TEMA PRELEGERIIChimioterapicele Antibacteriene cu Structur chimic divers.ANTUTUBERCULOASELEANTILEPROASELE

LUCIA URCAN dr.med., conf. universitar

DefiniieChimioterapice sunt medicamente cu toxicitate selectiv asupra diferitor ageni cauzali a maladiilor infecioase i parazitare (bacterii, riketsii, virui, fungi, protozoare, helmini etc.).

ChT includ urmtoarele grupe:Nitrofuranele (Nitrofurantoina, Nitrofural, etc)Derivaii Nafteridinei i Chinolonelor /Fluorochinolonele (ac nalidixic, ciprofloxacina)Derivaii Nitroimidazolului (Metronidazol)Derivaii Chinoxalinei (Chinoxidina, Dioxidina)Derivaii 8-oxichinolinei (Clorchinaldol, Nitroxolina)Derivaii Oxazolidinone (Linesolidul)Derivaii Tiosemicarbazonei (Ambazona) i P asemntoare (Falimint, Fitosept, Septolete, etc.)

Derivaii Nitrofuranelor A. cu aciune resorbtiv Nitrofurantoina (furodonina), Nitrofural (furacilina); Furazidina (furagina); Nifuratel (macmiror); NifurtoinolB. cu aciune intestinal nifuroxazida; furazolidona C.cu aciune topic nitrofural (furacilina); furazidina (furagina)

1. Bacteriile Gram + i Gram stafilococi, streptococci, enterococi, pneumococi, meningococi, colibacilul, salmonele, sighele, klebsiele, aerobacter, bacilul antrax, protei, v. holerei, anaerobi;

2. Protozoare: trichomonade, lamblii

3. Fungi: - candida

Spectrul de aciune

Mecanismul de aciune

A. n microorganisme reductazele reduc grupa nitro cu formarea de substane toxice ce afecteaz peretele celular, inhib ireversibil NADP, ciclul Krebs i alte procese biochimice cu dereglarea funciei membranei citoplasmatice i efect bactericid.

B. Preparatele pot forma complexe cu acizii nucleici, ce duce la inhibiia sintezei proteinelor i respectiv la efect bacteriostatic.

Indicaiile nitrofuranelor

A. Infeciile urinare (preparate de linia II, preponderent pentru profilaxia infeciilor urinare recidivante) - Nifurtoinol, Nifuratel, Furazidina, NitrofurantoinaB. Infeciile intestinale (enterite, enterocolite etc.) - Furazolidona Nifuroxazida C. Infeciile locale (Plgi purulente, ulcere, combustii gr. II-III, osteomielit, empiemul pleurei, artrit purulent, infecia anaerob )- Nitrofuralul Furazidina

Contraindicaiile nitrofuranelor - insuficien renal; - copii sub 1 an;- deficiena de glucozo-6 fosfat-dehidrogenaz; - sarcin (ultimul trimestru) alergii; - asocierea cu acid nalidixicReaciile adverse- digestive: grea, vom, colici, diaree, icter;- alergice: erupii cutanate, prurit, edem - SNC: cefalee, ameeli, nustagmus, ataxie, Anemie hemolitic i megaloblastic, sindrom lupoid.

Derivaii chinolonelor 1. Chinolonele nefluorate I generaie - Acidul nalidixic,II generaie - Acidul oxolinic, Acidul pipemidic, Rosoxacina,2. fluorchinolonele - III generaie A. MonofluorchinoloneleCiprofloxocina, ofloxacina, norfloxacina, pefloxacina, enoxacina B. Difluorchinolonele Lomefloxacina, difloxacina, sparfloxacina, amfloxacinaC. Trifluorchinolonele Fleroxacina, tosufloxacina, temafloxacina

Spectrul antimicrobian:

Chinolonele nefluorate : BACILI GRAM NEGATIVI ANAEROBI

Fluorchinolonele:Coci i bacili gram pozitivi bacili i coci gram negativi aerobi bacterii anaerobe chlamidii micoplasme ureaplasma ricketsii unele micobacterii

Composition and Comparison of the structure of gram+AND GRAM- CELL WALL

Cocii gram+: stafilococi; streptococi; enterococi; peptostreptococi; peptococi.Cocii gram-: neiseria (gonococi; meningococi)Bacilii gram+: bac.antracis; Clostridium perfrigens, Clostridum tetani; Clostridum dificile; Corinebacterium diphtheriae; Listeria monocytogenes; Erysipelotrix;Spirochete : treponema palidum; leptospiraActinomicete : actinomyces israeliAtipici (Micoplasma, legionele, chlamidia)- macrolide, azalide

Ex:

Mecanismul de aciune.

Fluorchinolonele blocheaz ADN-giraza i ADN-topoizomeraza IV a bacteriilor cu dereglarea transcripiei i replicrii ADN i respectiv a sintezei ARN, proteinelor. efect bacteriostatic.

QUINOLONESThe earliest prototype drug, Nalidixic acid, was previously used in a limited capacity for Gram- urinary tract infections. More recently developed fluoroquinolones (Ciprofloxacin, Norfloxacin,e.g.) have a much broader spectrum of action. Their full therapeutic potential is still being realized.

Particularitile farmacocinetice ale fluorchinolonelor:

Penetreaz bine n celulele bacteriene; biodisponibilitate nalt dup administrarea intern; volum aparent de distribuie mare; concentraii tisulare nalte; penetrarea bun n lichidele extravasculare; penetrarea nalt n macrofagi i celulele polinucleare; eliminarea lent din organism; nu cumuleaz la utilizarea ndelungat.

-infecii urinare necomplicate i complicate; prostatit bacterian;-infecii gonoreice (uretrit, proctit, faringit, cervicit); -infecii gastrointestinale (diareea cltorilor, gastroenterit, dizenteria bacterian, febra tifoid);-infecii pulmonare (epizoade acute ale bronitei cornice, pneumonii nozocomiale etc.);-osteomielit cronic; - infecii ale pielii cu bacili gram negativi;-prevenirea infeciei cu bacili gram negativi la neutropenici;-tuberculoza pulmonar (ofloxacina, ciprofloxacina, lomefloxacina);- infecii atipice (chlamidii, micoplasme, ureaplasma). Indicaiile:

Contraindicaii:-

sarcina (I trimestru), lactaie copii pn la pubertatedeficiena de glucozo-6 fosfatdehidrogenaz epilepsieinsuficiena renala i hepatic avansat expunerea la soareReaciile adverse-TGI - grea, vom, rar colit pseudomembranoas;-SNC convulsii, delir, halucinaii;-Snge leucopenie, eozinofilie;-Alergice erupii cutanate pruriginoase, urticarie, fotosensibilizare, edem angioneurotic, reacii ananfilactice, vasculit;-Oase leziuni i eroziuni la nivelul cartilagelor;Alte cristalurie, hematurie, nefrit interstiial, insuficien renal acut.

Derivaii nitroimidazolului

Preparatele monocomponenteA. cu aciune sistemic metronidazol (trihopol, flagic, metrogil, etc.), nimorazol (naxodjin), tinidazol (fasigin, tinimed, tiniba etc.), ornidazol (tiberal)

B. pentru uz topicAminitrozol - metronidazol

Preparatele combinate - pentru uz topic

-Helicocina (metronidazol + amoxicilin); -ginalgina (metronidazol + clorchinaldol); -clion-D (metronidazol + miconazol);

METRONIDAZOLUL, DERIVAT DE 5 - NITROIMIDAZOL

INTOXIC SPECIFIC UNELE PROTOZOARE (Entamoeba histolitica, Trichomonas vaginalis, Giardia intestinalis, etc.)Acioneaz bactericid fa de bacilii gram negativ anaerobi: Bacteroides (B.fragiles), HelicobacterCocci gram pozitiv anaerobi: - Peptostreptococcus Majoritatea Clostridiilor, inclusiv C. Difficile.

- Spectrul de aciune

Protozoare: -Entamoeba hystolitica, - Trichomonas vaginalis, - Giardia intestinalis,-Balantidium coli, - Blastocystis hominis,

Bacteriile anaerobe: Bacteroides (B.fragiles), Clostridium, Fusobacterium, H. Pylori, (campilobacter pylori), - Peptococcus - Peptostreptococcus

Mecanismul de aciune M ptrunde n celule prin difuziune i aici este activat printr-un proces de reducere enzimatic propriu microorganismelor anaerobe (protozoare, bacterii), impiedicarea producerii de hidrogen, lipsirea anaerobilor de echivalenii reductori, cu blocarea anumitor procese metabolice. Gruparea nitro accept electronii de la anumite proteine denumite ferodoxine.Se formeaz compui intermediari reactivi labili, care acioneaz bactericid prin afectarea ADN, PROTEINELOR I MEMBRANELOR. S-a constatat o deosebit sensibilitate a timinei, o baz component a ADN, fa de derivaii nitromidazolului. (Bactericid)

1. Infeciile anaerobe (cu scop profilactic i curativ)2.Trichomoniaz. 3. Giardioz4. Dizenteria amebian 5. Balantidiaz 6. Diarea produs de Closztridium difficile7. Forme moderate de tetanos8. Ind particular: inf cu H. Pylori, la bolnavii cu ulcer gastro-duadenal.Indicaii:

- Absorbia,biodisponibilitatea (rapid, bun i complet, 90%)- Distribuia (lichidul cefalorahidian, creier, bil, abcese, placent, lapte, urin )- Cuplarea cu proteine mic (5-20%); - C max peste 1-3 ore;- T0,5 6-14 ore;Se metabolizeaz intens cu formarea de mai muli metabolii prin oxidare, apoi se poate conjuga cu acidul glucuronic. O parte din metabolii sunt activi (cei cu caracter acid i alcoolic) i constituie circa 50-30% din cea a preparatului iniial. n 24 ore se elimin prin urin i/sau bil sub form de metabolii sau neschimbat (tinidazol) Farmacocinetica derivailor nitroimidazolului

Contraindicaiile-afeciuni cerebrale organice; - afeciuni hepatice grave;-sarcin cu pruden (evitat n I trimestru i natere) ; -lactaie ; - asocierea cu disulfiram.

Reacii adverse:

-frecvent: anorexie, grea, gust metallic;-rar: vom, diaree, cefalee, erupii cutanate;-timp ndelungat la doze mari: tulburri neurologice - toxice (slbiciune, nevrit, parestezii, vertij, ataxie, crize epileptice);-ocazional: neutropenie;-reacii de tip disulfiram (la asocierea cu alcoolul);reacii mutagene i cancerigene (la animalele experimentale);- colorarea urinei n rou-brun.

INTERACIUNI MEDICAMENTOASE ASOCIEREA CU ANICOAGULANTELE ORALE POATE FI CAUZ DE ACCIDENTE HEMORAGICE.

Cauza: inhibarea metabolizrii anticoagulantelor orale.

Derivaii chinoxalinei: Chinoxidina Dioxidina

Spectrul de aciune : Proteus, P.aeruginosa, Klebsiella, Bac.Fridlender, E.coli, Salmonella, Staphylococus, Streptococcus, Clostridium antracis Indicaiile: procese purulente abdominale, pielite, pielocistite, colecistite, colangite, abces pulmonar, empiem pulmonar, septicemie gram - Reaciile adverse: dereglri dispeptice, cefalee, ameeli, frisoane, fibrilaii musculare Particularitile de utilizare: Chinoxidina se indic cte 0,25 de 3-4 ori/zi dup mas. Dioxidina este mai puin toxic: i/v n caz de sepsis (ndeosebi de stafilacoci i bacilul piocianic); Soluia 1% numai la aduli pentru splturile vezicii urinare dup catetirizare.

Derivaii 8 oxichinolinei A. Cu aciune intestinal: clorchinaldol, cliochinol, diiodoxochinolin.-bacilii gram negativi; protozoare, ameba, fungiB. cu aciune resorbtiv:- nitroxolina.Bacteriile gram + (coci, bacili) i gram (intestinale); micobacteria tuberculozei, trichomonada, fungi.C. Cu aciune topic: - clorchinaldol.Bacteriile gram + i gram ameba, giardia, fungi.1.Inhib sinteza ADN bacterian, posibil ARN, i ca urmare a proteinelor (efect bacteriostatic)2. Complexarea cu ionii metalelor, ce sunt strict necesari pentru activitatea enzimelor microorganismelor (efect bactericid).Mecanismul de aciune:

Nitroxolina

-infeciile urinare acute i cronice (uretrite, cistite, pielite, pielonefrite, prostatite);- profilaxia complicaiilor infecioase dup proceduri diagnostice i curative (catefirizarea, cistoscopia), perioada postoperatorie asupra ureterilor i cilor urinare Indicaiile: Contraindicaiile:

afeciuni renale cu oligo- sau anurie; maladii grave ale ficatului; .cataracta; neurite, polineurite.; deficit de glucozo-6-fosfatdehidrogenaz; graviditatea (semestrului III); sensibilitatea la chinoline.

Clorchinaldol, cliochinol

Indicaiile:-infecii intestinale, bacteriene, amebiene, i micotice, dizenterie amebian(clorchinaldol, cliochinol); plgi infectate, plgi de decubit i n micoze cutanate(clorchinaldol);-n afeciunile vaginale cauzate de germenii sensibili.(clorchinaldol).Contraindicaiile- Sensibilitate la preparat - afeciunile glandei tiroideReaciile adverse-discofort gastric, grea, vom, diaree, cefalee;-fenomene de iodism, ocazional o cretere uoar a glandei tiroide-f.rar: sindrom de neuropatie mielopiccu tulburri neurologice, vegetative, psihice, de vedere;-Senzaie de usturime i prurit n vagin

Derivaii tiosemicarbazonei i preparatele asemntoare Ambazona (faringosept)aciune bacteriostatic fa de streptococul hemolitic i viridans, pneumococ.;- indic n infeciile acute ale cavitii bucale i faringelui (faringite, angine, tonzilite, stomatite) cu scop de profilaxie i tratament.;- reaciile adverse: se pot constata reacii alergice sub form de erupii cutanate.

-

Pronilidul (falimint)

- exercit efect antiseptic, anestezic slab, revulsiv (provoac o senzaie de rece n cavitatea bucal cu inhibarea reflexelor de tuse etc.) i deodorant.- Se indic ca adjuvant n procesele inflamatorii ale cavitii bucale i faringelui; pregtirea pacienilor pentru manipulaii n cavitatea bucal; nlturarea mirosului neplcut din gur.

-fitosept, cameton, camfomen, septolete, laripront-n majoritatea din ele componentul activ este un antiseptic din grupa detergenilor cationici.Preparatele pot exercita urmtoarele aciuni:-anestezic local (hexaliz);- antitusiv (septolete)-antiseptic (fitosept, cameton,camfomen, septolete, laripront, hexaliz)-deodorant (fitosept, septolete, laripront, hexaliz)-antiinflamatoare (cameton, camfomen, septolete, laripront, hexaliz)-regeneratoare (fitosept); - antiviral (laripront)- hemostatic (laripront, fitosept) Preparatele asemntoare:

Preparatele se indic n:

-afeciunile inflamatorii i infecioase ale cavitii bucale, laringelui i faringului-infecii respiratorii acute nsoite de modificarea tembrului vocii (rgueal) (septolete, fitosept)- miros neplcut din gur (septolete, laripront, hexaliz, fitosept)-rinite (cameton, canefomen)-paradontoz (fitosept)-combustii, ulceraii ale mucoasei cavitii bucale (fitosept)- tusea iritant, neproductiv (septolete) - pregtirea pentru investigaii instrumentale n cavitatea bucal.

OXAZOLIDINONEA member of theOXAZOLIDINONEclass of drugs, linezolid is active against most Gram-positive bacteria that cause disease, includingstreptococci, vancomycin-resistant enterococci (VRE), andmethicillin-resistant Staphylococcus aureus(MRSA).[

LinezolidSpectru ngustDOAR bacterii G +, VRE, MRSASubunitatea ribozomal 50 S

Oxazolidine

MoAAs aprotein synthesis inhibitor, it stops the growth of bacteria by disrupting theirproduction of proteins. Although many antibiotics work this way, the exactmechanism of actionof linezolid appears to be unique in that it blocks the initiation of protein production, and not one of the later steps.Bacterial resistance to linezolid has remained very low since it was first detected in 1999, although it may be increasing.

INDICATIONS of linezolid are infections of theskinandsoft tissues and pneumonia(particularlyhospital-acquired pneumonia), althoughoff-label usefor a variety of other infections is becoming popular. Linezolid is marketed byPFIZERunder the trade namesZyvox(in the United States, United Kingdom, Australia, and several other countries),Zyvoxid(in Europe), andZyvoxam(in Canada and Mexico). Generics are also available, such asLinospan(in India, by CIPLA).

CommonAEof short-term use includeheadache,diarrhea, andnausea. Long-term use, however, has been associated with serious adverse effects: linezolid can causebone marrow suppressionandlow platelet counts, particularly when used for more than two weeks. If used for longer periods still, it may causeperipheral neuropathy(which can be irreversible),optic nerve damage, andlactic acidosis(a buildup oflactic acidin the body), all most likely due to mitochondrial toxicity.

FE cost-effectiveLinezolid is very expensive, costing approximatelyUS$100 per pill in the United States.[5]Nonetheless, it appears to be morecost-effectivethan comparable antibiotics, such as vancomycin,[6]mostly because of the possibility of switching fromintravenousto oraladministrationas soon as patients are stable enough, without the need for dose adjustments.

The mainINDICATIONSof LINESOLID is the treatment of severe infections caused by Gram-positive bacteria that areREZISTANTto other antibiotics; it should not be used against bacteria that are sensitive to drugs with a narrower spectrum of activity, such asPENICILLINSandCEPHALOSPORINS. In both the popular press and the scientific literature, linezolid has been called a "reserve antibiotic"one that should be used sparingly so that it will remain effective as aDrug of last resortagainst potentially intractable infections.

Tuberculosisv Tuberculosis is a kind of communicablechronic disease caused by M.tuberculosis,which can invade various tissues and organs ofthe whole body.v The mycobacteria are slow-growingintracellular bacilli that cause tuberculosis.v In the past decade, tuberculosis cases havesignificantly increased, chiefly among AIDSand the homeless.

Tuberculosisv Tuberculosis is a kind of communicablechronic disease caused by M.tuberculosis,which can invade various tissues and organs ofthe whole body.v The mycobacteria are slow-growingintracellular bacilli that cause tuberculosis.v In the past decade, tuberculosis cases havesignificantly increased, chiefly among AIDSand the homeless.

HistoryUp to 1940 there were no effective CT agents for the treatment of TB, pacients were shifted to Sanatorium immediately after diagnosis.In 1947 Streptomycin was the first drug developed for the treatment of TB. It gave very good results initially, but later, relapse occurred even with continuation of therapy.

HistoryIn 1950s INH and PAS were developed.Up to 1960s 3 AT drugs were available and the patients were isolated in the Sanatorium.In the later 1960s, after the development of Ethambutol (E), domiciliary (home) treatment was started.In 1970s, after the development of R and Z the total duration of treatment was successfully reduced to 6-9 months.

HistorySubsequently, in later years, FLUOROQUINOLONS and MACROLIDS (Rifabutin and Rifapentin) were introduced for the treatment of TB.So, Newer Agents Fluoroquinolons (Ciprofloxacin, Moxifloxacin, Gatifloxacin), Claritromicin, Azitromycin, Rifabutin, Rifapentin)

A. Preparatele antituberculoase I. CLASIFICAREA DUP PROVENIEN : A. Antibioticele: 1. Ansamicinele: rifampicin, rifabutin, rifamicin, rifaximin2. Aminoglicozidele: streptomicin, kanamicin, amicacin3. Diverse: cicloserina, viomicina, capreomicinaB. Preparate sintetice: 1. Derivaii hidrazidei acidului izonicotinic: isoniazid, ftivazida, metazida, fenazida2. Derivaii butanolului: etambutol3. Derivaii nicotinamidei: pirazinamida, etionamida4. Fluorchinolonele: ofloxacina, ciprofloxacina, etc.5. Diverse: acidul aminosalicilic, tioacetazona.

I. CLASIFICAREA AT DUP PROVENIEN, continuare:C. Preparate combinate: Rifampicina+izoniazida (rimactazid, rifinag)Rifampicina+izoniazida + piridoxina (rifacomb)Rifampicina+izoniazida + etambutol (mairin, act 3, etc.)Rifampicina+izoniazida + pirazinamida (rifacomb plus, macox ZH, zucox, etc.)Rifampicina+izoniazida + pirazinamida +etambutol (mairin P, rucox 4, act 4, etc.)Rifampicina+izoniazida + pirazinamida+ etambutol+ piridoxina (repin B6, etc.)

II. CLASIFICAREA AT DUP UTILIZARE:A. Majore sau de prim elecie (f. active, difuzie bun, e.a.moderate): izoniazida, rifampicina, etambutol, pirazinamida, streptomicina, preparatele combinate)B. Minore sau de rezerve (active asupra mutanilor rezisteni la AT majore, penetrare medie, RA mai toxice ca cele de elecie): ftivazida, metazida, fenazida, rifabutina, rifamicina, kanamicina, cicloserina, capreomicina, etionamida, PAS, ac aminosalicilic, fluorchinolonele, etc.

Mecanismele de Aciune ale AT 1. Inhibarea sintezei ac.grai, precursori ai ac micolic-constituent major al peretelui bacilului Koch: izoniazida, ftivazida, metazida, openazida, fenezida2. mpiedicarea sintezei proteinelor prin:a) Formarea unui complex stabil cu ARN-polimeraza ADN-dependent: rifampicina, etc.b) Influeneaz subuniti 30 S a ribozomolor: aminoglicozidele-streptomicina, kanamicina, etc.3. Inhibarea sintezei peretelui celular: cicloserina4. Inhibarea ADN-girazei i ADN-topoizomerazei: FCh5. Inhibarea sintezei ac folic prin antagonism competitiv cu acidul paraaminobenzoic : ac aminosalicilic.

Schema peretelui Mtb

Mecanismul aciunii antituberculoase

IndicaiiTratamentul T Pulmonare i extrapulmonare;Profilaxia Tuberculozei;Pentru ansamicine i aminoglicozide se recomand asociaia cu alte AT.

C. Preparatele active n micobacteriile atipice

(M.kansasii, M.avium intracelulare, M.chelonae, M.scrofulaceum, M.fortuitum, M.ulcerans)1. macrolidele claritromicina, azitromicina2. fluorchinolonele - ofloxacina, ciprofloxacina3. tetraciclinele minociclina, doxiciclina4. carbapenemi imipinem5. aminoglicozide streptomicina, tobramicina, amikacina6. sulfamide co-trimoxazol7. antituberculoase izoniazida, etambutol, rifampicina, rifabutina, ansamicina

Mecanismele de aciune ale antituberculoaselor

1.inhibarea sintezei acizilor grai, predecesori ai acidului micolic, component de baz al peretelui bacterian al micobacteriilor - izoniazida, pirazinamida, etambutol;2.inhibarea sintezei proteinelor prin:complexarea ARN-polimerazei cu diminuarea formrii ARN rifampicina;-fixarea cu subunitatea 30S a ribozomilor cu inhibarea sintezei proteinelor streptomicina, amikacina, kanamicina;-diverse mecanisme : etionamida, capreomicina;

3.inhibarea sintezei peretelui bacterian cicloserina;4.inhibarea ADN-girazei i ADN-topoizomerazei lomefloxacina, ofloxacina5.inhibarea sintezei acidului folic acidul aminosalicilic6. inhibarea sintezei ARNm i metabolismului etambutol;

Hepatotoxicitatea antituberculoaselor dup gradul hepatotoxicitii: cu potenial mare (isoniazida, rifampicina, rifabutina, pirazinamida, etionamida, protionamida, acidul para-aminosalicilic) cu potenial mic sau foarte mic (streptomicina, canamicina, amikacina, capreomicina, etambutol, ofloxacina, levofloxacina, ciprofloxacina, cicloserina).

Efecte secundare antibacterienelor Rash cutanat Sindrom Stivens-Jonson

Common Side effects

IsoniazidInterferes with B6Peripheral neuritisRifampicinRed-orange discoloration of the secretionsHepatitisPyrazinamideHyperuricemiaEthambutolOptic neuritis

Precautions

IsoniazidLiver impairmentRifampicinLiver impairmentPyrazinamideLiver impairmentGoutPregnancyEthambutolLiver impairmentChildren less than 6 years old

Izoniazida

Contraindicaiile : epilepsia; - predispoziie la convulsii - poliomielit n anamnez; - afeciuni hepatice i/sau renale; - flebite. Doze mai mari de 10mg/kg nu sunt recomandate:-la gravide; - cardiopatie ischemic; - maladiile SNC; - astm bronic; -mixedem; - psoriazis; - eczem n acutizare; - n forme grave de insuficien cardiopulmonar i/sau hipertensiune arterial;Precauiile- hepatite; - asocierea cu alte preparate provoac hepatotoxicitate

Reaciile adverse1) hepatotoxicitate cu o frecven de 1-2,5% de hepatit manifestat clinic i pn la 10% anomalii subclinice; 2) din partea SNC i SNP: nevrit periferic cu o frecven de 15%, care este redus la asocierea vit. B6;-nervit optic; ameeli, ataxie; - euforie, agitaie, -ischemie, diminuarea memoriei; - fenomene psihice; - convulsii.

3) din partea tubului digestiv:-uscciunea n gur; - constipaie; - iritarea gastric;4) reacii alergice:-febr (1-2%); - erupii cutanate (1-2%); - limfadenit; - hepatit;- vasculit; - sindrom reumatoid; - sindrom lupic. 5) afectarea hemopoezei: -anemie; - trombocitopenie; - agranulocitoz; - anemie hemolitic la bolnavii cu deficit de glucozo- G-fosfatdehidrogenaz.

Etambutol Reaciile adverse1) din partea SNC i SNP:- nevrit optic (scderea acuitii vizuale, ngustarea cmpurilor vizuale periferice, discromatopsie pentru verde i rou etc.) cu frecvena de 1-5% n dependen de doz;2) reacii alergice (sub 1%):-erupii cutanate; -febr; - artralgii; - leucopenie.3) din partea tubului digestiv, ocazional:-anorexie; -diverse tulburri digestive.4) din partea SNC: -cefalee;-ameeli; - confuzie; -parestezie n extremiti.

PIRAZINAMIDA AT majorSe utilizeaz numai n terapia combinat, ca tratament iniial n forme grave de TP.Regim de dozare aduli 1,5-2g/zi sau 30 mg/kg/zi n 3-4 prize, sau intermetent 2-3 ori pe sptmn n doze de 40 mg/kg (fr a depi 2,5g).CI: afeciuni hepatice, sarcina, porfiriePrecauie: DZRA: hepatotoxicitate, hiperuricemie, accese de gut, dereglri digestive, reacii alergice.

What is the most potent Anti-TB Drug ? PAST- IsoniazidPRESENT - RIFAMPICINFUTURE - MOXIFLOXACINRESEARCH - TRANSITMYCIN

Recent WHO Classification:Group 1 first line oral agent-INHGroup 2 injectabile agent KanamycinGroup 3 Fluoroquinolons- Levofloxacin Group 4 oral bacteriostatic agent Ethionamid Group 5 agents with unclear efficacy- Linazolid, AMX-CLV

Treatment of TB WHO Recommendations:MDT Multidrug therapy for all case of TB.To make the patient non-infectious ASAP.To prevent the development of MDR To prevent relapse by killing the persistersTo reduce the total duration of effective therapy.

TB Courses therapy:Short 6-9 monthsIntensive Phase 2-3 monthsContinuation Phase 4-6 months Thrice a week (adults)/ Pediatric doses in DOTS:INH 600 mg/10mg/kg R 450 mg/15mg/kgZ 1500 mg/ 35mg/kg E 1200 mg/20mg/kgS 750 mg / 15mg/kg

TB during pregnancy:INH, R, Ethambutol along with pyridoxine for 9 months.Steptomycin and Pyrazinamid should be avoided due to the possible toxicity to the mother and foetus even in therapeutical doses.

Principii de tratament in tuberculoza 1. Orice tuberculoza cunoscuta trebuie tratata cu antibiotice specifice2. Tratament precoce =tratament eficace! 3. Tratament in cunostinta de cauza 4. Dus pina la capat - 6 luni !5. Tratament standardizat si nu individualizat

6. Combinatii de antibiotice si nu monoterapie7. Administarea n priza matinala unica a jeun!8. Doze adaptate n functie de ritmul de administrare: 7/7, 3/79. Tratament sub directa observare (DOT)10. Monitorizarea reactiilor adverse11. Pacient declarat, inregistrat corect12. Protectia Rifampicinei

Transmiterea tuberculozeiBolnavi cu TB pulmonara

tuse, stranut, vorbire

picaturi mici

nuclei de picatura

Gazda sanatoasa

Remediile AntileproaseLeprosy is a chronic infectious disease caused byMycobacterium leprae (M. leprae) which mainly affects the skin and peripheral nerves. The treatment of leprosy has been revolutionized since the introduction of multidrug therapy (MDT) in 1981, following the recommendation of the World Health Organization (WHO).[1] The global detection of new cases has declined by 4% during 2007 when compared to 2006.[2]

WHO Global Strategy In 2005, a strategic plan for the elimination of leprosy was introduced. By the end of 2005, all but six countries reported a prevalence of less than 1 per 10,000. The six countries are Brazil, Republic of Congo, Madagascar, Mozambique, Nepal, and Tanzania. For the period 20062010, WHO introduced the Global Strategy for Further Reducing the Leprosy Burden and Sustaining Leprosy Control Activities to address the remaining challenges in providing services for leprosy patients under conditions of low prevalence.

B. Preparatele antileproaseI. Preparatele de I linie 1.Sulfonii dapsona (diaminodifenilsulfona - DDS), solasulfon, diucifona.2.Fenazinele clofazimina (lampren).3.Antibioticele - rifampicina. II. Preparatele II linie1.fluorchinolonele - ofloxacina, pefloxacina.2.tetraciclinele minociclina.3. macrolidele claritromicina, azitromicina.

MDT (DDS, R i Clofazimina) - Tratament polichimioterapic ndelungat 2 ani

Scheme de MDT conf OMSn lepra multibacilar:DDS- (100mg+Clofazimina 50mg/zi ) +( R 600mg+C 300mg/lun) - 2 anin lepra paucibacilar:DDS- 100mg zilnic+ R 600mg o dat/lun), timp de 6 luni.Dac apar RA severe tratamentul cu DDS se ntrerupe imediat.

DDS FDMA similar Sulfamidelor: bacteriostatic n C obinuite, dar C max pot fi bactericide.Efectul bacterian se datorete interferrii procesului de sintez a acidului folic la nivelul microorganismelor sensibile.Molecula Sulfamidic prezint asemnri structurale cu acidul p-aminobenzoic, pe care l antagonizeaz competitiv. Consecutiv este blocat Dihidropteroat sintetaz, en responsabil de ncorporarea ac. p-ab n ac dihidropteroic, precursorul ac folic.

DDS. Datorit toxicitii relativ mari este utilizat exclusiv n tratamentul leprei, unde e de I alegere.FC: absorbie practic complet din TGI, T1/2 - 28 ore. Distribuie bun, prezent n toate esuturile. Adm oral, reinere n esuturi, relativ bine suportat.Doze mari-hemodializ, methemoglobinemie, anemii, SNC- nervozitate, psihoze, polinevrit, dereglri din partea TGI, hepatit, RA, etc.

VA MULUMESC PENTRU ATENIE !

***Antibiotic Resistance***etapele transmiterii tuberculozei, figurate in slide-ul urmator