Malaria Drugs - Chapter 52 review

• Contracted after inoculation of
• plasmodium parasites into the blood stream by the bite of a female Anopheles
• mosquito

• Primary Tissue phase
• •The parasites first undergo a primary
• developmental stage in the liver.

• Erythrocytic phase
• •The parasites then enter the blood and parasitize erythrocytes.

• P. falciparum
• P. malariae
• P.ovale
• P. vivax

• Tissue schizonticide
• –eliminates dormant or developmental liver forms
• Blood schizonticide
• -eliminates blood parasites
• Gametocide
• –kill sexual stages and
• prevents transmission to mosquitoes

Prevents polymerization of heme.

• –Intracellular accumulation of heme is
• toxic to the parasite.

CHLOROQUINE

- acute attacks of non-falciparum and sensitive falciparum malaria. 

•  - prophylaxis of malaria caused by
• P. vivax, P. ovale, P. malariae,
• and susceptible strains of P. falciparum.

• –GI irritation, rash, headache, peripheral
• neuropathy, auditory impairment, toxic psychosis, and precipitation of porphyria attacks, retinal damage, hemolysis in G6PD deficiency

–When combined with mefloquine will increase the risk of seizures and ECG abnormalities.

• Hair bleaching with over-exposure to drug.
• 

From the bark of the cinchona tree...

• –Complexes with double-stranded DNA to
• prevent strand separation.

–Solely a blood schizonticide.

• –Used in the treatment of chloroquine-resistant
• falciparum malaria.

• in pregnancy
• –(Category X)

Toxicity is known as cinchonism.

• GI distress, headache, vertigo, blurred
• vision, and tinnitus.

Blood schizonticide

–eliminates blood parasites

May cause hemolysis in G6PD deficient individuals.

QUININE

Intravascular hemolysis is the cause of blackwater fever.

• –With coumadin to prolong the prothrombin
• time.

–Increases digoxin levels.

–Do not administer concomitantly with mefloquine due to increased risk of cardiac arrest and seizures.

Related to quinine.

–Used for prophylaxis in all malarious areas except those resistant to chloroquine

• Used to treat acute malaria caused
• by  P. falciparum and P. vivax.

•  **Does not eliminate the liver phase of   
•      P. vivax

Contraindicated in patients with a history of psychiatric disease, and/or seizures.

Other quinine-like drugs can cause prolongation of the QT interval, and can cause seizures

vomiting, hallucinations

Tissue schizonticide. 

Also limits malaria transmission by acting as a gametocide.

• Used to eradicate the liver stage of 
• P. ovale and P. vivax. 

*Used in conjunction with a blood schizonticide.

Mechanism of action

–forms metabolites that are cellular oxidants.

–G6PD deficiency.

• hemolytic anemia,
• cardiac arrhythmias,
• dark urine (because red blood cell breaking down)

quinacrine decreases the metabolism of primaquine

disrupts mitochondrial electron transport in plasmodia.

The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis

Combined in a fixed combination with proguanil and marketed as Malarone.

• Indicated for the treatment and
• chemoprophylaxis of falciparum malaria. 

• Atovaquone is also approved for the
• treatment of P. jiroveci pneumonia.

– Allergy to the drug

fever, rash, nausea, vomiting, diarrhea, headache, and insomnia.

– coadministration of rifampin, or tetracycline will decrease plasma concentrations of atovaquone by 50%.

PRIMAQUINE

• CHLOROQUINE
• QUININE
• MEFLOQUINE (LARIAM)

PRIMAQUINE

is a tissue schizonticide and also limits malaria transmission by acting as a gametocide.

• Pyrimethamine,
• proguanil

–Acts slowly against erythrocytic forms of susceptible strains of all four human malaria species.

–Other anti-malarial agents are usually preferred due to severity of adverse reactions.

–seizure disorders

• seizures,
• folic acid deficiency,
• GI distress

• sulfonamides increase risk of megaloblastic
• anemia

–Formerly used in combination with chloroquine for prophylaxis of malaria in the parts of Africa without widespread chloroquine resistance.

Hepatic dysfunction

–Megaloblastic anemia in patients with renal failure, mouth ulcers and alopecia

–Safe to use in pregnancy.

–Oral contraceptive use prolongs the half-life of proguanil

Mechanics of action

–Sequential blockade of folate synthesis

• Combination of pyrimethamine
• and sulfadoxine

Intermittent preventative therapy in pregnant women and young children.

• Stevens-Johnson syndrome (SJS),
• Toxic epidermal necrolysis (TENs)

• Hypersensitivity to the drug,
• sulfa allergy,

- Effective against erythrocytic stages of all four types of malaria

 - Not used for chemoprophylaxis

• Alters cardiac conduction,
• dose related prolongation of QT interval

Contraindicated in pregnancy

with artemether (Coartem)

uncomplicated falciparum malaria,

Minimal cardiac toxicity

Mech of action

• production of free radicals
• or inhibition of parasite calcium ATPase

Used in China for over 2000 years

• combination therapy,
• is the standard treatment for uncomplicated falciparum malaria in many areas.

• IV artesunate,
• is used for complicated falciparum malaria,
• will eventually replace IV quinine as the treatment of choice.

• NVD,
• dizziness