MALARIA INFECTIONS-ANTI MALARIALS

MALARIA is a protozoal infection by the parasitic family plasmodia
Malarial parasites are of four types P.vivax; P.malariae;P.ovale and P.falciparum out of these  P.falciparum and P.malariae after infection the whole parasites mature as merozoites to have the erythrocytic cycle and nothing left in the liver or any other muscle to form the dormant hypnozoites. Hence these infections would not produce relapsed fever like the other two.

 THE LIFE STAGES OF MALARIA PARASITE

Malarial parasites from the stage of infection it needs 5 stages to produce the disease as follows

Stage-1: -A female Anopheles mosquito a carrier mosquito injects sporozoites into the human

Stage-2:- The Sporozoites is transformed into the Merozoites in the liver

Stage-3:-The Merozoites enter into the bloodstream to form the disease-producing sporozoites which invade the          Erythrocytes. These erythrocytic forms are known as Blood Schizonts

Stages-4:- The lysis of erythrocytes occurs in this stage with the release of Gametocytes

Stage-5:- These Gametocytes re-enter into a mosquito when the later bytes an infected man.

The P.ovale and the P.vivax are forming the dormant stage in the liver known as hepatic schizonts and remain in the liver years and years to relapse the fever in a favorable environment.

Treatments

1.Chloroquine

2.Quinine

3.Mefloquine

4.Pyrimethamine(Daraprim)

5.Pyrimethamine/Sulfadoxine(Fansidar)

6.Chloroguanide(Paludrine)

7.Primaquine

Chloroquine 

Chloroquine is the drug of choice in malaria in many situations it magically cures the P.vivax infection the common form of malaria.

It is said to be acting on the malarial parasites by deregulating the parasites DNA and RNA synthesis, by producing an unfavorable pH and prevent the parasites from consuming human red blood cell hemoglobin 

Also, these drugs block the plasmodial heme polymerase 

Beware of that chloroquine is distributed most of the body fluids, crosses the blood-brain barrier, and into the placenta. It is teratogenic and hence usage during pregnancy and lactation should be restricted, cautious, and with the supervision of the physician.

Chloroquine is useful in an acute attack of malaria as this drug is acting only on the erythrocytic schizonts only and hence it will not prevent the relapsing of P.ocale or P.vivax.

Toxicology In low dose Chloroquin can produce GI distress, headache, and rash. It is highly contraindicated with psoriasis and porphyria

In high doses peripheral neuropathy, myocardial depression, retinal damage, hearing damage, and mental psychoses.

Quinine 

This medicine also somewhat similar to chloroquine by acting on DNA synthesis of the erythrocytic form of the plasmodium.

It can be taken orally similar to chloroquine

most of these drugs are excreted by kidneys. Hence dosage should be adjusted and caution should be observed by a physician when this drug is taken by a kidney patient.

Quinine is the drug of choice in cases of chloroquine resisting organisms. It is very effective in combination with Pyrimethamine and Sulphonamide.

Toxicology 

Cinchonism such as nausea, vomiting, tinnitus, vertigo, headache, and blurred vision.

Hemolytic anemia in case of those who have Glucose-6-Phosphate Dehydrogenase deficiency 

Caution should be taken by those who are highly sensitive to Quinine as this drug can produce Black Water Fever a fatal condition in which red blood cell lysis occurs with the release and excretion of hemoglobin in the urine causes black urine and will eventually damage the Kidneys.

Mefloquine

similar to chloroquine and Quinine this drug also a blood shizonticide, killing the erythrocytic form of the malarial parasite and but the mechanism of action is unknown.

It can be taken orally.

Unlike Chloroquine and Quinine it is mainly distributed and concentrated in the liver and lungs.

It has a longer half live hence it has a longer effect than chloroquine and metabolized in the liver and excreted in stools.

It is the drug of choice for the prevention and treatment of the chloroquine-resistant and the most deadly fatal infection of P.falciparum.

Toxicology

It is less toxic than chloroquine and quinine

However it can produce nausea vomiting and dizziness.

At higher dosage, it can produce seizures, hallucination, and depression

Pyrimethamine(Daraprim)

This drug also blood schizonticide similar to chloroquine by interfering with the parasite's nucleic acid synthesis by depriving of purines and pyrimidines.

It can be taken orally

After a partial liver metabolism it is excreted by kidneys. Hence kidney patients should be cautious for dosage adjustment strictly at the supervision of a doctor.

With the combination of Sulphadiazine it is mostly used for the treatment of the deadly infection of P.falciparum.

Toxicology

High doses can produce Folic Acid Deficiency Syndrom

Rashes 

GI Distress

Hemolysis

Kidney Damage

Chloroguanide (Paludrine)

It is also a blood shizonticide and action is very similar to Pyrimethamine

It can be taken orally

It has a shorter duration of action (12 to14 hrs)

It is excreted in the urine

It is used as preventive and suppressive medicine owing to its shorter duration of action and the drug is of very limited use because of the development of rapid resistant strain.

Toxicology

Rash

GI Distress

Hemolysis 

Kidney failure

Primaquine

Unlike other medications Primaquine is the only antimalarial that is not acting on the erythrocytic form of the parasites rather it acts on tissue and liver dormant schizonts and the gametocytes the sexual form of the parasites and eradicate them. Hence Primaquine can be used as a preventive for relapses but not as a curative for acute attacks

It can be taken orally

It undergoes rapid biotransformation to form the active metabolites which are excreted by the urine

Primaquine is used to treat relapsing malaria because it eradicates the liver and tissue dormant schizonts of P.vivax and P.ovale and also as it kills the gametocytes of all four types it can use to prevent transmission of the disease.

Because it would not on the erythrocytic form of the plasmodium it has no effect on acute attacks.

Toxicology

Methemoglobinemia

GI Distress

Headaches

Pruritus

Hemolytic Anemia in G-6-PD deficiency

Granulocytopenia

Agranulocytosis-Rare