whats an ideal anti malarial drug:
- not expsenive
- rapid speed of action
- works for exoerthycotic rather than just for the rbc
- potent activity against all plasmodium species
- very strong and safe for children and preggos
— is an alkaloid from species cinchona
quinine
and its a 4-quinloin methanol
quinine is a —- and the side effects are – but is still used for severe malaria although parenteral artesunate superior
- 4-quinloin methanol
- vasodilation , hemolytic anemia , mycorcardial deoresson , curare effect
4-aminoquilonines and dertaives are developed from the prototype — and the deratives are:
- quinine e
as:
1- chlorquine
2- hydroxychlorquin
3- mefloquine
-amadiaquin - halofantrin ( a 9-phananthrenemathonal )
for 4-aminoquinlines the — is not important and nitrogen must be a — and the best subsutiuent for R1 is — and the X chain length is
- chirality is not important
- trisubutuited usually ethyl
- Cl
-c2-c5
the mode of action for 40aminoquilines is — hypothesis and it states that:
plasmodium digest the hosts —
—- is the waste product and it contains ——
the free FPIX is — so its normally —
the drug-FBIX complex contains the toxicity which leads to —-
- FPIX
- hemoglobin
- hemozoin
- contains ferriprotoporphyivn IX ( FPIX)
- toxic , bound
- cell death
— inhibits plasmodial dihydrofloate reductase
pyrimethamine
– inhibits the dihydropterotate synthase
sulfadoxine
— and — developed for prevention and treatment of chlorine resistant malaria and sometimes is used for intermitted preventative treatment ( IPT) for infarcts and pregnant women in regions with moderate to high or stable transmission
- prymithemaine and sulfadoxine
—- is a 8-aminoquilones
pamaquine ( paraquine was marked later )
- its active against tissue ad heptatic stages
— is often given with chloroquine to eradicate all stages of malaria
paraquine , and its not given long term to avoid toxity and resistance
the mechanism of action of 8-aminoqulone is –
interference with the cell redox system and causes oxidative stress and eventually cell death ( produces : quinoneimine which are very reactive species )
the structure of 8-aminoquinolines
- the second OCH3 on C4 or C5 increases the activity and the a second substuint increases the activity
- X can vary from C2 to C6
tafenoquine is a —-
and it aims to provide —–
its highly affective for —-
and — dose for vivax
- 8-aminoquilines
- longer acting and more potent and less toxic agent than primaquine
- radical cure of relapsing malaria and caudal prophylaxis of p.vivax
- single dose
—–is isolated from TCM and is template for synthetic dertaives and have reactive —- moity by ——
- artimisem
- endiperoxide
- free radical mechanism and oxidative damage to parasite membrane
- active in resistant and cerebral malaria
- cornerstone of ACT
— is a cornerstone of ACT
artimsiem
mechanism of artimisem
artimisem –> dihydroartominsm ( active metabolite ) which produces ethers where r= ch3 aka arthmether and esters which is sodium artesunate
recommendation of malaria treatment :
- 3 days treatment with ACT that is short and sharp treatment
- all artimisem containtaing dertaives are partnered with other drug even though artimism is fast but alone is not a good drug so the effect will go away fast , that’s why we give it with another drug so it can be long lasting and more effective so fewer chance of resistance
— is a newer derative of halofantrine and has an aryl amino alcohol and lipophilic substiunet
lumefantrine which is used in combination with artemther in falciparum malaria and acts over a longer period than rapidly acting artemther to eliminate the residual parasite than remain after artemether is cleared from the body and thus minimise the risk of recrudescence
the risk of pregnancy areas of low transmission has — than non pregnanct adults
and areas of high and stable malaria trasmission most woman have —-
— supplemts is important
drug treatment includes —-
for prophlyxix —-
- 2-3 folds higher risk
- enough immunity so infection doesn’t usually result in clinical symptoms
- Fe supplements
- quinine I , clindamycin , artimesim II , III
- mefloquine
malaria prophylaxis ( prevention ) can be — or —
and most common regimens are —-
- casual or suppressive
(travels need covers , expert advice essential , generally 1 week before and up to 4 after , protection against bites is vital and post travel illness must mean consideration of possible malaria )
-malarone ( atavoquone-pronguil ) - doxycylin
- maflaquine
atovaquine is a — hydroxynaphthoquine and inhibits —– and impairs — and is synergistic with —–
- lipophilic
- electron transport in mitochondria
- pyrimidine sytheis
- pronguil ( malarone)
common drug prescribed for travellers is doxycycline and it works for inhibiting —— and is used in malaria prophylaxis and especially if there’s mefloquine intolerance
- inhibition of prokaryote-like RNA
- its fat soluble and good tissue distribution
some antibiotics are effective in malaria due to the presence of plasmid like organelle called
apicoplast
