Suport ChFarm 2015 Aminoglicozide Amfenicoli

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    07-Apr-2016

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chimie farmaceutica

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ANTIBIOTICE AMINOGLICOZIDICEAMINOZIDE, AMINOCICLITOLIStreptomyces sp.Structural: aminooze legate glicozidic de un aglicon aminociclitol; de ex. Streptomicina= streptobiozamina + agliconul streptidina

Mecanism actiune antimicrobiana:Bactericide prin inhibarea sintezei proteice Spectru antimicrobian:bacili Gram-negativ aerobi: Enterobacter, E. coli, Klebsiella, Proteus,Ps. aeruginosa, Salmonella, Serratia, Shigella

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Streptomicina Aglicon streptidinastreptobiozaminaL-streptozaN-metil-L-glucozamina

Indice terapeutic mic; periodic, dozarea aminoglicozidelor n plasm

Actiune sinergic beta-lactamice; glicopeptide

R adv: Ototoxicitate (leziuni cohleare si vestibulare), nefrotoxicitate, reactii alergice, bloc neuromuscular (apnee)

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AMINOGLICOZIDE - Clasificareaglicon streptidinic STREPTOMICINESTREPTOMICINADIHIDROSTREPTOMICINA

aglicon dezoxistreptaminicNEOMICINE (Negamicine)GENTAMICINEKANAMICINETOBRAMICINE (Brulamicina)PAROMOMICINAAMIKACINANETILMICINA

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AMINOGLICOZIDE cu AGLICON STREPTidiNIC Streptomycinum (dci): streptomycini sulfas (fr X)Streptomyces griseus, S. bikinensisPF: SULFAT DE STREPTOMICINA (Antibiotice) pulb sol inj 1g (i.m.)STREVITAL (Antibiotice)- pulb sol inj 1 g

DIHIDROSTREPTOMICINA Dihydrostreptomycini sulfas-CHO -CH2-OH

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Streptomicina - ITInfectii Mycobacterium tuberculosis

Infectii non-tuberculoase cu germeni a caror sensibilitate la streptomicina este dovedita (endocardite, meningite, septicemii etc.)

AMINOGLICOZIDE cu AGLICON DEZOXISTREPTAMINICNEOMICINE (NEGAMICINE) A, B, C: neomycini sulfas (FR X)Streptomyces fradiaeSpectru antimicrobian: streptomicinei (bacil Koch, G-)Activitate antibiotic mai intens n mediu alcalinp.o.: infectii digestive cu germeni sensibili (1-2g/zi)

pregtirea interventiilor pe colon (4 g/zi 2-3 zile)Extern: neomicin+ bacitracin + polimixin B sulfat + corticosteroizi(ung, pulb, sol, spray): inf. dermatologice, oculare, ale urechii interne

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R.a.: frecvent reactii alergice (local); sdr. de malabsorbtie, disbacterioz sau candidoz intestinal (O)P.F. NEGAMICIN- cp

BANEOCIN (Sandoz) pulb cutanata; ung = Neomicin (5 mg; 5000 UI) + Zn-bacitracin (5 mg; 250 UI)

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Neomicin + corticosteroiziNEOPREOL ung (+prednisolon+untur de peste)NIDOFLOR ung (+ nistatin+triamcinolon acetonid)PANDERM ung (nistatin+triamcinolon+gramicidin)FLUMETAZON PIVALAT N ung, crem FLUOCINOLON N ung, cremLOCACORTEN with NEOMYCINMAXITROL suspensie si ung oftalmice ( + Dexametazona)OPHTAMETASONE N = solutie oculara, otica, nazala (+Betametazona)ANTIBIOPTAL colir (+Cloramfenicol)NEOSPORIN - ung oftalmic ( + polimixin B sulfat + bacitracin zinc)PIMAFUCORT ung, crema (+ hidrocortizon+ natamicina)DERMESONE N, SYNALAR N

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FRAMICETINA = NEOMICINA BFRAMYCETIN (DCI)

IT: infectii ORL, dermatologice germ Gram-negativ; Forma farm: preparate topice (solutii apoase uz extern, unguente etc)PF: SOFRAMYCINE, ISOFRAMICOL

GENTAMICINE GENTAMYCINI SULFAS (FR X)

i.m./ i.v.: infectii severe sau complicate (pielonefrite, septicemii, endocardite, inf. respiratorii, articulare, cutanate) cu germeni sensibili (Ps. aeruginosa, Enterobacter, Serratia, Proteus, Klebsiella); + beta-lactamine (carbenicilina/ ticarcilin/ benzilpenicilin)topic: arsuri infectate, inf. osoase, oculareCind.: alergie; tratamente de lung durat tulpini rezistente

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P.F.Sol.inj. 40 mg/ml, fiole 1 ml si 2mlGENTAMICIN KRKA; LYRAMYCINSol/ ung. oftalmiceGENTAMICIN SULPHATE (Eipico Med) colir 0.3%GARASONE colir, ottoguttae (+Betametasone)Prep. dermatologice (ung., crem) + corticosteroiziFLUOCINOLON G crema (+ fluocinolon acetonid)DIPROGENTA (betametazon dipropionat)BELOGENT ung crema (+betametazona)TRIDERM ung crema (+betametazon + clotrimazol)

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kanamicine (A) KANAMYCINI SULFAS (fr x)

aplicatii localei.m.: util. restrns n inf. grave; nlocuit de gentamicinO: sterilizarea preoperatorie a intestinuluiCind.: nefropatii; tratamente de lung durat rezistent microbian KANAMICINA SULFAT ung oftalmic 1%KANAMICINA SULFAT H ung oftalmic (+hidrocortizon)UNGUENT OFTALMIC CU KANAMICINA SI HIDROCORTIZONPAN KANAMICINE- flac.inj. 1g

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TOBRAMICINA (BRULAMICINA)

Ind.terap.: gentamicinei

BRULAMICIN, NEBCIN pulb sterila inj )

TOBRADEX unguent si suspensie oftalmica (+Dexametazona)TOBREX sol oftalmica 0.3 %; ung oftalmic 0.3%Tobrom, tobisol colir 0.3%

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DIBEKACINA

PF: DEBEKACYL, ICACINE solutie injectabila

AMIKACINA

(P) sol.inj; 7-10 zile, sub controlul functiei renale si al audiogrameiAMIKOZIT (Zentiva) sol inj 50 mg/ml; 250 mg/ml fiole 2 mlBIODACYNA sol inj 1g/ 4 ml

SISOMICINA : SISOLLINE solutie injectabila A (enterococi) > gentamicinei

NETILMICINA :

NETROMYCINE (Schering Plough) sol.inj. 100 mg/ml (flac 1.5 ml; 2 ml) 25 mg/ml flac 2 mlNETTACIN (SIFI Italia) sol oftalmica 0.3 %, flac unidozaNETTAVISC ung oftalmic 3 mg/g

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PAROMOMICINA

PF: HUMATIN capsule 250 mgHUMACORT ung. (Cloramfenicol+ Paromomicina + Hidrocortizon)

Fortimicina A : ASTROMICINE Spectru analog Amikacinei ; foarte activa asupra Ps. Aeruginosa

ISEPAMICINABactericid: bacili aerobi Gram-negativ; stafilococ meticilino-sensibilH. influenzae, Campylobacter, Listeria monocytogenes, Yersinia, Proteus, E. coli, Salmonella, ShigellaInd. terap:

R.a., Cind: analoge aminoglicozidelorISEPACIN-ISEPALLINE sol.inj.

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SPECTINOMICINA. SPECTINOMYCIN (DCI)*Streptomyces spectabilis; AminociclitolSpectru antimicrobian:Bacteriostatic : inhibarea reversibila a sintezei proteiceNeisseria gonorrhoeae

KIRIN flac inj.

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AMFENICOLI/ FENICOLI / ANTIBIOTICE ARILALCHILICECHLORAMPHENICOLUM * (FR X)

FR X: 2,2-dicloro-N-[(1R, 2R)-1-hidroxi-2-hidroximetil- 1-[(4-nitrofenil)-etil]-acetamida

(+) eritro-cloramfenicol si (+) treo-cloramfenicol;

D-(-)-treo-cloramfenicol= activitate antibiotica maximaD-(-)-treo-cloramfenicol

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CHLORAMPHENICOLUM (FR X)Spectru antimicrobianAntibiotic spectru larg; inhiba sinteza proteinelor Bacteriostatic: b. aerobe Gram-pozitive si Gram-negative (stafilococi, streptococi; Bacillus anthracis, Clostridii; E coli) anaerobi i.c. (Bacillus fragilis)Chlamydia, MycoplasmaRickettsiiBactericid: Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Salmonella typhi, S. paratyphiVirusuri mari, spirochete

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Ind. terap.

R adverse

Contraindicatii

Produse farmaceutice:CLORAMFENICOL CAPS 125 mg, 250 mgCLORAMFENICOL HEMISUCCINAT flac. inj. 1 gBERLICETIN compr. 250 mgSIFICETINA colir 0,4%BETABIOPTAL colir (+Betametazona)ANTIBIOPTAL colir (+Neomicina)SOLUTIE AURICULARA CU CLORAMFENICOL SI FLUOCINOLONTRICOMICON ovule (Cloramfenicol+ Metronidazol + Nistatin)HUMACORT ung. (Cloramfenicol+ Paromomicina + Hidrocortizon)

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Optimizarea unor proprietati biofarmaceutice ale Cloramfenicolului

1. Optimizarea gustului amar Esteri cu acizi grasi la grupa alcoolica primara

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PALMITAT DE CLORAMFENICOLR: -CO-(CH2)14-CH3CLORAMFENICOL PALMITAT suspensie oralabiodisponibilitate optima: pulbere amorfa 1-5 mm; cristale aciculare < 10 mmSTEARAT DE CLORAMFENICOLR: -CO-(CH2)16-CH3PALMITOIL GLICOLAT DE CLORAMFENICOL (n=14)STEAROIL GLICOLAT DE CLORAMFENICOL (n=16)R: -CO-CH2-O-CO-(CH2)n-CH3 stabilitatea, conc. serice

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2. Optimizarea solubilitatii in apa Esteri hidrosolubili cu acizi dicarboxiliciHemisuccinatul de cloramfenicol si sodiu: CHLORAMPHENICOLI NATRII SUCCINAS (FR X)R: -CO- CH2-CH2-COONapulbere alba, higroscopica; se solubilizeaza numai in momentul utilizarii;

CLORAMFENICOL HEMISUCCINAT DE SODIU

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Relatii structura chimica activitate in seria derivatilor cloramfenicoluluiGrupare functionalaModulare structuralaConsecinte /Activitate, toxicitate-NO2paraCH3-CO- Cetofenicol A; TCH3-SO2- Tiamfenicol A; durata actiuneAlte grupari (OH, OR, COOH, NH2, NH-R, NR2, CO-NH2, CN, X, Ar, alchil) A/ inactiviAlte pozitii pe nucleul aromatic ANucleul benzenicCiclohexil, naftil, ciclopentil, chinolil, furil A

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Grupare functionalaModulare structuralaConsecinte /Activitate, toxicitateAr-1CH-OHAr-1C=O CloramfeniconaantifungicC2-NH-COCHCl2substituireinactivare-CO-CH2-N=N+=NAzidamfenicolHidrosolubilitatea(colir)C2-NH-COCHBr2Bromamfenicol ACH2-OHesterificarePro-drug-uri (in vivo, hidroliza enzimatica) CloramfenicolOxidare, reducere, eliminareAcetilare (rezistenta bacteriana)Inactivare

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