Wesley mugambi

Tetracyclines:

Tetracyclines:

-a broad-spectrum antibiotics.

-It is commonly used to treat acne,infection, and other infections caused bybacteria.

-The first of these compounds waschlortetracycline followed byoxytetracycline and tetracycline.

Tetracycline divided into:

a) Naturally occurring:

1-tetracycline 2-chlortetracycline

3-oxytetracycline 4-demeclocycline

Semisynthetic occurring:

1-doxycycline 2-minocycline

3-meclocycline 4-lymecycline

5-methacycline 6-rolitetracycline

Total Synthesis of the Tetracyclines:

Structure and chemical characteristics

•

Structure activity relationship

• R5 R4 R3 R2 R1.

Chlortetracycline H H OH CH3 ClOxytetracycline H OH OH CH3 HTetracycline H H OH CH3 H

Demethylchlortetracycline H H OR H CI

Rolitetracycline + H OH CH3 HMetacycline H OH CH2 HDoxycycline H OH H CH3 HMinocycline H H H N(CH3)2

• Retention of the configuration of the asymmetric centres C-4, C-4a and C-12a is essential, whereas the configurations at C-5, C-5a and C-6 may be altered:

• 1- The amide hydrogen may be replaced with a methyl group, but larger groups have a deleterious effect except for those which are eliIminated spontaneously in water .

• 2-The dimethyl amino group may be replaced by a primary amino group without loss of in vitro activity but all other changes so far lead to decreased bacteriostatic action .

• The hydrophobic part of the molecule from C-5 to C-9 may be altered in various ways:

• modifications at C-6 and C-7 in particular afford products having greater chemical stability.

• increased antibiotic activity and more favourable pharmacokinetics

• Dehydrogenation to form a double bond between C-5a and C-11a markedly decreases activity

• Polar substituents at C-5 and C-6 contribute decreased lipid versus water solubility to the tetracycline

• . The drugs are amphoteric, meaning they will form salts with both strong acids and bases. Thus, they may exist as salts of sodium or chloride.

Spectrum:

-The tetracyclines are broad-spectrum antibiotics.

-They are active against the following microorganisms:

1_ gram-positive and gram-negative bacteria

2_ spirochetes

3_ mycoplasmas,

4_ rickettsiae,

6_ Candida albicans

7_Mycoplasma pneumoniae8_Chlamydia trachomatis9_Borrelia recurrentis.10_Yersinia pestis11_Vibrio cholerae12_ Campylabacter fetus13_Brucella specie14_Streptococcus pneumoniee. 15_Neisserie gonorrhoeae

Mechanism of action:

Mechanism of resistance :

There are three types of tetracycline

resistance:

1)tetracycline efflux.

2)ribosomal protection.

3)tetracycline modification.

Types of tetracyclines:

1-Demeclocycline:

Uses:

-treat cancer patients with SIADH.

-treat hyponatremia.

-combined with hydrocortisone in a paste used

by dentists .

-treat trachoma.

Side effect:

Dermatological:-Skin reactions, photosensitivity GIT:-nausea, vomiting, and diarrhea.

CNS:-Dizziness,visualdisturbances .

Immune System:-allergic reactions. Other:-yellowish-grayish-brown discoloration of the teeth.

Pharmacodynamics/Kinetics:

-Absorption: ~50% to 80%.

-Protein binding: 41% to 50%

-Metabolism: Hepatic.

-Half-life elimination: 10-17 hours

-Time to peak, serum: 3-6 hours

-Excretion: Urine

2-Chlortetracycline:

Uses:-used as antibacterial and antiprotozoal agent.-In veterinary medicine, it is commonly used to treat conjunctivitis in cats.

3-Oxytetracycline:

Uses:

-treat Spirochaetal infection.

-treating Non-Specific-Urethritis.

-treating Clostridial wound infection and Anthrax.

Side effects:

-Local irritation after intramuscular injection.

-Gastrointestinal:-anorexia, nausea, vomiting.

-Renal toxicity.

-Hypersensitivity reactions:  Urticaria.

-Blood:  Hemolytic anemia, thrombocytopenia, neutropenia

1-tetracycline:

Uses:

-Tetracycline's primary use is for the treatment of acne vulgaris and rosacea.

-It is also used to treat a very wide range of infections.

Side effects:

-Gastrointestinal: anorexia, nausea, vomiting, diarrhea,

-Skin: rashes, dermatitis.-Renal Toxicity-Hepatic Cholestasis: -HypersensitivityReactions:Anaphylaxis,Miscellaneous: Dizziness and headache

4- Minocycline:

Uses:

-typhus fever and Q fever.

-Psittacosis Trachoma

-Nongonococcal urethritis.

-Brucellosis.

Side effects:

-Hypersensitivity reactions:Urticaria,anaphylaxis.

-GI :Anorexia, nausea, vomiting, diarrhea.

-Hepatic toxicity: Hyperbilirubinemia.

-Respiratory:Cough, dyspnea.

-Blood:Agranulocytosis, hemolytic anemia.

-CNS: Convulsions, dizziness,sedation.

-Oral cavity discoloration.

Pharmacokinetics:

-rapidly absorbed from the GIT.

-The peak plasma concentrations slightly

decreased.

-serum half-life ranged from 11 to 16 hours in

hepatic dysfunction, and from 18 to 69 hours

with renal dysfunction.

5-doxycyclines

Uses:

used in the treatment of chronic adult

periodontitis.

Side Effects:

-Nausea, Vomiting,Diarrhea.

-photosensitivity, rash.

-dyspepsia

-dysphagia.

-Watery diarrhea

-Bloody stools

Drug interaction of tetracyclines::

antacids containing aluminum, calcium, or magnesium, and iron-containing preparations

Impaire the Absorption of tetracyclines

anticoagulant therapy Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

bacteriostatic drugs interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin.

oral contraceptives Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective.

ergot alkaloids or their derivatives are given with tetracyclines.

Increased risk of ergotism

Bile acid sequestrants May decrease tetracycline absorption

Iron preparations May decrease absorption of tetracyclines

Methoxyflurane: Methoxyflurane anesthes

when concurrent with tetracycline) may cause fatal nephrotoxicity; concurrent use is contraindicated.

Methotrexate: Clearance of methotrexate (high-dose therapy) may be decreased by tetracyclines.

TETRACYCLINES AVAILABLE IN THE UNITED STATES

Generic name Trade names Preparations

Demeclocycline Declomycin Oral

Doxycycline Vibramycin, Doryx, Doxycin, Monodox, and others

Oral and parenteral

Minocycline Minocin Oral and parenteral

Oxytetracycline Terramycin Oral and parenteral

Tetracycline Achromycin V, Panmycin, Robitet, Sumycin, Tetracyn, and others

Oral and parenteral