This chapter will be most useful after having a basic understanding of the material in Chapter 49, Chemotherapy of Malaria in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. In addition to the material presented here, Chapter 49 in the 12th Edition contains:
Tables 49-2, 49-3, and 49-4 which provide information about appropriate regimens, including adult and pediatric dosages, for the prevention, treatment, and presumptive self-treatment of malaria
Figure 49-4 which is an algorithm approach to the treatment of malaria
Know the stages of the malaria parasite in the human body.
Classify antimalarial drugs into those that are effective against only the blood stages of the parasite, those that are effective against both the blood and liver stages, and those that are effective against only the liver stages of the parasite.
Understand the use of antimalarial drugs in clinical context, particularly with regard to their mechanism of action, therapeutic uses, and toxicities.
Describe the principles and guidelines for the chemoprophylaxis and treatment of malaria.
DRUGS INCLUDED IN THIS CHAPTER
Artemisinin and Artemisinin—combination therapies
Doxycycline—see Chapter 41
CRITERIA FOR DIAGNOSIS OF SEVERE MALARIA ||Download (.pdf) CRITERIA FOR DIAGNOSIS OF SEVERE MALARIA
|Respiratory distress ||Acute renal failure |
|Multiple convulsions ||Disseminated intravascular coagulation |
|Circulatory shock ||Acidosis |
|Pulmonary edema ||Hemoglobinuria |
|Acute respiratory distress syndrome ||Parasitemia >5% |
|Abnormal bleeding |
CRITERIA FOR THE DIAGNOSIS OF MALARIA
ANTIMALARIAL DRUG MECHANISMS OF ACTION AND RESISTANCE ||Download (.pdf) ANTIMALARIAL DRUG MECHANISMS OF ACTION AND RESISTANCE
|DRUG ||MECHANISM OF ACTION ||MECHANISM OF RESISTANCE |
|Artemisinin and Derivatives ||Production of toxic heme-adducts ||Not known at this time |
|Atovaquone ||Inhibits mitochondrial electron transport in the cytochrome bc1 complex ||Nucleotide polymorphisms in the cytochrome b gene |
|Proguanil ||Inhibits dihydrofolate reductase-thymidylate synthase ||Mutations in the amino acid sequence near the dihydrofolate-reductase binding site |
|Pyrimethamine ||Inhibits Plasmodium dihydrofolate-reductase ||Mutations in dihydrofolate-reductase binding site |
|Sulfadoxine ||Inhibition of Plasmodium dihydropteroate synthase ||Mutations in dihydropteroate synthase gene |
|Chloroquine/Hydroxychloroquine ||Production of toxic heme adducts ||Production of a chloroquine efflux transporter |
|Quinine/Quinidine ||Production of toxic heme adducts ||Production of an efflux transporter; amplification of pfmdr 1 gene |
|Mefloquine || |
Production of toxic heme adducts
There is also a cytosolic mode of action
|Amplification of pfmdr 1 gene that accumulates drug in digestive vacuole away from cytosolic site of action |
|Primaquine ||Production of reactive oxygen species ||Not known at this time |