broad spectrum antibiotics
TRANSCRIPT
BROAD SPECTRUM ANTIBIOTICS
TETRACYCLINE&
CHLORAMPHENICOL
DR. MOHAMMED ABDUL RAOFPHARMACOLOGY(D.C.M.S).
STRUCTURE OF TETRACYCLINE
STRUCTURE OF TETRACYCLINE
TETRACYCLINES have a ring structure:FOUR-CYCLIC-ANTHRACYCLIN
Different substitution on ring structure affecting their pharmacokinetics
TETRACYCLINEIt is a BROAD-SPECTRUM ANTIBIOTIC. Obtained from soil actinomycetes.Slightly bitter & weakly water soluble. Discovered by- DR.YELLAPRAGADA SUBBA RAO.TETRACYCLINES have a ring structure: FOUR-CYCLIC-ANTHRACYCLIN Different substitution on ring structure
affecting their pharmacokinetics. Consumption of out-dated Tetracycline –
Fanconi’s syndrome.
CLASSIFICATION OF TETRACYCLINE:
GROUP 1: Shorter Acting (t1/2 =6-10 hours) TETRACYCLINE, CHLORTETRACYCLINE OXYTETRACYCLINE GROUP 2: Intermediate Acting(t1/2=12-13 hours) DEMECLOCYCLINE METHACYCLINE GROUP 3: Long Acting(t1/2=18-20 hours) DOXYCYCLINE MINOCYCLINE
Pharmacodynamics:
Tetracycline's are bacteriostatic. The carrier involved in the active transport of
tetracycline's are absent in the mammalian 60S/40S cellular ribosomal units, hence they cannot damage host but selectively toxic to the microorganisms only.
In Gram positive bacteria's – tetracycline's enter the cytoplasm by an energy-dependent active transport system, once inside the bacterial cell, tetracycline's inhibit the bacterial protein synthesis by binding to their 30S ribosomal subunit and blocking the attachment of t-RNA & m-RNA resulting in the peptide chain growth failure.
In Gram negative bacteria's - tetracycline's enter the outer membrane by passive diffusion through their pore channels.
The tetracycline's (T) bind to the 30S subunit and prevent binding of the incoming charged tRNA unit. Step 1 in protein synthesis.
Pharmacokinetics:Tetracycline's are absorbed from GIT with variable
bioavailability Tetracycline's are widely distributed except C.S.F. cross placental barrier excreted in the milk.Tetracycline's are readily deposited in teeth, bones and
tumours.Dairy products, antacids & iron preparation's impair
tetracycline's absorption either by chelation/altering the gastric PH except doxycycline and minocycline.
Tetracycline induces the action of Phenytoin, Warfarin & Chlorpropamide
Metabolized in the liver, concentrated in bile and excreted in urine.
In renal impairment needs dose adjustment for long acting tetracycline's except Doxycycline.
Anti Microbial spectrum:HIGHLY ACTIVE Rickettsia,
Chlamydia Psittaci, Chlamydia Trachomatis ,Chlamydia Pneumoniae.
HIGHLY EFFICACIOUS
Spirochete's like - Borrelia burgdorferi, Borrelia recurrentis.
HIGHLY SENSITIVE
Atypical pathogen like -Mycoplasma pneumoniae, -Ureaplasma urealyticum. Gram-negative bacilli like – Vibrio Cholerae,Brucella abortus Helicobacter pylori, Yersinia pestis Actinomyces israeli,Francisella tularensis.
RESISTANCE :•Four mechanisms by which an organism develops resistance to tetracycline's-Decreased cell permeability of the drug.Increased drug efflux from bacteria by energy-
dependant process.Initiation of ribosomal protection which results
in decreased affinity for the drug by ribosomes binding sites.
Enzymatic inactivation of the drug.•Almost all gram-positive and gram-negative cocci and gram negative bacilli have become resistant. Some gram positive bacilli are inhibited without clinical benefit.
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CONTRA INDICATIONS:• Renal impairment • Hepatic insufficiency• Pregnancy• Lactation • in Children’s less than 10years of age.• Intraathecial injections should be avoided.
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CLINICAL USES & DOSES:TREATMENT DISEASE CONTROL USES/DOSES
FIRST CHOICE Rocky mountain fever, Typhus fever, Relapsing fever, Psittacosis, Lyme disease, Atypical pneumonia.
Group1:250mg QID oral/ivGroup 2:300mg BID oralGroup 3:100mg BID oral/iv
EFFECTIVE Brucellosis,H.Pylori, Tularaemia,Plague, Bacteraemia,Acne v, Abscesses,Trachoma,Non specific urethritis / cervicitis,Chronic Amoebiasis,Resistant malaria.
Tetracycline in combination with Streptomycin/Bactrim DS/Amoxicillin.
ERADICATION OF CARRIER STATE
Meningococcal, swimming pool granuloma, Anthrax.
Minocycline 100mg BID oral for 5days
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Precautions• During pregnancy and lactation• Avoided in patients on diuretics• Renal/hepatic insufficiency• Avoid preparation beyond expiry date• Do not mix injectable TC with penicillin-
inactivation occurs.• Do not inject tetracycline's Intra-thecally.
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ADVERSE EFFECTS: ROUTE OF ADMINISTRATION
ADVERSE EFFECTS
ORAL ADMINISTRATION Nausea, Vomiting, Epigastric burning, diarrhoea, Stomatitis, Chronic fungal Esophagitis, Inhibit intestinal flora.
I.V. ADMINISTRATION Thrombophlebitis.I.M. ADMINISTRATION Painful local irritationOINTMENTS Painful local irritation & sensitization.CHRONIC ADMINISTRATION
Super infections, Stomatitis, Chronic fungal esophagitis, temporary suppression of bone growth, Staining of teeth, Headache, Pseudotumour cerebri,Vestibular toxicity, Anti-anabolic effects, Minocycline photosensitivity, Hepatotoxicity in pregnancy, Cumulative renal toxicity in impaired renal functions,Demeclocycline induced nephrogenic diabetes insipidus.
CHLORAMPHENICOL
It is a NATURALLY OCCURING BROAD-SPECTRUM ANTIBIOTIC largely bacteriostatic isolated from STREPTOMYCES VENEZUELAE.
It is yellowish white crystalline light-sensitive & intense bitter in taste.
CHLOROMYECTIN posses a NITRO GROUP AS NITROBENZENE MOIETY which is responsible for its anti-bacterial property.
Chloramphenicol is active against a wide range of Gram-negative organisms, Gram positive organisms and serious anaerobic infection.
Chloramphenicol is used topically for treating conjunctivitis and external ear infections.
Chloramphenicol was earlier drug of choice for typhoid fever.
Pharmacodynamics:Chloramphenicol is bacteriostatic in low doses
and bactericidal in high doses. MOA: inhibits bacterial protein synthesis by
binding to the 50S ribosomal subunit. In Gram positive bacteria-enter the cytoplasm
by an energy-dependent active transport system, tetracycline's inhibit the bacterial protein synthesis by binding to 50S ribosomal subunit and blocking the attachment of t-RNA & m-RNA resulting in the peptide chain growth failure.
In Gram negative bacteria’s-enter the outer membrane by passive diffusion through pores.
Chloramphenicol (C) and macrolides (M) bind to the 50S ribosomal subunit and block transpeptidation Step 2 in the bacterial protein synthesis.
Pharmacokinetics :Chloramphenicol on oral administration rapidly
and completely absorbed from GIT. Chloramphenicol widely distributed
throughout the body tissues and fluids including C.S.F.
Crosses placental barriers & also present in breast milk.
Metabolized in the liver by Glucuronyl conjugation, concentrated in bile or excreted in urine.
Plasma half-life is 3-5 hours.Paracetamol increases the bioavailability.Chloramphenicol is a potent enzyme inhibitor,
inhibits the metabolism of morphine, warfarin,..
Anti Microbial spectrum:HIGHLY ACTIVE
Salmonella typhi, Haemophilus influenza, Neisseria meningitides,Streptococcus pneumonia, Penicillin-resistant Bacteroides fragilis.
SENSITIVE Spirochetes',Rickettsia,Mycoplasma,Klebsiella,Chlamydia.
RESISTANCE :Three mechanisms by which a bacteria develops resistance to Chloramphenicol-Decreased cell permeability of the drug.Initiation of ribosomal protection which results
in decreased affinity for the drug by ribosomes binding sites.
Production of R-plasmid as well as chromosomal mediated chloramphenicol acetyltransferase that metabolizes chloramphenicol to an inactive form.
•CONTRA INDICATIONS:•Renal impairment, Hepatic insufficiency, Pregnancy, Neonates, blood forming diseases.
ADVERSE EFFECTS:Chloramphenicol induces bone marrow depression and
aplasia, use is no longer .SEVERE / FATAL
Idiosyncratic Aplastic anaemia –It is unrelated to the dose has a genetic cause. Gray baby syndrome –neonates cannot conjugate chloramphenicol, slow GFR can lead to fatal neonatal toxicity.Super-infection.
REVERSIBLE Dose related bone marrow depression when daily doses exceeds 3-4gram/day for more than 1-2weeks.Recovery after 3-6weeks of Discontinuation of treatment.
IRRITABLE EFFECTS
Nausea, Vomiting, Diarrhoea, Pain on injection.
As an clinician our advice to the patients:
THANK YOU