Antimalarials Flashcards
How is Chloroquine administered?
Oral
What is the MOA of Chloroquine?
Blood Schizonticide
Actively concentrated within plasmodia that reside within erythrocytes; May interfere with lysosomal degradation of Hb (reduces symptoms – “clinical cure”)
What are the uses of Chloroquine?
DOC:
P. falciparum
P. malariae (if no resistance)
What are the toxicities of Chloroquine?
- Accumulates in melanin-rich tissues: skin, retina (ototox)
- CNS (dizziness, HA, tinnitus)
- Hemolysis – use caution in G6PD deficient
- QT prolongation
What are contraindications of Chloroquine?
- Ocular disease
- Psoriasis
- Porphyria
How is resistance developed to Chloroquine?
Transport pumps
How is Artesunate & Artemether administered?
Oral
What are the uses of Artesunate & Artemether?
DOC:
Chloroquine resistant
P. falciparum
P. vivax
(must be used in combination with other antimalarials - “ACT”)
What is the DOC for P. falciparum and P. malariae?
Chloroquine
What is the DOC for uncomplicated Chloroquine resistant malaria?
ACT + Atovoquone-Proquanil
OR
ACT + Lumefantrine
What is the 2nd DOC for uncomplicated Chloroquine resistant malaria?
Quinine + Doxy/Tetra/Clinda
Tetra is the preferred combo, but Clinda is used in children under 8 and pregnancy
What is the MOA of Sulfadoxine-Pyrimethamine + ACT
Sulfa inhibits PABA into folic acid
Pyrimethamine inhibits DHFR, blocking conversion of DHF to tetrahydrofolic
What is the use of Sulfadoxine-Pyrimethamine + ACT?
Prophylaxis treatment of malaria in pregnant women who reside in areas where malaria is epidemic.
DO NOT give in a pregnant woman who has active disease
How is resistance acquired against Sulfadoxine-Pyrimethamine?
Mutation in DHFR
What is the MOA for Atovaquone-Proquanil + ACT?
Atovaquone – interferes with mitochondrial electron transport and ATP pyrimidine biosynthesis
Proquanil – prodrug; converted to cycloguanil – DHFR inhibitor
Synergistic combo – effective in regions where Chloroquine resistance is high
Combined with Artesunate for rapid clearance and decrease in resistance
What are the uses of Atovaquone-Proquanil + ACT?
Uncomplicated chloroquine-resistant malaria
Prophylaxis against chloroquine-resistant P. falciparum
What are the toxicities of Atovaquone-Proquanil + ACT?
- Rash, fever
- Vomiting and diarrhea reduce absorption and efficacy, so must be discontinued
What are the toxicities of Artemether + Lumefantrine?
- Headache
- QT prolongation
What is the DOC for complicated Chloroquine-resistance malaria?
Quinidine + Tetra/Doxy/Clinda
Tetra is the preferred combo, but Clinda is used in children under 8 and pregnancy
How is Quinine and Quinidine Gluconate administered?
Quinine (oral); Quinidine (IV)
Given in combination with Doxy, Tetra, or Clinda
Tetra is the preferred combo, but Clinda is used in children under 8 and pregnancy
What are toxicities of Quinine and Quinidine Gluconate?
- Cinchonsim – tinnitus, HA, dizziness, flushing, visual disturbances
- Antiarrhythmic agent – Class 1A
- QT elongation
- Diarrhea
- Hemolysis in G6PD deficiency
- Stimulates insulin release (caution in those with hypoglycemia)
What are the uses of Mefloquine + ACT?
Uncomplicated Chloroquine-resistant plasmodia, but only as a LAST RESORT
What are toxicities of Mefloquine + ACT?
- Depression of myocardium
- Seizures
- May aggravate latent psychoses
- Vivid dreams
- Teratogenic
What are contraindications to using Mefloquine + ACT?
- Pregnancy
- History of mental illness
- Epilepsy
What drug should not be given with Mefloquine and why?
Do not give with Quinine due to both having cardiac toxicity
What is the MOA for Primaquine?
Tissue Schizonticide
Eliminate plasmodia from tissue and acts on hepatic stages (exoerythrocytic) – Eliminates dormant phase to prevent relapse – “radical cure”
What are the uses of Primaquine?
Radical cure of P. vivax and P. ovale
What are toxicities of Primaquine?
- Hemolysis in G6PD deficiency (use low dose once daily x 8 wks)
- Fetal hemolytic anemia
- Teratogenic
What are contraindications of Primaquine?
- Pregnancy, breastfeeding
- Infants < 6 months
- SLE, RA
What is the MOA of Tafenoquine?
Tissue Schizonticide
Eliminate plasmodia from tissue and acts on hepatic stages (exoerythrocytic) – Eliminates dormant phase to prevent relapse – “radical cure”
What are the uses of Tafenoquine?
Prophylaxis ( > 18 years old)
Radical cure of P. vivax and P. ovale ( > 16 years old)
What are toxicities of Tafenoquine?
- Back pain, HA
- Keratopathy
- Teratogenic
What are contraindications of Tafenoquine?
- G6PD deficiency or unknown G6PD status
- Pregnancy
What are the uses of Quinine?
Uncomplicated Chloroquine-resistant plasmodia
