Test 3 Pharm: Antimalarials

Paroxysm: relapsing or periodic fever

• Periodicity corresponds to erythrocytic
• development (24, 48 or 72hours)
• –benign tertian: P. vivax
• –malignant tertian : P. falciparum
• –quartan : P. malariae

The pattern of intermittent chills/fever mirrors the synchronized parasite development in an infected person’s blood

• This response is primarily due to toxins released with rupture of RBCs containing
• schizonts

1. Causal prophylaxis – blocks liver growing stages of parasite

2. Suppressive prophylaxis – doesn’t block liver stage but as come out into blood blocks parasitemia from developing

3. Post exposure prophylaxis – prevent recurrence

4. Intermittent Presumptive Therapy – give ineffective drug once a month to pregnant woman, newborns

5. Radical cure – kill hypnozodic stages in liver (P. vivax, P. ovale)

• DOXYCYCLINE
• MEFLOQUINE
• MALARONE (PROGUANIL AND ATOVAQUONE)

• PREVENT/KILL THE PRIMARY LIVER SCHIZONT
• PREVENT/KILL THE HYPNOZOITE
• RX 7 DAYS, HAS TO BE TAKEN EVERY 14 DAYS

PRIMAQUINE

TAKE PRIMAQUINE AFTER RETURN

• CHLOROQUINE
• MEFLOQUINE
• DOXYCYCLINE
• MALORONE (PROGUANIL AND ATOVAQUONE)

• CHLOROQUINE
• MEFLOQUINE
• DOXYCYCLINE
• PRIMAQUINE
• MALARONE (PROQUANIL AND ATOVAQUONE)

• MALARONE (ATOVOQUONE/PROGUANIL)
• COARTEM (ARTEMETHER/LUMEFANTRINE)
• ACT = Artemisinin Combination Therapy. Taken for treatment of malarya, used in combination to prevent resistance

ARTESUNATE IV (COMPASSIONATE USE IND VIA CDC)

• MALARONE FIRST CHOICE
• MEFLOQUINE SECOND CHOICE

PRIMAQUINE

• Mech:
• Blocks the polymerization of soluble heme by plasmodium; soluble heme toxic to pathogen

• Use:
• - Clinical cure
• - Suppressive prophylactic
• - Highly active against blood stages

• Toxicity:
• Dose related retinopathy; hearing issues; cardiac issues; pruritus (itching) of palms, soles, and scalp; nausea and vomiting on empty stomach

• Metab/kinetics
• - Well absorbed orally
• - Can be gicen IM for severe cases
• - metabolysm: desethylchloroquine is active VS PARASITES!!

• Interaction/resistance
• Some falciparum is resistant to chloroquine via PfCRT--> transporter that pumps out chloroquine from digestive vacuole

• Mech:
• Possibly intermediate oxidants form that are toxic to exoerythorcytic forms

• Use:
• - Casual prophylaxis and radical cure.
• - Eradicates hepatic (latent) stages of vivax +ovale

• Toxicity:
• - Leucopenia
• - Agranulocytosis
• - Hemolysis in pts that are G6PD deficient (hemolytic anemia)
• - G6PD toxicity

• Interaction/resistance
• Falciparum is resistant to primaquine. Can lead to radical cures for P. vivax and P. ovales b/c effective against the exoerythrocytic form in liver. NOTE: Effective against erythrocytic forms

• Primaquine is the only thing that works to kill the dormant form in the liver.

• Mech:
• Blood schizonticidal activity
• Not active against gametophytes or hepatic stages of vivax.

• Use:
• For chloroquine resistant falciparum
• Prophylaxis for travelers

• Interaction/resistance:
• Contraindicated if: hx of epilepsy (can cause seizures if on anticonvulsive therapy), less than 2 yrs old, taking drugs that alter cardiac condition

• Mech:
• Reduces gametocyte form so can reduce transmission ; artemisinin reduces
• parasite load after which the partner drug (ex. Mefloquine) can finish off
• parasite due to being in supratherapeutic levels even if parasite is resistant;
• MOA is possibly blocking of SERCA Ca2+ pump in parasite or formation of highly
• active iron-oxo species

• Use:
• Can use as Aremisinin combination therapy (ACT); used on multidrug resistant P. falciparum
• Use for severe malaria, in the US, including cerebral malaria (Artesunate IV)
• Artesunate IV also used in high levels of parasites in blood

• Metabolism/kinetics:
• Obtained from plants; IV artesunate is 35% more efficacious than quinine
• Used due to lack of timely access to IV quinidine, or if quinidine intolerance or contraindication, or if quinidine failure

• Use:
• Suppressive prophylactic
• Taken with milk or food to increase absorption
• Suppression of blood stages; All four types of malaria if uncomplicated and not progressing rapidly
• Prophylaxis for travelers
• Acute uncomplicated malaria

Highly active against blood stages, partly against liver stages

• Metabolism
• –Atovaquone
• »Not metabolized in humans
• »Excreted via bile

• –Proguanil
• »Metabolized to active triazine (cycloguanil)
• »Affected by CYP2C19 mutations

First FDA approved ACT

• Use:
• Acute uncomplicated Malaria

• Contraindications:
• –Pregnancy or breast-feeding
• –Heart problems (eg, irregular heartbeat, QT prolongation)
• –Recent use of halofantrine or other drugs that can cause QT prolongation