Antimicrobials -The Nitroimidazoles.pptx

Metronidazole is a widely used antimicrobial agent that belongs to the nitroimidazole class of antibiotics. It is primarily effective against anaerobic bacteria and certain protozoa, making it an essential drug for treating infections caused by these microorganisms. Metronidazole works by disrupting the DNA of microbial cells, leading to cell death and the elimination of infection.

1. NITROIMIDAZOLES PRESENTED BY : DR. BHAVIKA CHHAJED GUIDED BY: DR. NEEMA SHETTY DR. ADITI MATHUR DR. ASHISH BALI DR. TRISHI

2. INTRODUCTION CLASSIFICATION MECHANISM OF ACTION PHARMACOKINETICS PHARMACODYNAMICS INDICATIONS CONTRAINDICATION DRUG DOSAGE DRUG INTERACTIONS APPLICATION IN PERIODONTAL DISEASES CONCLUSION REFERENCES CONTENTS

3. ANTIBIOTICS : Antibiotics are a naturally occurring, semisynthetic or synthetic type of antimicrobial agent that destroys or inhibits the growth of selective microorganisms, generally at low concentrations. It is well established that various periodontal diseases are caused by bacterial infection. Bacteria grow in an apical direction and become subgingingival and eventually bone is destroyed, a periodontal pocket is formed. It is therefore logical to treat periodontal pockets by mechanical removal of local factors ( including calculus that harbors bacteria) and also by disruption of the subgingival plaque biofilm itself. INTRODUCTION

4. Mechanical removal includes manual instrumentation ( eg. Scaling and root planing ) and machine driven instrumentation ( eg.ultrasonic scalers) and these procedures can be considered antiinfective therapy. Systemic antiinfective therapy (oral antibiotics) and local antiinfective therapy ( placing antiinfective agents directly into the periodontal pockets) can reduce the bacterial challenge to the periodontium. It is also possible that systemically administered NSAIDS may play a role in future adjunctive therapy . SYSTEMIC ADMINISTRATION OF ANTIBIOTICS : The treatment of periodontal disease is based on infectious nature of these disease. Currently, an ideal antibiotic for the treatment of periodontal disease does not exist Although oral bacteria are susceptible to many antibiotics, no single antibiotics at concentration achieved in body fluids inhibits all putative periodontal pathogens.

5. CLASSIFICATION 2- nitroimidazoles 4-nitroimidazoles 5-nitroimidazoles

6. NITROMIDAZOLES Metronidazole , the prototype member of this class was introduced in 1959 for trichomonas vaginitis and later found to be a broad-spectrum antiprotozoal drug against Entamoeba histolytica and Giardia lamblia. Its efficacy in anaerobic bacterial infection was a chance discovery, and it is now extensively used to treat oral and other anaerobic infections. Several congeners of metronidazole have been subsequently produced, of which Tinidazole, Secnidazole , Ornidazole and Satranidazole are in clinical use. Metronidazole is selectively toxic to anaerobic microorganisms.

7. Drug of choice for : - Anaerobic bacteria - Protozoan infections Prodrug Synthetic derivative of azomycin Nitro functional group (-NO2) at the fifth position Oxygen (furan) or sulphur ( thiazole) at position 1 for variants Kills Anaerobic bacteria like : Bacteroids fragilis spp , Fusobacterium spp , Peptpcoccus spp , Clostridium spp Protozoa like giardia lamblia which coz giardiasis Amoeba like entamoeba histolytica which can cause bacillary dysentery, hepatic abscess ( amoebema ).

8. PHARMACOKINETICS ABSORPTION: - Bioavailability : 60-80% absorption from GI tract and small intestine. Food delays the absorption - Absorption in variety of dosage forms like : oral tablets ,vaginal and rectal suppository ,as a topical gel . - Protein Binding (<20%) - Peak serum time: 1-2hr (oral), 20 min ( IV) DISTRIBUTION : - Widely distributed - Good penetration into cerebrospinal fluid and central nervous system - Croses placenta barrier and enters the breast milk

9. METABOLISM - Liver via hydroxylation, oxidation, glucuronidation. - Enzymes inhibited : hepatic ELIMINATION - Half life : 25-75hr (neonates): 8hr (others) : prolonged in patients with hepatic Impairment - Excretion : urine (77%) ; faeces (6-15%)

10. PHARMACODYNAMICS BACTERICIDAL EFFECT - Metronidazole appears to have an extremely rapid rate of killing against susceptible anaerobes. POST ANTIBIOTIC EFFECTS AND CONCENTRATION DEPENDENT KILLING - Metronidaziole had a concentration dependent killing effect against T-vaginalis under anaerobic conditions

11. MECHANISM OF ACTION Metronidazole acts by inhibiting nucleic acid synthesis by disrupting the DNA of microbial cells This function only occurs when metronidazole is partially reduced , and because this reduction usually happens only in anaerobic cells, it has relatively little effect upon human cells or aerobic cells

12. INDICATIONS 1. Anaerobic bacterial infections like : Intra abdominal abscess , Peritonitis , Empyema , Lung abscess , Diabetic foot ulcer , Meningitis, Septic wounds , Endocarditis 2. Surgical prophylaxis 2 hrs before surgery in risk procedures like colorectal surgery or appendectomies 3. Surgical and gynaecological septicaemia due to colonic anaerobes like bacteroides fragilis 4. Amoebic dysentery due to entamoeba histolytica.

13. 5.Tx of symptomatic bacterial vaginosis due to overgrowth of Gardenerella spp and co-infective anaerobes ( Mobiluncus , Bacteroides) 6.Pseudomembranous colitis due to clostridium difficile 7. Tx of peptic ulcer disease by eradicating Helicobacter pylori in a triple therapy regimen 8.Oral infections like Acute Necrotising Ulterative Gingivitis, periapical abscess , Pericoronitis, salivary gland infections 9.Crohn’s disease with colonic or perianal involvement in combination with ciprofloxacin

14. INDICATIONS FOR TOPICAL METRONIDAZOLES Treatment of Rosacea . Treatment of malodorous fungating wounds . Killing of malodorous producing anaerobic bacteria in fungating tumors like malignant melanomas .

15. Neurological diseases Blood dyscrasias 1st trimester of pregnancy Chronic alcoholism CONTRAINDICATIONS

16. Minor GI disturbances like: -Metallic and biter mouth taste - Diarrhoea -Nausea and vomiting - Oral mucositis -Anorexia 2. Thrombophlebitis after IV Drug OTHER VERY RARE SIDE EFFECTS Blood disorders like Thrombocytopenia, Neutropenia , Pancytopenia Hypersensitivity reactions like - Rash -Pruritis -Fevers - Flushing of the skin SIDE EFFECTS

17. Trade names : Flagyl, Metrogyl , Aristogyl . 200-400mg tabs. 200mg/5ml oral suspensions. 500mg/100ml i.v infusion PREPARATIONS AND DOSAGE

18. ORAL DOSAGES Anaerobic bacterial infections : Adult : Initially, 800 mg followed by 400 mg 8 hourly usually for about 7 days. Child : <8 weeks 15 mg/kg once daily or divided into 7.5 mg/kg 12 hourly. >8 weeklys to 12 years 20-30 mg/kg as a single dose or divided into 7.5 mg/kg 8 hourly for 7 days The daily dose may be increased to 40 mg/kg based on the severity of the infections

19. DRUG INTERATIONS

20. TINIDAZOLE It is an equally efficacious congener of metronidazole, similar to it in every way except: Metabolism is slower; t½ is ~12 hours; duration of action is longer INDICATIONS : Amoebiasis, Giardiasis and Trichomoniasis. SIDE EFFECTS : Metallic taste (2%), Nausea (1%), Rash (0.2%). DOSAGES : TINIBA 300, 500, 1000 mg tabs; 800 mg/400 ml i.v. infusion; TRIDAZOLE, 300, 500 mg tab; FASIGYN 0.5 g and 1 g tab.

21. USES: For orodental infections, tinidazole has been used in a dose of 0.5 g (10 mg/kg) BD for 5 days. In other serious anaerobic infections the recommended dose is 2 g orally followed by 0.5 g BD for 5 days. In case oral treatment is not possible, 800 mg can be infused slowly i.v. daily till oral therapy is instituted. A single 2 g (oral) or 0.8 g ( i.v. ) dose is given for prophylaxis of anaerobic infection before colorectal surgery.

22. SECNIDAZOLE A congener of metronidazole with the same spectrum of activity and potency Absorption after oral administration is rapid and complete metabolism is slower resulting in a plasma t½ of 17–29 hours. DOSAGES : A single 2 g dose has been found to yield cure rates equal to multiple doses of metronidazole and tinidazole. SECNIL, SECZOL 0.5, 1.0 g tabs; NOAMEBA-DS 1.0 g tab . SIDE EFFECTS : Similar to metronidazole It has not been used in dentistry to any significant extent.

23. Activity similar to metronidazole, but it is slowly metabolized has longer t½ (12–14 hr). USES : Amoebiasis, Gardiasis , Trichomoniasis, Anaerobic infections and bacterial vaginosis. SIDE EFFECTS : Profile is similar to Tinidazole. DOSAGES : DAZOLIC 500 mg tab, 500 mg/100 ml vial for i.v. infusion. ORNIDA 500 mg tab, 125 mg/5 ml susp. ORNIDAZOLE

24. Another nitroimidazole having longer t½ (14 hr ) and greater potency. ADVANTAGES : better tolerability—no nausea, vomiting or metallic taste, absence of neurological and disulfiram-like reactions and that it does not produce the acetamide metabolite which is a weak carcinogen. Its role in dental infections has not been defined. DOSAGES : SATROGYL 300 mg tab. SATRANIDAZOLE

25. Rams and Slots gave combination therapy involving the use of systemic metronidazole along with amoxicillin, amoxicillin– clavulanate (Augmentin), or ciprofloxacin. The metronidazole– amoxicillin and metronidazole–Augmentin combinations provided 3018 excellent elimination of many organisms in adults with LAP who had been treated unsuccessfully with tetracyclines and mechanical debridement. These drugs have an additive effect that involves the suppression of A. actinomycetemcomitans COMBINATION THERAPY

26. APPLICATION IN PERIODONTICS AGGRESSIVE PERIODONTITIS : Localised aggressive periodontitis involving Aggregatibacter Actinomycetemcomitans can be controlled or eradicated by Systemic Metronidazole-Amoxicillin comibiation therapy. Antibiotics therapy for the treatment of Aggressive and Refractory Periodontitis. Metronidazole 500mg tid for 8 days Metronidazole + amoxicillin 250 mg tid for 8 days Metronidazole + ciprofloxacin 500 mg bid for 8 days

27. NECROTIZING PERIODONTAL DISEASES : Patients with moderate to severe NUG/NUP , Local Lymphadenopathy ,and Systemic involvement need antibiotic therapy Antibiotics recommended are : Amoxicillin 500 mg tid for 8 days Metronidazole 500 mg Combination of amoxicillin + metronidazole 250 mg tid for 8 days

28. ACUTE DENTAL INFECTIONS BACTERIAS like P. gingivalis ,T forsynthia ,Treponema palilidnum Metronidazole 200 – 500 mg tid for 8 days The Efficacy of Metronidazole for the treatment of Periodontitis. A single dose of Metronidazole (250 mg orally) appears in both serum and GCF in sufficient quantities to inhibit a wide range of suspected periodontal pathogens. When it is administered systemically (i.e., 750 mg/day to 1000 mg/day for 2 weeks), Metronidazole reduces the growth of anaerobic flora, including spirochetes, and it decreases the clinical and histopathologic signs of periodontitis. The most common regimen is 250 mg 3 times daily for 7 days.

29. LOCAL DELIVERY OF METRONIDAZOLE The topical application of antimicrobial substances directly into the the infected pocket has been investigated for use in the treatment of periodontitis MOA : increased proportion of cocci decreased proportion of spirochaetes in subgingival microflora. Metronidazole applied locally both in high and low concentrations , effectively educed symptoms such as pocket depth and sulcus bleeding METRONIDAZOLE DENTAL GEL: ELYZOL : A Metronidazole Containing gel consisting of Metrinidazole Benzoate in a mixture of Monoglyceride and Triglycerides applied with a syringe into periodontal pockets.

30. Scaling and root planing alone are effective for reducing pocket depths, gaining increases in periodontal attachment levels, and decreasing inflammation levels (i.e., bleeding with probing). When 3023 systemic antibiotics are used as adjuncts to scaling and root planing , the evidence indicates that some systemic antibiotics (e.g., metronidazole, tetracycline) provide additional improvements in attachment levels (0.35 mm for metronidazole; 0.40 mm for tetracycline) when used as adjuncts to scaling and root planing . The use of anti-infective chemotherapeutic treatment adjuncts does not result in significant adverse effects for patients. The decision regarding when to use systemic antimicrobials should be made on the basis of the clinician's consideration of the clinical findings, the patient's medical and dental history, the patient's preferences, and the potential benefits of adjunctive therapy with these agents. CONCLUSION

31. REFERENCES Role of systemic antibiotics in the treatment of periodontal diseases- J Periodontal 2004;75:1553-1565 Essentials of pharmacology for Dentistry- KD Tripathi 2nd ed; Book of Pharmacology – Padmaja Textbook of pharmacology - Shanbag • Basic and clinical Pharmacology- McGrawHill Lange 10th ed; • Carranza’s Clinical Periodontology- 11th ed

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