anti-protozoal drugs
DESCRIPTION
Anti-protozoal Drugs. Protozoa are eukaryotes and unicellular organisms. Most of the protozoal infections are due to unhygienic conditions. Less easily treated than bacterial infections and antiprotozoal drugs are more toxic. - PowerPoint PPT PresentationTRANSCRIPT
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Anti-protozoal Drugs
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Protozoa are eukaryotes and unicellular
organisms.
Most of the protozoal infections are due to
unhygienic conditions.
Less easily treated than bacterial infections and
antiprotozoal drugs are more toxic.
Protzoal infections may be one or more infection results
from the following:
Amoebiasis, trypanosomiasis, girdiasis, leishmaniasis,
trichomoniasis, Malaria, toxoplasmosis.
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Anti - Ameobic Drugs
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Is due to infection with E histolytica
• Asymptomatic intestinal infection ( 90%)
• Mild to moderate colitis
• Severe intestinal infection (dysentery)
• Ameboma• Liver abscess• Other extraintestinal infections.
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Luminal amebicides: for treating intestinal infections.
( Diloxanide Furoate, Iodoquinol, Paromomycin,
Metronidazole.)
Tissue amebicides: used to destroy amoebae that have
invaded tissue, rapidly absorbed into the bloodstream and
transported to the site of infection.( Metronidazole, Tinidazole).
For amebic liver abscess: .( Metronidazole,
Tinidazole, Diloxanide Furoate).
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Metronidazole is an antibiotic, amebicide, and antiprotozoal
Effectively eradicates intestinal and extraintestinal tissue
infections. (drug of choice in the treatment of
extraluminal amebiasis)
It kills trophozoites but not cysts of E histolytica
Tinidazole: available 2004, Similar activity and a better
toxicity ,Simpler dosing regimens ( longer t½)
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MOA: MOA: It is a pro drug It is reduced by anaerobic
metabolism, (in anaerobic bacteria and sensitive
protozoans).
The reduced product is cytotoxic, it targets DNA & other The reduced product is cytotoxic, it targets DNA & other
proteins, resulting in cell death. proteins, resulting in cell death.
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Clinical use: Amoebiasis, Giardiasis, Trichomoniasis, Anaerobic infections,
Pseudomembranous enterocolitis, H. pylori – induced peptic
ulcer, Oral infections
A/EA/E: GI disturbance, Dry mouth, Metallic taste, headache, dizziness, dark urine.
metronidazole has a disulfiram-like effect, so that N/V,
flushing & tachycardia can occur if alcohol is ingested during
therapy.
I.V.: seizures or peripheral neuropath
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Drug interactionsDrug interactions
- Potentiate Anticoagulant effect of Warfarin.- Potentiate Anticoagulant effect of Warfarin.
- Metabolism of Metronidazole induced by - Metabolism of Metronidazole induced by Phenytoin & Phenobarbitone Phenytoin & Phenobarbitone
- Cimetidine may inhibit it.- Cimetidine may inhibit it.
Contra-indications :First trimester of pregnancyChronic alcoholism
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Effective against tissue trophozoites of E histolytica, (not used
nowadays because of high systemic toxicity )
Dehydroemetine is preferred: better toxicity profile.
Acts by inhibiting protein synthesis
used SC or IM.
A/E:
Injection site : pain, tenderness, and sterile abscesses. Cardiac side effects like myocarditis, tachycardia, Hypotension,
Cardiac arrhythmias Stiffness of muscles
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Diloxanide furoate
Effective luminal amebicides ,
Used with metronidazole to treat serious
intestinal and extraintestinal infections, by
unknown mechanism.
A/E:
GI disturbance, Headache, Rash, Pruritus.
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Used against Giardia lamblia
The active metabolite, inhibits the pyruvate:
ferredoxin oxidoreductase pathway. (essential to
anaerobic energy metabolism.)
Appears to have activity against metronidazole-
resistant protozoal strains
Is well tolerated {Greenish tint to urine}
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Is an aminoglycoside antibiotic
Not significantly absorbed from the GIT. (only as a
luminal amebicide).
MOA: Inhibits protein synthesis by binding to 30S
ribosomal RNA.
A/E: GI disturbance, ototoxicity, nephrotoxicity
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OTHER ANTIPROTOZOAL DRUGS
Trypanosomiasis
Pentamidine
Suramin
Melarsoprol
Nifurtimox
Leshmaniasis :
Sodium
stibogluconate
Pentamidine
Amphotericin Miltefosine
Benznidazole
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Pentamidine Active against trypanosomatid protozoans but toxicity is
significant.
Parentrally or inhalation
Only trace amounts appear in the CNS, ( not effective
against CNS african trypanosomiasis.)
The mechanism of action may interfere with synthesis of
RNA, DNA and proteins.
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Pneumocystosis
African Trypanosomiasis (Sleeping Sickness)
Leishmaniasis
A/E: Highly toxic
Rapid IV : Severe Hypotension, Tachycardia, Dizziness.
IM : Pain at the injection site, Sterile abscesses.
Inhaled : Cough, Dyspnea, Bronchospasm.
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Introduced in the 1920s.
Is the first-line therapy for early hemolymphatic East African
trypanosomiasis .
Does not enter the CNS .
It acts by inhibiting enzymes of energy metabolism
• A/E: common.
Immediate reactions : Fatigue, N/V
Rarely: Seizures, Shock.
Later reactions :Paresthesias, Renal Abnormalities, Hemolytic Anemia.
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Used for American trypanosomiasis
(Chagas' disease).
It acts by generating toxic radicals
A/E: GI disturbance, fever, rash,
neuropathies, and seizures.
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First-line agents for cutaneous and visceral leishmaniasis
IV,IM
MOA: It acts by inhibiting glycolysis and fatty
acid oxidation
A/E: Few but increases over the course of therapy.
GI symptoms, fever, headache, myalgias, arthralgias,rash.
IM: painful and lead to sterile abscesses.
arrhythmias & nephrotoxicity
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Four species of plasmodium typically cause human malaria:
Plasmodium falciparum,
P vivax, P malariae, P ovale. P knowlesi, is primarily
a pathogen of monkeys
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An anopheline mosquito inoculates plasmodium
sporozoites to initiate human infection. Circulating
sporozoites rapidly invade liver cells, and
exoerythrocytic stage tissue schizonts mature in
the liver. Merozoites are subsequently released
from the liver and invade erythrocytes.
Only erythrocytic parasites cause clinical illness.
Sexual stage gametocytes also develop in
erythrocytes before being taken up by mosquitoes,
where they develop into infective sporozoites.
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Treatment of malaria
• Type of malaria
• Knowledge of regional
resistance
• Severity of illness
(oral vs. intravenous)
• Age of patient
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Tissue schizonticides: eliminate developing or
dormant liver forms;
Blood schizonticides : act on erythrocytic
parasites;
Gametocides : kill sexual stages and prevent
transmission to mosquitoes.
Radical cure: eliminate both hepatic and
erythrocytic stages. Not available.
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For treatment and chemoprophylaxis since the
1940s,(drug resistance).
Oral use
Antimalarial Action:
Highly effective blood schizonticide.
Moderately effective against gametocytes of
P vivax, P ovale, and P malariae but not against
those of P falciparum.
Not active against liver stage parasites.
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Acts by :
concentrating in parasite food
vacuoles, preventing the
biocrystallization of the hemoglobin
breakdown product, heme, into
hemozoin, and thus eliciting parasite
toxicity due to the buildup of free heme.
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Usually very well tolerated
Pruritus, GI disturbance, headache, malaise, blurring of
vision, and urticaria
Rare : hemolysis in G6PD-deficient persons, impaired
hearing, agranulocytosis, alopecia, bleaching of hair,
hypotension,
Large IM injections or rapid IV infusions : severe
hypotension and respiratory and cardiac arrest.
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•First-line therapies for falciparum malaria.
•Oral administration.
•Higher plasma levels and half-life in infected persons
than in healthy controls, but toxicity is not increased,
apparently because of increased protein binding.
•MOA: is unknown, it may act like chloroquine
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Quinine:
Is rapid-acting, highly effective blood
schizonticide against the 4 species of human
malaria parasites.
Gametocidal against p vivax and p ovale but
not p falciparum
Not active against liver stage parasites.
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Quinidine : parenteral treatment of
severe falciparum malaria. continuous IV
infusion;
cardiac monitoring.
change to an effective oral agent as soon
as the patient has improved and can
tolerate oral medications.
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Quinine sulfate : uncomplicated falciparum
malaria
± second drug (most often doxycycline or, in
children, clindamycin) to shorten quinine's
duration of use (usually to 3 days) and limit
toxicity.
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Cinchonism:
Tinnitus,
Headache,
Nausea,
Dizziness,
Flushing,
Visual Disturbances Black water fever
rare severe illness
marked hemolysis ,
hemoglobinuria
Hypersensitivity
reactions
Hypoglycemia
Too-rapid IV infusions
: Severe hypotension
IV Quinidine : ECG
abnormalities.
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Used in chloroquine-resistant strains of P falciparum
and other species.
Is chemically related to quinine.
Can only be given orally because severe local
irritation occurs with parenteral use.
Has strong blood schizonticidal activity against
P falciparum and P vivax,
it is not active against hepatic stages or
gametocytes.
MOA: is unknown.
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GI disturbance, Rash, Dizziness,
Leukocytosis, Thrombocytopenia,
Aminotransferase Elevations
Arrhythmias , bradycardia.
Considered safe in young children and
throughout pregnancy.
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Hepatic stages of all human malaria parasites.
Chemoprophylaxis against all malarial species.
It is the only available agent active against the
dormant stages of p vivax and p ovale.
Gametocidal against the 4 human malaria species.
Acts against erythrocytic stage parasites, but this
activity is too weak to play an important role.
MOA: is unknown.
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Generally well tolerated.
• GI disturbance, Headache
•Leukopenia, Agranulocytosis,
•Cardiac Arrhythmias, Hemolysis
It is never given parenterally because it may induce
marked hypotension.
It should be avoided in pregnancy because the fetus
is relatively G6PD-deficient and thus at risk of
hemolysis.
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For treatment and prevention of malaria.
Only administered orally.
MOA: disrupting mitochondrial electron transport.
It is active against tissue and erythrocytic schizonts,
A/E: GI disturbance, Fever, Rash, Headache
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Pyrimethamine ,Proguanil
•Used in combination regimens, in the treatment and
prevention of malaria.
•Slowly but adequately absorbed from the GIT.
Fansidar, a fixed combination of the sulfonamide
sulfadoxine and pyrimethamine .
Act slowly against erythrocytic forms of susceptible
strains of all human malaria species.
Proguanil also has some activity against hepatic
forms.
Neither drug is adequately gametocidal or effective
against the persistent liver stages of p vivax or p ovale.
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Folate antagonists and sulfonamides ,bacterial protein
synthesis inhibitors
None should be used as single agents because their action
is much slower than that of standard antimalarials.
Tetracycline : erythrocytic schizonts , but not active
against liver stages.
Doxycycline : falciparum malaria in conjunction with
quinine, allowing a shorter and better-tolerated course of that
drug, it has also become a standard chemoprophylactic drug,
Clindamycin , Azithromycin , Fluoroquinolones
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Against erythrocytic (but not other) stages of all four
malaria species.
MOA: unknown.
A/E : GI disturbance, cough, rash, headache, pruritus,
and elevated liver enzymes, dose-related prolongation
of QT and PR intervals.
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Artemisinin: used orally.
Analogs are:
Artesunate (water-soluble; oral, IM, IV and rectally),
Artemether (lipid-soluble; oral, IM, and rectally),
Dihydroartemisinin (water-soluble; oral).
They are very rapidly acting blood schizonticides
against all human malaria parasites, no effect on hepatic
stages.
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