Edrick Glenn C. Ramoran PharChm 23CPh

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TetracyclinesMechanism of Action broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis. inside the cell, tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome, blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA ribosome complex which prevents addition of amino acids to the growing peptide. active against many gram-positive and gramnegative bacteria, including certain anaerobes, rickettsiae, chlamydiae,and mycoplasmas. antibacterial activities of most tetracyclines are similar except that tetracycline-resistant strains may be susceptible to doxycycline, minocycline, and tigecycline, all of which are poor substrates for the efflux pump that mediates resistance.StructureBasic structure for Tetracyclines

DrugR7R6R5Tetracycline-H-CH3-HMinocycline-N(CH3)2-H-HDoxycycline-H-CH3-OHOxytetracycline-H-CH3-OH amphoteric compound hydrochloride salts are used most commonly for oral administration and usually are encapsulated because they are bitter.

Tetracycline 4-dimethyl amino-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2 napthacene carboxamideMinocycline7-dimethylamino-6-demethyl-6-deoxytetracycline; Most Potent

Oxytetracycline(4S,4aR,5S,5aR,6S,12aS) -4-(dimethylamino)-3,5,6,10,11,12a-hexahydroxy -6-methyl-1,12-dioxo-1,4,4a,5,5a,6,12,12a-octahydrotetracene -2-carboxamideDoxycycline6-deoxy-5-oxytetracycline

Structure Activity Relationship characteristic broad-spectrum activity associated with this antibiotic class is 6-demethyl-6-deoxytetracycline The enolized tricarbonylmethane system at C-1 to C-3 must be intact for good activity Replacement of the amide at C-2 with other functions (e.g., aldehyde or nitrile) reduces activity Removal of the 4-dimethylamino group reduces activity even further Activity is largely retained in the primary and N-methyl secondary amines but rapidly diminishes in the higher alkylamines. Polar substituents (i.e., hydroxyl groups) at C-5 and C-6 decrease lipid versus water solubility of the tetracyclines.

Clinical Uses drug of choice in the treatment of infections caused by rickettsiae. treatment of Mycoplasma pneumonia , chlamydiae, and some spirochetes used in combination regimens to treat gastric and duodenal ulcer disease caused by Helicobacter pylori used in various gram-positive and gram-negative bacterial infections, including vibrio infections (cholera) used also for sexually transmitted infections treatment or prophylaxis of protozoal infections, eg, those due to Plasmodium falciparum treatment of acne, exacerbations of bronchitis, community-acquired pneumonia, Lyme disease, relapsing fever, leptospirosis, and some nontuberculous mycobacterial infections (eg, Mycobacterium marinum ).

Quinolones

Mechanism of Action block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division.

Structure

Ofloxacin9-Fluoro-2,3-dihydro-3-methyl-10(4-methyl-1-piperazin-yl)- 7-oxo-7H-pyrido[1,2,3-de]-1,4,-benzoxazine-6-carboxylic acidCiprofloxacin1-Cyclopropyl0-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 3-quinolinecarboxylicacid

Nalidixic Acid1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid

Structure Activity Relationship 1,4-dihydro- 4-oxo-3-pyridinecarboxylic acid moiety is essential for antibacterial activity position 2 greatly reduces or abolishes activity, positions 5, 6, 7 (especially), and 8 of the annulated ring may be substituted with good effects Fluorine atom substitution at position 6 is also associated with significantly enhanced antibacterial activity. Alkyl substitution at the 1-position is essential for activity, with lower alkyl (methyl, ethyl, cyclopropyl) compounds generally having progressively greaterpotency. Aryl substitution at the 1-position is also consistent with antibacterial activity

Antibacterial Activity Earlier quinolones such as nalidixic acid did not achieve systemic antibacterial levels and were useful only in the treatment of lower urinary tract infections. Fluorinated derivatives have greatly improved antibacterial activity . Fluoroquinolones have excellent activity against gram-negative aerobic bacteria; they had limited activity against gram-positive organisms.

Clinical Uses effective in urinary tract infections caused by many organisms, including P aeruginosa effective for bacterial diarrhea caused by Shigella , Salmonella , toxigenic E coli, and Campylobacter used in infections of soft tissues, bones, and joints and in intra-abdominal and respiratory tract infections, including those caused by multidrug-resistant organisms such as Pseudomonas and Enterobacter . Ciprofloxacin is a drug of choice for prophylaxis and treatment of anthrax

URINARY TRACT ANTISEPTICS

MethenamineMechanism of Action used internally as a urinary antiseptic for the treatment of chronic urinary tract infections.

Structure

1,3,5,7-Tetraazatricyclo[3.3.1.13,7]decane

Structure Activity Relationship exists as an odorless, white crystallinepowder that sublimes at about 260C. dissolves in water to form an alkaline solution liberates formaldehyde when warmed with mineral acids. weak base with a pKa of 4.9. free base has practically no bacteriostatic power formaldehyde release at the lower pH of the kidney is required To optimize the antibacterial effect, an acidifying agent such as sodium biphosphate or ammonium chloride generally accompaniesthe administration of methenamine. Certain bacterial strains are resistant to the action of methenamine because they elaborate urease, an enzyme that hydrolyzes urea to form ammonia which results to high urinary pH preventing the activation of methenamine

Nitrofurantoin

Mechanism of Action nitrofuran derivative that is suitable for oral use. It is recommended for the treatment of urinary tract infections caused by susceptible strains of E. coli, enterococci, S. aureus, Klebsiella, Enterobacter,and Proteus spp. common side effects are gastrointestinal (anorexia, nausea, and vomiting) macrocrystalline form (Macrodantin) is claimed to improve gastrointestinal tolerance without interfering with oral absorption.Structure

1-(5-nitro-2-furfurylidene)-1-aminohydantoinStructure Activity Relationship derivatives of 5-nitro-2-furaldehyde, formed on reaction with the appropriate hydrazine or amine derivative Antimicrobial activity is present only when the nitro group is in the 5-position. known to be mutagenic and carcinogenic under certain conditions

MISCELLANEOUS ANTIBACTERIAL DRUGS

Chloramphenicol

Mechanism of Action potent inhibitor of microbial protein synthesis bacteriostatic broad-spectrum antibiotic that is active against both aerobic and anaerobic gram-positive and gramnegative organisms active also against Rickettsiae

Structure white, crystalline compound that is very stable very soluble in alcohol and other polar organic solvents but only slightly soluble in water Biological activity resides almost exclusively in the D-threo isomer; the L-threo and the D- and L-erythro isomers are virtually inactive

2,2-dichloro-N-[1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide

Structure Activity Relationship Conversion of the alcohol group on C-1 of the side chain to a keto group causes appreciable loss in activity.

Clinical Uses treatment of serious rickettsial infections such as typhus and Rocky Mountain spotted fever alternative to a -lactam antibiotic for treatment of bacterial meningitis occurring in patients who have major hypersensitivity reactions to penicillin used topically in the treatment of eye infections

Clindamycin

Mechanism of Action inhibits protein synthesis by interfering with the formation of initiation complexes and with aminoacyl translocation reactions Streptococci, staphylococci, and pneumococci are inhibited by clindamycin

Structure

methyl 7-chloro-6,7,8-trideoxy-6-{[(4R)-1-methyl-4-propyl-L-prolyl]amino}-1-thio-L-threo--D-galacto-octopyranoside

Clinical Use indicated for the treatment of skin and soft-tissue infections caused by streptococci and staphylococci indicated for treatment of anaerobic infections caused by Bacteroides sp and other anaerobes that often participate in mixed infections active against community-acquired strains of methicillin-resistant S aureus , an increasingly common cause of skin and soft tissueinfections in combination with an aminoglycoside or cephalosporin, is used to treatpenetrating wounds of the abdomen and the gut recommended rather than erythromycin for prophylaxis of endocarditis in patients with valvular heart diseaseDapsone

Mechanism of Action/Clinical Use closely related to sulfonamides that have been used effectively in the long-term treatment of leprosy treatment of both lepromatous and tuberculoid types of lepros often used in combination with clofazimine and rifampin may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients

Structure odorless, white crystalline powder that is very slightly soluble in water and sparingly soluble in alcohol pure compound is light stable, but traces of impurities, including water, make it photosensitive drug should be protected from light

4-[(4-aminobenzene)sulfonyl]aniline

Vancomycin

Mechanism of Action inhibits cell wall synthesis by binding firmly to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide which prevents further elongation of peptidoglycan and cross-linking cell membrane is also damaged, which contributes to the antibacterial effect

Structure very soluble in water and insoluble in organic solvents. The salt is quite stable in acidic solutions. a glycopeptide containing two glycosidically linked sugars, glucose and vancosamine, and a complex cyclic peptide aglycon containing aromatic residues linked together in a unique resorcinol ether system.

(1S,2R,18R,19R,22S,25R,28R,40S)- 48- {[(2S,3R,4S,5S,6R)- 3- {[(2S,4S,5S,6S)- 4- amino- 5- hydroxy- 4,6- dimethyloxan- 2- yl]oxy}- 4,5- dihydroxy- 6 (hydroxymethyl)oxan- 2- yl]oxy}- 22- (carbamoylmethyl)- 5,15- dichloro- 2,18,32,35,37- pentahydroxy- 19- [(2R)- 4- methyl- 2-(methylamino)pentanamido]- 20,23,26,42,44- pentaoxo- 7,13- dioxa- 21,24,27,41,43- pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta- 3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49- pentadecaene- 40- carboxylic acid

*Vancomycin hydrochloride is always administered intravenously (never intramuscularly), either by slow injection or by continuous infusion, for the treatment of systemic infections.

Trimethoprim

Mechanism of Action selectively inhibits bacterial dihydrofolic acid reductase, which converts dihydrofolic acid to tetrahydrofolic acid, a step leading to the synthesis of purines and ultimately to DNA in combination with a sulfonamide blocks sequential steps in folate synthesis, resulting in marked enhancement (synergism) of the activity of both drugs The combination often is bactericidal, compared with the bacteriostatic activity of a sulfonamide alone.

Structure

5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine

Clinical Use treatment of UTI in combination with trimethoprim-sulfamethoxazole, it is effective for the treatment of a wide variety of infections including P jiroveci pneumonia, shigellosis, systemic salmonella infections, urinary tract infections, prostatitis, and some nontuberculous mycobacterial infections. (IV Trimethoprim-Sulfamethoxazole) agent of choice for moderately severe to severe pneumocystis pneumonia Pyrimethamine and sulfadiazine have been used for treatment of leishmaniasis and toxoplasmosis

List of Drugs

Brand NameGeneric NameManufacturer

VibramycinDoxycyclinePfizer

DoxiconDoxycyclineVendiz

BactidoxDoxyxyxlineUnison

MinocinMinocyclinePfizer

Tetracyclines

Quinolones

Brand NameGeneric NameManufacturer

CiprobayCiprofloxacinBayer

FloxilCiprofloxacinMarck Biosciences

CipromaxCiprofloxacinVerheilen

InofloxOfloxacinBiomedis

SensofloxOfloxacinSensomed

Urinary Tract AntisepticBrand NameGeneric NameManufacturer

MacrodantinNitrofurantoin macrocrystalsBoehringer Ingelheim

Miscellaneous Antibacterials

Brand NameGeneric NameManufacturer

PediachlorChloramphenicol palmitatePediatricha

AnpheclorChloramphenicol palmitateMedhaus

KlorfenChloramphenicol Na SuccinateKarnataka

Dalacin C HClClindamycin HClPfizer

ClindalClindamycinOne Pharma

Vancocin CPVancomycin HClGSK

VancometVancomycin HClKorea United Pharma