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Antiinfective & Antiinflammatory Drugs

Antiinfective & Antiinflammatory Drugs. Antibiotics Antiviral Antifungal Antimalarial Antiseptic & Disinfectant Agents Antiinflammatory & Antirheumatic. Antibiotics Definition. Medications used to treat bacterial infections

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Antiinfective & Antiinflammatory Drugs

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  1. Antiinfective & Antiinflammatory Drugs Antibiotics Antiviral Antifungal Antimalarial Antiseptic & Disinfectant Agents Antiinflammatory & Antirheumatic

  2. AntibioticsDefinition • Medications used to treat bacterial infections • Ideally, before beginning antibiotic therapy, the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilities

  3. Antibiotic Therapy • Empiric therapy: treatment of an infection before specific culture information has been reported or obtained • Prophylactic therapy: treatment with antibiotics to prevent an infection, as in intra-abdominal surgery or after trauma

  4. Antibiotic Therapy • Therapeutic response • Decrease in specific signs and symptoms of infection are noted (fever, elevated WBC, redness, inflammation, drainage, pain) • Subtherapeutic response • Signs and symptoms of infection do not improve

  5. Antibiotic Therapy • Superinfection • Antibiotic resistance • Host factors • Genetic host factors • G6PD deficiency • Slow acetylation • Allergic reactions

  6. AntibioticsClasses Sulfonamides Penicillins Cephalosporins Tetracyclines Aminoglycosides Quinolones Macrolides

  7. Other AntibioticsClasses • clindamycin (Cleocin) • dapsone • linezolid (Zyvox) • metronidazole (Flagyl) • nitrofurantoin (Macrodantin) • quinupristin and dalfopristin (Synercid) • daptomycin (Cubicin)

  8. Antibiotic Therapy Four common mechanisms of action • Interference with cell wall synthesis • Interference with protein synthesis • Interference with DNA replication • Acting as a metabolite to disrupt critical metabolic reactions inside the bacterial cell

  9. Actions of Antibiotics • Bactericidal: kill bacteria • Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death

  10. AntibioticsSulfonamides One of the first groups of antibiotics • Sulfadiazine (Coptin) • Sulfamethoxazole • Sulfisoxazole (Gantrisin) • Used to treat otitis media, UTIs, other conditions Often combined with another antibiotic • Sulfamethoxazole-trimethoprim (Bactrim)

  11. Sulfonamides: Mechanism of Action • Bacteriostatic action • Prevent synthesis of folic acid required for synthesis of purines and nucleic acid • Do not affect human cells or certain bacteria—they can use preformed folic acid • Only affect organisms that synthesize their own folic acid

  12. SulfonamidesIndications • Treatment of UTIs caused by susceptible strains of: • Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus • Nocardiosis (caused by Nocardia- pneumonia) • Pneumocystis jiroveci pneumonia (PJP) • co-trimoxazole (Bactrim, Septra) • Upper respiratory tract infections

  13. Sulfonamides:Combination Products • trimethoprim/sulfamethoxazole (co-trimoxazole, Bactrim, Septra) • Used to treat UTIs, PJP, otitis media, other conditions • erythromycin/sulfisoxazole (Pediazole) • Used to treat otitis media

  14. SulfonamidesAdverse Effects Body System Adverse Effects Blood Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis GI Nausea, vomiting, diarrhea, pancreatitis Other Convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria

  15. Nursing Implications Sulfonamides • Should be taken with at least 2000 mL of fluid per day, unless contraindicated • Oral forms should be taken with food or milk to reduce GI upset

  16. Penicillins • Natural penicillins • Penicillinase-resistant penicillins • Aminopenicillins • Extended-spectrum penicillins

  17. Penicillins Natural penicillins • penicillin G, penicillin V potassium Penicillinase-resistant drugs • cloxacillin, dicloxacillin, nafcillin, oxacillin Aminopenicillins • amoxicillin, ampicillin, bacampicillin Extended-spectrum drugs • piperacillin, ticarcillin, carbenicillin

  18. Penicillins • First introduced in the 1940s • Bactericidal: inhibit cell wall synthesis • Kill a wide variety of bacteria • Also called “β-lactams” • Bacteria produce enzymes capable of destroying penicillins • These enzymes are known as β-lactamases • As a result, the medication is not effect

  19. Penicillins • Chemicals used to inhibit these enzymes: Clavulanic acid Tazobactam Sulbactam • Bind with β-lactamase and prevent the enzyme from breaking down the penicillin --making the drug more effective • Penicillin-β-lactamase inhibitor combination drugs • ampicillin + sulbactam = Unasyn • amoxicillin + clavulanic acid = Augmentin • ticarcillin + clavulanic acid = Timentin • piperacillin + tazobactam = Zosyn

  20. Penicillins Mechanism of Action • Penicillins enter the bacteria via the cell wall • Inside the cell they bind to penicillin-binding protein • Once bound, normal cell wall synthesis is disrupted • Result: bacteria cells die from cell lysis • Penicillins do not kill other cells in the body

  21. PenicillinsIndications • Prevention and treatment of infections caused by susceptible bacteria, such as: • Gram-positive bacteria • Streptococcus,Enterococcus, Staphylococcus

  22. PenicillinsAdverse Effects • Allergic reactions occur in 0.7% to 4% of cases • Urticaria, pruritus, angioedema • Those allergic to penicillins have a fourfold to sixfold increased risk of allergy to other β-lactam antibiotics • Cross-reactivity between penicillins and cephalosporins is between 1% and 18% • Common adverse effects • Nausea, vomiting, diarrhea, abdominal pain • Other adverse effects are less common

  23. PenicillinsInteractions • MANY interactions! • NSAIDs • Oral contraceptives • warfarin • Others

  24. Nursing Implications Penicillins • Any patient taking a penicillin should be carefully monitored for an allergic reaction for at least 30 minutes after its administration • The effectiveness of oral penicillins is decreased when taken with caffeine, citrus fruit, cola beverages, fruit juices, or tomato juice • Administer with at least 6 ounces of water

  25. Cephalosporins • Four Generations: • Semisynthetic derivatives from a fungus • Structurally and pharmacologically related to penicillins • Bactericidal action • Broad spectrum • Divided into groups according to antimicrobial activity

  26. CephalosporinsFirst Generation • Used for surgical prophylaxis, URIs, otitis media • cefazolin (Ancef and Kefzol): IV or IM • cephalexin (Keflex): PO

  27. Cephalosporins: Second Generation • Good gram-positive coverage • Better gram-negative coverage than first generation • Cefmetazole IV Cefprozil (Cefzil) PO • Cefoxitin (Mefoxin) IV Cefaclor (Ceclor) PO • cefoxitin (Mefoxin): IV and IM • Used prophylactically for abdominal or colorectal surgeries • Also kills anaerobes • cefuroxime (Kefurox and Ceftin): PO • Surgical prophylaxis • Does not kill anaerobes

  28. Cephalosporins Third Generation ceftriaxone (Rocephin) • IV and IM, long half-life, once-a-day dosing • Elimination is primarily hepatic • Easily passes meninges and diffused into CSF to treat CNS infections • ceftazidime (Fortaz, Tazidime) • IV and IM forms • Excellent gram-negative coverage • Used for difficult-to-treat organisms such as Pseudomonas • Eliminated renally instead of biliary route • Excellent spectrum of coverage

  29. Cephalosporins Fourth Generation • Newest cephalosporin drugs • Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria • Tx: UTI, Skin infections, pneumonia • cefepime (Maxipime) GM +/- • cefdinir • cefditoren pivoxil (Spectracef)

  30. CephalosporinsAdverse Effects • Similar to penicillins • Mild diarrhea, abdominal cramps, rash, pruritis, redness, edema • Potential cross-sensitivity with penicillins if allergies exist

  31. Nursing ImplicationsCephalosporins • Orally administered forms should be given with food to decrease GI upset, even though this will delay absorption • Some of these drugs may cause a disulfiram (Antabuse)-like reaction when taken with alcohol

  32. Carbapenems • Very broad-spectrum antibacterial action • Reserved for complicated body cavity and connective tissue infections • May cause drug-induced seizure activity • All given parenterally imipenem-cilastatin (Primaxin) • Used for treatment of bone, joint, skin, and soft tissue infections • Cilastatin inhibits an enzyme that breaks down imipenem meropenem (Merrem) – bacterial meningitis ertapenem (Invanz) - newest

  33. Monobactams aztreonam (Azactam) • Synthetic β-lactamantibiotic • Primarily active against aerobic gram-negative bacteria (E. coli, Klebsiella spp., Pseudomonas spp.) • Bactericidal • Used for moderately severe systemic infections and UTIs

  34. Macrolides • Prevent protein synthesis within bacterial cells • Considered bacteriostatic - Bacteria will eventually die • In high enough concentrations, may also be bactericidal • erythromycin (E-mycin • azithromycin (Zithromax) • clarithromycin (Biaxin) Adverse Effects: GI effects, primarily with erythromycin • Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia • Newer drugs, azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration

  35. Nursing ImplicationsMacrolides • These drugs are highly protein-bound and will cause severe interactions with other protein-bound drugs • The absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many drugs are taken after a meal or snack

  36. Ketolide telithromycin (Ketek) • Only drug in this class • Better antibacterial coverage than macrolides • Active against gram-positive bacteria, including multi-drug resistant strains of S. pneumoniae • Active against selected gram-negative bacteria • Indications: • Community-acquired pneumonia, acute bacterial sinusitis, bacterial exacerbations of chronic bronchitis • Adverse reactions include: • Headache, dizziness, GI discomfort, altered potassium levels, prolonged QT intervals

  37. Tetracyclines • Natural and semisynthetic • Obtained from cultures of Streptomyces • Bacteriostatic—inhibit bacterial growth • Inhibit protein synthesis • Stop many essential functions of the bacteria • demeclocycline (Declomycin) • oxytetracycline • tetracycline • doxycycline (Doryx, Vibramycin) • Minocycline

  38. TetracyclinesAdverse Effects Strong affinity for calcium • Discoloration of permanent teeth and tooth enamel in fetuses and children, or nursing infants if taken by the mother • May retard fetal skeletal development if taken during pregnancy Alteration in intestinal flora may result in: • Superinfection (overgrowth of nonsusceptible organisms such as Candida) • Diarrhea • Pseudomembranous colitis

  39. Nursing ImplicationsTetraclyclines • Milk products, iron preparations, antacids, and other dairy products should be avoided because of the chelation and drug-binding that occurs • All medications should be taken with 6 to 8 ounces of fluid, preferably water • Due to photosensitivity, avoid sunlight and tanning beds

  40. Nursing Implications • Before beginning therapy, assess drug allergies; renal, liver, and cardiac function; and other lab studies • Be sure to obtain patient health history, including immune status • Assess for conditions that may be contraindications to antibiotic use or that may indicate cautious use • Assess for potential drug interactions • It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

  41. Nursing Implications • Each class of antibiotics has specific adverse effects and drug interactions that must be carefully assessed and monitored • The most common adverse effects of antibiotics are nausea, vomiting, and diarrhea • All oral antibiotics are absorbed better if taken with at least 6 to 8 ounces of water

  42. Nursing Implications Monitor for therapeutic effects • Improvement of signs and symptoms of infection • Return to normal vital signs • Negative culture and sensitivity tests • Disappearance of fever, lethargy, drainage, and redness Monitor for adverse reactions

  43. Antibiotic TherapyConcepts • Therapeutic drug monitoring • Minimum inhibitory concentration (MIC) • Concentration-dependent killing • Once-daily dosing vs. multi-daily dosing • Peak and trough blood levels • Synergistic effects • Post-antibiotic effect (PAE)

  44. Antibiotic TherapyToxicities • Ototoxicity • Temporary or permanent hearing loss, balance problems • Nephrotoxicity • Varying degrees of reduced renal function • Rising serum creatinine may indicate reduced creatinine clearance Monitor trough levels every 3 days while on therapy or as ordered

  45. Aminoglycosides • gentamicin (Garamycin) • kanamycin • neomycin (Neo-Fradin) • streptomycin • tobramycin (Nebcin) • amikacin (Amikin) • netilmicin • paromomycin

  46. Aminoglycosides • Natural and semisynthetic • Produced from Streptomyces • Poor oral absorption; no PO forms • Very potent antibiotics with serious toxicities • Bactericidal; prevents protein synthesis • Kill mostly gram-negative; some gram-positive

  47. AminoglycosidesIndications • Used to kill gram-negative bacteria Pseudomonas, E. coli, Proteus, Klebsiella, Serratia • Often used in combination with other antibiotics for synergistic effects • Certain gram-positive infections that are resistant to other antibiotics • Aminoglycosides poorly absorbed through the GI tract - given IV • Exception: neomycin • Given orally or by enema - decontaminate the GI tract before surgical procedures

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