Edrick Glenn C. Ramoran PharChm 23CPh
9
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