Sunday, December 2, 2007

Chap 53: Antiprotozoal drugs

- 4 species but falciparum causes nearly all significant cx and deaths
- resistance a major issue with falciparum
- parasite life cycle
  • anopheline mosquito --> inoculates sporozoite --> into blood stream --> invade liver cells --> schizonts mature in liver --> merozoites released from liver --> invade RBC --> gametocytes develop in RBC --> taken by mosquite
  • it's the RBC infection that causes clinical illness
  • falciparum + malariae --> 1 cycle of liver cell invasion --> then liver infection stops in 4wks --> treatment of erythrocytic parasites will cure infection
  • vivax + ovale --> dormant hepatic stage (hypnozoite) --> needs to treat RBC and hepatic parasites to achieve cure
- drug classification
  • tissue schizonticides - kills developing/dormant liver forms
  • blood schizonticides - kills RBC parasites
  • gametocides - kills sexual stage and prevent transmission to mosquitoes
- chemoprophylaxis and treatment

- for rx and chemoprophylaxis, drug of choice for sensitive falciparum and other species
  • blood schizonticide + gametocytes (for v,o,m not f), not active for liver
  • unclear MOA
  • resistance - very common in f, increasing in v due to mutation of transporter (to bring drugs into RBC)
- clinical
  • Rx: drug of choice in sensitive f and non-f, rapidly terminates fever (in 24-48 hrs) and clears parasite from blood (48-72hrs)
  • used in resistant falciparum cos eliminates symptoms quickly - but some has partial genetic immunity
  • primaquine is added for v and o to kill liver schizonts
  • chemoprophylaxis - preferred agent in sensitive f
  • amebic liver abscess - after failing flagyl
- SE
  • C/I in psoriasis/porphyria - can precipitate acute attacks
  • not used in retinal/visual field abnorm/myopathy
  • otherwise - renal, liver, eye (blurring of vision), blood (G6PD def)
Quinine & Quinidine
- 1st line for f malaria esp severe disease cos resistance is uncommon
- derived for cinchona tree in South America (used for intermittent fever)
- quinidine is stereoisomer of quinine
  • blood schizonticide for all
  • gametocidal for v and o (not f)
  • NOT liver schizonticide
  • overall unknown
  • resistance - uncommon only in SEA (esp Thai-Burma border) - but still has partial efx
- clinical uses
  • parenteral rx of severe f malaria - IV/IM - should change to po once pt improves
  • po rx - use as 1st line in resistant area, if not use chloroquine, need to add on other agent (doxycycline in adults or clindamycin in kids) to shorten duration to 3 days
  • babesiosis - 1st line therapy with clindamycin
- SE
  • cinchonism - neuro stuff (tinnitus, headache, nausea, dizzy, flush, visual)
  • hypersensitivity reaction
  • blood - hemolysis, WCC drop, agranulocytosis, thrumbocytopenia
  • hypoglycemia - induce insulin
  • blackwater fever - marked hemolysis, hemoglobinuria due to quinine - pathogenesis unknown - ?hypersensitivity reaction to drug
- effective for chloroquine-resistant f malaria
- recommended chemoprophylactic drugs
- blood schizonticidal f and v, not liver/gamet
- resistance uncommon except SEA (Thai burma)
- C/I - epilepsy, psych disorder, arrhythmia, cardiac conduction defects

- liver schizoncidal - only drug to eradicate dormant liver form of vivax, ovale
- gametocidal against 4 human malaria sp
- minimally RBC-cidal but insignificant
- resistance - PNG, SEA, central and south america - resistant vivax - needs repeated therapy for radical cure (eg for 14 days)
- clinical use
  • radical cure of acute v and o - add blood agents like chloroquine
  • terminal prophylaxis of v and o - prevent relapse
  • PCP infection - add clindamycin
- SE
  • C/I - granulocytopenia, methb, G6PD def
- tetracycline + doxy - RBC-cidal, not liver
- clindamycin - slowly active in RBC

Artemisinin & derivative
- active component of herbal medicine of China - antipyretic for 2000 yrs 青蒿素
- analogues - artesunate (water soluble), artemether (lipid soluble)
- rapid blood schizonticidal - not liver
- resistance is not an issue
- important in MDR falciparum malaria - only drug against quinine-resistant strains
- short T1/2 hence not used in chemoprophylaxis
- expensive and widely avaible
- clinical use
  • needs combination to treat highly resistant f malaria - with mefloquine
- Entamoeba histolytica
- spectrum of disease - asymptomatic intestinal infection/colitis/dysentry/liver abscess
- treatment options
  • metronidazole & tinidazole
  • iodoquinol
  • diloxanide furoate
  • paromomycin sulfate
  • emetine & dehydroemetine
- d

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