L14 Antimalarial Flashcards
Causative agents of malaria
Parasitic protozoa
Plasmodia falciparum: malignant tertian, most lethal, fever every third day, no secondary tissue forms
P. vivax: benign tertian, most common, fever and cills every third day, secondary tissue forms, relapses
P. malariae: quartan, rare, fever every 4th day, no secondary tissue forms
P. ovale: rare, like vivax
Patient with malaria has fever and chills every 3 days. What is the likely strain?
Plasmodia vivax
most common strain
Patient with malaria has fever every 3 days and is at risk of death. What is the likely strain?
Plasmodia falciparum
most lethal strain
Patient with malaria has fever every 4 days. What are the likely strains?
Plasmodia malariae
P. ovale
What is the definitive host of malaria?
Anopheles mosquito
Which strains of malaria can cause relapses and why?
P. vivax and P. ovale
Infected hepatocytes can become dormant and are called hypnozoites. When reactivated they cause a flare-up of the disease.
What are the basic life stages of malaria?
1) infection from anopheles mosquito transfers organism to human which is an intermediate host
2) hepatocytes infected as part of exoerythrocytic cycle
3) protozoa replicate asexually in hepatocytes and eventually burst and spread to the blood to infect RBC’s in the erythrocytic cycle, form schizonts or schiogeny, this stage is what causes the Sx of disease
4) transfer back to mosquitos where sexual reproduction occurs
Which strains have a secondary tissue form?
P. vivax and P. ovale
What are the major groups of drugs and their approach to treating malaria?
1) Blood schizonticides: erythrocytic phase, treats the Sx, does not treat the secondary tissues including the liver
2) Tissue schizonticides: liver stages of the disease, does not suppress Sx once erythrocytic stage has begun, prevents relapse, too toxic for prophylactic use
3) Gametocidal agents: kill gametocytes, slows the spread of the disease but does not help Sx
Clinical cure vs Radical cure
Clinical: erythrocytic stage eradicated but not necessarily completely free of disease
Radical: true and complete cure
What are the drugs of first choice for sensitive plasmodium?
Blood Schizonticides:
Chloroquine (Aralen)
Hydroxychloroquine (Plaquenil)
How is resistance forming in Blood Schizonticides?
Developing ability to pump out the drug, especially in P. falciparum
Where do Blood Schizonticides accumulate?
Infected RBC’s
Melanin-rich tissues like the skin and retina
Blood Schizonticides use for prophylaxis
These are used for prophylaxis though they will not prevent establishment of P. vivax or ovale in the liver
Toxicity of Blood Schizonticides
Retinal and corneal toxicity, seizures and cardiac arrest if parental admin too quick
Lupus-like Sx
Safe in pregnancy
What are the old malaria drugs that are from cinchona bark? How are they administered and when are they used?
Quinine Sulfate and Quinidine Gluconate
Quinine–oral
Quinidine–IV
Treat erythrocytic forms and are gametocidal
DOC for unconscious patients infected with chloroquine-resistant P. falciparum and vivax
Combined with doxy or clindamycin
Toxicity of Quinine Sulfate and Quinidine Gluconate
Quinidine is an antiarrhythmic agent
QT elongation
Blackwater fever
Quinine stimulates insulin release–caution in hypoglycemic patients
How is doxycycline used for malaria?
Combined with quinidine or quinine for complicated and resistant malaria
Prophylaxis against multi-drug resistant malaria
How are pyrimethamine and proguanil used in malaria?
These both inhibit dihydrofolate reductase in the parastite which inhibits the production of folic acid–parasites dependent on making own folic acid
Sulfadoxine inhibits different step of folic acid synth and combination–> synergistic effect
Mostly affects erythrocytic stage
Can be used for prophylaxis particularly in chloroquine resistant strains of P. falciparum
Proguanil has some causal prophylactic activity
Atovaquone + Proguanil (Malarone)
Interferes with plasmodial mitochondrial membrane potential
Good for uncomplicated infection with chloroquine-resistant malaria
Tissue and erythrocytic forms
Also used for Pneumocystis jiroveci in patients that cannot tolerate TMP-SMX
Pyrimethamine + Sulfadoxine (Fansidar)
Not for prophylaxis but for presumptive treatment
Artemisinin
Erythrocytic stage Oral, IV, IM, rectal Often used in combination CYP2D6 interactions Caution in pregnancy Not in patients with arrhythmias, severe cardiac disease, or prolonged QT
Mefloquine
Chloroquine-resistant P. falciparum Erythrocytic forms Oral Depresses myocardium, causes seizures, CI in patients with mental illness or epilepsy, teratogenic Do not combine with quinine or quinidine
Halofantrine
Drug of last choice
Erythrocytic forms
QT elongation, teratogenicity, hepatotoxic
Primaquine
Tissue Schizanticide and gametocidal
No erythrocyte effects
kills the secondary forms of vivax and ovale
Not used for prophylaxis but can be used after return from area with these strains as follow up
CI in pregnancy, G6PD deficiency, SLE, RA
Causes hemolytic anemia in G6PD deficiency and in the fetus
What is the basic treatment strategy for malaria?
Chloroquine is DOC for sensitive strains
Otherwise: Malarone or Mefloquine or many others
To prevent relapse: Primaquine
Check CDC for updates
