Therapeutics of Amebiasis, Malaria, and Helminthic Disease Flashcards
What are the 4 stages of development for the malaria parasite?
- Gametocyte
- Sporozoite
- Merozoites
- Trophozoites
What is the life cycle of malaria inside a human starting with injection by mosquito (9 steps)
- mosquito injests SPOROZITES into blood
- SPOROZITES infect liver cell
- Sporozites become SCHIZONT in liver
- Schizont ruptures releasing MEROZOITES into blood
- Merozoites infect RBC
- merozoite becomes trophozite in RBC
- trophozite becomes schizont in RBC
- Schizont ruptures in RBC to release more merozoites
- merozoites become gametocytes in RBC and get picked up by mosquito
What are the 6 antimalarial categories for the acute blood phase?
Schizonticides:
- 4-Aminoquinolones
- Quinolines
- Arteminisins
- Folate Synthesis inhibs
- Tetracyclines
- Halofantrine + Lumafantrine
What are some examples of 4-Aminoquinolones? What are they used for?
Shizonticides - acute blood phase malarial
Chloroquine, Amiodiaquine
What are some examples of Quinolines? What are they used for?
Schizonticides
Quinine (quinidine)
Mefloquine
What are some examples of Arteminisins? What are they used for?
Schizonticide
Artemether
What are some examples of Folate Synthesis Inhibitors? What are they used for?
Schizonticides:
Proguanil
Sulfadoxine
Pyrimethamine
What are the Schizonticides for chronic liver phase of malaria?
Primaquine
Atorvaquone
How does Chloroquine, Quinine, mefloquin work? what is it not effective against?
- concentrates in malarial food vacuoles
- prevents biocrystalization of heme into HEMOZOIN
- heme is toxic to schizont
NOT effective against P. vivax or P. ovale
What gene mutation mediates Chloroquine resistance? what 3 things give the parasite resistance?
PfCRT (plasmodium falciparum chloroquine Resistance Transporter)
- increased efflux of drug out of vacuole
- facilitated diffusion out of vacuole
- Change in acidity in vacuole = less drug accumulation
What are the two indications for chloroquine?
- P. falciparum
2. E. histolytica liver abscesses that fail to respond to metronidazole
What parasites require primaquine?
P. vivax
P. ovale
LIVER shizonts + gametocytes
What are adverse fx of chloroquine?
More common in African, Mediterranean descent
- Hemolytic anemia - G6D deficiency
- Pruritis
- Retinitis, hearing loss
What are indications for Amiodiaquine?
chloroquine resistant P. falciparum
What are adverse fx of Amiodiaquine?
agranulocytosis
aplastic anemia
hepatotoxicity
What is the mechanism of Quinine (oral) and Quinidine (IV) and what are indications?
same as Chloroquine (inhibit hemozoin formation)
indications:
1. chloroquine resistant P. falciparum
2. gametocidal against P. ovale, P. vivax
What are adverse fx of Quinine?
- Cinchonism (tinnitis, headache, VERTIGO, nausea)
- thrombocytopenia (IgG mediated)
- anticholinergic actions
- hypersensitivity (angioedema, bronchospasm, urticaria)
- Blackwater fever (RBC hemolysis, hemoglobinuria = blood becomes darker)
NEVER USE TOGETHER WITH MEFLOQUINE
What are indications for Mefloquine
BLOOD SCHIZONTS (no activity against gametocytes or liver schizonts)
chloroquine resistant P. fallciparum strains (cross resistance w quinine)
What are adverse fx of Mefloquine?
- reversible blood dyscrasias - leukocytosis, elevated liver enzymes, thrombocytopenia
- Neuropsychiatric disturbances
(contraindications = neuropsych, arrhythmia)
What is the mechanism of Artemisinins (artemether)
produce free radical = toxic to parasite
radicals bind to SERCA
iron-catalyzed cleavage of the drug
What is the WHO recommendation for acute therapy falciparum malaria (Standard of Care)?
What about the CDC?
WHO:
- artesunate + amiodiaquine
- lumafantrine or mefloquine
CDC:
- chloroquine
- artemether + lumafantrine
What are the adverse fx of Artemisinins?
- nausea, vomiting, diarrhea
- Neutropenia, anemia, hemolysis, elevated liver enzymes
- CAN USE DURING 2nd, 3rd trimester PREGNANCY!
What is the drug of choice to get rid of liver schizonts?
Primaquine
What are contraindications of Primaquine?
- do not use with chloroquine in pts with G6D deficiency
- DONT use in pregnancy
- gives blood dyscrasias
What is malarone? what does it do and what is it used for?
atovaquone + proguanil
mechanism:
1. disruption of plasmodium electron transport
2. inhibition of DNA synthesis, electron uncoupling
active against BLOOD + Liver schizonts (P. falciparum)
Which two other drugs are only effective against blood forms of malaria?
- Halofantrine, Lumefantrine
2. Doxycycline
What is the acute therapy options for malaria
- chloroquine sensitive - chloroquine
- Chloroquine resistant - artemether + lumefantrine or mefloquine
- complicated - quinine
What is the protocol of eradication of P. ovale or P. vivax?
acute therapy followed by Primaquine
What does Entamoeba histolytica cause? What are the drug options (systemic and luminal)?
causes Dysentery
Systemic: Metronidazole, Chloroquine
Luminal: Iodoquinol, Paromomycin
What is the mechanism of metronidazole?
What are adverse fx?
kills Entamoeba trophozoites (not cysts)
adverse fx
acute: nausea, diarrhea, alcohol intolerance
chronic: peripheral neuropathy, encephalopathy
What is the drug Tx for:
- Round worms (Ascaris lumbracoides)
- Hook worms
- Trichuriasis
Round + Hook Worms:
- Albendazole
- mebendazole
- Prantyl pamoate
trichuriasis: albendazole
What three parasites are Prantyl pamoate used for?
ascaris
hookworm
pinworm
What is Ivermectin used for? what is the mechanism?
Strongyloidosis - paralysis of the worm (intensifies GABAnergic nerve transmission)
What is the Tx for Cestode infection?
- Praziquantal (first)
- Niclosamide
Kills ADULT tapeworms, not larvae
