Transcript pharmacology-lect-15-n-40-antiprotozoal

Antiprotozoal drugs
Dr. Naza M. Ali
LEC 15
23-1-2017
Antiprotozoal drugs:
1. Amebiasis
2. Antimalaria
3. Toxoplasmosis
4. Leishmaniasis
5. Trypanosomiasis
6. Giardiasis
Chemotherapy of Amebiasis
• Is an infection caused by Entamoeba histolytica.
• Can be acute or chronic, with patients showing
varying degrees of illness, from no symptoms to
mild diarrhea to fulminating dysentery.
• Diagnosis by isolating E. histolytica from fresh
feces.
• Therapy is aimed not only at the acutely ill
patient but also at those who are asymptomatic
carriers, because dormant E. histolytica may cause
future infections.
Life cycle of Entamoeba histolytica, showing
the sites of action of amebicidal drugs.
Classification of amebicidal drugs
1. Mixed amebicides are effective against both
the luminal and systemic
2. Luminal amebicides act on the parasite in
the lumen of the bowel
3. Systemic amebicides are effective against
amebas in the intestinal wall and liver
Mixed amebicides:
• Metronidazole
• Tinidazole
Luminal amebicide
• Iodoquinol
• Paromomycin
• Diloxanide furoate
Systemic amebicide
• Chloroquine
• Emetine and dehydroemetine
Mixed amebicides:
Metronidazole: It is nitroimidazole use for
•
•
•
•
•
•
•
Amebic infections E. histolytica trophozoites
Giardia lamblia,
Trichomonas vaginalis,
Anaerobic cocci,
Anaerobic gram negative bacilli
Pseudomembranous colitis
In brain abscesses
Mechanism of action:
The nitro group of metronidazole is able to
serve as an electron acceptor, forming
reduced cytotoxic compounds that bind to
proteins and DNA, resulting in cell death.
Pharmacokinetics:
• Completely ,rapidly absorbed / orally
• Distributes well to body tissues & fluids.
• Therapeutic levels can be found in vaginal ,
seminal fluids, saliva, breast milk, and CSF .
• Metabolism by hepatic oxidation
• Accumulates in patients with severe hepatic
disease.
Tinidazole:
• Is a second-generation nitroimidazole
• Is similar to metronidazole in spectrum of
activity, absorption, adverse effects, and drug
interactions.
• Tinidazole is as effective as metronidazole,
with a shorter course of treatment
Luminal amebicides
• After treatment of invasive intestinal or
extraintestinal amebic disease is complete
• Luminal drugs should be administered for
treatment of the asymptomatic colonization
state.
• Iodoquinol
• Paromomycin
• Diloxanide furoate
Iodoquinol:
• The mechanism of action of iodoquinol against
trophozoites is unknown.
Paramomycin
• An aminoglycoside antibiotic
• Is directly amebicidal action
• Act by reducing the population of intestinal flora.
Diloxanide furoate
• In the gut, it split into diloxanide and furoic acid
• about 90% of the diloxanide is rapidly absorbed
and then conjugated to form the glucuronide,
which is excreted in the urine.
• The unabsorbed diloxanide is the active
antiamebic substance.
• The mechanism of action of diloxanide furoate is
unknown.
• Diloxanide furoate is the drug of choice for
asymptomatic luminal infections.
Systemic amebicides
are useful for treating liver abscesses and
intestinal wall infections
Chloroquine
Emetine and dehydroemetine
Chloroquine:
• Is used in combination with metronidazole
and diloxanide furoate
Emetine and dehydroemetine:
• They inhibit protein synthesis by blocking
chain elongation.
Chemotherapy of Malaria
• Malaria is an acute infectious disease
• Plasmodium falciparum is the most dangerous species,
causing an acute, rapidly fulminating disease
• That is characterized by persistent high fever, orthostatic
hypotension, and massive erythrocytosis (an abnormal
elevation in the number of red blood cells accompanied
by swollen, reddish limbs).
• P. falciparum infection can lead to capillary obstruction
and death if treatment is not instituted promptly.
Blood Schizonticide
1. Chloroquine
2. Mefloquine
3. Quinine
4. Pyrimethamine
5. Artemisinin
Tissue Schizonticide
Primaquine
Drug
Uses
MOA
Side effects
high dose:
Blood
Schizonticide
Prophylaxis & treat
Accumulates in the food vacuole
1. Chloroquine in area non resistant of plasmodia , prevents
P Falciparum ,
polymerization of hemoglobin
P vivax ,
P Ovale
Retinal damage,
auditory
impairment
2. Mefloquine
Prophylaxis & treat
Damage the parasite membrane
in area with
resistant P Falciparu
NV ,
hallucination
3. Quinine
Treatment of
multidrug- resistant
Malaria
Complexes with double stranded
DNA to prevent strand
separation
Cinchonsim,
hemolysis in
G6PD,
Fetotoxic
4.
Prophylaxis and
treatment of
multidrug- resistant
Inhibit dihydrofolate reductase
Treatment of
multidrug- resistant
Metabolite in food vacuole of
parasite forming toxic free
radicals
Pyrimethamine
5. Artemisinin
safe
Drug
Uses
MOA
Side effects
Eradicate of liver
stage P vivax,
P Ovale
As cellular oxidants
hemolysis in
G6PD
Tissue
Schizonticide
Primaquine
Action of chloroquine on the formation of
hemozoin by Plasmodium species.
Primaquine side effect:
drug-induced hemolytic anemia in patients with
genetically low levels of glucose-6-phosphate
dehydrogenase
Chemotherapy of Toxoplasmosis:
• Toxoplasma gondii, is transmitted to humans when they
consume raw or inadequately cooked infected meat.
• An infected pregnant woman can transmit the organism
to her fetus.
• Cats are the only animals that shed oocysts, which can
infect other animals as well as humans.
• The treatment of choice is a combination of
sulfadiazine and pyrimethamine.
• Leucovorin is administered to protect against folate
deficiency.
Chemotherapy of Leishmaniasis:
There are three types of leishmaniasis:
• Cutaneous,
• Mucocutaneous,
• Visceral.
[ The visceral type (liver , spleen), the parasite
is in the bloodstream and can cause very
serious problems.]
• Leishmaniasis is transmitted from animals to
humans by the bite of infected sandflies.
• The diagnosis by demonstrating the parasite
in biopsy material and skin lesions.
Treatment:
• Sodium stibogluconate used in the treatment of
leishmaniasis, with pentamidine and
amphotericin B as backup agents
Sodium stibogluconate
• Inhibition of glycolysis in the parasite at the
phosphofructokinase reaction.
• not absorbed orally, administered parenterally
Chemotherapy of Trypanosomiasis
• African sleeping sickness and
• American sleeping sickness,
two chronic and fatal diseases
A. Melarsoprol
• The drug reacts with sulfhydryl groups of
various substances, including enzymes in both
the organism and host.
• The parasite’s enzymes may be more sensitive
than those of host.
• is the agent of choice in the treatment of T.
brucei which rapidly invades the CNS
B. Pentamidine / T. Brucei
• The drug binds to the parasite’s DNA
interferes with its synthesis of RNA
C. Nifurtimox
• use only in the treatment of acute T. cruzi
infections
D. Suramin
• used in the early treatment and the
prophylaxis of African trypanosomiasis.