Introduction:
Tetracyclines are broad-spectrum antibiotics which possess bacteriostatic action.
They are protein synthesis inhibitors. Tetracyclines are not commonly prescribed because of the increased chance of resistance that is associated with it.
The official names of tetracyclines end with the suffix “cycline”.
download as "tetracycline pharmacology pdf".
Source and discovery:
Tetracyclines are obtained from natural sources. Various of its variants are isolated from different strains of soil-dwelling bacteria.
For example;
The prototype drug is isolated from a soil-living bacteria ”Streptomyces’s”.
Similarly, chlorotetracycline is isolated from “Streptomyces aurofacians”. Chlortetracycline was discovered by Dugger who was employed in lederle company in late 1940.
Oxytetracycline was isolated from Streptomyces for the first time by “ac finley”.
Chemistry:
Tetracyclines are derivatives of polycyclic naphthacene carboxamide.
The basic ring is a naphthacene nucleus which is common in all of its members with a difference in methyl groups.
Classification:
Tetracyclines are classified taking different basis of classification under considerations. These are their source, pharmacokinetic or duration-based classification.
Source based classification:
On basis of source, tetracyclines are classified into natural and semisynthetic.
Tetracyclines of natural source:
Following of its members are isolated from a natural source with no chemical modification involved;
- Tetracycline
- Chlortetracycline.
- Oxytetracycline.
- Demeclocycline.
Tetracyclines of semisynthetic source:
Semisynthetic, are those for which the starting material is of natural source followed by chemical modifications. These are;
- Doxycycline
- Lymecycline
- Meclocycline
- Methacycline
- Minocycline
- Rolitetracycline.
Duration/ pharmacokinetic-based classification:
In this classification tetracyclines are classified into short-acting, intermediate and long-acting i.e their duration of action. this is also called pharmacokinetic-based classification because these are directly associated with their pharmacokinetic properties like absorption etc.
Short-acting tetracyclines:
The duration of action of these drugs lasts from 6-12 hours. they are from 30-60% absorbed from the gut. These drugs as oral, topical or in iv.
Their dosage frequency is QID.
Short-acting includes the following examples.
- Oxytetracyclines
- Chlortetracycline
- Tetracycline (prototype drug).
Intermediate-acting:
Intermediate-acting tetracyclines last from 12-16 hours in their duration of action. and the peak git absorption from git is 60-80%. Their dosage frequency is two times daily B.D. and is often administered orally.
Following are the members of this class.
- Demeclocycline
- Methacycline etc.
Long-acting tetracyclines:
The long-acting tetracyclines as evident from their name have a long duration of action ranging from 16-24 hours.
The peak GIT absorption is more than 95%. These are administered often as oral or in IV.
Doxycycline and minocycline are the examples of long-acting.
Mode of action/ pharmacodynamics of tetracyclines:
Tetracyclines are protein synthesis inhibitors. This indicated that they alter the protein synthesis which involves the alteration of some steps which are involved in the protein synthesis in bacteria.
Following are some intermittent steps involved;
· tetracyclines enter the bacterial cell.
· They bind to 30S (smaller) ribosomal subunit.
· This prevents access of aminoacyl tRNA to mRNA-ribosome complex.
· This prevents the addition of amino acid to the growing peptide chain.
· The final effect is that the protein synthesis in inhibited.
The binding of tetracyclines to smaller subunit is irreversible that’s why these drugs are bacteriostatic however in large doses they behave bactericidally.
The spectrum of tetracycline antibiotics:
Tetracyclines are effective against a wide range of microbial infections caused by different species of gram positive and negative bacteria.
Following pathogens are included in its spectrum;
- Mycoplasma pneumoniae
- Chlamydia trachomatis
- Treponema pallidum
- Borrelia spp.
- Yersinia pestis spp.
- Brucella melitensis
- Francasilla tularensis
- Protozoal spp
- Plasmodium spp
- Bascillus anthrax
- Vibrio cholera
- Amoeba.
Tetracyclines are less efficacious against gram-positive than penicillin’s and cephalosporins and are less efficacious against gram-negative than aminoglycosides and chloramphenicol
They are also effective against some protozoans.
Tetracyclines also have considerable clinical effectiveness against rickettsia, chlamydia, spirochetes and mycoplasma.
Clinical uses of tetracyclines:
Tetracycline is the drug of choice for;
A) Chlamydial infections:
The chlamydial infections against which tetracycline is drug of choice includes; trachoma (infectious blindness), lymphogranuloma venurum (std infections). Pelvic inflammatory diseases like endometritis, salpingitis, urethritis.
B) Mycoplasma infections:
Tetracycline is the drug of choice for mycoplasmal infections like mycoplasma pneumonia.
C) Rickettsial infections:
Tetracycline is also found effective in rocky mountain spotted fever, typhus fever, rickettsialpox, Q-fever, scrub fever.
D) Spirochetes infections:
borellia, Lyme disease is caused by the bite of a tick infected with borrelia. This is an infection of spiral bacteria origin and can be clinically managed with spirochetes.
Bacterial Resistance against tetracyclines:
The bacterial resistance against tetracyclines may develop via different mechanisms. They may include;
Efflux pump development:
The bacteria develops permeases proteins that flush outs the drug from the cell via active transport.
Target site alteration:
Bacteria can modify the receptor site for tetracycline.
Enzymatic degradation:
The bacteria develop such enzymes that bring lyses of the bacterial cell wall.
Side effects:
tetracycline, when administered, may be accompanied by a long list of side effects i.e;
Git distress even opportunistic infections can develop like pseudomembranous enterocolitis can be caused which is characterized by bloody diarrhoea.
Nephrotoxicities can result especially by improper used i.e by the use of an expired drug.
The ailment is called Fanconi syndrome characterized by severe kidney damage.
It can adversely affect growing teeth and bones because of the deposition of calcium or phosphate complexes deposition. This discolouration is permanent.
Moreover, it also stops the growth of bones and cartilage and teeth so should not be used in children.
Hypersensitivity especially photosensitivity is also a common side effect with Sulphur containing drugs. So exposure to sun should be avoided.
Drug-induced diabetes insipidus can be caused by tetracyclines especially more prominent with minocycline. This is because of its antagonism with ADH. The syndrome is called SIADH syndrome if inappropriate adh secretion.
Demeclocycline is safe in terms of ADH antagonism and cannot induce diabetes insipidus which can serve as an alternate option.
With minocycline, oto and vestibular toxicities can result.
Tetracyclines can also necrosis.
Drug-drug interactions:
Tetracyclines should not be used with dairy products, multivitamins or antacids.
Because this can result in decreased bioavailability due to complexes formation.
Contraindications:
Tetracyclines are contraindicated in pregnancy, in children (except demecyclines) and in patients with renal insufficiency.
