31 Antiprotozoal drugs Flashcards
31.01 BLOOD SCHIZONTICIDES - MALARIA
Chloroquine, quinine, mefloquine, amodiaquine - actions
schizonticidal drugs kill malarial parasites in red blood cells
31.01 BLOOD SCHIZONTICIDES - MALARIA
Chloroquine, quinine, mefloquine, amodiaquine - MOA
inhibit haem polymerase which would normally degrade haem
the toxic haem molecules accumulate and kill the parasite
31.01 BLOOD SCHIZONTICIDES - MALARIA
Chloroquine, quinine, mefloquine, amodiaquine - abs/distrib/elim
given orally (IV quinine is used for severe falciparum malaria)
concentrates in parasitised erythrocytes
31.01 BLOOD SCHIZONTICIDES - MALARIA
Chloroquine, quinine, mefloquine, amodiaquine - clinical use
for acute attacks of malaria depending on local resistance patterns
chloroquine and mefloquine can be used for chemoprophylaxis of malaria in specific areas
chloroquine is also used in autoimmune conditions such as lupus erythematosus
31.01 BLOOD SCHIZONTICIDES - MALARIA
Chloroquine, quinine, mefloquine, amodiaquine - adverse effects
few when used for chemoprophylaxis
the larger doses used to treat the acute attack can cause GIT disturbances, dizziness and hearing abnormalities
arrhythmias and hypotension at high doses
31.01 BLOOD SCHIZONTICIDES - MALARIA
Chloroquine, quinine, mefloquine, amodiaquine - special points
for falciparum malaria, quinine is given together with antibiotics such as doxycycline or clindamycin or pyrimethamine/sulfadoxine
31.02 TISSUE SCHIZONTICIDE - MALARIA
Primaquine - actions
kills hypnozoites in the liver
kills gametocytes
31.02 TISSUE SCHIZONTICIDE - MALARIA
Primaquine - MOA
not really known
31.02 TISSUE SCHIZONTICIDE - MALARIA
Primaquine - abs/distrib/elim
given orally, rapidly metabolised
half-life 3-6h
31.02 TISSUE SCHIZONTICIDE - MALARIA
Primaquine - clinical use
for radical cure of Plasmodium vivax and P. ovale by eliminating the exo-erythrocytic stage
given as adjunct to chloroquine treatment of the acute attack
31.02 TISSUE SCHIZONTICIDE - MALARIA
Primaquine - adverse effects
dose-related GIT disturbances and methaemoglobinaemia
causes haemolytic anaemia in patients with genetic glucose 6-phosphate dehydrogenase deficiency (G6PD)
31.03 FOLATE INHIBITORS - MALARIA
Proguanil, pyrimethamine - actions
folate inhibition
these are slow blood schizonticides that have a greater affinity for the parasite’s enzymes than the equivalent human cellular enzymes
31.03 FOLATE INHIBITORS - MALARIA
Proguanil, pyrimethamine - MOA
inhibit the malaria parasite’s dihydrofolate reductase (DHFR) and thus interfere with its thymidylate synthesis
pyrimethamine is used in a combination tablet with sulfadoxine which inhibits dihydropteroate synthetase - an earlier step in thymidylate synthesis
proguanil is often given in combination with atovaquone which inhibits the parasite’s mitochondrial electron transport
31.03 FOLATE INHIBITORS - MALARIA
Proguanil, pyrimethamine - abs/distrib/elim
given orally, usually in combination tablet formulation
31.03 FOLATE INHIBITORS - MALARIA
Proguanil, pyrimethamine - clinical use
proguanil + atovaquone or chloroquine is used for chemoprophylaxis of malaria
pyrimethamine/sulfadoxine (with quinine) or proguanil + atovaquone can be used for treatment of acute uncomplicated falciparum malaria in some regions
toxoplasmosis can be treated with pyrimethamine/sulfadoxine
31.03 FOLATE INHIBITORS - MALARIA
Proguanil, pyrimethamine - adverse effects
GIT disturbances, rash, marrow suppression (with pyrimethamine)
31.04 ARTEMISININ DERIVATIVES - MALARIA
Artemether, artesunate, artemisinin - actions
a blood schizonticide combination
31.04 ARTEMISININ DERIVATIVES - MALARIA
Artemether, artesunate, artemisinin - MOA
artemisinin compounds become concentrated in parasitised red cells and give rise to highly reactive compounds that damage parasite proteins and membranes
artemether is usually combined with lumefantrine which prevents parasite detoxification of haem
31.04 ARTEMISININ DERIVATIVES - MALARIA
Artemether, artesunate, artemisinin - abs/distrib/elim
artesunate is a water-soluble version that can be IV, whereas artemether and artemisinin are given orally or IM
they are metabolised in the liver to the active compound dihydroartemisinin
31.04 ARTEMISININ DERIVATIVES - MALARIA
Artemether, artesunate, artemisinin - clinical use
fast-acting blood schizonticidal action against falciparum and non-falciparum malaria
31.04 ARTEMISININ DERIVATIVES - MALARIA
Artemether, artesunate, artemisinin - adverse effects
transient heart block, fever, decreased neutrophil count
31.05 TREATMENT OF AMOEBIASIS
Amoebicides: metronidazole, tinidazole, diloxanide - actions
metronidazole and tinidazole are active against the invasive motile forms of Entamoeba histolytica in the gut and liver
diloxanide acts against the non-invasive cysts in the gut lumen
31.05 TREATMENT OF AMOEBIASIS
Amoebicides: metronidazole, tinidazole, diloxanide - MOA
metronidazole and tinidazole are activated by anaerobic organisms to form free radicals that damage the DNA
the mechanism of diloxanide is not known but thought to affect protein synthesis
31.05 TREATMENT OF AMOEBIASIS
Amoebicides: metronidazole, tinidazole, diloxanide - abs/distrib/elim
given orally, can be given IV and rectally
tinidazole has longer action
diloxanide is given orally
31.05 TREATMENT OF AMOEBIASIS
Amoebicides: metronidazole, tinidazole, diloxanide - clinical use
metronidazole and tinidazole are used for amoebic liver abscess and amoebic dysentery (followed by eradication of cysts using diloxanide), trichomoniasis and giardiasis
31.05 TREATMENT OF AMOEBIASIS
Amoebicides: metronidazole, tinidazole, diloxanide - adverse effects
GIT disturbances, anorexia, dizziness
metronidazole and tinidazole can cause disulfiram reactions after alcohol
31.06 OTHER ANTIPROTOZOAL DRUGS
Suramin for human African trypanosomiasis
given by slow IV injection
inhibits key parasite enzymes, leading to gradual destruction of organelles
wide range of serious adverse effects in humans, including renal failure, agranulocytosis and shock
31.06 OTHER ANTIPROTOZOAL DRUGS
Pentamidine for trypanosomiasis, pneumocystis pneumonia, leishmaniasis
given by IV or deep IM injection with direct trypanocidal action
inhaled pentamidine for prophylaxis of pneumocystis pneumonia
hypotension, cardiac arrhythmias, dyspnoea, renal failure and hypoglycaemia are serious toxicities
31.06 OTHER ANTIPROTOZOAL DRUGS
Sodium stibogluconate for leishmaniasis
given by slow IV or IM injection
increased production of free oxygen radicals may lead to killing of parasite
