Anti-Malarial Drugs

Question 1

Chlorquine and Hydroxychlorquine

Answer 1

Antimalarial
MOA: acts on the erythrocytic form- schizontacidal, inhibts the digestion on hemoglobin by raising the pH of the parasites acidic food vacuoles - build up of heme elicits
parasite toxicity
- anti-inflammatory at high doses- RA and lupus erythematous
* resistance is developing
* okay to use in pregnancy
Pharmk:
- oral admin
- accumulation in melanin rich tissue - skin and retina
- concentration in parasitized erythrocyte
- metabolized in liver and excreted in kidney
Toxicity
- Less than quinine
- GI upset: take with food
Hemolysis, retinal and corneal toxicity, seizures and cardiac toxicity
** CI: in pts with psoriasis and porphyria- blood dyscrasia and lupus like symptoms
** Resistance to drug developing via pump mechanism

Question 2

Melfloquine

Answer 2

DOC for prophylaxis and tx of chlorquine resistant strains of P. falciparum
** strains can develop resistance to this drug as well
MOA: same as chloroquine
PK:
- oral
Toxicity
- Gi upset and some depression of the myocardium
- seizures and may aggravate latent psychoses
- teratogenic- CI in pregnancy
** CI: in pts with mental illness or epilepsy, teratogenic
** Don’t combine with quinidine or quinine

Question 3

Quinine Sulfate and Quinidine Gluconate

Answer 3

Anti-malarial drug
DOC for pt unconscious with chloroquine resistant P. falciparum of P. vivax when combined with doxycycline 
MOA: 
- schizonticidal
- gametocidal
- Exact MOA unknown 
PK: oral (quinine) and IV (quinidine) 
Toxicity
- Cinchonism - Tinnitus, HA, dizziness, flushing, visual disturbances 
- QT elongation 
- Blackwater fever
- Hemolysis in G6PD pts 
- Quinine stimulates insulin release 
- GI irritation 

Other:
- angalgesia and antipyretic, skeletal muscle relaxation, low doses for nocturnal leg cramps

Question 4

Doxycycline

Answer 4

Antimalarial
Good for last minute travel- can be taken 1-2 days before traveling to areas where malarial transmission occurs
Prophylaxis for multi-drug resistant malaria
Can be combined with quinidine gluconate for chloroquine resistant malaria

Question 5

Pyrimethamine and Proguanil

Answer 5

Antimalarial
- mostly erythrocytic forms, and some effect on pre-erythrocytic stages and secondary tissue forms
- prophylactic use - particularly against chlorquine resistant strains
- sometimes used in combination with sulfadoxine for presumptive tx
MOA: inhibits parasite dihydrofolate reductase

Question 6

Atovaquone and Proguanil

Answer 6

Antimalarial
-Acts on erythrocytic forms (schizonticidal)
-Good tx for uncomplicated infection with chloroquine resistant malaria
- also used for Pneumocystitis carinii in pts unable to tolerate TMP/SMX
MOA: interferes with plasmodial mitochondrial membrane potential - effect synergized by progaunil
PK:
oral, absorption inc. with fatty foods
Long half life
excreted unchanged in feces
high plasma protein bound- 99%
Toxicity
- well tolerated
- ab pain, N/V/D/HA/rash
- less commonly may cause reversible elevation of liver enzymes

Question 7

Artemisinin

Answer 7

Anti-malarial 
Act on erythrocytic forms
No cross resistance with other drugs 
PK: 
orally- take with food, Interactions with CYP2D6, induces own metabolism 
Toxicities
- CI in pregnancy 
- CI in ppl with arrhythmias, severe cardiac disease or prolonged QT interval

Question 8

Halofantrine

Answer 8

Antimalarial
Active against erythrocytic gorms
Toxicities: GI

Question 9

Primaquine

Answer 9

Antimalarial
- Active against the tissue forms (exoerythrocytic forms) of all species of plasmodia
—> Can kill the seconday forms of P. vivax. and P. ovale and produce a radical cure
- gameticidal
- Very toxicity so not used as routine prophylaxis although it can prevent the development of the disease
- Approved for tx of P. carinii pneumo in combo with clindamycin
Toxicity (mostly with chronic use)
- Hemolytic anemia in G6PD deficient pts
- GI upset
*CI in SLE or RA
* CI in pregnancy (fetal hemolytic anemia)