Drugs for Malaria

Question 1

Chloroquine:

Pharmacokinetics

Answer 1

very large volume of distribution

Question 2

Chloroquine:

MoA

Answer 2

prevents polymerization of hemoglobin breakdown product heme –> accumulation of heme toxic to parasite

Question 3

Chloroquine:

MoResistance

Answer 3

decreased intracellular accumulation

-membrane pumps

Question 4

Chloroquine:

use

Answer 4

• DOC for acure attacks of nonfalciparum and sensitive falciparum malaria
• DOC for chemoprophylaxis (except in resistant regions)
• drug solely a BLOOD SCHIZONTICIDE

Question 5

Chloroquine:

AE

Answer 5

• ECG changes
• mucosal pigmetary changes (blue-black)
• aplastic anemia
• pancytopenia
• retinopathy
• tinnitus and reduced hearing
  CI in patients with porphyria; psoriasis (may precipitate an attack)

Question 6

Quinine:

MoA

Answer 6

complexes with DS DNA to prevent strand separation –> blocks DNA replication and txn
- drug solely a BLOOD SCHIZONTICIDE

Question 7

Quinine:

use

Answer 7

P falciparum infections resistant to chloroquine

• can use with doxy or clindamycin to shorten duration of therapy and limit toxicity
• can use IV for severe or complicated falciparum

Question 8

Quinine:

AE

Answer 8

CINCHONISM - GI distress, HA, vertigo, blurred vision, tinnitus

• severe OD –> disturbance in cardiac conduction
• hemolysis in G6PD def. (blackwater fever)
• digoxin toxicity
• CI in pregnancy

Question 9

is quinine acidic or basic

Answer 9

basic

Question 10

How can urinary excretion of quinine be enhanced

Answer 10

acidify urine (Ammonium chloride)

Question 11

Mefloquine:

use

Answer 11

• a 1st line drug for prophylaxis in areas with chloroquine resistance
• alternate drug to quinine in acute attacks

Question 12

Mefloquine:

AE

Answer 12

• GI
• rash
• HA
• cardiac conduction defects
• neuro symptoms, psych disorders, seizures

Question 13

Primaquine:

MoA

Answer 13

• forms quinoline-quinone metabolites (cellular oxidants)
• TISSUE schizonticide
• limits malaria transmission by acting as a GAMETOCIDE

Question 14

Primaquine:

use

Answer 14

• eradicates liver stages of Pvivax and P ovale
• should be used with blood schizonticide
• 14 day course is standard after treatment with chloroquine

Question 15

Primaquine:

AE

Answer 15

• Methemoglobinemia
• hemolysis in G6PD def
• CI in pregnancy

Question 16

Antifolate Drugs:

name the 4

Answer 16

pyrimethamine
proguanil
sulfadoxine
dapsone

Question 17

Antifolate Drugs:

MoA of sulfonamides

Answer 17

antimetabolite of PABA –> block folate acid synth

Question 18

Antifolate Drugs:

MoA of pyrimethamine and cycloguanil

Answer 18

Selective inhibitors of protozoan DHFR

Question 19

Antifolate Drugs:

clinical use

Answer 19

blood schizonticides

- act mainly against P falciparum

Question 20

Doxycycline:

use

Answer 20

chemoprophylactic for travelers to geographical areas with qhloroquine and mefloquine resistant P-falciparum

Question 21

Artesunate and artemether:

MoA

Answer 21

metabolized in parasite forming toxic free radicals

Question 22

Artesunate and artemether:

Use

Answer 22

blood schizonticides active against multidrug resistant P falciparum

• short half life
• *Only drug reliably effective against quinine-resistant strains