L28- Antimalarial Drugs Flashcards
list the Malaria causing species (parasites)
- plasmodium falciparum
- plasmodium vivax
- plasmodium malariae
- plasmodium ovale
describe the life cycle of plasmodium spp.
1) mosquito injects Gametoytes
2) Gametocytes fuse rapidly into Sporozoites into blood / lymph
3) Sporozoites travel and enter the liver
4) Merozoites are generated
5) release of Merozoites due to liver cell rupture
* 6) Merozoite feed on RBCs (repeated process)
7) asexual reproduction occurs produces male/female gametes
8) mosquitoes uptake gametes
(1) forms of plasmodium will have only one cycle of liver cell invasion. Liver infection will stop after (2) of time. Only (3) need to be dealt with clinically.
1- P. malariae, P. falciparum
2- 4 wks
3- erythrocytic parasites (to be eliminated)
(1) forms of plasmodium have dormant hepatic stages, therefore (2) needs to be dealt with clinically.
1- P. vivax, P. ovale
2- erythrocytic and hepatic parasites (to be eliminated)
describe the symptoms and occurrence of Malarial Paroxysm
Sxs: cyclical fever, anemia, jaundice, hepatosplenomegaly
Typically occurs every 2-3 days
(1) plasmodium causes the most severe malaria and its the only one that may cause (2), usually due to (3) symptoms which are unique to its species. (4) are the additional symptoms noted in malaria due to (1) infection.
1- P. falciparum
2- death
3- cerebral malaria: irritability –> seizures –> coma
4- respiratory distress syndrome, diarrhea, severe thrombocytopenia, spontaneous abortion, hypoglycemia
what are the 3 factors that guide malaria treatment
1) infecting Plasmodium species
2) clinical status of patient
3) drug susceptibility of infecting parasites
Name the infecting Plasmodium for the following:
-(1) can cause rapidly progressive severe illness or death
- (2) infection require treatment for the Hypnozoite forms dormant in the liver
- (3) forms have different drug resistance in different geographic areas
1- P. falciparum
2- P. vivax, P. ovale
3- P. falciparum, P. vivax
in uncomplicated malaria, treatment requires….
oral antimalarials
in complicated malaria treatment requires…
aggressive treatment with parenteral antimalarial
describe the factors that make malaria a ‘complicated malaria’
(1 or more of the following- essentially single organ failure)
- impaired consciousness / coma, repeated generalized convulsions
- severe normocytic anemia, parasitemia >5%, acidosis, circulatory shock
- renal failure, hemoglobinuria
- pulmonary edema, ARDS
- DIC, spontaneous bleeding
list the major antimalarial drugs
- chloroquine
- quinine, quinidine
- mefloquine
- primaquine
- atovaquone
- sulfadoxine-pyrimethamine
- doxycycline
- artemisinins
______ is the drug of choice for treatment and prophylaxis of all P. vivax and P. ovale infections
chloroquine
Chloroquine:
- use of it is changing due to (1)
- drug of choice for Tx of (2) and (3) malarias
- preferred prophylactic agent in (4) type areas
1- drug resistance (severely compromised use)
2- non-falciparum malaria
3- sensitive uncomplicated falciparum malaria
4- areas w/o resistant falciparum malaria
Chloroquine is highly effective against (1), but not active to fight against (2)
1- Blood parasites
2- Liver parasites
Chloroquine works by first adjusting to (1) which will then function to prevent (2).
1- become concentrate in parasitic food vacuoles
2- prevent biocrystallization of Hb breakdown product heme to non-toxic hemozoin
Chloroquine MOA:
- the parasite will digest (1) in order to obtain (2)
- the process of (1) generates a lot of (3) which is toxic to the parasites
- for protection from (3), parasites function to (4)
-chloroquine prevents (4), in order to raise levels of (3), which is toxic to the parasites
1- Hb
2- essential AAs
3- heme
4- polymerizes heme to nontoxic hemozoin (sequestered in parasitic food vacuole)
Chloroquine:
- (1) route of administration
- (2) half-life
- (3) frequency of taking drug
1- oral
2- 3-5 days
3- once a week
(1) species of malaria has resistance to chloroquine because of mutations in (2) which functions to (3)
1- P. falciparum
2- PfCRT, putative transporter
3- pump chloroquine out
Chloroquine AEs:
- (1) is common in Africans
- (2) is seen in G6PD deficient patients
- (3) are many other AEs
- (4) changes maybe seen during cardiac investigation
1- pruritus
2- hemolysis
3- n/v, abd. pain, HA, anorexia, malaise, blurry vision, urticaria (uncommon)
4- ECG changes
Chloroquine is not used in (1) or (2) patients, although it is safe in (3) and (4) patients.
1- psoriasis, porphyria –> may precipitate attacks
2- retinal or visual field abnormalities
3- young children
4- pregnancy
(1) are the first line treatment for P. falciparum malaria mainly because (2) is uncommon, but increasing
1- quinine, quinidine (stereoisomers)
2- drug resistance
(1) is parenteral Tx of severe P. falciparum malaria
(2) is oral Tx of falciparum malaria, and an alternative to (3) in (4) areas
1- quinidine
2- quinine
3- chloroquine
4- chloroquine-resistant areas
Quinine and Quinidine are rapidly, highly effective against (1), but not active to fight against (2)
1- Blood parasites
2- Liver parasites