Antimalarial drugs -

dale1994's version from 2016-04-30 16:17

Section 1

Question Answer
-intercalate between bases of protozoal DNA
-fragments protozoal RNA
-inhibits polymerisation of the free haem to haemazoin
-this free haemoprotoporphyrin lX-antimalarial, when accumulated, is toxic to parasites

blood schizonticidal action (All species)
Well Tolerated often used with Proguanil
Quinine/Quinidine(arylamino alcohols)
-blood sch against all four parasites
-gametocidal activity against vivax/ovale
-not effective against hypnozoites
-often given with antibiotic
-Quinidine is a diastereomer

-very useful standby for sever p.falc infection
-fails to completely eliminate infection (combi)
-not used in prohylaxis

-irritates gastic mucosa/ nausea/ pain
-type 2 hypersensitivity
Mefloquine-blood sch again falc / vivax
-inhibits haem polymerase
-little gametocidal activity

-malaria prophylaxis in chloroquine resistant areas
-slow onset but can cure moderate cases of p.falciparum

-extensively distrubted (inc. CNS)
-not prescribed to history of epileps/psycho/arrhythmias
-should not be given with quinine
-interacts with epileptics/cardiac drugs
Artemisinin (Artesunate)-fast acting on blood stage
-no action on tissue stage

-short half life, not useful for prophylaxis
-acute infections with chloroquine resistant strains
-hepatocytic stages of all infections
-especially effect on hypnozoites
-non-routine (after exposure) prophylaxis
-well tolerated/ haemolysis
-caution in pregnancy

-competes with pteridine moiety of folic acid
-converted to cycloguanil
-suppressive agent & causal prophylactic
-widespread resistance use with atovaquone

-few side effects/ ok in prenancy
Halofantrine-blood sch against all 4 parasites
-no action on gametocytes or liver stages

-well tolerated but can cause fatal arrhythmias
-restricted for use in multidrug resistant p.falc cases

-avoid during pregnancy as embryoctytoxic
Atovaquine (+ Proguanil)Inhibits mitochondrial electron transport chain of parasite
-effective on blood stage and early liver
-expensive to produce

-well tolerated, some GI side-effects

Doxycyline-inhibits ribosomal protein synthesis
-slow acting blood sch but not active against liver stages

-Prophylaxis (mefloquine resistant areas)
-Used with Quinine for acute attacks

-24 hour gap before vaccinations
Folic Acid AntagonistsProgaunil
Tissue SchizonticidesPrimaquine/Proguanil
Tcn AntibioticDoxycycline

Section 2

Question Answer
GI, Retinopathy, Allergic rxnsChloroquine/Hcq
Cinchonism ( tiinitus, diplopia, HA, nausea) NMB, Myocardial dep, hypoglycemiaQuinine/ Quinidine Gluconate
Behavioral disturbances, Psychotic rxns, Seizures, Teratogen, Diarrhea, Dizzy, Ataxia, N/D,GI, Mefloquine
GI, HAArtemisinin analog (Artemether)
Hemolytic anemia (in pts w/ G6PD deficiency), methermoglobinemiaPrimaquine
Skin rashes, bone marrow supressionPyrimethamine
Non toxicProgainil / Atovaquine + Proguanil
Allergic rxn to sulfonamidesPyrimethamine + Sulfadoxine
Photoxicity, permanent discoloration of teeth in childrenDoxyycline

Section 3

Question Answer
Intereferes with parasites feeding mechanismChloroquine/Hcq, Quinine/Quinidine Gluconate, Mefloquine
Generate free radicals that kill parasiteArtemisinin analog (Artemether)
Inhibit plasmodial dihydrofolate reductase, mainly affects *erythrocytic* formsPyrimethamine and Proguanil
Inhibit dihydrofolate reductase and blockade of PABA incorporationPyrimethamine + Sulfadoxine
Inhibit of electron transport and inhibition of reductaseAtovaquine + Proguanil
Inhibition of plasmodial protein synthesisDoxycycline

Section 4

Question Answer
Long T1/2, Given once/week for prophylaxis, resistance big problem with P. falciparumChloroquine/Hcq
Not used for prophylaxis due to toxicityQuinine/ Quinidine Gluconate
DOC for TX + Prophylaxis of chloroquine resistant P. falciiparum, CI in pts w/ active psychosis/epilepsy/heart problemsMefloquine
Drug of choice for TX of chloroquine resistant P. falciiparumArtemisinin analog (Artemether)
Only for presumptive TxPyrimethamine + Sulfadoxine
Considered an alternative to MefloquineAtovaquine + Proguanil
CI in pts < 8 yo and PregnantDoxycycline