Classification of Antimalarial Drugs

Study Notes

Classification of Antimalarial Drugs

Quinoline-containing compounds:
- Chloroquine (most commonly used)
- Hydroxychloroquine
- Amodiaquine
- Quinine
Antifolates:
- Pyrimethamine
- Proguanil
- Trimethoprim-sulfamethoxazole
** Artemisinin-based compounds**:
- Artemisinin
- Artesunate
- Artemether
- Dihydroartemisinin
Other antimalarials:
- Atovaquone
- Primaquine
- Mefloquine
- Halofantrine
- Lumefantrine

Mechanisms of Action

Quinoline-containing compounds: Inhibit heme polymerization, leading to accumulation of toxic heme in the parasite
Antifolates: Inhibit dihydrofolate reductase, necessary for parasite's DNA synthesis and cell growth
Artemisinin-based compounds: Inhibit parasite's sarco/endoplasmic reticulum calcium ATPase (SERCA), leading to disruption of calcium homeostasis and parasite death
Atovaquone: Inhibits electron transport in the parasite's mitochondrial membrane
Primaquine: Inhibits glutathione reductase, leading to oxidative stress and parasite death

Resistance to Antimalarial Drugs

Chloroquine resistance: Widespread in Plasmodium falciparum, due to mutations in PfCRT and PfMDR1 genes
Artemisinin resistance: Emerging in Southeast Asia, due to mutations in PfKelch13 gene
Multidrug resistance: Can occur due to mutations in PfMDR1 gene, leading to reduced efficacy of multiple antimalarial drugs

Adverse Effects and Contraindications

Chloroquine: Pruritus, gastrointestinal disturbances, and retinopathy (with long-term use)
Artemisinin-based compounds: Nausea, vomiting, and allergic reactions
Mefloquine: Neuropsychiatric adverse effects, including anxiety, depression, and psychosis
Pregnancy and breastfeeding: Some antimalarials, such as primaquine, are contraindicated or require caution due to potential risks to the fetus or baby

Classification of Antimalarial Drugs

Quinoline-containing compounds include chloroquine, hydroxychloroquine, amodiaquine, and quinine.
Antifolates include pyrimethamine, proguanil, and trimethoprim-sulfamethoxazole.
Artemisinin-based compounds include artemisinin, artesunate, artemether, and dihydroartemisinin.
Other antimalarials include atovaquone, primaquine, mefloquine, halofantrine, and lumefantrine.

Mechanisms of Action

Quinoline-containing compounds inhibit heme polymerization, leading to accumulation of toxic heme in the parasite.
Antifolates inhibit dihydrofolate reductase, necessary for the parasite's DNA synthesis and cell growth.
Artemisinin-based compounds inhibit the parasite's sarco/endoplasmic reticulum calcium ATPase (SERCA), leading to disruption of calcium homeostasis and parasite death.
Atovaquone inhibits electron transport in the parasite's mitochondrial membrane.
Primaquine inhibits glutathione reductase, leading to oxidative stress and parasite death.

Resistance to Antimalarial Drugs

Chloroquine resistance is widespread in Plasmodium falciparum due to mutations in PfCRT and PfMDR1 genes.
Artemisinin resistance is emerging in Southeast Asia due to mutations in PfKelch13 gene.
Multidrug resistance can occur due to mutations in PfMDR1 gene, leading to reduced efficacy of multiple antimalarial drugs.

Adverse Effects and Contraindications

Chloroquine can cause pruritus, gastrointestinal disturbances, and retinopathy with long-term use.
Artemisinin-based compounds can cause nausea, vomiting, and allergic reactions.
Mefloquine can cause neuropsychiatric adverse effects, including anxiety, depression, and psychosis.
Primaquine is contraindicated or requires caution during pregnancy and breastfeeding due to potential risks to the fetus or baby.

Description

This quiz covers the different types of antimalarial drugs, including quinoline-containing compounds, antifolates, artemisinin-based compounds, and other antimalarials. It also explores their mechanisms of action.