ANTIMALARIAL DRUGS

MALARIA

from mala aria (bad air)

called ague, intermittent fever

marsh fever and the fever.
VECTOR/CARRIER
Anopheles
carrier of the causative agent of malaria.
Dr. Ronald Ross
Aedes aegypti

carrier of Yellow Fever

CAUSATIVE AGENT
caused by the parasitical protozoa of the Plasmodium genus transmitted by
the female anopheles mosquitoes through their saliva.

Plasmodium vivax
Plasmodium falciparum
Plasmodium malariae
Plasmodium ovale
Plasmodium knowlesi

1.) P. falciparum

2.) P. vivax

3.) P. malariae

4.) P. ovale

causes approximately 50% of all malarial cases.

infects up to 65% of the patient's erythrocytes.
causes approximately 40% of malarial cases.
can be very chronic (can re-infect liver cells)
causes only 10% of malarial cases.
relapses are very common.
the least common species.

MALARIAL INFECTION
SYMPTOMS

PREVENTION
These symptoms of malaria are seen only after a period of few days after the
infectious bite, which is called as incubation period.
The incubation period - after the bite and before showing of symptoms varies anywhere between 7 and 30 days.
SEVERE MALARIAL SYMPTOMS

Altered consciousness

Convulsions

Severe anemia

Breathing difficulties

Prostration

Limited urine production

HOW IT KILLS

If drugs are not available or if the parasites are resistant to them,

malaria infection can develop to anemia, hypoglycemia or
cerebral malaria, in which capillaries carrying blood to the brain
are blocked.

Cerebral malaria can cause coma, life-long-learning disabilities,

and death.
DIAGNOSIS

Dichloro-diphenyl-trichloroethane

Insecticidal spray to kill malaria carrying mosquitos

DDT affects the nervous system by interfering with normal nerve

impulses

PREVENTION/TREATMENT

stereochemistry is important because it provides a significantly

different pharmacological spectrum.
CINCHONA ALKALOIDS

TREATMENT
Four possible sites for Drug therapy:
1. Kill the sporozites injected by the mosquito and/or prevent the sporozites
from entering the liver.
2. Kill the schizonts residing in hepatocytes and/or prevent them from
becoming merozoites
3. Kill the merozoites in the blood and/or prevent them from developing
into gametocytes.
4. Kill the gametocytes before they can enter the mosquito and reproduce
into zygotes.
DRUGS
New drug discoveries by:
Plasmodium Genome
genomics
proteomics
*find the protein that is unique to plasmodium species.
*understand and the genetic changes that lead to drug resistance.

CINCHONISM

Toxic syndrome caused by cinchona.

Symptoms:

Tinnitus

Headache

Nausea

Disturbed vision

CINCHONA ALKALOIDS

CINCHONA MODE OF ACTION

the inhibition of protein synthesis

the inhibition of food vacuole phospholipases

the inhibition of aspartic proteinases

and the effects on DNA and RNA synthesis

ferriprotoporphyrin IX,
CINCHONA MODE OF ACTION

Quinine

stereoisomer, quinine, is a more potent antimalarial, but it is also

more toxic lethal for all Plasmodium schizonts, and the
gametocites from P. vivax and P. malariae spectrum of activity is
considered too narrow for prophylactic use

Quinidine

The stereoisomer, quinidine, is a schizonticide, but its primary

indication is cardiac arrhythmias. It is a good example where

4-AMINOQUINOLINES
closest of the antimalarials that are based on the quinine structure.

PRIMAQUINE

the only 8-aminoquinoline currently in use for the treatment of

malaria

not used for prophylaxis spectrum of activity is one of the

narrowest of the currently used antimalarial drugs being indicated
only for exoerythrocytic P. vivax malaria

also inhibits the gameocyte stage

POLYCYCLIC ANTIMALARIAL DRUGS

considered the prototypical structure that succeeded quinine and

came into use in the mid-1940s
Until recently, chloroquine has been the main antimalarial drug
used for both prophylaxis and treatment
chloroquine and the other 4-aminoquinolines are not effective
against exoerythocytic parasites

Hydroxychloroquine

marketed as the R,S-isomer

differs significantly from the other agents in this class by having
two trifluromethyl moieties at positions 2 and 8 and no
electronegative substituents at either positions 6 (quinine) or 7
(chloroquine).
Schizonticide
acting before the parasite can enter the erythrocyte
FDA-required warning that this drug can cause exacerbate mental
disorders and is contraindicated in patients with:
o
active depression,
o a recent history of depression,
o generalized anxiety disorder,
o psychosis,
o schizophrenia, and other major psychiatric disorders or
a history of convulsions

8-AMINOQUINOLINES

DOXYCYCLINE

phosphate salt is used in oral dosage forms (tablets)

hydrochloride salt is administered parenterally

Amodiaquine

When used for prophylaxis of malaria, it had a higher incidence of

hepatitis and agranulocytosis than that was chloroquine.

Halofantrine

based on the cinchona alkaloid

quinoline moiety.
All can cause hemolytic anemia in
erythrocytic G6PD deficient patient.

Mefloquine HCl

use for malaria is limited to prophylaxis against strains of P.

falciparumn resistant to chloroquine and sulfadoxine
pyrimethamine.
use normally should not exceed 4 months (tetracyclines
chelate calcium)

a schizonticide

prominent warning that halfantrine can affect nerve conduction in

cardiac tissue

QUINACRINE

Sulfadoxine and Pyrimethamine

an acridine dye (cause yellow discoloration of the skin and

urine)
one of the most toxic of the antimalarial drugs even though, at
one time, it was commonly used
It may be tumorgenic and mutagenic and has been used as a
sclerosing agent.

FIXED COMBINATION

combination of two drugs that have distinctly different

mechanism.
*Sulfadoxine and Pyrimethamine
*Atovaquone and Proguanil HCl
RESISTANCE

uses a drug from the sulfonamide antibacterial group and a

pyrimidinediamine similar to trimethoprim combination is
considered to be a schizontocide
The sulfonamide, sulfadoxine, interferes with the parasites
ability to synthesize folic acid, and the pyrimidinediamine,
pyrimethamine, inhibits the reduction of folic acid to its active
tetrahydrofolate coenzyme form.

Atovaquone and Proguanil HCl

One combination inhibits folic acid biosynthesis and

dihydrofolate reductase, and another combination acts on the
parasites mitochondria and its dihydrofolate reductase. Both
drugs in the third combination act on hematin, but by two
different mechanisms.

are administered in combination in the ratio of 2.5 atovaquone to

1 proguanil HCl measured in mg (not mmoles).

Atovaquone is a selective inhibitor of the Plasmodiums

mitochondrial electron transport system, and cycloguanil
(proguanil) is a dihydrofolate reductase inhibitor

ARTEMISIN

NEW MODIFICATIONS