Antihelmintice

7/24/2019 Antihelmintice

1/58

Chimioterapice antiparazitare

Antihelmintice

Antiprotozoarice

AntimalaricePlasmodium sp. AntitrichomonaziceTrichomonas sp.

AntiamoebieneEntamoeba sp.

AntilambliaziceGiardia lamblia

AntitoxoplasmoziceToxoplasma gondii


2/58

ANTIHELMINTICE


3/58

Generaliti asupra helmintiazelor

Rspndire: > din populaia globului

Clasificare

- nematodoze (viermi cilindrici)

- cestodoze

- trematodoze- sindroame de larva migrans

(viermi plai)


4/58

Contaminare:

- ap, alimente infestate

- penetrare dermic

- autoinfestare

- vectori (insecte, molute)

Diagnostic:

- examen coproparazitologic (ou,

larve, viermi aduli)

- eozinofilie crescut

- ponderal, tulb. gastro-

intestinale

- reacii alergice..


5/58

1. Nematodoze

Inciden:

- 1 miliard de cazuri de ascaridioz

- 800 milioane: trichiuriaz(trichocefaloza)- 200 milioane: oxiuroz(enterobioza)

Clasificare (criteriul localizrii)

a. Intestinale

b. Tisulare


6/58

Nematodoze intestinale

- Ascaridioza/Ascaris lumbricoides

- Enterobioza (oxiuroza)/Enterobius vermicularis- Trichocefaloza/Trichiuris trichiura

- Anchilostomiaza/Ancylostoma duodenale, Necator americanus

- Strongiloidoza/Strongiloides stercoralis


7/58

Ascaris lumbricoides

F: 20-35 cm, 200.000. ou/ zi
http://www.curezone.com/image_gallery/parasites/ascaris/default.asp?i=4&n=24


8/58

Ascaris lumbricoides - ciclul evolutiv


9/58

Enterobius vermicularis

Oxiur la

colonoscopie
http://desciclo.pedia.ws/wiki/Ficheiro:CuBichado.jpg


10/58

Enterobius

vermicularis

Ciclul evolutiv


11/58

Nematodoze tisulare

Trichineloza /Trichinella spiralis

Filarioze

- Filarioza limfatic/Wurchereria bancrofti

- Loiaza/Loa-loa

- Onchocercoza/Onchocerca volvulus


12/58

Trichinella spiralis

Trichinellan muchiul striat

Stadiul intestinal
http://images.google.ro/imgres?imgurl=http://web.quick.cz/veterina-ko/myslivci/mysl_soubory/trichinela_1.jpg&imgrefurl=http://web.quick.cz/veterina-ko/myslivci/mysl_soubory/trichina_2.html&h=945&w=633&sz=186&hl=ro&start=2&tbnid=ZZ-A4djSRu94YM:&tbnh=148&tbnw=99&prev=/images%3Fq%3DTrichinela%2Bspiralis%26svnum%3D10%26hl%3Dro%26lr%3Dlang_fr%7Clang_rohttp://images.google.ro/imgres?imgurl=http://www.infovek.sk/predmety/biologia/metodicke/hlistovce/obrazky/mrla.jpg&imgrefurl=http://www.infovek.sk/predmety/biologia/metodicke/hlistovce/index.php&h=203&w=300&sz=12&hl=ro&start=1&tbnid=eJMvTYQudHakhM:&tbnh=78&tbnw=116&prev=/images%3Fq%3DTrichinela%2Bspiralis%26svnum%3D10%26hl%3Dro%26lr%3Dlang_fr%7Clang_ro


13/58

Trichinella spiralis

Ciclul evolutiv


14/58

Filarioze

Onchocercoza = ,,orbirea de ru,,(Onchocerca volvulus)

Vector: musca

neagrcecitate noduli subcutanai
http://images.google.ro/imgres?imgurl=http://www3.imperial.ac.uk/portal/pls/portallive/docs/1/891900.JPG&imgrefurl=http://www3.imperial.ac.uk/people/m.charalambous/research&h=283&w=203&sz=11&hl=ro&start=20&tbnid=sCOxQ7LmLg6ciM:&tbnh=114&tbnw=82&prev=/images%3Fq%3DOnchocerca%2Bvolvulus%26start%3D18%26gbv%3D2%26ndsp%3D18%26svnum%3D10%26hl%3Dro%26sa%3DNhttp://www.who.int/entity/pbd/blindness/onchocerciasis/en/onchocerca_volvulus.jpg


15/58

Filarioze

Elefantiaza (Wurchereria bancrofti)

Vector: narul


16/58

Filarioze

Loiaza (Loa loa)

Vector: insecte Chrysops

Edeme subcutanate

i localizare ocular


17/58

2. Sindroame de larva migrans

Determinate de migrarea n diferite esuturi i organe a larvelorinfecioase ale unor helmini care sunt parazii naturali ai animalelor

!n organismul uman, larvele nu pot ajunge la stadiul de vierme adultinu i pot continua ciclul evolutiv

- Larva migrans cutanat

- Dermatita cu anghilule


18/58

Larva migrans cutanat
http://images.google.ro/imgres?imgurl=http://www.cfsph.iastate.edu/DiseaseInfo/ImageDB/LV/LV_001.jpg&imgrefurl=http://www.cfsph.iastate.edu/DiseaseInfo/ImageDB/imagesLV.htm&h=425&w=600&sz=118&hl=ro&start=19&tbnid=4EQ8PnCnEUS8mM:&tbnh=96&tbnw=135&prev=/images%3Fq%3DLarva%2Bmigrans%26start%3D18%26gbv%3D2%26ndsp%3D18%26svnum%3D10%26hl%3Dro%26sa%3DN


19/58

Chimioterapice active pe nematode. Clasificare,

reprezentani

1. Derivai ai piperazinei:Dietilcarbamazina

2. Colorani cianici : Pirvinium (embonat)3. Imidazotiazoli: Levamisol (clorhidrat)

4. Benzimidazoli: Mebendazol, Albendazol, Tiabendazol

5. Amidine ciclice: Pirantel (pamoat)

6. Ivermectine: Ivermectinele B1a i B1b


20/58

1. Dietilcarbamazina1-dietilcarbamoil-4-metil-piperazina

Spectru: microfilarii

- Wurchereria bancrofti- Loa-loa

- Onchocerca volvulus


21/58

2. Colorani cianiciPirvinium(embonat)

Spectru: oxiuri, strongiloizi Mecanism: interfer cu absorbia glucidelor VERMIGAL- suspensie 1% - oral

De ales la gravide (non-absorbie gastric)


22/58

3. Imidazotiazoli: LevamisolClorhidrat de (-)-2,3,5,6-tetrahidro-6-fenil-imidazo[2,1-b]-tiazol

Spectru : ascarizi, ancylostomeMecanism: inhibiie neuromuscularprin activarea receptorilor N

Alte indicaii:- boli autoimune- adjuvant n cancere de colon rezectate- carcinom pulmonar rezectat

DECARIS- cp. 50 mg, 150 mg.- 1cp.d.u, se repet la 7 zile


23/58

Sinteza levamisolului

Levamisolacid D (-) camforosulfonic

Tetramisol (+-)

. (CH3CO)2O

. SOCl2

2

1

OH

C6H5H

S

N

NH

OC6H5

S

N

NH

HS

H2NNH

CH2Br

CH2Br

S

N

N

H

C6H5


24/58

4. Benzimidazoli

TIABENDAZOL2-(4'-tiazolil)-benzimidazol

MINTEZOL - susp. uz oral, cp. 500mg

MEBENDAZOL5-benzoil-2-benzimidazolil-carbamatde metil

VERMOX, THELMOX-cp. 100mg

ALBENDAZOL

5-propiltio-2-benzimidazolil-carbamatde metil

ZENTEL-cp. 200mg, susp. oral200mg/5ml, ESKAZOLE

N

N

N

SH

2 4'

HN

NC6H5-OC

NH-CO-OCH3

HN

N

NH-CO-OCH3

CH3CH2CH2S

5

5


25/58

Sinteza tiabendazolului

Tiabendazol

HN

N

N

S

2500

C

APP

X=OH ou

X=NH2

N

S

C

O

XNH2

NH2


26/58

Sinteza carbamat-benzimidazolilor

N

N

NHCOOCH3

R H

Cl-COOCH3

N

N

NH2

R H

NH2

H2N

MeSR

NH2

NH2


27/58

Benzimidazoli. Mecanisme de aciune

inhib polimerizarea tubulinei, protein dimeric prin a crei

polimerizare se formeaz microtubulii

blocheaz recaptarea glucozeila nivelul celulelor intestinale ale

parazitului


28/58

Indicaiile benzimidazolilor

Tiabendazol Indicaii majore: strongiloidoza, scabia

Mebendazol Indicaiamajor: trichocefaloza; util in cazuri de infestaremultipl, inclusiv cu larve de Taenia

Albendazol Spectru larg: nematode, cestode + Giardia intestinalis(copii 2-12 ani)

Contraindicaii: sarcin, afeciuni hepatice


29/58

5. Amidine ciclice: Pirantel (embonat)

Spectru: ascarizi, oxiuri

embonat de 1-metil-1,4,5,6-tetrahidro-2-[trans-2-(2-tienil-vinil)]-pirimidin


30/58

6. Ivermectine

R2=C2H5-Ivermectine B1aR2= CH3-Ivermectine B1b

= amestec de ivermectine B1a iB1b, obinuteprin hidrogenarea legturiiduble22 (23) i demetilarea n 5 a avermecinelor naturale A1a i A1b (obinute dinStreptomyces avermitilis).


31/58

Ivermectinele B1a i B1b

Spectru:- microfilarii-alte nematode: Strongiloides

Studii recente = utilizarea oral nscabie complicat (Sarcoptesscabei) i pediculoz (Pediculuscapitis)

MECTIZAN-cp.3 mg, 6 mg- Ci: alptare, copii < 5 ani- Utilizare larg i n medicinaveterinar(administrare s.c.)
http://www.dermis.net/bilder/CD008/550px/img0038.jpg


32/58

Alegerea chimioterapiei n ascaridioz

Chimioterapic Observaii

Albendazol

Mebendazol

Embonat de pirantel

Levamisol

400mg, d.u.

200mg/zi, 3 zile (100 mg dimineaa a jeun +

100 mg seara la 3 ore dup cin)

11mg/kg

150mg d.u. (adult), 2,5-3 mg/kg(copil).

Se repetla 7 zile

Dozele nu trebuie reinute


33/58

Tratamentul complicaiilor ascaridiozei

Ascaridioza pulmonar - prednison (ai., antialergic)

Ocluzie intestinal - hidratare parenteral, antispastice, aspiraienaso-gastric, administrarea pe tub naso-gastric

de ulei de parafin i piperazin citrat

Ascaridioz biliar - idem ocluzie intestinal + antibiotice pentrusuprainfecia bacterian

Ascaridioz refractar - intervenie chirurgical


34/58

Alegerea chimioterapiei n oxiuroz

Observaii

Elecie

Mebendazol -100 mg, d.u.Albendazol400 mg, d.u.(adult)

-copil >2 ani: 10-14mg/kg

Embonat de pirantel -11mg/kg, d.u.

Se repetla 2 sptmniSe repetla 2 sptmni

Se repetla 2+2 sptmni

Alternativ

Pamoat de pirvinium

Nonabsorbabil, nontoxic-de ales lagravide


35/58

Recomandri n oxiuroz

- Tratament simultan pentru toi membrii familiei sau colectivitii

- Reguli stricte de igien

- Evitarea autoinfectrii (gratajul)

- Aplicarea perianal a unui unguent


36/58

Alegerea chimioterapiei n strongiloidoz

n strongiloidoz, corticoterapia este contraindicat (risc de diseminare ainfeciei, cu prognostic sever)


Tiabendazol

Ivermectine

50mg/kg/zi (max. 3 g/zi), 2-3 zile sau 7-10 zile (nsuprainfecie)

-oral, d.u., 1-2 zile

- elecie i n oncocercozi alte microfilarioze;toleran tiabendazolului


37/58

Alegerea chimioterapiei n trichineloz

Observaii

Albendazol-2x400mg/zi, 14zile

sau

Mebendazol - 3x200-300 mg/zi, 3zile, apoi 3x400-500/zi, 10 zile

La nevoie -corticosteroizi (prednison)

Tratament simptomatic

- miorelaxante

- sedative, reechilibrare

hidroelectrolitic, etc! Anchet epidemiologic obligatorie


38/58

Cestodoze adulte-Taenia solium

-Taenia saginata

-Hymenolepis nana

-Diphyllobothrium latum

Cestodoze larvare

- cisticercoza (T. solium)- echinococoza = boala chistic (T. echinococcus)

- cenuroza (T. multiceps)

Infestare: consum de carne de porcsau vitinsuficientprelucrat termic

3. Cestodoze


39/58

Taenia

Diphyllobothrium latum
http://images.google.ro/imgres?imgurl=http://i.onmeda.de/taenia_saginata.jpg&imgrefurl=http://www.onmeda.de/lexika/krankheitserreger/krankheitserreger_a_z/zestoden_hoehere.html&h=153&w=200&sz=21&hl=ro&start=69&um=1&tbnid=k2eoYmkgIpdxsM:&tbnh=80&tbnw=104&prev=/images%3Fq%3DDiphyllobothrium%2Blatum%26start%3D54%26ndsp%3D18%26svnum%3D10%26um%3D1%26hl%3Dro%26lr%3Dlang_en%257Clang_fr%257Clang_ro%26sa%3DN


40/58

Taenia saginata, solium. Ciclul evolutiv


41/58

Cisticercoz cerebral (T. solium)


42/58

Echinococoza hepatic (chist hidatic)


43/58

Chimioterapice active pe cestode

Salicilianilide: Niclosamid

Piperazino-tetrahidroizochinoline: Praziquantel

Acridine: Mepacrina(vezi antimalarice)

Benzimidazoli (vezi nematodoze)

Fosfonai:Metrifonat(vezi trematodoze)


44/58

Chimioterapice active pe cestode

NICLOSAMID2',5-dicloro-4' nitro-salicilanilida

NICLOSAMID, YOMESAN cp. 500

mg

PRAZIQUANTEL

CESOL-cp.150mg


45/58

Sinteza Niclosamidului

OH

COCl

Cl

Cl

NO2

H2N

+

Cl

Cl

OH

CONH NO2


46/58


47/58

Alegerea chimioterapiei n teniaze(cestodoze intestinale)

Scheme terapeutice Observaii

Elecie

Praziquantel-5-10 mg/kg, d.u., adult i copil

> 2 ani

Alternativ

Niclosamid

2 g/zi, d.u., adult1 g/zi, d.u., copil>5 ani

0,5g/zi, copii 2-5 ani

n teniaze cu T. solium

purgativ salin i eventual oclism evacuatoare (evitareaapariiei cisticercozei)


48/58

Alegerea chimioterapiei n cisticercoz (T. solium)


Praziquantel- 50mg/kg/zi, 15-30zile

Albendazol-15 mg/kg/zi, 8-30zile

Metrifonat-7,5 mg/kg/zi, 5 zile,de 6 ori, la intervale de 2sptmni

Cisticercoz muscular sausubcutanat

Neurocisticercoz

(+ corticosteroizi)

Cisticercoza ocular,subcutanat, cerebral


49/58

Alegerea chimioterapiei n echinococozahidatic(hidatidoza)

Adeseori necesit intervenie chirurgical (chist hidatic hepatic,cerebral, renal, pulmonar)

Chimioterapie

- Mebendazol: 50-150 mg/kg/zi, 3 luni (n chist hidatic inoperabil)

- Albendazol: 800mg/zi, adult, 28 zile, 3-4 cure

- Praziquantel: 10-15 mg/kg/zi, 10 zile


50/58

4. Trematodoze

4.1. Distomatoze

- hepatobiliare (Fasciola)

- digestive (Fasciolopsis)

- pulmonare (Paragonimus)

4.2. Schistosomiaze(Bilharzioze)

- sanguine sau urinare: Schistosoma

- haematobium

- japonicum

- mansoni

- intercalatum
http://knol.google.com/k/-/-/xk923bc3gp4/dzqfug/schistosomamansoni.jpg


51/58

Fasciola hepatica

Ciclul evolutiv


52/58

Fascioloza hepatic


53/58

Chimioterapia Fasciolozei hepatice

Chimioterapic ObservaiiPerioada de invazie

Dehidroemetina- 1mg/kg/zi, 10 zile

Perioada de stare

Bithionol-oral, 30-50mg/kg/zi, 10-15 doze,din 2 n 2 zile

Toxicitate ridicat;supraveghere neurologic i

electrocardiografic

Dehidroemetina Bithionol

Schistosomiaze


54/58

Schistosomiaze


55/58


56/58

Terapia schistosomiazelor

Schistosomiazele specifice zonelor tropicale isubtropicale

Gazde intermediare: molute

Chimioterapice active-Praziquantel(vezi cestodoze)

-Metrifonat

-Niridazol


57/58

Metrifonat

Produs organo-clorofosfonic, inhibitor alcolinesterazei paraziilor

Indicaii:

- schistosomiaz

- cisticercoz(ocular, subcutanat,cerebral)

BILARCIL-cp.

Acizi fosfonici


58/58

Niridazol

Spectru: Schistosome

AMBILHAR-cp.

1-(5 nitro-2- tiazolil)-imidazolidin-2-ona

Documents

Antihelmintice