Antiprotozoal drugs

 

Antiprotozoal drugs

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Protozoa are eukaryotic unicellular organisms. They cause a wide range of diseases in man and animals causing extensive morbidity and mortality. Protozoa are difficult to eliminate completely because they are frequently transmitted by ticks, mosquitoes, flies and some other arthropods.  Many protozoal infections are zoonotic and affect equally both animals and humans. The common protozoal diseases of veterinary importance are Coccidiosis, Babesiosis, Theileriosis, Toxoplasmosis, Giardiosis, Leishmaniasis, Trypanosomiasis, Trichomoniosis and Amoebiasis. This chapter deals with the pharmacological aspects of important antiprotozoal drugs.

 

1. Imidocarb dipropionate: This drug is mainly used for the treatment or prophylaxis of babesiosis in cattle, sheep, horses and dogs. It is also useful in treating anaplasmosis in cattle and ehrlichiosis in dogs. It appears that Imidocarb dipropionate acts directly by combining with DNA in susceptible protozoa leading to unwinding and denaturation of DNA. Imidocarb dipropionate is given by S/C or I/M injection but not by I/V. Imidocarb dipropionate is well absorbed after parentral (S/C or I/M) administration and distributed throughout the body. Excretion of Imidocarb dipropionate is slow due to its accumulation in tissues and high protein binding therefore, one injection of the drug is sufficient to impart antiprotozoal activity for several weeks (approximately 4 weeks). Adverse effects of Imidocarb dipropionate include mild cholinergic signs like salivation, restlessness, diarrhoea and fainting. Antimuscarinic drug, Atropine may be useful to relieve these symptoms. It has long-lasting residues in tissues (upto 170 days), so it is not recommended in food-producing animals. Imidocarb dipropionate should not be used with anticholinesterase agents (like Physostigmine and Neostigmine etc.) or pesticides (such as organophosphates) as these drugs may potentiate its cholinergic adverse effects.

 

2. Diaminazine: It is a diamidine compound that has antibabesial and antitrypanosomal activity. It is mainly used for the treatment of trypanosomiasis and babesiosis in animals. It acts mainly by binding to the DNA containing organelles, first in the kinetoplast and subsequently in the macronucleus. Diminazine has good antitrypanosomal and antibabesial activity and some bactericidal action against brucella and streptococcus species. Multiple therapeutic doses of Diminazine can produce several nervous signs in dogs with lesions in the brain.

 

3. Quinapyramine: It is widely used in veterinary practice for the treatment and prevention of trypanosomiasis. The mode of action of Quinapyramine is attributed mainly to inhibition of growth and cell division in susceptible parasites. Quinapyramine has significant activity against several species of trypanosoma. It is not absorbed by oral route so it has to be given parentrally. In cattle and other species, Quinapyramine is administered as 10% solution by S/C injection in dewlap or neck and the site is massaged nicely. In horses it is given intramuscularly as 5% solution. Quinapyramine is usually well tolerated at recommended doses. Subcutaneous injection of 10% Quinapyramine may cause localized pain, inflammation and sloughing of tissues at injection site in horses. Therefore, in horses Quinapyramine is generally administered by I/M injection as a 5% solution or the dose is administered in small amounts at two or three different sites.

 

4. Isometamedium: Isometamedium is active against trypanosomiasis in cattle, horses and camels. It has no activity against other protozoa. As a prophylactic agent it provides protection against trypanosma species for two months or more. This drug is always administered by deep intramuscular injection.

 

5. Suramin: Suramin has been used in veterinary practice for both curative and prophylactic control of trypnosomiasis. It is also used in human medicine for treating African trypnosomiasis. Suramin binds firmly to host plasma proteins to form a drug-protein complex, which enters the trypanosome by endocytosis. Once inside trypanosomes, Suramin is released from the protein complex by lysosomal proteases. The free Suramin then selectively acts on some trypanosomal enzymes, particularly trypanosomal cytosolic serine oligopeptidase. The antitrypanosomal activity of Suramin is slow in onset, which probably occurs from slow endocytic uptake of the drug-protein complex by the susceptible parasites. It is not absorbed after oral administration. Suramin tends to accumulate in mononuclear phagocytic system and proximal renal tubules of the host, but fails to enter the CSF. Suramin extensively (97%) binds to plasma proteins. It has a low margin of safety and may cause a variety of unwanted effects including nausea, vomiting, diarrhea and seizures. Parasite destruction has been associated with fever and skin hypersensitivity. A small proportion of individuals show idiosyncratic reaction to Suramin in terms of shock and loss of conscousness. Horses and donkeys are highly susceptible to the toxic effects of Suramin, but camels are quite resistant.

6. Metronidazole: It is a synthetic antiprotozoal and antibacterial agent. It is suggested that Metronidazole enters the susceptible protozoa by diffusion and is reduced to an intermediate cytotoxic metabolite. The active metabolite interacts with the protozoal DNA, where it causes loss of helical structure and strand breakage. It has a broad spectrum of activity against protozoa (including Giardia, Trichomonas, Entamoeba histilytica, Babesia and Histomonas) and anaerobic bacteria (such as Fusobacterium necrophorum, Clostridium perfringens, Helicobacter pylori). It is widely used in humans and small animals for the treatment of giardiais, amoebiasis and trichomoniasis. Metronidazole may also be used for the treatment of histomoniasis and baesiosis but its efficacy is unreliable. It is an effective drug against anerobic bacterial infections. The oral bioavailbility of Meteronidazole in animals varies from 50% to 100%. If given with food, absorption is enhanced in dogs attributable to increased bile secretion that helps to dissolve Meteronidazole. It possesses very low protein binding capacity and is well distributed in body tissues and body fluids including bones, abscesses, CNS and seminal fluid. Following high doses the colour of urine may become dark due to presence of metabolites. Low concentration of drug may be seen in milk and saliva. High doses may produce neurological disturbances characterized by tremors, ataxia, nystagmus, disorientation, head tilting and seizures. Because Metronidazole affects DNA synthesis, it may have teratogenic, carcinogenic and mutagenic effects. It should be used with extreme caution in animals suffering from neurological diseases. It prolongs bleeding time in patients taking Warfarin or other anticoagulants. Cimitidine on the other hand can reduce the metabolism of Metronidazole and increases the likelihood of dose-related side effects.

 

7. Furazolidone: It is a synthetic nitrofuran used for the treatment of enteric infections especially in cats (feline giardiosis) and birds (avian coccidiosis and avian colibacillosis). It is often used in comination with Colistin (a polymyxin antibiotic) for the treatment of enteric infection in birds caused by gram negative bacteria. Unwanted effects at recommended doses are limited.

 

8. Buparvaquone: It is a synthetic naphthoquinone that is used to treat theileriosis in cattle. It appears to act by interfering with cytochrome C-mediated electron transport in susceptible parasites.

 

9. Haolfuginone: Halofuginone is primarily an anticoccidial drug but it also possesses good efficacy against bovine theileriosis. It is an extremely potent drug and its administration may result in transient diarrhea in treated animals therefore it must be cautiously used.

 

10. Tetracyclines: Some tetracyclines like Oxytetracycline, Chlortetracycline and Doxycycline also possess antibabesial action. Tetracyclines are also useful in treating theilerial infections in cattle, but they are required in high doses and for longer periods.