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):
- ciprofoxacin
- norfloxacin
- ofloxacin
- pefloxacin
- lomefloxacin
2) 8-oxiquinolines derivates:
- nitroxoline (5-NOK)
- chlorchinaldol
3) nitrofurans derivates:
- nitrofural
- nitrofurantoin
- furazolidon
- furazidine
4) Quinoxalins derivatives:
- quinoxidine
- dyoxidine
5) nitroimidasoles derivatevs:
- metronidazole
- tinidazole
6) oxazolydinones:
- linezolid (zivox)

B. wide spectrum of action

(Gr + and Gr -)
- levofloxacin
- hemifloxacin
- moxifloxacin
- gatifloxacin

Gyrase inhibitors. The enzyme gyrase (topoisomerase II) permits the orderly accommodation of a
~1000 mlong bacterial chromosome in a bacterial cell of ~1 m. 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 4quinolone-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, Sigella
Gr+ 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 fragillis
Pharmacokinetics: Internal
and i/venous administration, maximum absorption,
100%bioavialability, hepatic metabolisation, renal elimination.
Indications: septicemia. Pneumonia ,various infections produced by specific agents
Side effects: taste perversion, abdominal pain, reversible anemia.

Chinoxalins 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 Infections

Classification of drugs for tuberculosis according to the origin
B.

Synthetic drugs:
- isoniazid
- prothyonamide
- ethambutol
- pyrazinamide
- para-aminosalicylic acid - methazide
C.
Antibiotics:
- rifampicin
- streptomycine sulphate
- streptomicine calcium chlorate complex
- cycloserine
- canamycine sulphate
- florimycine sulphate
Antituberculosis remedies I group
a) synthetic drugs:
- isoniazid
b) antibiotics:
rifampicins group
- rifampicin
- rifamycin
Antituberculosis remedies II group
a) synthetic drugs:
- ethambutol
- prothyonamide
- ethethyonamide
- pyrazinamide
b) antibiotics:
streptomycines 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
- ethambutol
rifampicin
- streptomycine
- thyoretazon
Antileprous drugs
1. diaphenylsulfone(dapson)

- bepasc
- thyacetazone

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 treatment
with two or more drugs. Combination therapy prevents the emergence of resistant mycobacteria.
Because the antibacterial effects of the individual substances are additive, correspondingly
smaller 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 to
the 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 synthesis
It 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 rashes
Clofazimine 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). Redbrown skin pigmentation is an unwanted effect, particularly in fair-skinned patients.