Aminoglycosides & macrolides

1. Aminoglycosides & macrolides SHRAVAN PASWAN MASTER OF PHARMACY SEMESTER-I DEPARTMENT OF PHARMACOLOGY ADVANCE INSTITUTE OF BIOTECH AND PARAMEDICAL SCIENCES, KANPUR 208012 paswanshravan@gmail.com

2. What is Aminoglycosides?These are natural and semisnthetic antibiotics having polybasic aminogroup linked glycosides to two or more aminosugar. OrThese are antibiotics which contain amino glycosides or two or more aminosugars It is the drug which is effective against gram -ve bacteria.Strptomycin was the first member discovered in 1944 by Waksman. paswanshravan@gmail.com

3. Classification- paswanshravan@gmail.com

4. Transport of aminoglycosides through the bacterial cell wall and cytoplasmic membrane Binds to the several sites at 30s nd 50s subunits as well as interface interfare with polysome formation Cause misreading of mRNA Inhibit protein synthesis Mechanism of action paswanshravan@gmail.com

5. Resistance-it is due to 1. decreased membrane permeability.2. alteration of ribosomal binding site.3. elaboration of enzyme which destroy the drugs. Pharmacokinetics-1. Administration2. DistributionPRECAUTIONS AND INTERACTIONS-Avoid aminoglycosides during pregnancy risk of foetal ototoxicity.Donot mix aminoglycosides with other drugs in same syringe. paswanshravan@gmail.com

6. Avoid drugs in kidney damage.Avoid concurrent uses of other ototoxic drugs.e.g.- high ceiling diuretics.Avoid concurrent use of other nephrotoxic drugs.e.g- amphoteracin B, Vanomycin. paswanshravan@gmail.com

7. Adverse effect-OtotoxicityVestibular damageNephrotoxicityNeuromuscular blockadeNauseaHeadacheDizzinessVertigo paswanshravan@gmail.com

8. Uses- • In treatment of tuberculosis. • In treatment of plague. • In treatment of diarrhoea. • In repiratory infections. • In treatment of pneumonia paswanshravan@gmail.com

9. Common Market Preparation- • Amikacin Amicin Biochem • Gentamicin Biogracin/Genticyn Biochem/Nicholas • Kanamycin Kanamycin Biochem/Alembic • Streptomycin Ambistryn-S Sarabhai • Tobramycin Tobraneg Elililly/Ranbaxy • Polymixin Neosporin Wellcome paswanshravan@gmail.com

10. STREPTOMYCIN- It is obtained from Streptomyces griseus. MECHANISM OF ACTION:- • The 30s subunit of cell ribosome is primarily affected causes inhibition of protein synthesis. • It also causes elongation of cell without permitting final division. • Ribosomal protein synthesis is inhibited in three ways by aminoglycosides • They interfere with the initiation complex of peptide formation. paswanshravan@gmail.com

11. - • They interfere with the initiation complex of peptide formation. • They induce misreading of the code on the m-RNA & prematuration termination of peptide chain. • They cause a breakup of polysomes into non functional monosomes. RESISTANCE AND DEPENDANCE:- • Mutation • Inability to transport • Induction of enzymes. paswanshravan@gmail.com

12. - Pharmacokinetics:- • Highly ionized • IM absorption is rapid • Distributed only extracellular • Vol. of distribution 0.3L/kg. • Plasma t half-2-4 hrs. • Excretion mainly by the glomeruli of kidney in an unchanged form in 6-8 hrs. • Does not cross placenta. • It is not metabolized. paswanshravan@gmail.com

13. - Therapeutic Uses:- • Tuberculosis • Plague • UTI • Meningitis • Gonorrhoea Adverse Effect:- • Ototoxicity • Nephrotoxicity • Neuromuscular transmission • Intolerance & Superinfection paswanshravan@gmail.com

14. Antibiotics that inhibit Protein synthesis by binding to Ribosome- paswanshravan@gmail.com

15. Other Aminoglycosides Antibiotic:- paswanshravan@gmail.com

16. Common Market Preparation- • Amikacin Amicin Biochem • Gentamicin Biogracin/Genticyn Biochem/Nicholas • Kanamycin Kanamycin Biochem/Alembic • Streptomycin Ambistryn-S Sarabhai • Tobramycin Tobraneg Elililly/Ranbaxy • Polymixin Neosporin Wellcome paswanshravan@gmail.com

17. MACROLIDES • These are the antibiotics having a macrocyclic lactone ring with attached sugar. • Erythromycin is the first member discovered in 1950s…..it was isolated from Streptomyces erythreus in1952. • Following are the later addition Roxithromycin Clarithromycin methylated form of erythromycin Azithromycin Telithromycin semisynthetic derivative of Erythromycin paswanshravan@gmail.com

18. Transport of aminoglycosides through the bacterial cell wall and cytoplasmic membrane Binds to the several sites at 50s subunits interfare with translocation ribosomes fails to move along the mRNA to expose the next codon Peptide chain terminated and protein synthesis terminated…. Mechanism of action paswanshravan@gmail.com

19. .Antimicrobial spectrum- • It is narrow includes mostly gram+ve bacteria and gram-ve bacteria. Resistance- • All cocci readily develop resistance to erythromycin, mostly by mechanisms which render them permeable to erythromycin or acquire the capacity to pump it out. • The inability of the organism to take up the antbiotics • Decrease affinity of the 50s ribosomal subunit for the antibiotic resulting from the methylation of an adenine in the 23s bacterial ribosomal RNA. • Presence of a plasmid associated erythromycin esterase. paswanshravan@gmail.com

20. Pharmacokinetics- • Erythromycin base is acid labile. To protect it from gastric acid, it is given as enteric coated tablets, from which absorption is incomplete and food delays absorption by retarding gastric emptying.its acid stable esters are better absorbed. • Plasma t1/2 is 1.5 hrs, but erythromycin persists longer in tissues. paswanshravan@gmail.com

21. Pharmacokininetics (contd.)- • Administration:- cla,azi,telithromycin are stable to stomach acid & readily absorbed. • IV administration of erythromycin lead thrombophlebitis. • Distribution:- distribute to all body fluids except the CSF. and widely distributed in tissue. • Excretion:- Erythro and azithromycin are primarily concentrated & excreted in an active form of the bile. • Parietal reabsorption occur through enterohepatic circulatiion. • Inactive maetabolite are excreted into Urine. paswanshravan@gmail.com

22. Adverse effect- • Erythromycin base is remarkably safe drug.but gastrointestinal, epigastric pain is experienced by many patients. • Diarrhoea is occasional. • Very high doses of erythromycin have caused reversible hearing impairment. • Hypersensitivity. • Patient with hepatic dysfunction should be treated cautiously. • Ery, Teli, Azithromycin accumulate in liver. contraindicated in patient with myasthenia gravis paswanshravan@gmail.com

23. SOME PROPERTIES OF MACROLIDES paswanshravan@gmail.com

24. USES- • In treatment of respiratory infection. • Diptheria • Tetanus • Syphills and gonorrhoea • Leptospirosis • Whooping cough paswanshravan@gmail.com

25. ERYTHROMYCIN It is isolate from streptomycesErythrosus. MECHANISM OF ACTION:-- ERYTHROMYCIN More effective in alkaline PH Bind to 50s ribosome & interfaces Bacteriostatic at low With translocation and cidal at high concentration • Inhibit bacterial protein synthesis paswanshravan@gmail.com

26. Resistance:- • Resistance to macrolides is acquired through plasmid. • Cross resistance with Clindamycin & Chloromphenicol also occur. • Low permeability of the bacteria to the antibiotic. • Low affinity of ribosome to macrolides. • Resistant enterobacteriaceae have been found to produce an erythromycin esterase. Antimicrobial spectrum:- • Narrow • Include methyl gm+ve & gm-ve bacteria • Highly active against--- G.erythromycin Str.pneumonia N. gonorrhea paswanshravan@gmail.com

27. PHARMACOKINETICS:- • Erythromycin base is acid labile. • To protect in from gastric acid. It is given as enteric coated tablets. • Erythromycin is widely distributed in the body, enter cells & crosses serous membrane & placenta but not BBB. • PPB-70-80% • Partly metabolized & excreted primarily in bile in active form. • Renal excretion is minor. • Plasma t ½ —1.5 hrs. paswanshravan@gmail.com

28. ADVERSE EFFECT:- • Hepatitis with cholestatic jaundice start after 2-3 weeks of T/t. and lead symptom nausea,vomitting,abdominl cramps, cholecystis • Gastrointestinal mild to severe epigastric pain is experienced. • Very high dose of erythromycin have caused reversible hearing impairment. • Hypersensitivity • Cardiac arrhythmia are reported in patient with cardiac disease. paswanshravan@gmail.com

29. INTERACTION:- • Erythromycin & Clarithromycin inhibits metabolism rise the plasma level of carbamazpine,theophylline,valproate. • Erythromycin inhibits hepatic oxidation of many drugs. • Clinically significant interactions are rise in plasma level of theophylline,carbamazepine,valproate,ergotamine and warfarin. • Serious ventricular arrhythmia. • Several cases of Q-T Prolongation. paswanshravan@gmail.com

30. USES:- • As an alternative to penicillin. • As a first choice drug • As a 2nd choice drug • A typical pneumonia caused by mycoplasm chlamydia • Whooping cough • Streptococcal infections • Diptheria • Topical :-erythromycin ointment 2-4% is used for skin infections & boils. • Syphillis, gonorrehea, tetanus, anthrax • erythromycin is an alternative to penicillin paswanshravan@gmail.com

31. Newer macrolides • For overcome the limitations of erythromycin like narrow spectrum, gastric intolerance, gastric acid lability, low oral bioavailability, poor tissue penetration and short half life,……………………some semisynthetic macrolides introduced. they are- • Clarithromycin • Azithromycin • Roxithromycin • Spiramycin • Rovamycin paswanshravan@gmail.com

32. Other Macrolides Antibiotic:- paswanshravan@gmail.com

33. THANK YOU paswanshravan@gmail.com