Antiprotozoals and antihelminthics

===Lecture Details===
Liz Davis; Week 9 MED1022; Pharmacology
===Lecture Content===
Parasites can be commensal, pathogenic under certain circumstances (opportunistic) or always pathogenic. Prevention requires sanitation and hygeine, control vectors, chemo-prophylaxis. Intestinal and luminal protozoa: Entamoeba histolytica, Giardia lamblia, malaria. Chemotherapy aims to reduce numbers of organisms or reduce to a level that can be controlled by the immune system, should get to agent of infection, destroys pathogens and remains there long enough to be effective. Protozoa are unicellular, gain entry to hosts by sex, blood, bites, ingestion, inhalation, mostly resistant to drugs used to treat other infectious organisms. They differ in sensitivity to drugs and can develop resistance. 
Malaria is caused by P falciparium (malignant), malarial syndrome characterised by fever and chills (haemolytic anaemia). There is pigmentation of skin, enlarged liver, spleen and lymph nodes, renal block/failure and convulsions/hallucinations. Chloroquinine is resisted in many places. 
Amoebiasis is caused by Entamoeba histolytica. Most are asymptomatic but they still excrete cysts for short periods of time. Treat confirmed cases to prevent transmission. It is endemic in Australia, more common in immigrants, male gays, travellers coming home. Symptomatic patients have invasive amoebiasis, can be long latent period- colitis (diarrhoea/abdominal cramps/pain), liver abscess, can also have central amoebiasis, genitourinary. Cysts can survive for weeks in external environment. Treatment is with luminal amoebicide in asymptomatic patients; in invasive metronidazole or tinidazole (include luminal).
Paromomycin is an aminoglycoside related to gentamicin- irreversibly inhibits the 30S subunit. Has poor absorption from GIT. Can cause abdominal cramps, nausea, diarrhoea. Increased GI absorption increases risk of ototoxicity &/or nephrotoxicity. 3/day for 5-10 days.
Giardiasis has asymptomatic or anorexia, nausea, malaise, vomiting, diarrhoea, abdominal cramps & distension. Chronic infection is assoicated with malabsorption syndrome, weight loss. Fecal-oral spread. Drugs of choice are metronidazole/tinidazole.
Nitroimidazoles are tinidazole/metronidazole, used for some protozoal infections (giardia, trichomonas) and some bacterial infections (clostridium). Mechanism of action is inhibition of DNA synthesis, is chemically reduced in sensitive protozoa. Side effects are less in tinidazole than metronidazole- nausea, dry mouth, metallic taste, headache. Interacts with alcohol metabolism.
Antihelminthic drugs are used in giardiasis; nematide, cestode and trematode infection. Helminths are multicellular organisms with complex life cycles, are common infections of humans, pets, stock and wildlife. Nematodes are elongated, cylindrical, non-segmented worms. Can be free-living vs parasitic. Infections vary from asymptomatic to mild, serious morbidity. Intestinal nematodes can be large human roundworms, threadworm/pinworm, whipworm, hookworm.
Antihelminthic drugs are mostly broad spectrum, well tolerated. Benzimidazoles (albendazole/mebendazole), diethylcarbamazine, ivermectin, praziquantal control majority of helminth infections. GI worms are susceptible to drugs that act at the helminth NMJ. Agents can act indirectly (benzimidazoles) or directly (piperacine, ivermectin) to cause paralysis of the worm. Benzimidazoles such as mebendazole or albendazole are active against nematodes/some cestodes. They inhibit microtubule synthesis (impairs glucose uptake and decreases ATP formation). They are teratogenic. Pyrantel is broad spectrum, depolarises neuromuscular blocking agent and inhbits cholinesterase. Poorly absorbed GI. Adverse effects rare. Mebendazole is poorly absorbed from GIT, has few side effects (diarrhoea, abdominal discomfort if heavy worm load). Albendazole is absorbed from GIT and has mild GI effects, drug of choice for mixed infection. Works against some protozoa. Ivermectin is broad spectrum antihelminthic, inhibits helminth muscle, well tolerated. 
Cestodes are segmented and flattened. Attach to host using their head (scolex) which can generate new segments. Usually of minor clinical significance. Eaten by definitive host (predator) and cysts are eaten by intermediate host (prey).
Praziquantel causes tetanic contractions by altering Ca permeability, increases susceptibility to host's immune response. Side effects are GI intolerance, nausea, more marked with heavy worm load. It is broad spectrum.
===Readings===
====Rang (5) 46, 47====