Macrolide antibiotics

28
MACROLIDE S G Vijay Narasimha Kumar Asst. Professor, Dept. of. Pharmacology Sri Padmavathi School of Pharmacy

Transcript of Macrolide antibiotics

Page 1: Macrolide antibiotics

MACROLIDES

G Vijay Narasimha KumarAsst. Professor,

Dept. of. PharmacologySri Padmavathi School of

Pharmacy

Page 2: Macrolide antibiotics

INTRODUCTION

The Macrolides are a group of closely related compounds characterized by a macrocyclic lactone ring (usually containing 14 or 16 atoms) to which deoxysugars are attached.

The prototype drug Erythromycin, which consists of two sugar moieties attached to a 14-atom lactone ring.

Page 3: Macrolide antibiotics

It was obtained in 1952 from Streptomyces

erythreus. Clarithromycin and Azithromycin are semisynthetic derivatives of Erythromycin.

Page 4: Macrolide antibiotics

CLASSIFICATIONMACROLIDESi. ERYTHROMYCINii. CLARITHROMYCINiii. AZITHROMYCINiv. ROXITHROMYCINv. SPIRAMYCIN

KETOLIDESvi. TELITHROMYCIN

Page 5: Macrolide antibiotics

MECHANISM OF ACTION

Inhibits protein synthesis by reversibly binding to the 50S ribosomal subunit Suppression of RNA-dependent protein synthesis by inhibition of translocation of mRNA.

Typically bacteriostatic activity Bactericidal at high concentrations against

very susceptible organisms

Page 6: Macrolide antibiotics
Page 7: Macrolide antibiotics

SPECTRUM OF ANTIBACTERIAL ACTIVITY

Macrolides are similar to Penicillins regarding their spectrum of activity.

They are effective against Penicillin-resistant strains.

GRAM +VE COCCI

GRAM +VE BACILLI

Streptococcus pneumoniae,

Bacilus anthracis,

Strepto. pyogens Listeria monocytogenes

Staphylococci ( most or penicillin resistant species and these are now macrolide resistant also)

Clostridium tetani

GRAM –VE COCCI

GRAM -VE BACILLI

Nesseria gonorrhoeae

Legionella pneumophila

Moraxella catarrhalis

Bordetella pertussis

Bartonella henselae

Haemophilus influenzae, h. ducreyi.Campylobacter jejuniHelicobacter pylori

Page 8: Macrolide antibiotics

ACID FAST BACILLI

SPIROCHETES MISCELLANEOUS

Mycobacterium kanasii

Treponema pallidum

Mycoplasma pneumoniae

Mycobacterium avium intracellulare

Ureaplasma urealyticum

Mycobacterium avium complex

Chlamydia trachomatis

Mycobacterium leprae

Chlamydia pneumoniae

Chlamydia psittaci

Page 9: Macrolide antibiotics

BACTERIAL RESISTANCE

Methylation of a guanine residue on ribosomal RNA leads to lower affinity toward Macrolides

An active efflux systemPresence of a plasmid-associated

Erythromycin esterase.

Page 10: Macrolide antibiotics

Clarithromycin and Azithromycin show cross-resistance with Erythromycin, but Telithromycin can be effective.

Against Macrolide-resistant organisms.Lack of cell wall permeability to Macrolides is

the reason why G(-) bacteria are resistant to antibacterial effects of these agents.

Page 11: Macrolide antibiotics

PHARMACOKINETICS ABSORPTIONERYTHROMYCIN – variable absorption, food may

decrease the absorption. Base: destroyed by gastric acid;

Enteric coated Esters and ester salts: more acid stableCLARITHROMYCIN – acid stable and well-absorbed

regardless of presence of food.AZITHROMYCIN –acid stable, food decreases absorption

of capsules.

Page 12: Macrolide antibiotics

DISTRIBUTION:Extensive tissue and cellular distributionClarithromycin and Azithromycin with extensive penetration .No BBB and CSF penetration

Erythromycin accumulates in the prostatic fluid and also in macrophages.

Azithromycin accumulates in Neutrophils, Macrophages, Fibroblasts. Has Large volume of distribution and longest half life (greater than 40 hrs)

Page 13: Macrolide antibiotics

ELIMINATION:Clarithromycin is the only Macrolide partially

eliminated by the

Kidney(18% of parent and all

metabolites).

Hepatically eliminated: ALL.

NONE of the macrolides are removed during

hemodialysis

Erythromycin and Azithromycin are primarily

concentrated and excreted through bile as active drugs.

Page 14: Macrolide antibiotics

Administration and fate of the Macrolide antibiotics.

Page 15: Macrolide antibiotics

ADVERSE EFFECTS GASTROINTESTINAL EFFECTS: Anorexia, nausea, vomiting, and diarrhoea

occasionally accompany oral administration. Gastrointestinal intolerance, which is due to a direct

stimulation of gut motility, is the most common reason for discontinuing Erythromycin and substituting another antibiotic.

Page 16: Macrolide antibiotics

LIVER TOXICITY: Erythromycins, particularly the estolate, can produce acute

cholestatic hepatitis (fever, jaundice, impaired liver function), probably as a hypersensitivity reaction.

Most patients recover from this, but hepatitis reoccurs if the drug is

Re administered. Macrolides get deposited in perilymph and causes ototoxicity. Other allergic reactions include fever, eosinophilia, and rashes. Prolong QT WAVE

Page 17: Macrolide antibiotics

DRUG INTERACTIONS• Erythromycin metabolites can inhibit

cytochrome P450 enzymes and thus increase the serum concentrations of numerous drugs including,

• Theophylline, • Oral anticoagulants, • Cyclosporine, and • Methylprednisolone,• Erythromycin increases serum concentrations

of oral Digoxin by increasing its bioavailability.

Page 18: Macrolide antibiotics
Page 19: Macrolide antibiotics

THERAPEUTIC USES OF ERYTHROMYCINIt is used to treat a. The upper part of the respiratory tract infections, b. Soft tissue G(+) infections, c. Urethritis caused by (MRSA, Ureaplasma

Urealyticum)

d. Mycoplasma pneumonia caused pneumonia, Campylobacter jejuni -- Enteritis,

Page 20: Macrolide antibiotics

e. Chlamydia infections Majorly C. Trachomatis - (may result in Urethritis, epididymitis, cervicitis, pelvic inflammatory disease (PID) and other conditions. )

C. Pneumonia – causes respiratory illness (prolonged cough, bronchitis, and pneumonia as well as a sore throat, laryngitis, ear infections, and sinusitis)

f. Gonorrhoea caused by Nesseria gonorrhoea

g. Treatment and prophylaxis of ophthalmic infections and also neonatal conjuctivitis

Page 21: Macrolide antibiotics

h. To treat acnei. Pelvic inflammatory disease due to

susceptible organisms (e.g., Streptococcus

Pneumoniae, Streptococcus pyogenes,

Haemophilus influenzae, Chlamydia,

Legionella, Mycoplasma, Nesseria

gonorrhoeae, Treponema)

Page 22: Macrolide antibiotics

ADVERSE DRUG REACTIONS: Ventricular arrhythmias, QT interval

prolongation, Pseudomembranous colitis, Nausea/Vomiting, abdominal pain, cramping,

diarrhea, hepatitis, rash, pruritis, phlebitis at IV site, allergic reactions.

Page 23: Macrolide antibiotics

THERAPEUTIC USES OF ROXITHROMYCIN

Roxithromycin has same spectrum as of Erythromycin butit is more potent against moraxella catarrhalis andlegionella and less potent against bordetella pertusis

THERAPEUTIC USES OF SPIRAMYCIN It also resembles Erythromycin in its spectrum, though ithas weaker activity. However, it is highly efficacious againsttoxaplasma gondii and cryptosporidium causesWaterydiarrhoea with abdominalcramps.

Page 24: Macrolide antibiotics

CLINICAL APPLICATIONS OF CLARITHROMYCIN

It is used to treat Respiratory tract infections

(pharyngitis/tonsillitis ).

skin/skin structure infections due to susceptible

organisms (e.g., S. pneumo, S. pyogenes, S. aureus, M.

catarrhalis, Hemophilus influenza, Chlamydia

pneumoniae, Mycoplasma).

To prevent or treatment of disseminated MAC infection.

(Anemia is common in patients with disseminated MAC

disease)

Page 25: Macrolide antibiotics

d. To Eradicate of H. pylori associated with peptic ulcer disease.

ADVERSE DRUG REACTIONS :Hepatic failure, Pseudomembranous colitis,Stevens-Johnson syndrome, Toxic epidermal necrolysis, Drug rash (with eosinophilia)

Page 26: Macrolide antibiotics

THERAPEUTIC USES OF AZITHROMYCIN

It has an extended spectrum compared to Erythromycin. It has a higher activity against Chlamydia trachomatis,

Mycoplasma pneumoniae, Nesseria gonorrhoeae, toxoplasma gondii.

Campylobacter jejuni (It is among the most common bacterial infections of humans, often a foodborne illness.)

H. Influenza (Bacteremia , Meningitis,Epiglotittis, Cellulitis, Infectious arthritis).

Moraxella catarrhalis (can cause infection  of the respiratory system, middle ear, eye, central nervous system).

Page 27: Macrolide antibiotics

It is used to acute bacterial infection Single dose treatment mild to moderate sinusitis Chancroid ( STD; Caused by haemophilus ducreyi) To treat non gonococcal infections (urethritis, cervicitis) Prevention or treatment of MAC infection in patients

with advanced HIV.

ADVERSE REACTIONS: Pseudomembranous colitis, Abdominal pain, Nausea /Vomiting, Rash

Page 28: Macrolide antibiotics

THANK YOU