Tetracyclines

Tetracyclines

 

Description:

Tetracyclines generally act as bacteriostatic antibiotics. Broad spectrum antibiotics with activity against Gram-positive and Gram-negative bacteria. Resistance is widespread. The tetracyclines are a closely related group of antibiotics with comparable pharmacological properties but different pharmacokinetic characteristics.

 

Mechanism of action:

Tetracyclines inhibit bacterial protein synthesis. Their site of action is the bacerial ribosome - 30 S subunit, thereby preventing binding to those ribosomes of aminoacyl transfer-RNA. Active transport of the drug into the bacterial cell must occur in order for the drug to be effective. Doxycycline enters the cell by passive diffusion.

Source:
Chlortetracycline Streptomyces aureofaciens
Oxytetracycline Streptomyces rimosus
Doxycycline

Semisynthetic

 

Chemical structure:

The basic chemical structure of tetracyclines consists of a hydronaphthacene nucleus containing four hexacyclic fused rings. The chemical differences between the main members of the tetracycline family are in the substituents of three carbon atoms (C5, C6 and C7).
 
   
 
Tetracycline
C5 group
C6 group
C7 group
Tetracycline
- H
- CH3;- OH
- H
Chlortetracycline
- H
- CH3;- OH
- Cl
Oxytetracycline
- OH
-CH3; - OH
- H
Doxycycline
- OH
- CH3
- H

 

Indications: Mycoplasma, Chlamydia, Pasteurella, Ornithobacterium rhinotracheale, Clostridium spp., Spirochetes and some protozoa.

 

Dosage:
Chickens:
Turkeys:
Pigeons:
Oxytetracycline
50 mg/kg
50 mg/kg
ND
Doxycycline
ND
25 mg/kg
ND

 

Drug-Drug Interctions:

Co-administration of tetracyclines with antacids or other drugs containing divalent or trivalent cations, such as calcium, magnesium, iron or sodium content, is contraindicated. Tetracyclines form complexes with such cations, which are very poorly or not at all absorbed.

 

Incompatibility: Penicillins, cephalosporins. 

 

Pharmacokinetics: Variations in clinical efficacy of individual tetracyclines are attributable to differences in their pharmacokinetic properties rather than to differences in quantitative susceptibility of micro-organisms. The factor that underlies the pharmacokinetic properties of tetracyclines is lipid solubility; the degree of lipid solubility differs between individual tetracyclines.

 

OXYTETRACYCLINE
Chemical structure:
Animal species
mg/kg bw
PO
t1/2
(Hr)
Tmax
F (%)
Turkey
10
0.73±0.23
 
* 9.4
**47.6
Chicken 15  0.49 ± 0.38 2.85 ± 0.98 12.13 ± 4.56
 
mg/kg bw
SC

   
Chicken 15  1.19 ± 0.52 3.95 ± 1.71 92.20 ± 10.53
 
mg/kg bw
IM
     
Chicken 15  1.23 ± 0.36 2.6 ± 1.88 76.88 ± 12.90

*Fed; **Fasted

 

DOXYCYCLINE
Chemical structure:
Animal species
Mg/kg bw
PO
t1/2
(Hr)
Tmax
(Hr)
F (%)
Chickens
20
6.03±0.45
0.35±0.02
41.33±2.02
Turkeys 3 day-old
25
10.6
*4.2
**4.7
* 40.0

** 83.7

Turkeys 3 wks-old
25
10.8
*5.3
**1.5
Turkeys 6 wks-old
25
7.9
*4.5
**2.8
Turkeys 12 wks-old
25
10.0
*7.5
**5.4
Turkeys continous 4 day treatment
25
ND
72±42.0
ND

*Fed; **Fasted

Comments: Doxycycline is a second generation tetracycline mainly active against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Doxycycline has low affinity for calcium and is relatively more stable in aqueous solution. It has a high relative liposolubility which readily compensates for the high protein binding. Doxycycline has several advanteges over other tetracycline analogues:

1. Absorption is almost complete
2. Tissue penetration is good
3. Elimination is slower