L14 Antimalarial

Question 1

Causative agents of malaria

Answer 1

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

Question 2

Patient with malaria has fever and chills every 3 days. What is the likely strain?

Answer 2

Plasmodia vivax

most common strain

Question 3

Patient with malaria has fever every 3 days and is at risk of death. What is the likely strain?

Answer 3

Plasmodia falciparum

most lethal strain

Question 4

Patient with malaria has fever every 4 days. What are the likely strains?

Answer 4

Plasmodia malariae

P. ovale

Question 5

What is the definitive host of malaria?

Answer 5

Anopheles mosquito

Question 6

Which strains of malaria can cause relapses and why?

Answer 6

P. vivax and P. ovale
Infected hepatocytes can become dormant and are called hypnozoites. When reactivated they cause a flare-up of the disease.

Question 7

What are the basic life stages of malaria?

Answer 7

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

Question 8

Which strains have a secondary tissue form?

Answer 8

P. vivax and P. ovale

Question 9

What are the major groups of drugs and their approach to treating malaria?

Answer 9

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

Question 10

Clinical cure vs Radical cure

Answer 10

Clinical: erythrocytic stage eradicated but not necessarily completely free of disease
Radical: true and complete cure

Question 11

What are the drugs of first choice for sensitive plasmodium?

Answer 11

Blood Schizonticides:
Chloroquine (Aralen)
Hydroxychloroquine (Plaquenil)

Question 12

How is resistance forming in Blood Schizonticides?

Answer 12

Developing ability to pump out the drug, especially in P. falciparum

Question 13

Where do Blood Schizonticides accumulate?

Answer 13

Infected RBC’s

Melanin-rich tissues like the skin and retina

Question 14

Blood Schizonticides use for prophylaxis

Answer 14

These are used for prophylaxis though they will not prevent establishment of P. vivax or ovale in the liver

Question 15

Toxicity of Blood Schizonticides

Answer 15

Retinal and corneal toxicity, seizures and cardiac arrest if parental admin too quick
Lupus-like Sx
Safe in pregnancy

Question 16

What are the old malaria drugs that are from cinchona bark? How are they administered and when are they used?

Answer 16

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

Question 17

Toxicity of Quinine Sulfate and Quinidine Gluconate

Answer 17

Quinidine is an antiarrhythmic agent
QT elongation
Blackwater fever
Quinine stimulates insulin release–caution in hypoglycemic patients

Question 18

How is doxycycline used for malaria?

Answer 18

Combined with quinidine or quinine for complicated and resistant malaria
Prophylaxis against multi-drug resistant malaria

Question 19

How are pyrimethamine and proguanil used in malaria?

Answer 19

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

Question 20

Atovaquone + Proguanil (Malarone)

Answer 20

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

Question 21

Pyrimethamine + Sulfadoxine (Fansidar)

Answer 21

Not for prophylaxis but for presumptive treatment

Question 22

Artemisinin

Answer 22

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

Question 23

Mefloquine

Answer 23

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

Question 24

Halofantrine

Answer 24

Drug of last choice
Erythrocytic forms
QT elongation, teratogenicity, hepatotoxic

Question 25

Primaquine

Answer 25

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

Question 26

What is the basic treatment strategy for malaria?

Answer 26

Chloroquine is DOC for sensitive strains
Otherwise: Malarone or Mefloquine or many others
To prevent relapse: Primaquine

Check CDC for updates