ANTIMALARIAL DRUGS
These are drugs used for prophylaxis, treatment and prevention of
relapses of malaria. Malaria caused by 4 species of the protozoal parasite
Plasmodium.see the life cycle of malaria (Fig 1)
Fig 1 (Internet)
Table 1
CLASSIFICATION of antimalarial drugs
1.4-Aminoquinolines
Chlorquine, Amodiaquine,
Hydroxychloroquine
2. Quinoline-methanol
Mefloquine
3. Acridine
Mepacrine (Atabrine, Quinacrine).
4. Cinchona alkaloid
Quinine
5. Biguanides
Chloroguanide (Proguanil), Cycloguanil
6. Diaminopyrimidines
Pyrimethamine, Trimethoprim
7. 8-Aminoquinoline
Primaquine
8. Sulfonamides
Sulfadoxine, Sulfamethopyrazine,
Dapsone.
9. Tetracyclines
Oxytetracycline and others.
10. Newer drugs
Halofantrine, Artemisinin (quinghaosu).
OBJECTIVES AND USE OF ANTIMALARIALS
This aims of using drugs in relation to malarial infection are:
(i)
To prevent and treat clinical attack of malaria.
(ii)
To completely eradicate the parasite from the patient's
body.
(iii)
To reduce the human reservoir of infection – cut down
transmission to mosquito.
1- Chloroquine
 The mechanism of action of chloroquine is not clearly known.
 Resistance in P. falciparum is associated with a decreased ability of
the parasite to accumulate chloroquine .
 Other actions Chloroquine is active against Entamoeba histolytica
and Giardia lamblia also.
Adverse effects
 nausea, vomiting, itching, difficulty in accommodation and
headache which are not serious.
 Parentral administration can cause hypotension, cardiac depression
and arrhythmias.
 CNS toxicity including convulsions is more likely in children.
C. Uses
1. Chloroquine is the drug of choice for clinical cure and suppressive
prophylaxis of all types of malaria, except that caused by resistant P.
falciparum.
2. Extraintestinal amoebiasis.
3. Giardiasis .
4. Rheumatoid arthritis
2- Mefloquine
It is a drug developed to deal with the problem of chloroquine
resistant P. falciparum.
B. Adverse effects
 Mefloquine is bitter in taste;
 common reaction is dizziness, disturbed sense of balance and
sinus bradycardia. Nausea, vomiting, abdominal pain
3- Quinine
Quinine it the levo rotatory alkaloid from cinchona bark. Its disomer quinidine is used as an anti arrhythmic .
B. Adverse effects
 Cinchonism: Large dose or higher doses taken for few days
produce a syndrome called cinchonism. .
 It consists of ringing in ears, nausea, vomiting (due to gastric
irritation and CTZ stimulation), headache, mental confusion, and
vertigo, difficulty in hearing and visual defects.
C. Uses
1.
Treatment of resistant falciparum malaria.
2.
Quinine is the drug of choice for cerebral malaria (falciparum
malaria with impaired consciousness)
4- Pyrimethamine
It is a directly acting inhibitor of DHFRase .It has high affinity for
plasmodial enzyme.
Adverse effects
 Pyrimethamine is relatively safe. The only side effects are
occasional nausea and rashes.
 Pyrimethamine is contraindicated during pregnancy and lactation.
Uses
Because of its slow action, pyrimethamine alone is not suitable for
the treatment of an acute attack of malaria. It is primarily used as a
prophylactic
5- Primaquine
The mechanism of action
Is not known. However, it is different from that of chloroquine.
C. Adverse effects
 Abdominal pain, GI upset, weakness ( These can be minimized
by taking the drug with meals)
 CNS and cardiovascular symptoms are infrequent.
 Leucopenia occurs rarely with larger doses.
D. Uses
The only indication of primaquine is for the radical cure of relapsing
malaria, given with full curative dose of chloro-quine (to cover the
erythrocytic phase).
ANTIAMOEBIC
These are drugs useful in infection caused by the protozoa Entamoeba
histolytica see Fig 2. Amoebiasis has a world wide distribution; Poor
environmental sanitation and low socio-economic status are important
factors in the spread of the disease, which occurs by fecal contamination
of food and water.
CLASSIFICATION
1. Tissue amoebicides
(a) For both intestinal and extraintestinal amoebiasis:
a)Nitroimidazoles : Metronidazole, Tinidazole.
b)Alkaloids :Emetine, Dehydroemetine.
(b) For extraintestinal amoebiasis only: Chloroquine.
2. Luminal amoebicides
(a)
Amide
Diloxanide furoate.
(b)
8-Hydroxyquinolines: Quiniodochloro (lodochlorohydroxyquin,
Clioquinol); Diiodohydroxyquin,
Broxyquinoline.
(c)
Antibiotics
Tetracyclines.
1- Metronidazole
A. The mechanism of action Is not well understood, it is reduced to
intermediate compounds which cause cytotoxicity, probably by damaging
DNA. Its selectively high activity against anaerobic organisms .
B. Pharmacokinetics
Metronidazole is almost completely absorbed form the small
intestines: little unabsorbed drug reaches the colon. It is widely
distributed in the body, attaining therapeutic concentration in vaginal
secretion, semen, saliva and CSF. It is metabolized in liver.
C. Adverse effects
Side effects to metronidazole are relatively frequent, but mostly
nonserious.
Anorexia, nausea, metallic taste and abdominal cramps are the most
common. Loose-ness of stool is occasional.
Less frequent side effects are—headache, glossitis, dryness of
mouth, dizziness, rashes and transient neutropenia.
Prolonged administration may cause peripheral neuropathy and CNS
effects. Seizures have followed very high doses.
D. Contraindications
In neurological disease, blood dyscrasias, first trimester of
pregnancy (though no teratogenic effect has yet been demonstrated,
its mutagenic potential warrants caution).
E. Uses
1. Amoebiasis: It is the drug of choice for all forms of amoebic
infection. Metronidazole is less effective in eradicating amoebic cysts
from the colon, because it is nearly completely absorbed from the upper
bowel.
2.Giardiasis It is highly effective.
3.Trichomonas vaginitis It is the drug of choice. The male partner
should be treated concurrently in cases of recurrent infections.
4. Ulcerative gingivitis, trench mouth 200-400 mg TDS is quite
effective; combine with penicillin or tetracycline.
5. Guinea worm infestation Niridazole is considered to be the drug
of choice.
2- Tinidazole
It is an equally effective as metronidazole, similar to it in every way
except:
Metabolism is slower; duration of action is longer; thus, it is more suited
for single dose or once daily therapy.
It is claimed to be better tolerated; the incidence of side effects is lower:
metallic taste (2%), nausea (1%), rash (0.2%).
Amoebiasis: 2g OD for 3 days
Trichomoniasis and giardiasis: 2 g single dose or 0.6 g OD for 7 days.
Anaerobic infections', prophylactic-2 g single dose before colorectal
surgery; therapeutic- 2 g followed by 0.5 g BD for 5 days.
3- Emetine
i.
It is an alkaloid from Cephaelis ipecacuanha.
ii.
Emetine is a potent and directly acting amoebicide—kills
trophozoites but has no effect on cysts.
iii.
Emetine cannot be given orally because it will be vomited out.
iv.
It is administered by S.C. or I.M. injection: 60 mg OD. It should be
given only till acute symptoms subside; not more than 10 days in
any case.
v.
It is concentrated in liver, kidney, spleen and lungs. Emetine is
very slowly excreted in urine, taking 1-2 months. Thus, a second
course should not be repeated within 6 weeks, otherwise
cumulative toxicity can occur.
Uses
Because of the above drawbacks, emetine is now seldom used as a
reserve drug in severe intestinal or extraintestinal amoebiasis.
4- Dehydroemetine
It is a semi synthetic derivative of emetine; equally effective but
less cumulative and less toxic to the heart.
5- Diloxanide furoate
-
It is a highly effective luminal amoebicide: directly kills
trophozoites responsible for production of cysts.
-
Diloxanide is a weaker amoebicide than its furoate ester.
-
It is primarily metabolized by glucuronidation and is excreted in
urine.
Anti-Helmintics
1- mebendazole :
 Decrease parasite microtubules synthesis (transport system.)
 Decrease glucose uptake.
 Side effects; abdominal pain – diarrhea.
 Contraindicated in pregnancy .
2- pyrantel pamoate :
 Pyrantel pamoate acts as a depolarizing neuromuscular blocking
agent, thereby causing sudden contraction, followed by
paralysis, of thehelminths

Side effects : nausea – vomiting – diarrhea .
kill
worms
3- Thiabendazole:
 The mechanism of action :Inhibition of the mitochondrial
helminth-specific enzyme, fumarate reductase,.
 Medicinally, thiabendazole is also a chelating agent, which
means that it is used medicinally to bind metals in cases of
metal poisoning, such as lead poisoning, mercury
poisoning or antimony poisoning
 Side effects: anorexia – nausea – vomiting .
4- paraziquantel :
 Makes Paralysis of worms .
 Crosses b.b.b– short t half
 Not used in pregnancy & lactation
Notes:1- Laxative should be adminstered with anthelmintic drugs.
2- Drug should be repeated after 2—3 weeks
Anti-helmintics
Choice of drugs for Helminthiasis
Table 2
Worm
First Choice Drugs
Alternatives
1. ROUND WORM
Mebendazole,
Piperazine,
Albendazole,
Tetramisole,
Pyrantel
Levamisole
2. HOOKWORM
Pyrantel,
Levamisole,
Ancylostoma
Mebendazole,
Bephcnium,
duodenale
Albendazole
Thiabendazole
Nicator americanus
Mebendazole,
Pyrantel, Bephenium,
Albendazole
Thiabendazole
3.THREADWORM
Mebendazole,
Piperazine
Enterobius(Oxyuris)
Albendazole,
vermicularis
Pyrantel
4. Stronfyloides
Thiabendazole
Ascaris lumbricoides
See Fig 6
stercoralis
Albendazole,
Pyrantel
Thiabendazole
5. WHIP WORM
Trichuris oichiura
Mebendazole,
Albendazole
6. Trichinella spriralis
Thiabendazole
Mebendazole
7. FILARIA
Diethyl carbamazine
Ivermectin
Niridazole,
Thiabendazole
Wuchereria
bancrofti,
Brugia malayi
8. GUINEA WORM
Dracunculus
Metronidazole
medinensis
9. TAPEWORMS
Niclosamide,
Mebendazole,
Taenia saginata
Praziquantel
Albendazole
Taenia solium
Praziquantel
Mebendazole,
Hymenolepis nana
Niclosamide,
Niclosamide
Praziquantel
Albendazole
10. HYDATID
DISEASE
Echinococcus
granulosus,
E. multilocularis
Albendazole,
Mebendazole