-
Malaria signs/symptoms:
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
-
USE OF ANTIMALARIAL DRUGS
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)
-
Suppressive prophylaxis for P. vivax in travelers: prevents the primary blood stage
infection, does not prevent relapse from hypnozoite, Rx 28 days after return for doxy and MQ
- DOXYCYCLINE
- MEFLOQUINE
- MALARONE (PROGUANIL AND ATOVAQUONE)
-
CASUAL PROPHYLAXIS: TARGETS THE GROWING IN THE LIVER STAGES
- PREVENT/KILL THE PRIMARY LIVER SCHIZONT
- PREVENT/KILL THE HYPNOZOITE
- RX 7 DAYS, HAS TO BE TAKEN EVERY 14 DAYS
PRIMAQUINE
-
PRESUMPTIVE ANTI-RELAPSE THERAPY (PART)
TAKE PRIMAQUINE AFTER RETURN
-
SUPPRESSIVE PROPHYLAXIS: SUPPRESSION OF BLOOD STAGES
- CHLOROQUINE
- MEFLOQUINE
- DOXYCYCLINE
- MALORONE (PROGUANIL AND ATOVAQUONE)
-
MAJOR ANTIMALARIAL DRUGS
- CHLOROQUINE
- MEFLOQUINE
- DOXYCYCLINE
- PRIMAQUINE
- MALARONE (PROQUANIL AND ATOVAQUONE)
-
TREATMENT OF ACUTE UNCOMPLICATED MALARIA
- MALARONE (ATOVOQUONE/PROGUANIL)
- COARTEM (ARTEMETHER/LUMEFANTRINE)
- ACT = Artemisinin Combination Therapy. Taken for treatment of malarya, used in combination to prevent resistance
-
TREATMENT OF SEVERE MALARIA, INCLUDING CEREBRAL MALARIA
ARTESUNATE IV (COMPASSIONATE USE IND VIA CDC)
-
PROPHYLAXIS FOR TRAVELERS, MILITARY, PEACE CORPS, ETC
- MALARONE FIRST CHOICE
- MEFLOQUINE SECOND CHOICE
-
POSTEXPOSURE PROPHYLAXIS (PREVENTS RELAPSE)
PRIMAQUINE
-
CHLOROQUINE
- 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/resistanceSome falciparum is resistant to chloroquine via PfCRT--> transporter that pumps out chloroquine from digestive vacuole
-
PRIMAQUINE
- 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.
-
Mefloquine
- 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
-
Artemisinin
- 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
-
MALARONE (Atovaquone/proguanil)
- 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
-
COARTEM (Artemether/lumefrantine)
First FDA approved ACT
- 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
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