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fancony like syndrome – outdated tetracycline (epitetracycline, anhydrotetracycline and anhydroepitetracycline) – glycosuria,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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