class broad spectrum antibiotics
TRANSCRIPT
BROAD SPECTRUM ANTIBIOTICS
Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.
Mechanism of action
The tetracyclines reversibly bind to the 30S ribosome and inhibit binding of aminoacyl-t-RNA to theacceptor site on the 70S ribosome.
G+ve -active transportG-ve-porin channels
Classification
Shorter acting: TETRACYCLINE CHLORTETRACYCLINE OXYTETRACYCLINE
Intermediate acting: DEMECLOCYCLINE METHACYCLINE
Long acting: DOXYCYCLINE MINOCYCLINE
Tetracyclines
Spectrum of activity - Broad spectrum; Useful against intracellular bacteria
They are broad spectrum antibiotics, active against most bacteria except Proteus or Pseudomonas.
Resistance
Decreased cell permeability of the drug
Increased drug efflux from bacterial cell by an energy dependent process
Ribosomal protection Enzymatic inactivation of the drug
Pharmacokinetics
Tetracycline, oxytetracycline have short half-lives. Doxycycline has a longer half-life and can be given once per
day. They bind avidly to heavy metal ions and so absorption is
greatly reduced if taken with food, milk, antacids or iron tablets.
They should be taken at least half an hour before food. Tetracyclines concentrate in bones and teeth.
Pharmacokinetics
Distribution: wide Concentrated in liver, spleen and bone & teeth –
minocycline in fats Good CSF penetration Excretion: Primarily in urine (dose adjustment in
renal failure) Doxycycline is exception (bile)
Doxycycline
Longer t1/2, biliary excreation
Demeclocycline-inhibits ADH
Minocycline- 100mg BD for meningococcal carriers Swimming pool granuloma, Chronic facial dermatosis
ADR- vestibular toxicity, skin pigmentation
Clinical uses
1. Rocky mountain spotted fever
2. Relapsing fever3. Psittacosis 4. Pasteurella abscess 5. Plague 6. Pneumonia (mycoplasma)7. Peptic ulcer
8. Acne 9. Amoebiasis 10. Brucellosis11. Borrelia burgdorferi
(Lymes disease)12. Granuloma inguinale13. Tularensis14. Typhus fever15. Malaria
Adverse effects
Gastrointestinal upsets Superinfection- Destruction of normal intestinal flora
resulting in increased secondary infections; Discolouration and deformity in growing teeth and bones
(contraindicated in pregnancy and in children < 12 years) Renal impairment (should be also avoided in renal
disease) Hepatotoxicity Pulmonary eosinophillic syndrome Pseudo tumor cerebri
Adverse effects
fancony like syndrome – outdated tetracycline (epitetracycline, anhydrotetracycline and anhydroepitetracycline) – glycosuria,
proteinuria and aminoacidria etc.1. Phototoxicity: Sunburn like - Skin rashes, mainly after topical
application1. Erythema, brown black discolouration of nails and loosening
etc.2. Teeth and Bones: Brown discolouration - Calcium tetracycline
chelate (orthophosphate)3. Antianabolic effect: reduction in Protein synthesis4. Diabetes Insipidus: antagonizes ADH and urine conc. property5. Vestibular toxicity: Minocycline (ataxia, vertigo, nystagmus)
Drug interaction
Al, Ca, Zn, Mg and iron preparations decrease tetracycline absorption by chelation.
Barbiturates, phenytoin, and carbamazapine Inhibit vitamin K producing intestinal flora
ContraindicationsRenal impairmentHepatic insufficiencyPregnancy
Glycylcyclines
Tigecycline It is a minocycline analogue It binds to 30s ribosomal subunits Spectrum –MRSA, VRE, MDR-strepto.pneummoniae Gram neg cocci-N.gonorrhoea Clostridium, bacteroides 100 mg loading dose, 50mg 12th hourly Eliminated through bile
Chloramphenicol
From streptomyces venezuelae Antimicrobial spectrum- salmonella typhiHaemophilus influenzae,Nisseria meningitidisStreptococcus pneumoniae,Bacteroides fragilis
Mode of action
These antimicrobials bind to the 50S ribosome and inhibit peptidyl transferase activity.
This inhibits bacterial protein synthesis by binding to 50s ribosome and hinder access to amino acyl t-rna site. prevents formation of
peptide bond.
Pharmacokinetics
-Chloramphenicol palmitate used for oral suspensionOrally/IVGlucuronide conjugation and excreated through urineT1/2 -3-5hrsIt is well absorbed and widely distributed , including to
the CNS. It is metabolized by glucoronidation in the liver. Although an effective broad-spectrum antibiotics, its
uses are limited by its serious toxicity.
Clinical uses
The major indication is to treat bacterial meningitis caused by Haemophilus influenzae, or to Neisseria menigitidis or if organism is unknown.It is also specially used for Rickettsia (typhus).
It was used for typhoid fever Dose -50-75mg/kg/day Pelvic and brain abscess Conjunctivitis and external ear infections
Adverse effects
Idiosyncratic apastic anaemia : A rare irreversible anemia, probably immunological in origin but often fatal,
Reversible bone marrow depression caused by its effect on protein synthesis in humans
Gray baby syndrome-abdominal distension, progressive cyanosis, hypothermia, vomiting
Super infection
Drug interaction
PCT- increases bioavailability Potent enzyme inhibitor- inhibits metabolism of
morphine, clhorpropamide, warfarin
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