widely used orally for a range of bacterial and protozoal infections. It acts as a potent aldehyde DEHYDROGENASE INHIBITOR, which can lead to Significant interactions with other drugs. It is also a diamine oxidase INHIBITOR. 

The historical development of organo-arsenicals, -antimonials and -phosphates has been dealt in Chapter 4. This chapter will be confined to a discussion of their therapeutic value in the management of protozoal infections organometallic drugs continue to be used/ though to a limited extent in the treatment of leishmaniasis and trypanosomiasis. 

Compounds of this class constitute the front-line therapy for many protozoal diseases of man. In fact, emergence of drugs like metronidazole and tinidazole has revolutionised the treatment of intestinal protozoal infections [20,27,64-66]. The therapeutic profile of a few nitroimidazole drugs is given below. 

Tracey JW, Webster LT Jr. Drugs used in the chemotherapy of protozoal infections Malaria. In Hardman JG, Limbird LE, Gilman AG, eds. The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001 1069-1095. 

Table V-4-1. Major Protozoal Infections and the Drugs of Choice...

Table V-4-1 lists the major types of protozoal infections and the drugs of choice for their treatment, j j with various relevant comments. j... 

---