Antibiotics (Part 2) PDF

Antibiotics (Part 2) Dr. Dina Abdel Hamid Derbala Lecturer of Oral and Maxillofacial Surgery Oral Surgery Division - BMC - Jeddah Cephalosporins Beta-lactam antibiotic Cephalosporins Cephalosporins are β-lactam antibiotics closely related both structurally and functionally to penicillin....

Antibiotics (Part 2) Dr. Dina Abdel Hamid Derbala Lecturer of Oral and Maxillofacial Surgery Oral Surgery Division - BMC - Jeddah Cephalosporins Beta-lactam antibiotic Cephalosporins Cephalosporins are β-lactam antibiotics closely related both structurally and functionally to penicillin. Cephalosporins are produced semi synthetically. All cephalosporins are bactericidal. All cephalosporins have the same mechanism of action as penicillin, i.e. inhibition of bacterial cell wall synthesis. Cephalosporins start with cef, ceph, or kef. Cephalosporins are classified into five generations. First and second generations are mostly used in dentistry. Each newer generation of cephalosporins is increasingly resistant to B lactamase. B lactamase: is a n enzyme produced by certain bacteria that is resistant to B lactam antibiotics. Antibacterial Spectrum of Cephalosporins: 1960s 1970s 1980s 1990s 2010 First Generation Second Generation Third Generation Fourth Generation Fifth Generation ▪ Cephalexin (Keflex) ▪ Cefuroxime (Zinnat) ▪ Ceftriaxone (Rocephin) ▪ Cefepime ▪ Ceftaroline ▪ Cephradine (Velosef) ▪ Cefaclor ▪ Cefoperazone (Cefobid) ▪ Cefpirome ▪ Ceftobiprole ▪ Cefadroxil (Duricef) ▪ Cefoxitin ▪ Ceftibuten ▪ Cefazolin ▪ Cefprozil ▪ Cefixime ▪ Cephalothin ▪ Cefotetan ▪ Ceftazidime ▪ Cefotaxime (Cefotax – Claforan) G+ve G-ve First Generation Second Generation Third Generation Fourth Generation Fifthe Generation EACH NEWER GENERATION OF CEPHALOSPORINS IS INCREASINGLY RESISTANT AGAINST B-LACTAMASE  Pharmacokinetics Absorption: ▪ Most of the cephalosporins must be administered IV or IM due to their poor oral absorption. ▪ Only few exceptions can be given by the oral route (e.g., Cephalexin, 1st generation).. Distribution ▪ They cross placental barrier but they are not teratogenic. Excretion ▪ Cephalosporins are excreted by the kidneys and the doses must be adjusted in renal dysfunction to guard against accumulation and toxicity. ▪ Ceftriaxone, is excreted through the bile into the feces (so, it is used employed in patients with renal insufficiency). Pharmacotherapeutics Routine Management Of Odontogenic Infections ▪ Cephalosporins are generally not preferred in management of odontogenic infections. ▪ Second-generation cephalosporins should be selected for management of odontogenic infections, as this group possesses greater antibacterial efficacy against gram-negative anaerobes.(The only commercially available cephalosporins with appreciable activity against gram-negative anaerobic bacteria) − Rx: Cefaclor (Ceclor) 500 mg PO TID / 5 days. Ceftriaxone(3rd generation): is used in the treatment of Meningitis. Meningitis: It is an inflammation of the protective membranes covering the brain and spinal cord. Pharmacotherapeutics Safety in Pregnancy : ▪ Because cephalosporins act by inhibition of bacterial cell wall synthesis, they have little systemic toxicity in mammals. Safety in Lactation: ▪ Cephalosporins are excreted in breast milk. ▪ Cephalosporins are considered to be compatible with breastfeeding. Allergy: ▪ Cephalosporins should be avoided in individuals with penicillin allergy. ▪ Patients who have had immediate hypersensitivity reaction in response to penicillin should not be given cephalosporins. Drug Interactions: Drugs that reduce the absorption of oral cephalosporins: − H2-Histamine Receptor Antagonists (Ranitidine) − Iron Supplements (Feroglobin) Intravenous Ceftriaxone − Intravenous ceftriaxone should not be given with any calcium-containing solution (e.g., Ringer’s solution), (It is an isotonic fluid used to restore electrolyte balance) − This combination produce a dangerous compound (ceftriaxone-calcium) microcrystalline precipitates in lungs and kidney. INHIBITORS OF BACTERIAL PROTEIN SYNTHESIS Inhibition of Protein Synthesis : Macrolides Macrolides ▪ Erythromycin (Natural) ▪ It is the first macrolide antibiotic to have a clinical application. ▪ Formerly, it was the most commonly prescribed macrolide Macrolides ▪ Clarithromycin [Klacid] (Semi-Synthetic) antibiotic in dentistry to manage infections in penicillin allergic patients. ▪ Azithromycin [Zithromax] ▪ Nowadays, it is the most commonly used macrolide in (Semi-Synthetic) Dentistry to manage infections in penicillin allergic patients. Macrolides inhibit bacterial protein synthesis by binding to the to the bacterial ribosomes. Macrolides are active against most streptococci, staphylococci, and some anaerobes.(Bacteriostatic) Absorption ▪They are stable in stomach acid and are readily absorbed. Metabolism: ▪They are extensively metabolized by the liver. Excretion ▪ All are excreted in the bile (Safe in renal dysfunction patients) except Clarithromycin is excreted in the urine. Dental Uses: ERYTHROMYCIN AZITHROMYCIN It is not preferred penicillin-alternative drug It is the preferred penicillin-alternative drug when a severe infection exists or when the of choice in penicillin allergic patients patient is immunocompromised and requires and in patients who cannot tolerate bacteriocidal activity. clindamycin due to its favourable pharmacokinetics. When Erythromycin is used in combination with anticoagulant drug (Warfarin), it improves the effect of anticoagulant, thereby increasing risk of Azithromycin is concentrated in neutrophils, bleeding. and macrophages, so they have a long half time and given once daily  Dental Uses of Azithromycin: 1) Prophylactic Use: ▪ Endocarditis Prophylaxis (Oral: Azithromycin 500 mg Po ac 1 hour before the procedure) (Parenteral: Azithromycin 500 mg vial IV 1 hour before the procedure) 2) Therapeutic Uses: ▪ A second line treatment for Syphilis ($) ▪ Treatment of acute orofacial infections (e.g., acute periapical abscess - Sinusitis). Oral: Azithromycin 500 mg Tab po ac od / 3 days Drug Interactions Combination of macrolides with penicillin antagonize the bactericidal effect of penicillin. Oral anticoagulants: it improves the effect of anticoagulant (warfarin), thereby increasing risk of bleeding. (Erythromycin) Anticonvulsant drugs can have altered levels in the presence of macrolides. Theophylline (anti-asthma): Erythromycin and clarithromycin can increase the level of Theophylline leading to toxicity. Adverse Effects: -GIT issues: nausea, vomiting and diarrhea. (Erythromycin) -Cardiotoxicity is associated with high serum levels -Hepatotoxicity (in pregnant women with Erythromycin) -Hearing loss (rare) Lincosamides Lincosamides CLINDAMYCIN: (semisynthetic). − It inhibits protein synthesis by binding to the bacterial ribosomes. − Lincosamides are bacteriostatic in normal concentrations. − The use of Lincosamides (e.g., Clindamycin) is popular for the treatment of dental infections due to its activity against anaerobic and aerobic bacteria (i.e., streptococci and staphylococci) as well as Bacteroides.  Pharmacokinetics : ▪ Absorption: Oral clindamycin is well absorbed from GIT. ▪ Distribution: The drug penetrates well into body tissues including bone as well as body fluids except CSF. ▪ Metabolism: The drug undergoes metabolism in the liver and kidneys. ▪ Excretion: − Primarily in bile and very little amount is excreted in urine. − Accumulation has been reported in patients with either severe renal impairment or hepatic failure. Adverse Effects (Clindamycin) 1) Skin rash 2) Metallic taste, stomatitis, glossitis and esophagitis. - stomatitis: inflammation of mucous membranes of the mouth 3) Pseudomembranous colitis (PMC): It is a serious condition of the colon that can occur as a side effect of antibiotic, It is caused by Clostridium difficile. Clostridium difficile: -It is a bacterium. Clindamycin and Pregnancy: -Most commonly AdverseClindamycin Effects is considered a safe antibiotic during associated with use of antibiotics; pregnancy. (Diarrhea- nausea abdominal cramps- inflammation of the Clindamycin and Lactation: colon or colitis) It can be prescribed to a lactating woman. However, It has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora. Dental Uses Prophylactic Use In Penicillin Allergic Patient : ▪ Oral: Clindamycin 600mg (300mg 2Cap PO) 1 hour before the procedure ▪ Parenteral: Clindamycin 600mg amp IV / IM 1 hour before the procedure Therapeutic Uses In Penicillin Allergic Patient: Rx: Clindamycin 300mg Cap PO QID / 5days TETRACYCLINES Pharmacokinetics: ▪ Tetracyclines are Broad Spectrum Bacteriostatic Antibiotics. ▪ They inhibit bacterial protein synthesis. ▪ Absorption: ▪ All tetracyclines are partially absorbed from the stomach and upper GIT (they can disturb the intestinal flora).. ▪ ALL tetracyclines have poor absorptionif they are taken with Calcium (e.g.,milk) ▪ Distribution: -They reach all body fluids, but they Can not Penetrate CSF even in presence of infection. -They chelate with calcium (deposited in growing bones and teeth causing yellow discoloration of teeth). ▪ Metabolism − Tetracyclines are metabolized in liver. ▪ Excretion: − All tetracyclines are eliminated in urine. Dental Uses: ▪ Tetracyclines Have: (1) An Anticollagenase Effect (i.e., inhibit the break down of tissue). Collagenase : is an enzyme that breaks down collagen found in connective tissue (PDL tissue). (1) A High Bioavailability In the Gingival Sulcus. ▪ These properties make them useful for treatment of periodontal and peri-implant disease.  Adverse Effects: Intrinsic Tooth Staining: ▪ It occurs when tetracycline is administered in growing children due to chelation of tetracycline with calcium. ▪ It affects both deciduous and permanent teeth. ▪ Tetracyclines are contraindicated in children, pregnant and lactating women. Phototoxicity/Photosensitivity Bone weakness: ▪ Deposition in the bone occurs during calcification in growing children. Tetracyclines are Teratogenic drugs. Aminoglycosides Aminoglycoside -Aminoglycoside are BACTERICIDAL DRUGS that act by inhibition of bacterial protein synthesis. -They can Cross Placental Barrier and may cause CONGENITAL DEAFNESS. ( ototoxicity or toxic to the ears) Pharmacokinetics: ▪ Absorption : − All aminoglycosides have poor absorption after oral administration. − All aminoglycosides must be given parenterally to achieve adequate serum levels. ▪ Distribution : − They are distributed in all body fluids. − All aminoglycosides cannot penetrate CSF. − They can Cross Placental Barrier and may cause CONGENITAL DEAFNESS.(NOT SAFE IN PREGNANCY) ▪ Metabolism : − Aminoglycosides does not metabolized in the body. ▪ Excretion : − All aminoglycosides are excreted unchanged in urine (avoid its use in renally impaired patients). − Neomycin is primarily excreted unchanged in stool. Neomycin is used for bowel decontamination before colorectal surgery (to decrease bacterial load in the intestine).  Adverse effects: 1) Nephrotoxicity (due to accumulation of aminoglycosides in the renal tubular cells). 2) Ototoxicity : due to accumulation of aminoglycosides in the lymphatics of the inner ear causing damage to the hair cells and auditory impairment that may be permanent hearing loss. 3) Neuromuscular paralysis is associated with a rapid increase in concentration. Penicillin & Aminoglycosides: ▪ The antibacterial effects of all B-Lactam antibiotics are synergistic with the aminoglycosides. ▪ Penicillin inhibits cell wall synthesis and facilitate the entry of aminoglycosides to inside the bacterial cell. ▪ These drugs should never be combined in the same syringe because the acidic penicillin will react with the basic aminoglycosides and form an inactive complex (salt).  INHIBITORS OF BACTERIAL NUCLEIC ACID (DNA) SYNTHESIS Metronidazole (Flagyl)  Metronidazole (Flagyl) It works by Inhibition of DNA synthesis Metronidazole Spectrum ► Metronidazole is only effective against Anaerobic Bacteria. ► Metronidazole has no effect on bacteria that are aerobic or facultative (grow in presence and in absence of oxygen). ▪ Absorption: -Metronidazole is completely and rapidly absorbed after oral administration. ▪ Distribution: − Metronidazole distributes well throughout body tissues and fluids. - Therapeutic levels can be found in saliva, breast milk, and cerebrospinal fluid (CSF). ▪ Metabolism: − Metronidazole is metabolized in the liver through hepatic oxidation. ▪ Excretion: − It is excreted in the urine. Metronidazole (Flagyl) Therapeutic Uses: 1) Management of periodontal diseases. 2) Management of anaerobic odontogenic infections alone or in combination with other antibiotics such as penicillin (to cover the entire spectrum of aerobic and anaerobic microbes). Routes of Administration: 1) Oral: Metronidazole 500 mg (TID) PO 7 to 10 days 2) Parenteral through slow intravenous infusion. Adverse Drug Effects: 1) Nausea, vomiting, epigastric distress, and abdominal cramps. 2) Unpleasant, metallic taste is commonly experienced due to the excretion of metabolites in the saliva. 3) Hairy tongue, glossitis, dry mouth and stomatitis. 4) Disulfiram-like reaction may occur If taken with alcohol. Disulfiram: medication used to treat alcoholics to make drinking alcohol produce unpleasant after effects. Reference Reference: Chapter 33: Pharmacology of Specific Drug Groups: Antibiotic Therapy Thank You