Antiparasitics

Question 1

List the available antimalarial drugs

Answer 1

Artemether w/ lumefantrine = p. falciparum and p. vivax

Atovaquone with proguanil = p. falciparum

Mefloquine = p. falciparum and p. vivax

Chloroquine

Proguanil

Primaquine

Pyrimethamine w/ sulfadoxine

Quinine

doxycycline

Question 2

What is the MOA of artemether w/ lumefantrine?

Answer 2

Acts in food vacuole of malaria parasite –> prevent conversion of haem to non-toxic haemozoin

Inhibits nucleic acid and protein synth

Question 3

What is the MOA of atovaquone w/ proguanil?

Answer 3

Atovaquone selectively inhibits parasite mitochondrial electron transport –> reduces pyrimidine biosynth –> prevent malarial parasite replication

Synergistic combination

Question 4

What is the MOA of mefloquine?

Answer 4

May form toxic complexes w/ free haem –> damage membranes –> interact w/ other plasmodial components

Inhibits erythrocyte schizogeny can also inhibit nucleic acid synth

Question 5

What are some ADRs of mefloquine?

Answer 5

CNS effects = Anxiety, panic attacks, agitation, aggression, acute psychosis, depression, encephalopathy

75% by third dose will have ADRs, 30% by first

Dose dependent effect

Question 6

What are some risk factors to mefloquine neuropsychiatric disorders?

Answer 6

Hx of CNS events

mefloquine dose

severity of malaria

mefloquine w/in previous 2 month

Greater risk in females

Question 7

What is the MOA of Chloroquine?

Answer 7

Accumulates in the food vacuole of the parasite
- traps ion following protonation specific transport, and/or binding to the target

Major action = inhibits formation of hemozoin (Hz) from the heme release by digestion of hemoglobin –> free heme lyses membranes —> parasite death (DNA/RNA damage)

Question 8

What are some secondary effects of chloroquine?

Answer 8

anti-inflammatory

Immunosuppressive

Question 9

What is the MOA behind chloroquine resistance?

Answer 9

dec accumulation of chloroquine in food vacuole

CRT and MDR1 transporters responsible

Question 10

What are some notable ADRs of chloroquine?

Answer 10

Common = headache, skin eruptions, itch, GI dist

Psychotic episodes, anxiety, personality changes, visual dist, corneal opacities (Reversible), irreversible retinopathy

Hair loss, bleaching hair, blue-black pigmentation of mucous membranes and skin, prolonged GT interval

Question 11

What is proguanil and what is its MOA?

Answer 11

Tissue schizonticide converted to cycloguanil –> plasmodial dihydrofolate reductase inhibitor

Question 12

What is the MOA of quinine?

Answer 12

Binds plasmodial DNA and prevents replication and transcription during erythrocytic schizogeny

Question 13

What are the ADRs for Quinine?

Answer 13

Abdominal cramps, diarrhoea, vomiting, cinchonism (blurred vision, tinnitus), QT interval prolonging

Question 14

What drugs belong to the benzimidazole anthelmintic class?

Answer 14

Albendazole

Mebendazole

Question 15

What are “other” anthelmintics?

Answer 15

Ivermectin

Praziquantel

Pyrantel

Question 16

What is the MOA for the benzimidazoles?

Answer 16

Bind and inhibit polymerization of tubulin dimers to form cytoplasmic microtubules

Impairs glucose uptake and depletes glycogen stores

Question 17

What is the MOA of ivermectin?

Answer 17

Activates glutamate-gated Cl- ion channels —> prevent depolarisation —> pharyngeal muscle hyperpolarization and paralysis

Releases worm and makes them non-motile

Question 18

What is the MOA of praziquantel?

Answer 18

Low concentrations = inc muscular activity followed by paralysis of worms –> detach from host

High concentrations = integumental damage –> activates host defences to destroy worms
- inc Ca2+ permeability of schistosome tegument —> contraction and exposing antigens to host immunity

Question 19

What is the MOA of pyrantel?

Answer 19

Depolarising neuromuscular blocking agent

Activate anti-chol nicotine receptor in somatic muscles

Inhibits cholinesterase –> neuromuscular blockage –> spastic paralysis –> worm detachment and expulsion