Pharmacology: Chapter 13: Tetracycline Antibiotics

I. Mechanism of Antibacterial Action:

• Tetracycline:

• Mechanism: Bacteriostatic, acting on bacterial ribosomes, binding to the 30S subunit, preventing tRNA from binding to mRNA, inhibiting protein synthesis.

• Efficacy: Highly effective against both Gram-negative and Gram-positive bacteria.

II. Classification:

• Natural Tetracycline:

• Tetracycline

• Chlortetracycline

• Oxytetracycline

• Demeclocycline

• Synthetic Tetracycline:

• Meclocycline

• Methacycline

• Minocycline

• Rolitetracycline

• Tigecycline

III. General Chemical Properties:

• Structural features:

• Derivatives of polycyclic napthacene carboxamide (octahydronaphtacen)

• 4 fused hydrocarbon rings

• Physical properties:

• Fluorescent in alkaline media.

• Dimethylamin at position 4 imparts alkalinity.

• Gives alkaloid reaction with picric acid, iodomercuric, iodoiodid.

• Forms color with Fe3+, forms insoluble chelate complexes with metal ions.

• Aqueous form produces anhydrotetracycline derivative when exposed to acidic environment.

IV. Pharmacological Properties:

• Absorption:

• Absorbed through the gastrointestinal tract, but affected by factors such as pH, metal ions, etc.

• Minocycline has the best absorption, almost 100% through the gastrointestinal tract.

• Chlortetracycline has the poorest absorption.

• Distribution:

• Widely distributed throughout the body, entering various tissues and body fluids.

• Excretion:

• Primarily excreted in urine and feces.

• Half-life:

• Doxycycline and Minocycline have a half-life of over 16 hours, providing prolonged efficacy.

• Efficacy:

• Minocycline > Doxycycline > Tetracycline and Oxytetracycline…

• Effects:

• Against bacterial infections caused by various Gram-negative and Gram-positive bacteria.

• Used to treat various bacterial infections, especially acne.

V. Notes:

• Specific indications:

• For acne.

• Drug interactions:

• Phenytoin and barbiturates reduce the effect of Tetracycline by increasing the induction of liver enzymes responsible for drug metabolism.

• Contraindications:

• Pregnancy and children under 8 years old.

• Side effects:

• Superinfection => pseudomembranous colitis.

• Formation of Tetracycline-calcium-orthophosphat complex => tooth discoloration.

VI. Resistance mechanism:

• Resistance due to efflux pumps (Efflux system).

VII. Preparation:

• Minocycline:

• Removal of OH and CH3 at position 6.

• Replacement of halogen with amine at position 7.

• Doxycycline:

• Catalytic hydrogenation of metacyclin under pressure.

VIII. Types of Tetracycline:

• Tetracycline:

• Used to treat respiratory, skin, and urinary tract infections.

• Absorption is reduced by dairy products, iron, and antacid drugs.

• Chlortetracycline:

• Lowest gastrointestinal absorption.

• Oxytetracycline:

• Used to treat respiratory, skin, and urinary tract infections.

• Absorption is reduced by dairy products, iron, and antacid drugs.

• Demeclocycline:

• Used to treat urinary tract infections.

• Meclocycline:

• Has prolonged action.

• Methacycline:

• Has prolonged action.

• Minocycline:

• Best absorption, almost 100% through the gastrointestinal tract.

• Absorption is not reduced by dairy products, iron, and antacid drugs.

• Twice as active as other Tetracyclines against Gram-negative and Gram-positive bacteria.

• First choice for “traveler’s diarrhea”.

• Rolitetracycline:

• Has prolonged action.

• Tigecycline:

• The best drug in the Tetracycline group for treating anaerobic bacteria and used to prevent leptospirosis.

• Has prolonged action.

IX. Structure and Activity:

• Structure at position 6:

• No change in effect when changing the CH3 (alpha) and OH (beta) groups at C6.

• Structure at position 7:

• Adding a dimethylamino group to C7 increases lipophilicity, aiding in ribosome binding.

• Structure at position 4:

• Epimerization of the N(CH3)2 group at C4 reduces activity by 90%.

• A/B ring cis:

• Increases antibacterial activity.

• C12 bearing alpha OH group:

• Increases antibacterial activity.

X. Notes:

• Food significantly affects the absorption of Tetracyclines, except for Minocycline and Doxycycline.

• Tetracycline does not treat H. pylori.

• In pH < 2, the OH group (C6) is removed, leading to loss of activity.

• In pH > 8.5, Tetracycline decomposes to form inactive derivatives.

• Doxycycline is stable in the gut environment due to the absence of OH-C6.

• The multiple keto-enol pairs of Tetracycline form chelate complexes with metals.

XI. Summary:

• Tetracycline is a group of bacteriostatic antibiotics that act on bacterial ribosomes, inhibiting protein synthesis.

• There are many types of Tetracycline, both natural and synthetic, each with its own characteristics and indications.

• Absorption of Tetracycline is affected by many factors, with Minocycline having the best absorption.

• Side effects of Tetracycline include superinfection, tooth discoloration.

• Resistance mechanism is primarily due to efflux pumps.

XII. Additional Information:

• Tetracycline is used to treat various bacterial infections, especially acne.

• Tetracycline should be used according to the doctor’s prescription to avoid side effects.

• Tetracycline should be avoided for pregnant women and children under 8 years old.

XIII. References:

• Pharmacology lectures.

• Specialized materials on antibiotics.

Note:

• The information in this article is for reference only.

• Consult with a doctor before using Tetracycline.