Edrick Glenn C.

Ramoran
3CPh

PharChm 2

TETRACYCLINES
Mechanism 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 tetracyclineresistant strains may be susceptible to doxycycline, minocycline, and tigecycline, all
of which are poor substrates for the efflux pump that mediates resistance.

Structure
Basic structure for Tetracyclines
Drug
Tetracycline
Minocycline
Doxycycline
Oxytetracycline

R7
-H
N(CH3)2
-H
-H

R6
-CH3
-H

R5
-H
-H

-CH3
-CH3

-OH
-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,6,11,12aoctahydro-3,6,10,12,12a-pentahydroxy-6methyl-1,11-dioxo-2 napthacene
carboxamide

Minocycline
7-dimethylamino-6-demethyl-6deoxytetracycline; Most Potent

Oxytetracycline

Doxycycline
6-deoxy-5-oxytetracycline

(4S,4aR,5S,5aR,6S,12aS) -4-(dimethylamino)3,5,6,10,11,12a-hexahydroxy -6-methyl-1,12-dioxo1,4,4a,5,5a,6,12,12a-octahydrotetracene -2-carboxamide

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Structure Activity Relationship
characteristic broad-spectrum activity associated with this antibiotic class is 6demethyl-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

Ofloxacin
Ciprofloxacin
9-Fluoro-2,3-dihydro-3-methyl-10(4-methyl-11-Cyclopropyl0-6-fluoro-1,4-dihydro-4-oxo-7-(1piperazin-yl)- 7-oxo-7H-pyrido[1,2,3-de]-1,4,piperazinyl)- 3-quinolinecarboxylicacid
benzoxazine-6-carboxylic acid

Nalidixic Acid
1-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
Methenamine
Mechanism 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-aminohydantoin
Structure 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

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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-galactooctopyranoside
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 disease
Dapsone
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

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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- 4,6dimethyloxan- 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- 21,24,27,41,43pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta3,5,8(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

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Brand Name
Vibramycin
Doxicon
Bactidox
Minocin
Tetracyclines

Generic Name
Doxycycline

Manufacturer
Pfizer

Doxycycline
Doxyxyxline
Minocycline

Vendiz
Unison
Pfizer

Quinolones
Brand Name
Ciprobay
Floxil
Cipromax
Inoflox
Sensoflox

Generic Name
Ciprofloxacin
Ciprofloxacin
Ciprofloxacin
Ofloxacin
Ofloxacin

Manufacturer
Bayer
Marck Biosciences
Verheilen
Biomedis
Sensomed

Urinary Tract Antiseptic

Brand Name

Generic Name

Manufacturer

Macrodantin

Nitrofurantoin
macrocrystals

Boehringer Ingelheim

Miscellaneous Antibacterials
Brand Name

Generic Name

Manufacturer

Pediachlor

Chloramphenicol
palmitate
Chloramphenicol
palmitate
Chloramphenicol Na
Succinate
Clindamycin HCl
Clindamycin
Vancomycin HCl
Vancomycin HCl

Pediatricha

Anpheclor
Klorfen
Dalacin C HCl
Clindal
Vancocin CP
Vancomet

Medhaus
Karnataka
Pfizer
One Pharma
GSK
Korea United Pharma