Broad spectrum antibiotic tetracycline converted

Broad Spectrum Antibiotic:Tetracycline,four cyclic rings,Physicochemical Properties,Classification-According to source and Based on Duration of action ,Mechanism of action-30S ribosomes ,Inhibit protein synthesis,Antimicrobial spectrum
Resistance
Adverse effects
Precautions,Uses by snehal chakorkar

1. Miss Snehal S. Chakorkar (M.pharm)
Dept Of Pharmacology
1
Broad Spectrum Antibiotic:
Tetracycline
Miss Snehal S. Chakorkar (M.pharm)
Dept Of Pharmacology

2. 2
Introduction:
•It contains nucleus of four cyclic rings.
•Tetracycline obtained from
soil actinomycetes.
The firstintroduced was
chlortetracycline in 1948 under the
nameaureomycin (because of the
golden yellow colour of S.
aureofacienscolonies producing it)
Tetracycline

3. 3
All tetracyclinesare slightly bitter solids.
which are slightly water soluble, but their
hydrochlorides are more soluble.
Aqueous solutions are unstable.
The subsequently developed members have high
lipid solubility, greater potency and some other
differences.
Physicochemical Properties:

4. 4
Classification
According to source:
Naturally occurring :
Ex-Tetracycline, Chlorotetracycline, Demeclocycline.
Semi-synthetic:
Ex-Doxycycline, Lymecycline, Meclocycline.
Prodrugs:
Ex-Rolitetracycline, Lymelicycline, Pipacycline,
Guamecycline.

5. 5
Based on Duration of action :
Short acting(half-life 6 8hrs):
Ex-Tetracycline, Chlortetracycline, Oxytetracycline.
Intermediate acting(half-life12hrs):
Ex-Demeclocycline, Methacycline.
Long acting(half-life is 16hrs):
Ex-Doxycycline,Minocycline,Tigecycline.

6. 6
Mechanism of action: Tetracycline
primarily bacteriostatic; inhibit protein synthesis
peptide chain fails to grow.
30S ribosomes
Tetracycline
bind to
In gram-negative bacteria tetracycline's diffuse through porin
channels.
More lipid-soluble members (doxycycline, minocycline) enter by
passive diffusion (higher potency).
Inhibit protein synthesis

7. 7
Most all types pathogenic microorganisms except fungi
and viruses;
More antibacterial action on
1. Cocci: Gram-positive and gram-negative cocciwere originally
sensitive, but now only few Strep. pyogenes, Staph. aureus
(includingMRSA) and enterococcirespond.
Tetracyclines(especially minocycline) are now active against N.
gonorrhoeae and N. meningitidis.
2. Most gram-positive bacilli, e.g. Clostridia and other
anaerobes, Listeria, Corynebacteria, Propionibacteriumacnes, B.
anthracisareinhibitedbut not Mycobacteria, except M. Leprae(to
minocycline) and some atypical ones.
Antimicrobial spectrum

8. 8
3. Sensitive gram-negative bacilli are—H. ducreyi,
Calymmatobacteriumgranulomatis, V. Choleraeetc many
anaerobes.
4. Spirochetes, including T. pallidumand Borreliaare quite
sensitive.
5. All rickettsiae(typhus, etc.) and chlamydiaeare highly sensitive.
6. Mycoplasmaand Actinomycesare moderately sensitive.
7. Protozoa like Entamoeba histolytica and Plasmodia are inhibited
at high concentrations.

9. 9
Resistance
Resistance develops by following mechanism;
•Bacteria acquire capacity to pump tetracycline
out.
•Bacterial Plasmid synthesize ‘protection’ protein
which prevent the tetracycline to bind with
ribosomal binding site.
•Elaboration of tetracycline inactivating enzymes
(tetracyclineresistance)

10. 10
Pharmacokinetics
Absorption:incompletely absorbed from GIT. absorption is
better if taken in empty stomach.
Tetracyclineshave chelating property and form insoluble and
unabsorbablecomplexes with calcium and other metals. Milk,
iron preparations, nonsystemicantacids and sucralfatereduce their
absorption.
Distribution:widely distributed in the body (volume of
distribution > 1 L/kg). concentrated in liver, spleen and bind to the
connective tissue in bone and teeth.
Metabolism: Liver.
Excretion:urine by glomerularfiltration.

11. 11
Dosage forms
Capsule:Oral capsule is the dosage most preferred. The capsule
should be taken ½ hr before or 2 hr after food.
Liquid oral preparations for paediatric use are banned in India.
I.m. route produces pain, Slow i.v. injection may be given in
severe cases.
A variety of topical preparations (ointment, cream, etc.) are
available, but should not be used causes sensitivity reaction.

12. 12
Adverse effects
A.Irritative effects Tetracyclines.
B.Organtoxicity is dose related.
1.Liver damage
2.Kidney damage
3.PhototoxicityA sunburn
4.Teeth and bones
5.Antianaboliceffect
6.Increased intracranial pressure
7.Diabetes insipidus
8.Vestibular toxicity
C.Hypersensitivity.
D.Superinfection

13. 13
A.Irritativeeffects :
Tetracyclineshave irritant property; on oral
administration causes epigastricpain, nausea, vomiting
and diarrhoea.
Odynophagia(esophagealulceration) occurred when
material from capsules releases in the esophagusduring
swallowing.
Intramuscular injection of tetracyclinesis very painful;
thrombophlebitisoccurs on repeated i.v. injection.

14. 14
B. Organ toxicity: This is dose related.
1. Liver damage Fatty infiltration of liver and jaundice may
occurs. Oxytetracyclineandtetracyclineare safer in this regard.
Tetracyclinesare risky in pregnant women; can precipitate acute
hepatic necrosis which may be fatal.
2. Kidney damage If existing kidney disease is present then
kidney damage is more.A reversibleFanconisyndrome like
condition is produced due to degraded products—epitetracycline,
anhydrotetracyclineand epianhydrotetracyclinewhich damage
proximal tubules.
Exposure to acidic pH, moisture and heat favours sucdegradation.
3. PhototoxicityA sunburn-like or other severe skin reaction on
exposed parts. A higher incidence has been noted with
demeclocyclineand doxycycline.

15. 15
4. Teeth and bones Tetracyclineshave chelating property.
Calcium-tetracycline chelategets deposited in developing teeth and
bone.
Given from midpregnancyto 5 months of extrauterinlife, the
deciduous teeth are affected: brown discolouration, ill-formed
teeth.
Given during late pregnancy or childhood, cause temporary
suppression of bone growth, deformities and reduction
in height are a possibility with prolonged use.
5. Antianaboliceffect Tetracyclinesreduce protein synthesis and
have an overall catabolic effect.
They induce negative nitrogen balance and can increase blood urea.

16. 16
6. Increased intracranial pressure is noted in some infants.
7. Diabetes insipidus Demeclocyclineantagonizes ADH action and
reduces urine concentrating ability of the kidney.
8. Vestibular toxicity Minocyclinecan cause ataxia, vertigo and
nystagmus.
C. Hypersensitivity:Skin rashes, urticaria, glossitis, pruritus
aniand vulvae, even exfoliativedermatitis.
Angioedemaand anaphylaxis are extremely rare.
D.SuperinfectionTetracyclinescause more marked suppression of
the resident flora.
Though mouth, skin or vagina may be involved, intestinal
superinfectionby Candida albicanspseudomembranousenterocolitis
is rare.

17. 17
1. Tetracyclinesshould not be used during pregnancy,
lactation and in children.
2. They should be avoided in patients on diuretics: blood
urea may rise in such patients.
3. They should be used cautiously in renal or hepatic
insufficiency.
4. Preparations should never be used beyond their expiry
date.
5. Do not mix injectable tetracyclineswith penicillin—
inactivation occurs.
6. Do not inject tetracyclinesintrathecally.
Precautions

18. 18
Tetracyclinesare broad-spectrum antibiotics. Due to availability
of fluoroquinolonestetracyclinesis less preferd.
1. Empirical therapy : When the nature and sensitivity of the
infecting organism cannot be guessed then tetracycline is used .
They used for initial treatment of mixed infections.
2. Tetracyclinesare the first choice drugs: In following
condition.
A. Venereal diseases
a. Lymphogranulomavenereum
b. Granuloma inguinale: due to Calymm.
c.granulomatis.
B. Atypical pneumonia: due to Mycoplasmapneumoniae.
C.Cholera.
D.Brucellosis.
E.Plague
F.Relapsingfever
G.Rickettsialinfections
Uses

19. 19
3. Tetracyclinesare second choice drugs:
•To penicillin/ampicillinfor tetanus, anthrax, actinomycosisand
Listeriainfections.
•To ceftriaxone, amoxicillin or azithromycin for gonorrhoea,
especially for penicillin resistant non-PPNG; also in patients
allergic to penicillin, but response rate has decreased.
•To ceftriaxonefor syphilis in patients allergic to penicillin; early
syphilis can be treated in 2 weeks but late syphilis requires 1
month.
•To penicillin for leptospirosis; doxycycline100 mg BD for 7
days is curative. Weekly doxycycline(200 mg) has been used as
prophylactic

20. 20
4. Other situations in which tetracyclinesmay be used are:
•Urinary tract infections: Odd cases in which the organism has
been found sensitive.
•Community-acquired pneumonia, when a more selective
antibiotic cannot be used.
•Amoebiasis:along with other amoebicides
•for chronic intestinal amoebiasis.
•As adjuvant to quinine or artesunatefor chloroquine-resistant P.
falciparum malaria .
•Acne vulgaris: prolonged therapy with low doses may be used in
severe cases.
•Chronic obstructive lung disease: prophylactic use may reduce
the frequency of exacerbations, but the risk : benefit ratio is
controversial.

21. 21
Reference:
Rang H.P. and Dale M.M.: Pharmacology, Churchill
Livingstone, Edinbergh.
KatzungB.G.: Basic and Clinical Pharmacology, Lange
Medical Publications, California.
Craig C.R. and StitzelR.E.: Modern Pharmacology, Little
Brown and Co., Boston.
Bowman W.C. and Rand M.J.: Textbook of Pharmacology,
Blackwell Scientific Publications, Oxford.
P.N Bennett & M J Brown: Clinical Pharmacology,
Churchill Livingstone, Edinburgh.
TripathiK.D.: Essentials of Medical Pharmacology, Jaypee
Brothers, Medical Publishers, New Delhi.

22. Any query don’t hesitate to contact & If like then comment in box 22