1 ANTI PROTOZOAL DRUGS. INTRODUCTION They are eukaryotes and have metabolic processes closer to those of human host. Protozoal infections are common among.
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1 ANTI PROTOZOAL DRUGS
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INTRODUCTION They are eukaryotes and have metabolic processes
closer to those of human host. Protozoal infections are common
among people in underdeveloped tropical and subtropical countries
where sanitary conditions, hygienic practices and control of the
vectors of transmission are inadequate. 2
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Are less easily treated than bacterial infections Many of the
antiprotozoal drugs cause serious toxic effects in the host,
particularly cells showing high metabolic activity, e.g., neuronal,
renal tubular, intestinal and bone marrow stem cells 3
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Overview of antiprotozoal drugs Chemotherapy for amebiasis
Chemotherapy for malaria Chemotherapy for trypanosomiasis
Chemotherapy for leishmaniasis Chemotherapy for toxoplasmosis
Chemotherapy for giardiasis 4
8 Transmitted through female anopheles mosquito. Plasmodium
falciparum is the most dangerous. High fever, erythrocytosis,
capillary obstruction & death.
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9
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10 Antimalarial agent efficacy species life-cycle
stage-dependencies Parasitic Life Cycle Sporozoites Exoerythrocytic
stage Forming tissues schizonts Merozoites Gametocytes
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11 Tissue schizonticides PRIMAQUINE SITE : EXO ERYTHROCYTIC
STAGE ALSO : GAMETOCYTES NOT ERYTHROCYTIC SCHIZONTS ORAL ROUTE,
RENAL EXCRETION SE : GIT, ANEMIA IN G6PD def pt AGRANULOCYTOSIS IN
Pt LUPUS USE : RADICAL CURE (P. vivax & ovale)
13 CHLOROQUINE MECH : Inhibits polymerization to hemozoin FORMS
SOL. HEME in food vacuole Leading to oxidative damage to the
membranes lysis of both the parasite and RBC
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15 Most widely used drug DOC : ERYTHROCYTIC FALCI. MALARIA (NON
RESISTANT ) Other uses: It is used also in extra intestinal
amebiasis, rheumatoid arthritis, discoid lupus
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16 ORAL, PARENTERAL MET : LIVER EXCRETION : RENAL SE : GIT,
pruritus Blurring of vision, HEADACHE NAIL BED DISCOLORATION
Prolongs QT-interval cos of its quinidine like effect INTERACTIONS
: GOLD compounds, PHENYLBUTAZONE CI : PSORIASIS, PORPHYRIA
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17 Quinine & Quinidine Highly effective blood
schizonticides No effect on Sporozoites or liver stages of any
parasite. MOA: similar to chloroquine Use : reserved for severe
infestations and strains resistant to other drugs
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18 SE Gastrointestinal Effects: Cinchonism: slight visual
disturbances mild tinnitus dizziness headache nausea rapid IV
infusion: hypotension, seizures, ventricular fibrillation and
prolongation of QT-interval.
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Drug interactions: Potentiation of neuromuscular blocking
agents Elevation of digoxin levels if taken concurrently with
quinine Quinine absorption is decreased when drug is taken with
aluminum-containing antacids. CI: is fetotoxic 19
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20 Mefloquine Mech : unknown Use : Resistant cases of P. falci.
SE: nausea, dizziness, hallucinations
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pharmacokinetics Half life : long (17 days) Well absorbed after
oral administration Excretion: feces CI: with quinine and beta-
blockers due to development of cardiac arrest 21
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22 Blood schizonticide, sporonticide PYRIMETHAMINE MOA:INHIBITS
DIHYDRO FOLATE REDUCTASE Pyrimethamine alone: used against
P.falciparum IN COMBINATION with sulfonamides : against P.malaria
&toxoplasmosis OTHER USE : TOXOPLASMOSIS
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Other blood schizonticides Artemisinin MOA: production of free
radicals within the plasmodium food vacuole Uses: treatment of
severe, multidrug-resistant P.falciparum 23
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Route: oral, rectal and intravenous Metabolism: extensively in
the liver Excretion: in bile Adverse effects: nausea, vomiting,
diarrhea, neurotoxicity and prolongation of QT-interval 24
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25 PROPHYLAXIS CHLOROQUINE SENSITIVE CHLOROQUINE CHL. RESISTANT
MEFLOQUINE, Artemisinin In pregnancy: chloroquine OR
mefloquine
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26 AMOEBIASIS Caused by E. histolytica Disease can be acute or
chronic with pts showing varying degrees of illness from no
symptoms(carriers) to mild diarrhea to fulminant dysentry
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Drugs for amebiasis Luminal amebiasis Systemic amebiasis Mixed
amebiasis 28
30 SYSTEMIC AMEBICIDES EMETINE DEHYDRO EMETINE MOA: inhibit
elongation step of protein synthesis ROUTE : IM SE : RASHES, PAIN,
MUSCULAR WEAKNESS, CARDIOTOXICITY.
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CHLOROQUINE combination with metronidazole and diloxanide
furoate LIVER ABSCESS 31
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32 MIXED(luminal and systemic) METRONIDAZOLE MOA: The nitro grp
serves as an electron acceptor forming reduced cytotoxic compds
that binds proteins and DNA, resulting in cell death Administered
with a luminal amebicide with a cure rate of >90%
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SE : MC GIT METALLIC TASTE, ORAL CANDIDIASIS RARE : DIZZINESS,
VERTIGO Avoid alcohol disulfiram like effect Other uses:
trichomonia, giardiasis, pseudomembranous colitis 33
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Metabolized by cyt-P450 system. Inducers of cytP450 increases
its rate of metabolism Inhibitors of cytP450 prolongs its half-life
Excretion: urine 34
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35 TRYPANOSOMIASIS AFRICANSLEEPING SICKNESS -TRYPANOSOMA BRUCEI
GAMBIENCE & RODIENSE. Transmitted by bite of TSE TSE FLY
AMERICAN SS -CHAGAS TRYPANOSOMA CRUZI
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African sleeping sickness Trypanosoma brucei gambiense and
trypanosoma brucei rhodiense, initially live and grow in the blood
but can invade the CNS causing inflammation of the brain and spinal
cord that produces the characteristic lethargy and, eventually
continuous sleep and death. 36
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37 MELARSOPROL ---treatment of trypanosomal infections usually
in the late stage with CNS involvement MOA: REACTS WITH THE
SULFHYDRYL GROUPS. SLOW IV HIGHLY IRRITATING ENTERS THE CSF QUICKLY
DOCTREPANOSOMAL MENINGOENCEPHALITIS caused by T.brucei rhodesiense
which rapidly invades the CNS SECNS TOXICITY, HYPERSENSITIVITY,
HEMOLYTIC ANEMIA G 6 PD DEFICIENCY.
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38 PENTAMIDINE Effective against T.brucei gambiense for the
treatment and prevention of the organisms hematologic stage. MOA:
not known but binds to the parasites DNA interfering with the
synthesis of DNA, RNA &protein of the parasite. Adverse effect:
hypotension, dizziness, rash and toxic to pancreas
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Other uses: Rx AND PROPHYLAXIS BLASTOMYCOSIS DOCPCP not
responding to TMP-SMX Alternative for treatmnent ofLEISHMANIASIS.
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SURAMIN USED FOR THE PROHYLAXIS OF AFRICAN TRYPANOSOMIASIS MOA:
inhibits many enzymes and those involved in energy metabolism
(glycerol phosphate dehydrogenase) 40
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Route: must be IV SE: Vomiting, nausea, shock, loss of
consciousness, urticaria and neurologic problems(paresthesia,
photophobia, palpebral edema), albuminuria 41
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NIFURTIMOX FOR acute Rx CHAGAS MOA: undergoes reduction,
generating free radicals which are toxic to T-cruzi SE:
hypersensitivity(dermatitis, icterus), GIT disturbances, peripheral
neuropathy 42
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43 LEISHMANIASIS-CUTANEOUS, MUCOCUTANEOUS,& VISCERAL SODIUM
STIBOGLUCONATE (I.V,) INHIBITION OF GLYCOLYSIS --URINE EXCRETION
GIARDIASIS BINUCLEATE WITH 4 FLAGELLA DOC--METRONIDAZOLE CI:
PREG,
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44 TOXOPLASMOSIS ONE OF THE MOST COMMON INFECTIONS CAUSED BY
PROTOZOAN T.GONDI TRANSMITTED BY CONSUMING RAW, UNCOOKED INFECTED
MEAT. DOC-PYRIMETHAMINE LEUCOVORIN GIVEN TO PREVENT FOLATE
DEFICIENCY