2. BIGUANIDES
• The one in use is PROGUANIL
• Its action against the malaria parasites is very slow and thus not used
in clinical attack of malaria.
• Proguanil is mainly used in prophylaxis in sickle cell disease.
• A combination regimen with ATOVAQUONE is used in the treatment
of resistant malaria.
MOA: inhibits the enzyme dihydrofolate reductase.
3. Diaminopyrimidines
• Include pyrimethamine and trimethoprim.
• They also inhibit the enzyme dihydrofolate reductase.
• Pyrimethamine antimalarial action resembles that of proguanil but is
more potent.
• For clinical cure pyrimethamine is used in combination with
sulphonamides the so called SP drugs i.e P + SULPHADOXINE and P+
sulphamethopyrazine
• OTHERS agents used in Malaria: antimicrobials and atovaquone.
4. CHEMOTHERAPY OF AMOEBIASIS,
TRICHOMONIASIS AND GIARDIASIS
AMOEBICIDES, TRICHOMONICDES & ANTIGIADIAL DRUGS.
• The choice of drug for amoebiasis depends with specific form of
amoebiasis and on the desired site drug action.
• It is thus important to know how amoebiasis is manifested i.e
asymptomatic intestinal infection, luminal intestinal infection, severe
instestinal infection( amoebic dysentery) or amoebic liver abscess.
• The drug used in the treatment of amoebiasis can be categorized as
follows; 1) 5-nitroimidazoles – metronidazole, tinidazole, ornidazole,
secnidazole and satranidazole.
these act in the intestines, colonic wall as well as in the liver.
2) Chloroquine and emetine = act in the colonic wall as well as in the liver.
5. Amoebicides contd.
3) Antibiotics = tetracycline and erythromycin, these affect the trophozoites
by depriving them of their nutrients.
4) others: -diloxanide furoate
- aminosidine sulphate
METRONIDAZOLE
• IS effective in intestinal and extra-intestinal amoebiasis BUT more effective
on the latter.
• Metronidazole kills trophozoites but NOT cysts of entamoeba histolytica
thus is not effective in chronic intestinal amoebiasis
6. Metronidazole contd.
in which cystic forms persist in the bowel lumen.
• Pharmacokinetics: metronidazole is rapidly absorbed and widely
distributed in the tissues.
- Peak plasma concentrations are reached in 1-3hrs. Half-life is 7.5hrs
- It is metabolized in the liver and together with its metabolites
excreted in the urine.
CLINICAL USES
- Intestinal and amoebic liver abscesss. The treatment with
metronidazole should be followed by diloxanide to clear the cysts.
- Giardiasis.
7. Clinical indications contd.
- Trichomoniasis
- Pseudomembraeous colitis = bacterial anerobic infection .
Metronidazole is an alternative to VANCOMYCIN.
- Surgical and gynaecological sepsis in which its activity against colonic
anaerobes especially bacteroides fragilis is important.
- i.v metronidazole is used for the treatment of established tetanus.
8. Adverse effects of metronidazole
• GIT disturbances are the most common = nausea and vomiting,
epigastric pain, abdominal cramps, unpleasant metallic taste,
stomatitis and furry tongue. Taking the drug with meals lessen
gastrointestinal irritation.
• Metronidazole has disulfiram- like effect if alcohol is ingested during
therapy. Patient taking metronidazole should be warned not to use
alcohol before starting the drug and 48hrs after last dose.
contraindications
-avoided in pregnancy and nursing women.
9. TINIDAZOLE
• Has a higher duration of action than metronidazole thus used ONCE daily.
Clinical uses: - amoebic dysentery
- amoebic liver abscess
- giardiasis
- trichomoniasis
• Adverse effects
- N & V
- metallic taste
- furred tongue NB. Disulfiram- like effect with alcohol.
10. Secnidazole and ornidazole
• Secnidazole and ornidazole have properties similar to metronidazole.
• Both have much longer plasma half- lives thus used once daily.
• Adverse effects: -N & V
- epigastric pain
- metallic taste
- furred tongue
- disulfiram- effects with alcohol.
11. Satranidazole
• Is the newest 5-nitroimidazole with potent activity against E.
histolytica, G.lamblia and T. vaginalis.
• It also have activity against anerobes e.g B. fragilis.
• It is rapidly absorbed and have higher plasma and liver concentration
than metronidazole.
• CLINICAL USES: - intestinal and hepatic amoebiasis
- giardiasis
- trichomoniasis
12. Adverse effects of satranidazole
• Unlike other 5-nitroimidazoles satranidazole does NOT produce N & V
and there is NO metallic taste in the mouth.
• Side effects are: -dry mouth
- weakness and dizziness
-headache
13. CHLOROQUINE
• Chloroquine is used to treat hepatic amoebiasis only when
metronidazole is not successful or contraindicated.
• The response is prompt and highly effective.
• Chloroquine is NOT effective against intestinal amoebiasis because is
completely absorbed from small intestines and attains low
concentration in intestinal wall.
14. DILOXANIDE FUROATE
• Diloxanide is a luminal amoebicide.
• In the intestine is split into diloxanide and furoic acid.
• About 90% diloxanide is rapidly absorbed and excreted in urine.
• The unabsorbed diloxanide is the active amoebicidal substance.
• It is mainly used in eradicating the cystic forms from the intestinal
lumen.
CLINICAL USES: - is the drug of choice for asymptomatic and mild
intestinal amoebiasis.
- is used with other drugs in symptomatic and
15. Intestinal amoebiasis to eradicate the cystic forms. Normally given
after the 5-nitroimidazole.
- In amoebic liver amoebiasis to eradicate the intestinal cystic forms
ADVERSE EFFECTS
- Are uncommon but can cause = flatulence
= N& v
= dryness of mouth and urticaria
16. AMINOSIDINE SULPHATE( paromomycin)
• It is an aminoglycoside with antibacterial and antiprotozoal activity.
• It is active against: - salmonella spp.
- shigella spp.
- Escherichia coli
- E. histolytica
-G. lamblia
• Aminosidine is poorly absorbed from the GIT and most of it is excreted
unchanged in faeces.
• It is thus administered orally strickly for intestinal infections caused by
susceptible bacteria and protozoa.
17. CLINICAL USES OF AMINOSIDINE
• Amoebiasis and giardiasis
• Salmonellosis and giardiasis
• Parenteral aminosidine is used for the treatment of VISCERAL
LESHMANIASIS.
ADVERSE EFFECTS
- In large doses aminosidine may cause –nausea, vomiting and
anorexia. Abdominal cramps and diarrhea.
- Nephrotoxicity and otoxicity have very rarely been reported.
