Antimicrobial Drugs PDF

ΙΙ.PROTEIN SYNTHESIS INHIBITORS dDental Practice This antibacterial group include: practice A.Aminoglycosides B. Macrolides C. Tetracyclines D.Lincosamides E. Chloramphenicol F. Linezolid Which antibiotics work on the bacterial 30S ribosomal subunit?...

ΙΙ.PROTEIN SYNTHESIS INHIBITORS dDental Practice This antibacterial group include: practice A.Aminoglycosides B. Macrolides C. Tetracyclines D.Lincosamides E. Chloramphenicol F. Linezolid Which antibiotics work on the bacterial 30S ribosomal subunit? Aminoglycosides Tetracyclines Which antibiotics work on the bacterial 50S ribosomal subunit? Chloramphenicol Macrolides Chloramphenicol It is a bacteristatic broad spectrum antibiotic It is bactericidal at higher concentration & against some organisms What is the mechanism of action? It binds reversibly to 50S ribosomal subunit Inhibits bacterial protein synthesis The clinical uses of this drug Typhoid fever Alternative :Ciprofloxacin Topical antimicrobial agent  Adverse reactions GiT disturbances Aplastic anemia Rare Gray Baby syndrome Cyanosis Super-infection Tetracyclines Tetracycline Doxycycline Demeclocycline Minocycline oxytetracycline  Mechanism of action of tetracyclines Bind to 30S ribosomal subunit Inhibit bacterial protein synthesis Therapeutic uses of tetracyclines: Tetracyclins are concentrated several folds in gingival fluid, so they can eradicate resistant bacteria to other antibiotics specifically in chronic periodontal disease. However, the usefulness of tetracyclines in the treatment of acute orodental infections is limited they are next choice behind pencillin erythromycin ,chephalosporin and clindamycin. Other uses of tetracyclines Eradication of H.Pylori Prevent of malaria Treatment of amebiasis Treatment of acne  List the adverse effects of tetracyclines administration? Heart burn Nausea Vomiting NO milk or antacid to relieve heart burn Alteration in the normal Flora colitis Oral candida C. difficile Oral Nystatin Oral Vancomycin  List the adverse effects of tetracyclines administration Bone Teeth Tooth Enemals hypoplasia Irregularity in the bone growth Contraindicated in pregnancy Young children Discoloration and hypoplasia of the teeth MACROLIDES GROUP 1. Erythromycin 2. Clarithromycin 3. Azithromaycin.  Macrolides They include erythromycin, clarithromycin, azithromycin. Spectrum: They are Bacteriostatic narrow spectrum antibiotics having the following antimicrobial activity against: 1. Gram-positive cocci, e.g., Streptococci and Gram-positive bacilli. 2. Few Gram-negative bacilli. 3. Most useful against atypical organisms. 4. No anaerobic coverage.  Kinetics Erythromycin Clarithromycin Azithromycin Not affected by Oral absorption Affected by food Affected by food food Wide distribution except CSF and concentrated inside Distribution macrophages (especially azithromycin 10-100 times plasma concentration) Half-life 6 hours 12 hours >24 hours Dose adjustment in Not needed needed Not needed renal patients Hepatic Inhibit metabolism of some drugs, e.g., cytochrome No effect warfarin. P450 inhibition  Therapeutic Uses: 1. Streptococcal throat infection in penicillin allergic patients. 2. Community acquired pneumonia (CAP): Due to increasing evidence of macrolide resistant Streptococcus pneumoniae (the most common organism of CAP), it is recommended that macrolides are combined with beta lactams (amoxicillin/clavulanic or cefuroxime). Beta lactams will cover macrolide resistant Streptococcus pneumoniae and H. influenzae, while macrolide will cover the atypical bacteria like Chlamydia. 3. Clarithromycin is a component of H. pylori eradication drug regimens for peptic ulcer disease. Adverse Reactions: 1. Gastrointestinal upsets that are less with azithromycin and clarithromycin. 2. QT interval prolongation: combination with other drugs that prolong QT Erythromycin occupy a secondary choice because : It is bacteriostatic rather than bactericidal. Resistance can develop rapidly during treatment. It is inferior to the penicillin in eradicating most of orodental infections. What are the adverse effects associated with the macrolides? Epigastric distress Nausea , vomiting and diarrhea Cholestatic hepatitis Aminoglycosides Protein synthesis inhibitors What is the mechanism of action? Outer membrane Porin Channels O2dependent active transport Cell wall 50S 50S 30S 30S Cell membrane Inhibit bacterial protein synthesis Aminoglycosides transport enhanced by cell wall synthesis inhibitors Are aminoglycosides bacteristatic or bactericidal? Bactericidal What are the pharmacokinetics of aminoglycosides Polar compounds : not absorbed when given orally GivenGiven orallyIV forfor systemic local effect effects in the GIT Eliminated Dose should by renal be adjusted excretion in through renal insufficiency glomerular to avoid filtration toxic accumulation What are the adverse effects of aminoglycosides? Ototoxicity May Vestibular Auditory be irreversible Damage damage More common : With renal impairment : if the dose in not adjusted In the presence of other ototoxic drugs :Loop Diuretics Ototoxicity may follow fetal exposure Aminoglycosides contra-indicated in pregnancy What are the adverse effects of aminoglycosides? Nephrotoxicity Reversible More common : Elderly Pt. In the presence of other Nephrotoxic drugs :cephalosporines ,Amphotericin B or Vancomycin  Linezolid Spectrum: It has an activity against all Gram- positive cocci including MRSA, Vancomycin Resistant Staph aureus (VRSA). Therapeutic Uses: MRSA infections..  Lincosamides Clindamycin is a broad-spectrum bacteriostatic antibiotic that covers both aerobic and anaerobic pathogens Clindamycin could be prescribed in the case of persistent infections, as it has more efficacies in comparison with penicillin and metronidazole.Clindamycin is also an excellent choice for patients who have an allergy to beta-lactam group antibiotics. The drug is also a proffered alternative for prophylaxis in penicillin-allergic patients for prophylaxis. The most common side effects of clindamycin are vomiting, nausea, diarrhea, exanthem, jaundice, hepatitis, neutrophil reduction, eosinophilia, agranulocytosis, blood platelet count change, and pseudomembranous colitis. The agent is contraindicated for cirrhotic patients and for patients with a history of ulcerative and pseudomembranous colitis. Fluoroquinolones  III. NUCLEIC ACID SYNTHESIS INHIBITORS Nucleic acid synthesis inhibitors are classified into: A.DNA inhibitors: quinolones and metronidazole. B.RNA inhibitors: rifampin. Mechanism of action: They inhibit DNA synthesis by inhibition of DNAgyrase.  Fluoroquinolones First generation Second generation: (Anti-pseudomonal fluoroquinolones): e.g., ciprofloxacin, Third generation: (Respiratory fluoroquinolones): e.g., levofloxacin. Fourth generation: e.g., moxifloxacin. Therapeutic uses: ⚫ They are bactericidal used for treatment of orodental infections caused by gram-negative bacilli resistant to other antibiotics. ⚫ Because gatifloxacin ( third group) are more active against gram positive bacteria and anaerobes, they have more potential utility in dentistry. ⚫ Ciprofloxacin may be combined with metronidazole for some refractory mixed infections like periodontitis  Moxifloxacin can be considered as a good choice to treat odontogenic and periodontal infections as well, since it has high penetration capacity through periodontal and bone tissues. Moreover, this could be prophylactically prescribed to beta- lactam-allergic patients to prevent bacteremia. However, moxifloxacin is not used as the first-line treatment because of its high price and is usually prescribed when the first-line antibiotics and surgical procedures are failed  What are the adverse effects of fluoroquinolones ? Headache ,dizzness ,insomania CNS Seizures Nausea ,diarrhea, GIT abnormal liver functions Skin Rashes ,photosensitivity Musculoskeletal Tendonitis Tendon rupture Can fluoroquinolones be used in children ? No They cause cartilage erosions They must not also be used in Pregnancy or Nursing  Metronidazole Spectrum: - Metronidazole is effective against nearly all anaerobic Gram-negative bacteria, and most anaerobic Gram-positive bacteria. It is one of the few antibiotics that has activity against Clostridium difficile and is the treatment of choice for infections caused by this organism (pseudomembranous colitis). - It is an antiprotozoal agent against Adverse Reactions: 1.Gastrointestinal upsets are the most common. 2.Metallic taste. 3.Seizures and cumulative peripheral neuropathy are rare but serious, therefore multiple therapeutic courses for recurrent C. difficile infection should be avoided. Drug Interactions: 1. Since metronidazole can prolong QT intervals, drugs with a possible risk for QT prolongation should be used cautiously with it, e.g., clarithromycin, azithromycin. 2. It is an inhibitor of cytochrome P450, thus it can potentiate the anticoagulant effect of warfarin, resulting in prolongation of prothrombin time and increased risk of bleeding.  METRNIDAZOLE protozoa Clostridium dificile METRONIDAZOLE Well absorbed and distributed Metronidazole Longer half life, better tolerated Oral , parenteral , Vaginal, topical METRONIDAZOLE THERAPEUTIC USES: Amebiasis Antibiotic associated colitis (pseudomemb ranous ) Combined administration of amoxicillin and metronidazole could cover most of the oral bacteria. Prescription of this combination or metronidazole is also recommended for the treatment of periodontal infections , severe odontogenic infections, such as abscess and pulpitis. The drug is commonly prescribed with a dosage of: Metronidazole : 500–750 mg every 8 hours co-amoxiclav (875/125 mg every 8 hours or Indications of antibiotics in dental practice. DENTAL IMPLICATION OF CHEMOTHERAPEUTIC AGENTS I. Treatment of an acute dental infection. II. Prophylactic use for dental procedures that should be given in some cases e.g.: a. Patients with congenital or history of rheumatic fever. b. Patients with transplanted organs. c. Patients Disease, e.g. uncontrolled diabetes mellitus or Drugs and other therapy, e.g. immunosuppressant drugs and corticosteroids. d. Patients with the certain orofacial traumatic wounds or compound mandibullar fractures.  The most commonly used antibiotics in dental practice, penicillins the most commonly prescribed antibiotics by dentists; was amoxicillin, metronidazole and the combination of amoxicillin and clavulanic acid.  Azithromycin can be used in penicillin allergy Patients who are allergic to penicillin clindamycin; - which is active against some oral anaerobic and has the advantage of good bone penetration. - serious side effects such as neutropenia and pseudomembranous colitis.  The ideal duration of antibiotic treatment is the shortest cycle Most acute infections are resolved within 3–7 days.  In dentistry, the antimicrobials active against gram positive cocci and oral anaerobes Amoxycillin, safe & bactericidal in nature is generally the drug of choice. Antiseptic rinse (chlorhexidine 0.2%) is also used as an adjuvant to reduce the bacteremia following dental extraction. Metronidazole is drug of choice in anaerobic gum infection. Antifungal Drugs Classification of antifungal They can be classified as systemic or topical antifungal agents and some are used both Systemically as well as topically NYSTATIN It is highly toxic and used topically only. It is effective against Candida, It is indicated in Candida albicans especially oral moniliasis, monilial vaginitis,conjunctival, cutaneous and corneal candidiasis. GRISEOFULVIN It is isolated from Penicillium griseofulvium. It is active against Microsporum causing superficial infection or dermatophytosis. AMPHOTERICIN B It is poorly absorbed from GIT and topically. After IV administration it is widely distributed in tissues. About 60% drug is metabolized in liver and excretion occurs slowly both in urine and bile. Therapeutic uses It is used orally for intestinal candidiasis, Topically for oral, vaginal and cutaneous candidiasis Hospital treatment of progressive and potentially fatal systemic fungal infections. Adverse effects include nausea, vomiting, Headache , fever, breathlessness, Thrombophlebitis on IV administration. On long term use, dose related nephrotoxicity and anaemia occurs. ANTIVIRAL DRUGS  Oral viral infections encountered in the dental practice are including: - herpes simplex virus types 1 and 2 - Epstein‐Barr virus; - varicella‐zoster virus; - Coxsackie virus; - human papilloma virus; - human immunodeficiency virus Classification of Antiviral Drugs Drugs for herpes: Acyclovir Ganciclovir Drugs for influenza: Amantadine Zanamivir Drugs for HBV and HCV: INF-_ Lamivudine Ribavirin Drugs for HIV: Zidovudine , Didanosine  What is its mechanism of action ? Acyclovir-P-P-P Competitive substrate for DNA polymerase Inhibits DNA polymerase & Incorporated into viral DNA Premature chain termination Acyclovir What is the route of administration? Oral IV Topical  Acyclovir Indications Prophylaxis against herpetic infections in AIDs and in other immuno- suppressed patients.  Treatment of herpes simplex virus infection of the skin and mucous membrane. Treatment of varicella (chickenpox) and herpes zoster (shingles) infections. Acyclovir adverse effects Few side effects Nausea, diarrhea, headache Nephrotoxicity Hepatotoxicity