antibiotics and its classification of drugs

antibiotics, its classification of drugs and antibiotic resistance

1. A NTIBIOTICS Presented by : Dr. M. Gayathri Post graduate

2. CONTENTS : Introduction History Definition Classification of antibiotics Mechanisms of antibiotics Principles of antibiotics use Commonly used antibiotics Drug interaction Drug combination Antibiotic resistance

3. INTRODUCTION Antibiotics are one of the most important discoveries in medical science. They are chemical substances produced by microorganisms (like bacteria and fungi) or synthesized artificially, which can inhibit the growth of or destroy other microorganisms , particularly bacteria.

4. H ISTORY Paul Ehrlich (1854–1915) – “The Magic Bullet” Ehrlich was a German scientist who introduced the concept of a “magic bullet” — a chemical that could selectively target disease-causing organisms without harming the host. In 1909 , he discovered Salvarsan (arsphenamine) , the first effective treatment for syphilis . This marked the beginning of chemotherapy (the use of chemicals to treat diseases).

5. The first antibiotic discovered was Penicillin , by Alexander Fleming in 1928 , which marked the beginning of the “antibiotic era.” Since then, many classes of antibiotics have been developed to combat various bacterial infections.

6. Antibiotics are chemical substances obtained from living organisms or by synthetic means , capable of inhibiting the growth or destroying microorganisms , especially bacteria , at low concentrations. DEFINITION:

7. CLASSIFICATION On the basis of chemical structure: B-lactams– Penicillin, cephalosporins, monobactams, carbapenem Tetracycline- Doxycycline, Oxytetracycline Aminoglycosides - Gentamicin , Neomycin, streptomycin Macrolides - Clarithromycin, Erythromycin, Azithromycin Quinolones - Ciprofloxacin , Norfloxacin Sulfonamides – Sulfadiazine Lacosamide – Clindamycin, Lincomycin Glycopeptides – Vancomycin Nitroimidazoles - Metronidazole

8. On the basis of spectrum of activity: - Narrow spectrum : Penicillin G, Streptomycin, Erythromycin - Broad spectrum : Tetracycline, Chloramphenicol On the basis of type of action: - Bacteriostatic : Macrolides, Tetracycline, Sulfonamides, Chloramphenicol, Clindamycin - Bactericidal : Penicillin, Cephalosporin, Fluo r oquin o lones, Metronidazole, Aminoglycoside

9. Acting on cell membrane polypeptides bacitracin Daptomycin

10. Age Immune system Renal dysfunction Hepatic dysfunction Pregnancy and lactation Narrow-spectrum preference Route of administration Avoid unnecessary combination therapy Monitor response and adjust therapy Correct dose and duration Prevent resistance

11. Indicated clinical conditions for antimicrobial therapy Pyrexia within last 24 hours – indicates a systemic response to the infection Systemic symptoms like malaise, fatigue, weakness, dizziness, rapid respiration and local tender lymphadenopathy – indicate an impending sepsis Trismus – indicates spread to peri mandibular spaces and can extend to secondary spaces that can be potentially dangerous.

12. As a prophylaxis in patients with systemic conditions like rheumatic heart disease, endocarditis, heart / orthopedic prosthesis. In patients with any kind of immunocompromise – AIDS, cancer, autoimmune diseases, corticosteroid therapy, patients with immune compromised diseases like cyclic neutropenia, pancytopenia, uncontrolled diabetes…etc.

13. BETA –LACTAM ANTIBIOTICS

14. Beta-Lactam Antibiotics Includes Penicillin , Cephalosporin , Monobactam, Carbapenem MOA : Inhibits cell wall formation by inhibiting transpeptidase

15. P enicillin Types: Natural penicillin : Penicillin G and Penicillin V --- gram-positive and gram-negative cocci, gram-positive bacilli Anti-staphylococcal penicillins : Methicillin, nafcillin, oxacillin, dicloxacillin (penicillinase resistant penicillin) Extended-spectrum penicillins : Ampicillin, Amoxycillin --- additional action against gram negative bacilli Antipseudomonal penicillins : Piperacillin, Ticarcillin

16. Natural Penicillin They are obtained from the fungus Penicillium chrysogenum. Penicillin G (Benzyl Penicillin) Active against a number of gram positive and gram-negative cocci and gram-positive bacilli. Poor oral absorption as it is readily destroyed by gastric acids. Penicillin V (Phenoxy methyl penicillin) Similar to Penicillin G in action but it is resistant to gastric acids and can be taken orally. They are ineffective against Penicillinase producing bacteria

17. Penicillinase resistant penicillin (Anti-staphylococcal penicillins ) Methicillin, nafcillin, oxacillin, dicloxacillin Extended-spectrum penicillins : Ampicillin, Amoxycillin Antibacterial spectrum is similar to penicillin G but they have an additional action against gram negative bacilli.

18. ADVERSE REACTIONS: Hypersensitivity Rash, urticaria, anaphylaxis Gastrointestinal Nausea, diarrhoea, colitis Neurological Seizures (high doses) Hematologic Hemolytic anemia Electrolyte disturbance Hyperkalaemia, hypernatremia Local Pain at injection site Superinfection Oral/vaginal candidiasis

19. Beta-lactamase inhibitors: Clavulanic acid + amoxicillin [Clavum, Mega-CV] Clavulanic acid + ticarcillin Sulbactam + ampicillin Tazobactam + piperacillin Adverse reactions : Elimination = by kidney

20. D ose : Amoxicillin [Amoxil, Ranoxyl ] Adult : 250-500 mg every 8 hour Child 125-250 mg every 8 hour Ampicillin [ Ampilin , Zycilin ] Adult : 250-500 mg every 6 hour Child : 50-100 mg/kg daily Cloxacillin [ Klox ] Adult : 250-500 mg every 4 hour Child : 50-100 mg/kg daily Amoxicillin is the most commonly used to treat odontogenic infections followed by amoxicillin + clavulanic acid Amoxycillin is available as : capsules, tablets, chewable tablets, oral suspension

21. CEPHALOSPORINS

22. C ephalosporins First generation – action similar to penicillin G Second generation – greater action against gram negative organism Third generation -- enhanced activity against gram-negative bacilli Fourth generation – wide antibacterial spectrum GENERATION: PARENTERAL ORAL FIRST GENERATION CEFAZOLIN CEPHALEXIN CEPHADROXIL SECOND GENERATION CEFUROXIME CEFOXITIN CEFACLOR CEFUROXIME AXETIL CEFPROZIL THIRD GENERATION CEFOTAXIME CEFTIZOXIME CEFTRIAXONE CEFTAZIDIME CEFOPERA ZONE CEFEXIME CEFPODOXIME PROXETIL CEFDINIR CEFTIBUTEN CEFTAMET PIVOXIL FOURTH GENERATION CEFEPIME CEFPIROME

23. A dverse reactions : -Similar to Penicillin Patients who have had an anaphylactic response, Stevens-Johnson syndrome to penicillins should not receive cephalosporins The cross-reactivity between penicillin and cephalosporins is around 3% to 5% Elimination – by kidney but ceftriaxone is excreted through the bile into the feces and, should be employed in patients with renal insufficiency.

24. TETRACYCLINES

25. TETRACYCLINES Doxycycline, Minocycline, Demeclocycline Mechanism of action : Inhibits protein synthesis by binding to 30s ribosomes

26. Adverse reactions They are effective in treating periodontal diseases because their concentration in the gingival crevice is 2-10 times that in serum They inhibit synthesis and release of collagenase from human polymorphonuclear leukocytes and inhibit tissue destruction and may aid bone regeneration.

27. E limination = by kidney In renally compromised patients, doxycycline is preferred, as it is primarily eliminated via the bile into the feces. The tetracyclines should not be used in pregnant or breast-feeding women or in children less than 8 years of age. May cause discoloration and hypoplasia of teeth. Do not take tetracyclines with antacids, iron, dairy products . Dose : [Doxy, Emdox ] 100-200 mg once daily

28. 20 mg of Doxycycline Hyclate is used in host modulation therapy. Used as an adjunct to SRP in treatment of chronic periodontitis. Taken twice daily for 3-9 months. Suppress the activity of Collagenase. No antibacterial activity. Doxycycline as Host modulating agent

29. Doxycycline gel (10%): Applied in periodontal pocket in cases of chronic periodontitis

30. MACROLIDES

31. M acrolides Azithromycin Clarithromycin Erythromycin Telithromycin MOA : The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting translocation steps of protein synthesis.

32. Alternative to penicillin in individuals with an allergy to beta-lactam antibiotics in treatment of acute oro -facial infection. Erythromycin dose: 250-500 mg orally every 6hrs

33. Adverse reactions Should be used cautiously in patients with hepatic dysfunction. Interference with the metabolism of drugs, such as theophylline, statins, antiepileptics, digoxin

34. LINCOSAMIDES

35. LINCOSAMIDE CLINDAMYCIN MOA : similar to macrolides Better bone penetration due to relatively small molecular size. So used in treatment of Osteomyelitis. Most common adverse effect is diarrhea, due to pseudomembranous colitis caused by overgrowth of C. difficile . significant activity against many gram-positive and gram negative anaerobic and aerobic microorganisms, including Bacteroides, Prevotella, Porphyromonas, Veillonella, Dose : 600mg IV/PO

36. FLUOROQUINOLONES

37. Fluoroquinolones Inhibits bacterial DNA gyrase which results in relaxation of supercoiled DNA, promoting DNA strand breakage. 1 st Generation : Nalidixic acid 2 nd Generation: Norfloxacin, Ciprofloxacin 3 rd Generation: Levofloxacin 4 th Generation: Moxifloxacin effective against gram-negative organisms

38. ADR : Phototoxicity, Diarrhea, Nausea, Headache, Tendon rupture They are not indicated for any acute orofacial infections unless dictated by culture and sensitivity tests. Drugs with better antimicrobial spectra are readily available. Prescribed in dentistry if a patient is allergic to penicillin and/or has substantial gastrointestinal upset with erythromycin and clindamycin.

39. METRONIDAZOLE

40. M etronidazole MOA: Nitro group reacts with bacterial DNA, causing inhibition of DNA replication, fragmentation of existing DNA Effective against Gram-negative anaerobes such as Prevotella intermedia, Porphyomonas gingivalis , Bacteroides , Fusobacterium Used in : -Necrotizing ulcerative gingivitis -Aggressive periodontitis -Abscesses -Orofacial infection along with Penicillins Developed as antiprotozoal drug

41. Ingestion of alcohol when taking metronidazole could cause Disulfiram like reaction i.e hallucinations and confusion, abdominal cramps, nausea, facial flushing and headache can occur. Also avoid alcohol containing mouth rinses. Decreases the metabolism of Warfarin resulting in bleeding ADR : Dose: [Metron, Flagyl] 200-400 mg 8 hourly

42. Drug interactions ß-lactams : Tetracyclines and other bacteriostatic antibiotics = effectiveness is decreased Tetracyclines: Antacids and dairy products = decreases absorption Metronidazole: Ethanol = severe disulfiram like reaction Lithium = decreases its excretion Carbamazepine = increases blood level Cephalosporins and macrolides: Warfarin = increased anticoagulant effect

43. Combination of antimicrobial drugs

44. Commonly used combinations : Ampicillin (250mg) + Cloxacillin (250mg) [ Megapen , Ampikem ] Amoxicillin (500mg) + Clavulanic Acid (125mg) [Clavam, mega-cv]

45. Quadrajel dental gel : Lidocaine hydrochloride 2 % w/w + Metronidazole benzoate 1 % w/w + Chlorhexidine gluconate 1 % w/w Delta gel: Metronidazole + Lidocaine + Chlorhexidine

46. Disadvantages of combination : Increased incidence and variety of adverse effects Vancomycin + gentamicin  exaggerated kidney failure Increases the chance of superinfections Inadequate dose of non-synergistic drugs  emergence of resistance Higher cost of therapy

47. Topical antibiotics : Chlorhexidine digluconate MOA : has antibacterial and antiplaque action. At low concentration increases the permeability of cell membrane causing leakage of intracellular components including potassium. At high concentration, chlorhexidine causes precipitation of bacterial cytoplasm and cell death. Effective against : Bacteria, Some fungi (candida), some viruses (HIV, HBV) Shows Substantivity i.e gets adsorbed to tooth surfaces and shows a persistent antibacterial action lasting in excess of 12 hours Available as : Mouthrinse (0.2%, 0.12% ) Gels [ Hexi gel chlorhexidine gluconate 1 %] Spray 0.1 %

48. Adverse effects : Mucosal desquamation Hypersensitivity reaction Hairy tongue Teeth discoloration

49. Uses : As an adjunct to oral hygiene and professional prophylaxis Post oral surgery including periodontal surgery or root planning Medically compromised individuals predisposed to oral infections Recurrent oral ulceration Denture stomatitis Oral malodor

50. A ntibiotic resistance

51. Reference : A review of use of antibiotics in dentistry and recommendations for rational antibiotic usage by dentists, Dr. Akilesh Ramasamy, THE INTERNATIONAL ARABIC JOURNAL OF ANTIMICROBIAL AGENTS

52. Condition Procedure Recommended Antibiotic Dose & Timing Prosthetic heart valve Any procedure with bleeding Amoxicillin (oral) 2 g, 1 hour before Previous infective endocarditis Any dental procedure with bleeding Amoxicillin 2 g, 1 hour before Certain congenital heart diseases Procedures with bleeding Amoxicillin 2 g, 1 hour before Cardiac transplant with valvulopathy Procedures with bleeding Amoxicillin 2 g, 1 hour before Allergic to penicillin Any of the above Clindamycin (oral) 600 mg, 1 hour before Azithromycin / Clarithromycin 500 mg, 1 hour before Antibiotic Prophylaxis in Dentistry

53. References : Lippincott Illustrated Reviews, Pharmacology Essentials of medical pharmacology, KD Tripathi Pharmacology and therapeutics for dentists, John A. Yeigla

54. Thanks!