Antibiotic

WHAT ARE MACROLIDES?

They are antibiotics having a macrocyclic lactone ring with attached sugars.
THE COMMONLY USED MACROLIDES ARE:
Erythromycin
Clarithromycin
Roxithromycin
Azithromycin
Spiramycin
Josamycin

ERYTHROMYCIN

First isolated from Streptomyces erythreus in 1952
Widely employed as an alternative to penicillin

MECHANISM OF ACTION

It is bacteriostatic at low conc & bactericidal at high conc
Bactericidal property depends on the conc, organism concerned and its rate of multiplication
Erythromycin acts by inhibiting bacterial protein synthesis. It combines with 50s ribosome subunits and prevent translocation.


ANTIMICROBIAL SPECTRUM
Spectrum is similar to Pencillin G. Mostly gram +ve and few gram –ve bact.
Str. pyogenes , Str. Pneumonia, N. gonorrhoea, Clostridium, C. diphtheriae and Listeria
In addition, Campylobacter, Legionella, Branhamella catarrhalis, G. vaginalis and Mycoplasma (which are not affected by pencillin are also highly susceptible to erythromycin)
Moderately sensitive to, H. influenza, B. pertussis, C. trachomatis, N. meningitidis and Rickettsiae
Ineffective against Enterobacteriaceae, other gram negative bacilli and B. fragilis

Pharmacokinetics

Absorption incomplete but adequate from intestine
Inactivated by gastric HCL, hence given as :
Enteric coated tablets or ester (stearate, ethyl succinate )
Food delays absorption
Not metabolized and actively secreted in bile ( major route of excretion )
Widely distributed into most tissues, except the brain and CSF
Cross the placental barrier
Protein binding – 70- 80 %
Half – life approx. 1.6 hr

Major excretion through liver. Renal excretion is minor

Only 2-5 % is excreted in active form in urine


Adverse Effects
• Gastrointestinal – epigastric pain, diarrhea
• Reversible hearing loss
• Hypersensitivity – fever, rash
• Cholestatic hepatitis - rare
• > 1 to 2 weeks of erythromycin estolate
Interaction
It inhibits hepatic oxidation of many drugs – it rises plasma level of theophylline, carbamazepine, valproate, ergotamine and warfarin

USES

As an alternative to penicillin
• Streptococcal pharyngitis, tonsillitis, mastoiditis and OM
• Alternative prophylaxis for RF and SABE
• Diphtheria
• Tetanus as an adjuvant to TT
• Syphilis and gonorrhoea
• Leptospirosis
•
As a first choice drug for
• Atypical pneumonia caused by Mycoplasma
• Whooping cough
• Chancroid


NEWER MACROLIDES
ROXITHROMYCIN
CLARITHROMYCIN
AZITHROMYCIN

Clarithromycin

Pharmacokinetics
Acid stable
Food delays absorption but does’nt alter its extent
Metabolized by the liver to 14- hydroxy clarithro. ( active )
Widely distributed, except brain and CSF
Protein binding 40 – 70 %
Excreted in Urine – unchanged 20 – 40 %
Biliary 14- H. clarithromycin 10 – 15 %
Half- life clarithromycin 3 – 7 hr
14 – H. clarithromycin 5- 9 hr
Advantage over erythromycin
Lower frequency of GI intolerance
Less frequent dosing ( twice daily )
• Indications
• Pharyngitis / tonsilitis
• Otitis, sinusitis
• Adjunct in treatment of duodenal ulcer ( H. pylori )


MACROLIDES ( cont. )
Azithromycin
Pharmacokinetics
Rapidly absorbed from GIT
Food delays absorption
Widely distributed ( extensive tissue distribution ), except CSF
Protein binding 51%
Undergo some hepatic metabolism ( inactive )
Biliary route is the major route of elimination
Only 6% is excreted unchanged in the urine
Half- life approx. 3 days
Mainly effective on G- bacteria but less active against G+(s.pneumoniae & s.pyogenes) than erythromycin
Advantage over erythromycin & clarithromycin
Once daily dosing
No inhibition of cytochrome P- 450
• Indications
• Pharyngitis/ tonsilitis ( s. pyogens ), otitis, sinusitis ( Staph. Aureus & H. influenzae )
• Uncomplicated genital chlamydial infections

By Pulse MBBS visit as at pulsembbs.blogspot.com

Spiramycin crosses the placenta and reaches a concentration 5 times higher than the serum so used in therapy of toxoplasmosis during pregnancy


NOTE: Azithromycin is less active than erythromycin and clarithromycin against streptococcus and staph. Aureus but more than them in activity against H. influenza.

By Pulse MBBS visit as at pulsembbs.blogspot.com

• With regard Macrolides, all the followings are false except
• It act on the 30S subunit of the bacterial ribosomes.
• Food do affect absorption of erythromycin from stomach.
• Azithromycin do affect cytochrome P-450 seriously.
• Azithromycin is more effective than clarithromycin against G+ve aerobic bacteria.
• Clarithromycin is more effective than azithromycin against G -ve aerobic bacteria.

By Pulse MBBS visit as at pulsembbs.blogspot.com

• With regard Chloramphenicol, all the followings are false except
• It act by inhibiting bacterial cell wall synthesis.
• It did not crosses blood brain barrier.
• It act on the 30 S subunit of the bacterial ribosome.
• It can inhibit mitochondrial protein synthesis in mammalian cells.
• It devoid antibacterial activity against anaerobe.