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Chapter 4 Antibiotics Chapter 4 Topics • • • • • • Bacteria How Antibiotics Work Classes of Antibiotics Antibiotics Independent of Classes Adjunct in Treating Sepsis Discussion Questions Learning Objectives • Identify the major types of antibiotics by drug class. • Know which auxiliary labels to use when dispensing major types of antibiotics. • Define therapeutic effects, side effects, and administration routes of major antibiotics. • Use antibiotic and general drug terminology correctly in written and oral communications. Fighting Bacterial Infections • Bacteria: microorganisms that cause infection • Bactericidal agent: kills the invading organism • Bacteriostatic agent: inhibits the growth or multiplication of bacteria Types of Bacteria • Aerobic bacteria • Anaerobic bacteria Types of Bacteria • Aerobic bacteria needs oxygen to survive • Anaerobic bacteria survives in the absence of oxygen Bacteria Shapes (a) Round cocci (b) Rod-like bacilli (c) Spiral-shaped spirochetes Gram’s Stain Results and Related Diseases Shape Gram’s Stain Bacteria Related Disease rods gram-positive Corynebacteria endocarditis gram-negative E. Coli UTI Gram’s Stain Results and Related Diseases Shape Gram’s Stain Bacteria Related Disease cocci gram-positive Staphylococcus toxic shock syndrome gram-negative Neisseria gonorrhea Gram’s Stain Results and Related Diseases Shape Gram’s Stain Bacteria Related Disease curved or spiral rods gram-negative Campylobacter septicemia spirochetes gram-negative Treponema palladium syphilis How Antibiotics Work • Block protein formation How Antibiotics Work • Block protein formation – Macrolides – Tetracyclines – Aminoglycosides How Antibiotics Work • Block protein formation • Inhibit cell wall formation How Antibiotics Work • Block protein formation • Inhibit cell wall formation – Penicillins – Cephalosporins How Antibiotics Work • Block protein formation • Inhibit cell wall formation • Interfere with DNA formation How Antibiotics Work • Block protein formation • Inhibit cell wall formation • Interfere with DNA formation – Nalidixic acid How Antibiotics Work • • • • Block protein formation Inhibit cell wall formation Interfere with DNA formation Prevent folic acid synthesis How Antibiotics Work • • • • Block protein formation Inhibit cell wall formation Interfere with DNA formation Prevent folic acid synthesis – Sulfonamides Antibiotic Dispensing Issues Warning! • Mix exactly as directed by manufacturer • Swab counting tray with alcohol between drugs to prevent cross-contamination Antibiotic Side Effects • Most antibiotics should be taken on an empty stomach to attain faster absorption Antibiotic Side Effects • Most antibiotics should be taken on an empty stomach to attain faster absorption • Examples of exceptions – nitrofurantoin (Macrobid, Macrodantin) – cefuroxime (Ceftin, Zinacef) Antimicrobial Resistance • Developing largely because of –overuse –misuse Antimicrobial Resistance • Developing largely because of – overuse – misuse • The Pharmacy Technician’s role – Place an label on antibiotics advising the patient to take all of the medication Discussion How might the widespread use of antibacterial soaps affect the population? Classes of Antibiotics • • • • • Sulfonamides Penicillins Cephalosporins Tetracyclines Macrolides • • • • • Ketolides Quinolones Streptogramins Aminoglycosides Cyclic Lipopetides Sulfonamides • AKA “sulfa drugs” • Effective against a broad range of microorganisms • Block specific step in biosynthetic pathway of folic acid • Interfere with PABA and folic acid formation, thereby destroying bacteria Drug List Sulfonamides and Related Drugs • nitrofurantoin (Macrobid, Macrodantin) • sulfamethoxazole-trimethoprim (Bactrim DS, Septra DS) • sulfisoxazole (Gantrisin) Sulfonamides • If patient is allergic to sulfa…. Sulfonamides • If patient is allergic to sulfa…. nitrofurantoin (Macrobid, Macrodantin) Therapeutic Uses of Sulfonamides • • • • • Urinary tract infections (UTIs) Otitis media Ulcerative colitis Lower respiratory infections Prophylaxis in Pneumocystis carinii pneumonia in immunocompromised patients Sulfonamides’ Side Effects • • • • • • • Rash Nausea Drug fever Vomiting Jaundice Blood complications Kidney damage Sulfonamides’ Dispensing Issues • Avoid the sun • Maintain adequate fluid intake Penicillins • Low toxicity • Effective derivatives created from manipulating drug’s basic molecular structure • Kills bacteria by preventing them from forming the rigid cell wall • Because human cells do not have cell walls, they are not affected Drug List Penicillins • • • • • amoxicillin (Amoxil, Trimox) amoxicillin-clavulanate (Augmentin) ampicillin (Principen) ampicillin-sulbactam (Unasyn) carbenicillin (Geocillin) Drug List Penicillins • • • • • • dicloxacillin nafcillin oxacillin penicillin G (various) penicillin V (Veetids) piperacillin Drug List Penicillins • piperacillin-tazobactam (Zosyn) • ticarcillin (Ticar) • ticarcillin-clavulanate (Timentin) Therapeutic Uses of Penicillins • • • • • • • • • Abscesses Beta-hemolytic streptococcus Meningitis Otitis media Pneumonia Respiratory infections Tooth and gum infections Venereal diseases (syphilis and gonorrhea) Endocarditis due to streptococci Penicillins’ Side Effects • Diarrhea • Allergies in 7% to 10% of population Penicillins’ Dispensing Issues • Take on an empty stomach – Food slows absorption – Acids in fruit juices or colas could deactivate the drug Penicillin Resistance • Penicillinase-resistant penicillins work against gram-positive aerobes • Extended-spectrum penicillins are more resistant to gram-negative bacteria • Penicillin combinations improve effect Cephalosporins • Have a mechanism of action similar to penicillins • A person allergic to penicillin, about 10% chance of being allergic Cephalosporins Warning! Alert the Pharmacist if a patient allergic to penicillins is receiving a cephalosporin prescription. Cephalosporins • First-generation Cephalosporins • First-generation – Similar to penicillinase-resistant penicillins with greater gram-negative coverage – Used for • community-acquired infections • mild to moderate infections Cephalosporins • Second-generation Cephalosporins • Second-generation – Increased activity, especially against Haemophilus influenzae – Used for • Otitis media in children • Respiratory infections • UTIs Cephalosporins • Third-generation Cephalosporins • Third-generation – Active against a wide spectrum of gramnegative organisms – Long half-life, so once-a-day dosing for some – Used for • Ambulatory patients • Children (dosing before or after school) Cephalosporins Side Effects • Share side effects of penicillin • Few may initiate unique toxic reactions • Lower frequency of toxicity than many other antibiotics Cephalosporins Warning! All of the cephalosporins look alike when written in the generic form. Watch for dosing and indications for use. Drug List Cephalosporins • • • • • • cefaclor (Ceclor) cefadroxil (Duricef) cefazolin (Ancef) cefdinir (Omnicef) cefditoren (Spectracef) cefepime (Maxipime) Drug List Cephalosporins • • • • • • • cefotaxime (Claforan) cefotetan (Cefotan) cefoxitin (Mefoxin) cefpodoxime (Vantin) cefprozil (Cefzil) ceftazidime (Fortaz) ceftibuten (Cedax) Drug List Cephalosporins • • • • • ceftizoxime (Cefizox) ceftriaxone (Rocephin) cefuroxime (Ceftin, Zinacef) cephalexin (Keflex) cephradine (Velosef) Tetracyclines • Broad-spectrum bacteriostatic antibiotics • Inhibit protein synthesis in bacteria by binding to ribosomes • Suppress the infection and require phagocytes to complete the eradication of the bacteria Therapeutic Uses of Tetracyclines • • • • • • Acne Chronic bronchitis Lyme disease Mycoplasma pneumoniae infection Rickettsia infection Some venereal diseases, such as Chlamydia infection • Traveler’s diarrhea Tetracyclines’ Side Effects • Gastrointestinal upset with nausea and vomiting Tetracyclines’ Dispensing Issues • Avoid antacids to avoid chelation with minerals • Photosensitization • To be avoided by pregnant women and children • Expired drugs are dangerous Drug List Tetracyclines • • • • demeclocycline (Declomycin) doxycycline (Vibramycin) minocycline (Minocin) tetracycline (Sumycin) Macrolides • Inhibit protein synthesis by combining with ribosomes • Used primarily to treat pulmonary infections Macrolides Drugs of choice for the following illnesses and specific bacteria: – – – – – – Chlamydia Group A beta-hemolytic streptococcus H. influenzae Legionnaire’s disease M. pneumoniae S. pneumoniae Macrolides’ Dispensing Issues Although most antibiotics should be taken on an empty stomach, erythromycins usually cause severe GI distress, so should be taken with food Macrolides Warning! Erythromycin and azithromycin can be misread, but the dosing should help. Drug List Macrolides • • • • • • • • azithromycin (Zithromax, Z-PAK) clarithromycin (Biaxin) dirithromycin (Dynabac) erythromycin base (Eryc, Ery-Tab) erythromycin ethylsuccinate (E.E.S., EryPed) erythromycin lactobionate (Erythrocin) erythromycin stearate (Erythrocin) erythromycin-sulfisoxazole (Pediazole) Ketolides • Block protein synthesis by binding to ribosomal subunits • May inhibit the formation of newly forming ribosomes • Bacteria resistant to macrolides, lincomycin derivatives, and streptogramins are also resistant • Used to treat bacterial infections in the lungs and sinuses Drug List Ketolides • telithromycin (Ketek) Quinolones • Strong, rapid bactericidal action against most gram-negative and many grampositive bacteria • Antagonize the enzyme responsible for coiling and replicating DNA, causing DNA breakage and cell death Therapeutic Uses of Quinolones • Bone and joint infections caused by gramnegative organisms • Infectious diarrhea • Ophthalmic infections • Some sexually transmitted diseases • Upper respiratory infections • UTIs Quinolones’ Side Effects • Primarily gastrointestinal, with nausea and vomiting • Dizziness • Unpleasant taste • Can cause joint problems such as swelling and malformations • Patients taking them have a tendency to injure tendons Quinolones’ Dispensing Issues • Not to be given with theophylline • Antacids interfere with absorption • Avoid exposure to sun Drug List Quinolones • • • • • • • ciprofloxacin (Ciloxan, Cipro) gatifloxacin (Tequin) gemifloxacin (Factive) levofloxacin (Levaquin) moxifloxacin (Avelox, Vigamox) norfloxacin (Noroxin) ofloxacin (Floxin, Ocuflox) Streptogramins • Inhibit protein synthesis within the bacterial ribosomes • Alternative to vancomycin • Side effects similar to quinolones nausea and vomiting joint swelling dizziness Drug List Streptogramins • quinupristin-dalfopristin (Synercid) Aminoglycosides • Treat serious infections • Inhibits bacterial protein synthesis by binding to ribosomal subunits Aminoglycosides’ Side Effects • Nephrotoxicity, destructive to kidney • Ototoxicity – Tinnitus – Permanent deafness – Equilibrium problems • Neuromuscular blockade Aminoglycosides • Less frequent dosing may help reduce toxicity – Less drug accumulates in the kidney and ear – Simplified drug monitoring • Levels should be checked prior to administration of second dose to confirm drug elimination Drug List Aminoglycosides • • • • • • amikacin gentamicin (Garamycin, Genoptic) kanamycin (Kantrex) neomycin (Myciguent, Neo-Fradin) streptomycin (none) tobramycin (Nebcin) Cyclic Lipopetides • Bind bacterial membranes and cause the cell membrane to depolarize • Leads to – Inhibition of DNA and RNA synthesis – Bacterial death Drug List Cyclic Lipopetides • daptomycin (Cubicin) Warning! Do not take with statins. Antibiotics Independent of Classes These antibiotics are independent of other classes and each other due to structural differences. Drug List Antibiotics Independent of Classes • • • • • • chloramphenicol (Chloromycetin) clindamycin (Cleocin) linezolid (Zyvox) metronidazole (Flagyl) pentamidine (NebuPent, Pentam) vancomycin (Vancocin) Antibiotics Independent of Classes vancomycin (Vancocin) Warning! Bacterial resistance is increasing due to overuse. Antibiotics Independent of Classes Uses of clindamycin (Cleocin) – – – – – – – Acne Alternative to penicillin in dental prophylaxis Anaerobic pneumonia Bone infections Bowel infections Female genital infections Intra-abdominal infections Antibiotics Independent of Classes clindamycin (Cleocin) Warning! If patient develops diarrhea, the drug must be discontinued. Antibiotics Independent of Classes metronidazole (Flagyl) Place a do not drink alcohol warning sticker on this medication. Adjunct in Treating Sepsis • Sepsis is a life-threatening result of serious infections. • Properties of drotrecogin alfa (Xigris) – Anticoagulant – Anti-inflammatory Drug List Adjunct in Treating Sepsis • drotrecogin alfa (Xigris) Discussion Why is resistance developing to antibiotics? Is this a problem? What role can the pharmacy technician play in regards to this problem?