Antiprotozoal drugs antimalarials

This section consists of antiprotozoal drugs. Note that antimalarials are also antiprotozoals but have been described in a separate section Antibiotics with antiprotozoal activity are not included in this chapter. These include clindamycin, co-trimoxazole/trimethoprim, dapsone, doxycydine and metronidazole ... 

Pyrimethamine and proguanil are used as oral antimalarials.and inhibit the utilization of folate by the malarial parasite, so are valuable in chemoprophylaxis and in preventing the transmission of malaria. (See ANTIMALARIALS.) Trimethoprim is a useful antibacterial, and as an antiprotozoal in antimalarial therapy. The selectivity of these agents derives, in part, from the fact that whereas mammals can obtain folic acid from the diet, bacteria and the asexual forms of the malarial parasite must synthesize it. Also, the dihydrofolate reductase enzyme in humans is less sensitive to these drugs than that of the parasites. 

Plants accumulate STLs as a means of chemical defence. Thus, one of the primary ecological benefits of these compounds is certainly the fact that they are toxic to all kinds of microorganisms. Once more it is their alkylant potency that is most obviously responsible. The work on antimicrobial activity of earlier years has been summarized in various reviews, e.g. [1-3]. More recent work has indicated that some STLs may have potential as leads for new antiprotozoal drugs. Apart from the prominent antimalarial artemisinin which will be treated separately in the following section, several more common STLs have been demonstrated to possess antiplasmodial [77-79], antileishmanial [80] and antitrypanosomal activity [81-84], Unfortunately, in most cases such activities are accompanied by high non-specific cytotoxicity so that it is always necessary to compare the antiprotozoal activity with cytotoxic effects determined under the same conditions. 

VENLAFAXINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS-TCAs 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemetherwith lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS -sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

Among the various natural products, which have been found to possess antiprotozoal activity in humans, quinine (2) and qinghaosu (7) have undergone extensive molecular modifications to obtain better antimalarial drugs. The salient results of these studies are described below. 

---