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Tetracycline

Tetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and, more recently, rosacea, and is historically important in reducing the number of deaths from cholera.

The term "tetracycline" is also used to denote the four-ring system of this compound; "tetracyclines" are related substances that contain the same four-ring system.

Therapeutic use

Used to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease. May be used to treat infections caused by Chlamydiae spp., B. burgdorferi (Lyme disease), and upper respiratory infections caused by typical (S. pneumoniae, H. influenzae, and M. catarrhalis) and atypical organisms (C. pneumoniae, M. pneumoniae, L. pneumophila). May also be used to treat acne. Tetracycline may be an alternative drug for people who are allergic to penicillin.

Tetracycline hydrochloride is indicated for the treatment of the following infections:

Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox and tick fever caused by Rickettsiae.

Respiratory tract infections caused by Mycoplasma pneumoniae.

Lymphogranuloma venereum caused by Chlamydia trachomatis.

Psittacosis and ornithosis due to Chlamydia psittaci.

Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immuno- fluorescence.

Inclusion conjunctivitis caused by Chlamydia trachomatis.

Tetracycline hydrochloride is indicated for the treatment of uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis.

Nongonococcal urethritis caused by Ureaplasma urealyticum. Relapsing fever due to Borrelia recurrentis.

Tetracycline hydrochloride is also indicated for the treatment of infections caused by the following gram-negative microorganisms:

Chancroid caused by Haemophilus ducreyi.

Plague due to Yersinia pestis (formerly Pasteurella pestis).

Tularemia due to Francisella tularensis (formerly Pasteurella tularensis).

Cholera caused by Vibrio cholerae (formerly Vibrio comma).

Campylobacter fetus infections caused by Campylobacter fetus (formerly Vibrio fetus).

Brucellosis due to Brucella species (in conjunction with streptomycin).

Bartonellosis due to Bartonella bacilliformis.

Granuloma inguinale caused by Calymmatobacterium granulomatis.

Because many strains of the following groups of microorganisms have been shown to be resistant to tetracycline hydrochloride, culture and susceptibility testing are recommended.

Tetracycline hydrochloride is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:

Escherichia coli

Enterobacter aerogenes (formerly Aerobacter aerogenes)

Shigella species

Acinetobacter species [formerly Mima species and Herellea species]

Respiratory tract infections caused by Haemophilus influenzae

Respiratory tract and urinary tract infections caused by Klebsiella species

Tetracycline hydrochloride is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicated appropriate susceptibility to the drug:

For upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae)

Skin and skin structure infections caused by Staphylococcus aureus. Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infections.

When penicillin is contraindicated, tetracycline hydrochloride is an alternative drug in the treatment of the following infections:

Uncomplicated gonorrhea caused by Neisseria gonorrhoeae.

Syphilis caused by Treponema pallidum.

Yaws caused by Treponema pertenue.

Listeriosis due to Listeria monocytogenes.

Anthrax due to Bacillus anthracis.

Vincent's infection caused by Fusobacterium fusiforme.

Actinomycosis caused by Actinomyces israelii.

Infections caused by Clostridia species.

In acute intestinal amebiasis, the tetracycline hydrochlorides may be a useful adjunctive therapy to amebicides.

In severe acne the tetracycline hydrochlorides may be useful ad- junctive therapy.
 

Dosage and Administration

 

Toxicology

 

LD50=808mg/kg (oral, mice)

 

Pharmacokinetic

Bioavailability 60-80% oral, fasted

<40% intramuscular

Metabolism Not metabolised
Cmax (mg/ml)  
tmax (hrs)  
Half-life 6-12 hrs
AUC (mg.h/l) 26.9 6.0 (300mg)

5575 (500mg)

Eliminiation rate Constant  
Excretion fecal and renal
Protein binding 20-67%

Absorption

Bioavailability is less than 40% when administered via intramuscular injection, 100% intravenous, and 60-80% oral (fasting adults). Food and/or milk reduce GI absorption of oral preparations of tetracycline by 50% or more.

Distribution

 

Elimination

 

Metabolism

 

Mechanism of action

Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also reversibly binds  to the 50S ribosomal subunit. Moreover, tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell. Tetracycline passively diffuses through porin channels in the bacterial membrane. 

 


Medicinal Chemistry

CAS number: 60-54-8  EINECS: 200-481-9

Molecular Formula:  C22H24N2O8

Average mass: 444.434601 Da

Monoisotopic mass:  444.153259 Da

Systematic name: (4S,4aS,5aS,6S,12aS)-4-(Dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboxamide

SMILES: C[C@]1(c2cccc(c2C(=O)C3=C([C@]4([C@@H](C[C@@H]31)[C@@H](C(=C(C4=O)C(=O)N)O)N(C)C)O)O)O)O

Std. InChI: 1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1

 

ACD/LogP: 0.617 # of Rule of 5 Violations: 2
ACD/LogD (pH 5.5): -1.91 ACD/LogD (pH 7.4): -2.23
ACD/BCF (pH 5.5): 1.00 ACD/BCF (pH 7.4): 1.00
ACD/KOC (pH 5.5): 1.00 ACD/KOC (pH 7.4): 1.00
#H bond acceptors: 10 #H bond donors: 7
#Freely Rotating Bonds: 7 Polar Surface Area: 181.62 2
Index of Refraction: 1.741 Molar Refractivity: 109.088 cm3
Molar Volume: 270.304 cm3 Polarizability: 43.246 10-24cm3
Surface Tension: 100.608001708984 dyne/cm Density: 1.644 g/cm3
Flash Point: 431.953 C Enthalpy of Vaporization: 120.61 kJ/mol
Boiling Point: 790.622 C at 760 mmHg Vapour Pressure: 0 mmHg at 25C

Melting point = 172.5C

Water solubility = 231 mg/L (at 25C)
logP = -1.30
logS = -3.12
pKa = 3.3 (at 25C)
 

 

 

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