Synthetics antibacterial with various chemical structures:

1) Derivatives of Quinolones and Fluoroquinolones:a) quinolones derivates :- nalidixic acid - oxolynic acid- cinoxacin - pypemidinic acid

b) fluoroquinolones: A.narrow spectrum ( only Gr- flora): B. wide spectrum of action

- ciprofoxacin (Gr + and Gr -)- norfloxacin - levofloxacin- ofloxacin - hemifloxacin- pefloxacin - moxifloxacin- lomefloxacin - gatifloxacin

2) 8-oxiquinolines derivates:- nitroxoline (5-NOK) - chlorchinaldol

3) nitrofuran’s derivates:- nitrofural- nitrofurantoin- furazolidon- furazidine

4) Quinoxalin’s derivatives: - quinoxidine

- dyoxidine

5) nitroimidasole’s derivatevs:- metronidazole - tinidazole

6) oxazolydinones: - linezolid (zivox)

Gyrase inhibitors. The enzyme gyrase (topoisomerase II) permits the orderly accommodation of a ~1000 µmlong bacterial chromosome in a bacterial cell of ~1 µm. Within the chromosomal strand, double-stranded DNA has a double helical configuration. The former, in turn, is arranged in loops that are shortened by supercoiling. The gyrase catalyzes this operation by opening, underwinding, and closing the DNA double strand such that the full loop need not be rotated. Derivatives of 4-quinolone-3-carboxylic acid are inhibitors of bacterial gyrases. They appear to prevent specifically the resealing of opened strands and thereby act bactericidally. These agents are absorbed after oral ingestion. The older drug, nalidixic acid, affects exclusively gram-negative bacteria and attains effective concentrations only in urine; it is used as a urinary tract antiseptic. Spectrum of action: Only Gr -: Enterobacteriacea, E. coli, Clebsiela, Proteus, Serratia, Salmonela, SigellaGr+ flora is resistance. Mechanism of action: It blocks reversible DNA-girase. Indications are acute and chronic urinary infectious.Norfloxacin has a broader spectrum. Ofloxacin, ciprofloxacin, and enoxacin, and others, also yield systemically effective concentrations and are used for infections of internal organs. Spectrum of action includes: aerobal and anaerobal agents, chlamidia, mycoplasma, clebsyella, salmonella, chlostridium, shigella, proteus

Description: The remedies inhibit DNA-gyrase, acting on the i/cellular agents too. Duration of action is long (11 hours). The resistance appears slowly. Group of drugs is characterized by high bioavialability, without cumulating effects.

Indication for this group: abdominal typhus, in complex therapy of TBC, respiratory infections, sallmonelose, leprosy, urinary infections, shigelose, intestinal infections, skin infections, mycoplasmoses, chlamidioses Besides gastrointestinal problems and allergy, adverse effects particularly involve the CNS (confusion, hallucinations, seizures). Since they can damage epiphyseal chondrocytes and joint cartilages in laboratory animals, gyrase inhibitors should not be used during pregnancy, lactation, and periods of growth.

1. nitroimidazole derivatives, such as metronidazole, damage DNA by complex formation or strand breakage.

2. They are captured by anaerobal agens and inhibit H+ synthesis into their cell.3. Drugs nitrogroup is reduced by some electrons from bacteria cell, producing free radicals, that inhibit AND transcription and replication.

This occurs in obligate anaerobes, i.e., bacteria growing under O2 exclusion. Under these conditions, conversion to reactive metabolites that attack DNA takes place (e.g., the hydroxylamine shown). The effect is bactericidal. A similar mechanism is involved in the antiprotozoal action on Trichomonas vaginalis (causative agent of vaginitis and urethritis) and Entamoeba histolytica (causative agent of large bowel inflammation, amebic dysentery, and hepatic abscesses). Metronidazole is well absorbed via the enteral route; it is also given i.v. or topically (vaginal insert). Because metronidazole is considered potentially mutagenic, carcinogenic, and teratogenic in the human, it should not be used longer than 10 d, if possible, and be avoided during pregnancy and lactation. Timidazole may be considered equivalent to metronidazole.Linezolid: Mechanism of action: It binds with 70 S and deregulates protein synthesis

Spectrum of action: wide:Cholynobacterium, Enterococcus, Listeria, Staphylococcus, Streptococcus, Chlamidia, Mycoplasma, Legionella, Bacillus fragillisPharmacokinetics: Internal and i/venous administration, maximum absorption, 100%bioavialability, hepatic metabolisation, renal elimination.Indications: septicemia. Pneumonia ,various infections produced by specific agentsSide effects: taste perversion, abdominal pain, reversible anemia.

Chinoxalin’s derivatives: (chinoxidine, dyoxidine)Spectrum of action: Proteus vulgaris, Pseudomonas aeruginoza, bacillus Fridlender E. coli, Shigella, salmonella, staphilococus, Clostridium perfringers.Indications: severe purulent inflamatiouns ( pielitis, pielocystitis, cholecistitis, cholangitis, pulmonary abscesses, sepsis.They are reserved drugs.Side effects: dyspepsia, neurological deregulations, allergy, dysbacteriosis, feber, convulsions.

Pharmakocinetics: 0,25 g –3 time a day. –7-14 days

Drugs for Treating Mycobacterial InfectionsClassification of drugs for tuberculosis according to the origin

B. Synthetic drugs:- isoniazid - prothyonamide - bepasc - ethambutol - pyrazinamide - thyacetazone - para-aminosalicylic acid - methazide

C. Antibiotics:- rifampicin- streptomycine sulphate- streptomicine calcium chlorate complex- cycloserine- canamycine sulphate- florimycine sulphate

Antituberculosis remedies I groupa) synthetic drugs:

- isoniazidb) antibiotics: rifampicin’s group

- rifampicin- rifamycin Antituberculosis remedies II group

a) synthetic drugs:- ethambutol - prothyonamide- ethethyonamide - pyrazinamide

b) antibiotics: streptomycine’s group

- streptomycine sulphate- streptomicine calcium chlorate complex

various antibiotics- cycloserine- canamycine- capreomycine- florimycine sulphate Antituberculosis remedies III group

a) synthetic drugs:- para-aminosalicylic acid- thyocetazone

6 based drugs for tuberculosis:-isoniazid - pyrazinamide - ethambutolrifampicin - streptomycine - thyoretazon

Antileprous drugs1. diaphenylsulfone(dapson)2. solusulfone 3. diucifone

Mycobacteria are responsible for two diseases: tuberculosis, mostly caused by M. tuberculosis, and leprosy due to M. leprae. The therapeutic principle applicable to both is combined treatmentwith two or more drugs. Combination therapy prevents the emergence of resistant mycobacteria. Because the antibacterial effects of the individual substances are additive, correspondinglysmaller doses are sufficient. Therefore, the risk of individual adverse effects is lowered. Most drugs are active against only one of the two diseases.Antitubercular Drugs (1)Drugs of choice are: isoniazid, rifampin, ethambutol, along with streptomycin and pyrazinamide. Less well tolerated, second-line agents include: p-aminosalicylic acid, cycloserine, viomycin, kanamycin, amikacin, capreomycin, ethionamide. Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. (In the bacterium it is converted to isonicotinic acid, which is membrane impermeable, hence likely to accumulate intracellularly.)Also, Isoniazid inhibits synthesis of mycolic acid and mycobacterial cell walls. Isoniazid is rapidly absorbed after oral administration. In the liver, it is inactivated by acetylation, the rate of which is genetically controlled and shows a characteristic distribution in different ethnic groups (fast vs. slow acetylators). Notable adverse effects are: peripheral neuropathy, optic neuritis, preventable by administration of vitamin B6 (pyridoxine); hepatitis, jaundice. Hemolysis has occurred in pacients with glucose-6-phosphate dehydrogenase deficiency. A lupus-like syndrome has been reported.Rifampin inhibits the bacterial enzyme that catalyzes DNA template-directed RNA transcription, i.e., DNA-dependent RNA polymerase. Rifampin acts bactericidally against mycobacteria (M.tuberculosis, M. leprae), as well as many gram-positive and gram-negative bacteria. It is well absorbed after oral ingestion. Because resistance may develop with frequent usage, it is restricted tothe treatment of tuberculosis and leprosy.Rifampin is contraindicated in the first trimester of gestation and during lactation.Rifabutin resembles rifampin but may be effective in infections resistant to the latter.Albeit mostly well tolerated, this drug may cause several adverse effects including hepatic damage, hypersensitivity with flu-like symptoms, disconcerting but harmless red/orange discoloration of body fluids, and enzyme induction (failure of oral contraceptives). Ethambutol. The cause of its specific antitubercular action is unknown. It inhibits arabinosyl transferase involved in the synthesis of arabinogalactan, a component of mycobacterial cell wall. Resistance occurs rapidly if the drug is used alone. Dose reduction is necessary in renal failure. Ethambutol is given orally. It is generally well tolerated, but may cause dosedependent damage to the optic nerve with disturbances of vision (red/green blindness, visual field defects).Pyrazinamide exerts a bactericidal action by an unknown mechanism. It is given orally. Pyrazinamide may impair liver function; hyperuricemia results from inhibition of renal urate elimination, polyarthralgia, myalgia, gastrointestinal irritation. Streptomycin must be given i.v like other aminoglycoside antibiotics. It damages the inner ear and the labyrinth. Its nephrotoxicity is comparatively minor.Antileprotic Drugs (2)Rifampin is frequently given in combination with one or both of the following agents:Dapsone is a sulfone that, like sulfonamides, inhibits dihydrofolate synthesisIt is bactericidal against susceptible strains of M. leprae. Dapsone is given orally. The most frequent adverse effect is methemoglobinemia with accelerated erythrocyte degradation (hemolysis). Other side effects are gastrointestinal irritation, fever, skin rashesClofazimine is a dye with bactericidal activity against M. leprae and antiinflammatory

properties. It is given orally, but is incompletely absorbed. Because of its high lipophilicity, it accumulates in adipose and other tissues and leaves the body only rather slowly (t1/2 ~ 70 d). Red-brown skin pigmentation is an unwanted effect, particularly in fair-skinned patients.