ANTIPROTOZOAL DRUGS.ppt

ANTIPROTOZOAL

1. ANTIHELMINTHIC AND
ANTIPROTOZOAL DRUGS

2. •Antihelminticsaredrugsthateitherkill
(vermicide)orexpel(vermifuge)infesting
helminths.
•Nematodes,trematodes,andcestodesarethree
majorgroupsofhelminthes(worms)thatinfect
humans.
•Nematodesareelongatedroundwormsthat
possessacompletedigestivesystem.They
causeinfectionsoftheintestineaswellasthe
bloodandtissues.
•Weuse:mebendazole,albendazole,pyrantel,
levamisol,piperazine.

4. Mebendazole
•Uses:whipworms(Trichuristrichiura),pinworms
(Enterobiusvermicularis),hookworms(Necator
americanusandAncylostomaduodenale),and
roundworms(Ascarislumbricoides);
inhighdoses:extraintestinalhelminthiasis
(trichinellosisandechinococcosis)
•Itinhibitstheassemblyofthemicrotubulesand
glucoseutilizationinhelminthesandparalysesthem.
ItkillsovaandlarvaeofAscaris.
•Absorptionfromintestines–10-15%
•Adverseeffects:abdominalpain,diarrhea,
headache,allergicreactions

5. Albendazole
Uses: ascariasis, hookworms and enterobiasis
(a single dose) , toxocariasis, filariasis,
cysticercosis, echinococcosis (long-term
therapy).
It is absorbed from GIT, metabolized in the
liver.
Adverse effects: headache, diarrhea, dizziness,
leucopenia, skin rashes, abdominal pain,
vomiting.

6. Levamisole
Uses:asingledose–ascariasis,lesseffective
–ankylostomiasis,strongyloidiasis,filariasis.
Mechanism:stimulationofganglia,drug-
inducedparalysisofhelminthesdueto
depolarizationoftheirmuscles,inhibitionof
fumaratereductaseandmetabolism.
Adverseeffects:abdominalpain,diarrhea,
nausea

8. •PyrantelisactiveagainstAscaris,Enterobius,
Ancylostoma,Necator,Strongyloides
•Mechanism:activationofnicotiniccholinergic
receptorsintheworms→persistent
depolarization→ slowlydeveloping
contractureandspasticparalysis.
•AbsorptionfromGIT–10-15%.
•Adverseeffects:nausea,vomiting,abdominal
pain,headacheanddizziness

9. Diethylcarbamazine citrate is
microfilaricidal.Ithasahighlyselectiveeffect
onmicrofilariaeandagainstadultworms.
Itisrapidlyabsorbedfollowingoral
administrationwithmealsandisexcreted
mainlyintheurine.
Adverseeffectsmayincludefever,nausea,
vomiting,arthralgia,andheadache.

10. Niclosamide
•Uses:Taeniasaginata,Diphyllobothriumlatum
andHymenolepisnana.
•Itinhibitsthemitochondrialphosphorylationof
adenosinediphosphate(ADP).Anaerobic
metabolismmayalsobeinhibited.
•IncasesofT.solium,digestionofthedead
segmentscanbehazardous,becausetheova
releasedfromthemmaydevelopintolarvaeinthe
intestine,penetrateitswallandcausevisceral
cysticercosis.
•ItisminimallyabsorbedfromGIT.
•Adverseeffects:dyspepsia,allergicreactions.

12. Praziquantel
Uses:allformsofschistosomiasis,other
trematodeinfections,cestodeinfectionssuchas
taeniasis,cysticercosis(causedbyTaeniasolium
larvae)
Mechanism:leakageofintracellularcalciumfrom
themembranes→contractureandparalysis.
Itisrapidlyabsorbedafteroraladministrationand
distributesintothecerebrospinalfluid(CSF).Itis
extensivelymetabolized,andtheinactive
metabolitesareexcretedprimarilyintheurine.
Adverseeffects:dizziness,malaise,headache

13. Antiprotozoal drugs are used for the treatment
and prophylaxis of:
Malaria
Amebiasis
Giardiasis (Metronidazole, furazolidone)
Trixomoniasis (Metronidazole, furazolidone,
Diiodohydroxyquin rect.)

15. Toxoplasmosis (pyrimethamine,
sulfadimidine)
Balantidiasis (tetracyclines, monomycin,
quiniofone)
Leishmaniasis (solusurmine,
stibogluconate, amphotericin B,
paromomycin)
Trypanosomiasis (melarsoprol,
primaquine, suramin)

16. Antiamoebicdrugs-drugs useful in infection
caused by the anaerobic protozoa Entamoeba
histolytica.

17. CLASSIFICATION
1. Tissue amoebicides
For both intestinal and extraintestinal amoebiasis:
Nitroimidazoles: Metronidazole, Tinidazole,
Ornidazole
For extraintestinal amoebiasis only: Chloroquine
2. Luminal amoebicides: Tetracyclines

18. •Nitroimidazoles(Metronidazole)is used for the
treatment of infections caused by:
•Entamoeba histolytica,
•Giardia lamblia,
•Trichomonas vaginalis,
•anaerobic cocci, and anaerobic gram-negative
bacilli (Bacteroides species),
•for the treatment of pseudomembranous colitis
caused by the anaerobic, gram-positive bacillus
Clostridium difficile.

20. •ThenitrogroupofNitroimidazolesisableto
serveasanelectronacceptor,formingreduced
cytotoxiccompoundsthatbindtoproteinsand
DNA.Thedrugsdisruptmetabolismandcause
deathofmicroorganisms.
•TheyareabsorbedwellfromGIT,distributewell
throughoutbodytissuesandfluids.Therapeutic
levelscanbefoundinvaginalandseminalfluids,
saliva,breastmilk,andcerebrospinalfluid(CSF).
•Tinidazoleandornidazolearewellabsorbedfrom
GIT,accumulatedintheplasmainhigher
concentrationsthanMetronidazoleandprovide
longereffectthanit.

21. Adverse effects:
nausea, vomiting, epigastric distress, and
abdominal cramps, an unpleasant,
metallic taste,
oral moniliasis (yeast infection of the
mouth),
neurotoxicity (dizziness, vertigo, and
numbness or paresthesia),
a disulfiram-like reaction (if taken with
alcohol).

22. •Malariaisoneofthemostcommondiseases
worldwideandaleadingcauseofdeath.Plasmodium
speciesthatinfecthumans(Pfalciparum,Pmalariae,
Povale,Pvivax)undergoaprimarydevelopmental
stageintheliverandthenparasitizeerythrocytes.P
falciparumandPmalariaehaveonly1cycleofliver
cellinvasion.Theotherspecieshaveadormant
hepaticstageresponsibleforrecurrentinfectionsand
relapses.Primarytissueschizonticides(eg,
primaquine)killschizontsintheliver,whereas
bloodschizonticides(eg,chloroquine,quinine)kill
theseparasiticformsonlyintheerythrocyte.
Sporonticides(proguanil,pyrimethamine)prevent
sporogonyandmultiplicationinthemosquito.

23. DRUGS FOR MALARIA

24. Principals of antimalarialdrugs use
1.Individualchemoprophylaxis:preventionofthe
developmentofmalariainmenduringthetime
ofresidencyinaareawhichhasahighriskof
malaria.Wecanusedrugsinfluencingon
preerythrocyticformsorhematoshizotropic
drugs(pyrimethamine,chloroquin)
2.Thetreatment:oraladministrationof
hematoshizotropicdrugs,whichinfluence
erythrocyticformsofplasmodia.Thesedrugsare
usedtocuretheacuteattacksofM.

25. 3.Preventionofdelayedrelapses:administration
ofdrugswhichhavetropismtowards
paraerythrocyticforms(primaquine).
4.Socialchemoprophylaxis:preventionofthe
transmissionoftheinfectionbyasickperson.
Weusegametotropicdrugs(primaquine,
pyrimethamine).

27. •Chinine (Quinine) complexes with
doublestrandedDNAandpreventsstrand
separation,blocksDNAreplicationand
transcriptiontoRNA.Itissolelyablood
schizonticide.
•Itisrapidlyabsorbedorallyandismetabolized
beforerenalexcretion.Intravenousadministration
ofquinineispossibleinsevereinfections.
•Itisusedinthetreatmentofsevereor
complicatedfalciparummalaria.
•Adverseeffects:cinchonism(gastrointestinal
distress,headache,vertigo,blurredvisionand
tinnitus).

28. •Chloroquineisrapidlyabsorbedwhengiven
orally,iswidelydistributedtotissues.
•Itaccumulatesinthefoodvacuoleofplasmodia
andpreventspolymerizationofthehemoglobin
breakdownproducthemeintohemozoin.
Intracellularaccumulationofhemeistoxictothe
parasite.
•Itisthedrugofchoiceforacuteattacksofmalaria
andforchemoprophylaxis.
•Sideeffects:gastrointestinalirritation,skinrash,
andheadaches;peripheralneuropathies,
myocardialdepression,retinaldamage,auditory
impairment,andtoxicpsychosis

29. •SulfonamidesactasantimetabolitesofPABAand
blockfolicacidsynthesisbyinhibiting
dihydropteroatesynthase.
•Pyrimethamineisaselectiveinhibitorof
protozoandihydrofolatereductases.The
combinationhassynergisticantimalarialeffects
(blockadeof2stepsinfolicacidsynthesis).
•The antifols are blood schizonticides that act
mainly against P falciparum.
•Adverse effects: skin rashes, gastrointestinal
distress, hemolysis, kidney damage.

30. •Primaquineisasynthetic8-aminoquinoline.It
isusedorally.
•Itformsquinoline-quinonemetabolites,which
areelectron-transferringredoxcompoundsthat
actascellularoxidants.Thedrugisatissue
schizonticideandalsolimitsmalaria
transmissionbyactingasagametocide.
•Uses:EradicationofliverstagesofPvivaxandP
ovale,primaryprevention
•Adverse effects: GI distress,
methemoglobinemia,hemolysisinG6PD
deficiency

31. Nitrofuranderivatives
Nitrofural: antiseptic
Furazolidon: intestinal infections, giardiasis,
Trichomonascolpitis
Nitrofurantoin(Furadonin), Furazidin
(Furagin): uroinfection.
Spectrum:
Gram-negative bacteria: Escherichia coli, Shigella,
Salmonella, Klebsiella
Cocci(entero-, staphylo-,strepto-, meningo,
gonorrhea)
Vibriocholerae, Giardia, Trichomonas

32. Mechanism:
The restoration of the nitro group to the amino
group under the influence of reductase
microbial cells.
The formation of complexes with nucleic acids,
Disruption of the respiratory chain of
microorganisms.
Increase in the body's resistance to infections.
The decline in the production of toxins.
Type of action: bacteriostatic or bactericidal

33. Side effects
Dyspeptic disorders: nausea, vomiting,
diarrhea;
Cholestasis; disorders of liver function;
Allergic reaction;
Headache, dizziness;
Hemolytic anemia,
Methemoglobinemia in children
up to a year;
Arterial hypertension

34. •Melarsoprolisusedforthetreatmentof
trypanosomalinfections.Thedrugreactswith
sulfhydrylgroupsofvarioussubstances,including
enzymesinboththeorganismandhost.
•ItisadministeredbyslowIVinjectionandhas
irritatingeffect.Adequatetrypanocidal
concentrationsappearintheCSF.Thedrughasa
veryshorthalf-lifeandisrapidlyexcretedinurine.
•Adverseeffects:CNStoxicity,peripheral
neuropathy,hypertension,albuminuria;allergy,
febrilereactions;hemolyticanemiainpatients
withglucose-6-phosphatedehydrogenase
deficiency.

36. Leishmania,transmittedbyflesh-eatingflies,
causevariousdiseasesrangingfromor
mucocutaneouslesionstosplenicandhepatic
enlargementwithfever.

37. •SolusurminumandSodiumstibogluconate
(pentavalentantimony)killstheparasiteby
inhibitionofglycolysisoreffectsonnucleic
acidmetabolism.
•Stibogluconatemustbeadministered
parenterallyandispotentiallycardiotoxic
(QTprolongation).Alternativeagents
includefluconazoleormetronidazole(for
cutaneouslesions),andamphotericin(for
mucocutaneousleishmaniasis).

38. Literature
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