Nursing 3703 Pharmacology

1. Nursing 3703Pharmacology Antimicrobials By Linda Self

2. Microorganisms and Infections • Microbes attach to host receptors • Attracted to a specific body tissue, invade and multiply • Most survive in more than one type of environment • Symptoms are result of immune response

3. Age-Related Considerations-Children • Penicillins and Cephalosporins generally safe • Fewer clinical trials on children • Erythromycin, Zithromax (azithromycin) and Biaxin (clarithromycin) considered safe

4. Antimicrobials and Children • Aminoglycosides can cause ototoxicity and nephrotoxicity. • Tetracyclines are contraindicated in children younger than 8 years old, effects on teeth • Cleocin (clindamycin) admin. requires liver and kidney monitoring in neonates and infants

5. Antimicrobials and Children • Fluoroquinolones contraindicated in children under 18 yo. May have effects on weight bearing joints. • Bactrim (trimethoprim-sulfamethoxazole) no longer 1st line due to resistance

6. Antimicrobials and Older Adults • Penicillins are generally safe, IV admin. can cause hyperkalemia • Cephalosporins are considered sage but can affect or worsen renal failure • Macrolides are generally safe • Aminoglycosides are contraindicated in severe renal impairment

7. Antimicrobials and Older Adults • Aminoglycosides can also cause ototoxicity • Cleocin (clindamycin)-diarrhea, colitis • Bactrim (trimethoprim-sulfamethoxazole) may be associated with impaired liver or kidney function

8. Antimicrobials and Older Adults • Tetracyclines (except doxycycline) and Macrodantin (nitrofurantoin) are contraindicated in impaired renal function

9. In General • With most oral antibiotics, liberal fluid intake is recommended • Always be aware of pregnancy category before administering medication

10. Bacteria • Aerobic • Anaerobic • Gram’s Stain-microscopic appearance and color • Pathogenic • Normal flora

11. Lab ID of Pathogens • Culture and sensitivity • Serology-measures antibody levels • Polymerase Chain Reaction (PCR) detects the specific DNA for a specific organism

12. Common Human Pathogens • Viruses • Gram+ enterococci, streptococci and staphylococci • Gram- organisms: E.coli, Bacteroides, Klebsiella, Proteus, Pseudomonas • Opportunistic • Community-acquired vs. nosocomial

13. Antibiotic-Resistant Microorganisms Occurs when: • Clinical condition of host is impaired • Normal flora have been suppressed • w/interrupted or inadequate tx • Type of bacteria • Widespread use of broad spectrum abx • Environmental setting of host

14. Mechanisms of Resistance By: • Generating enzymes that inactivate the antibiotic (beta lactamase) • Changing structure of target site (beta lactams and aminoglycosides) • Preventing cellular accumulation of abx by altering outer membrane proteins or using efflux pumps

15. Mechanisms of Resistance cont. • Changing the metabolic pathway that is being blocked • Overproducing the target enzyme to overpower the effects of antibiotics • Gram negatives possess an outer membrane and cytoplasmic membrane preventing passage of abx through porins

16. Mechanisms of Resistance cont. • Mycoplasma lacks a cell wall makingit impervious to penicillins • Sulfonamides have no impact on bacteria that obtain their folate from environment

17. Characteristics of Anti-Infectives • Includes antibacterials, antivirals and antifungals • Antibacterials (antibiotics) refer to drugs which treat bacterial infections • Narrow spectrum • Broad spectrum • Bactericidal (kills) vs. Bacteriostatic (inhibits)

18. Host Defense Mechanisms • Breaks in skin and mucous membranes • Impaired blood supply • Neutropenia • Malnutrition • Poor personal hygiene • Suppression of normal flora • Diabetes, advanced age or immunosuppression

19. Mechanisms of Action • Inhibition of bacterial cell wall synthesis or activation of enzymes that disrupt cell walls (PCNs, Cephalosporins, Vancomycin_ • Inhibition of protein synthesis (EES, tetracyclines, clindamycin, aminoglycosides)

20. Mechanisms of Action cont. • Disruption of microbial cell membranes (anti-fungals) • Inhibition of organism reproduction by interfering w/nucleic acid synthesis (fluoroquinolones, HIV anti-retrovirals) • Inhibition of cell metabolism and growth (sulfonamides)

21. Prophylactic Therapy or Empiric Therapy • STD exposure • Recurrent UTIs • TB • Perioperative infections in high risk patients or high risk surgeries • Bacterial endocarditis—w/cardiac valvular disease undergoing dental, surgical or other invasive procedures

22. Drug Selection • Best if based on culture and sensitivity—”match the drug to the bug” • MIC—minimum inhibitory concentration—lowest concentration of a drug that prevents visible growth of microorganisms

23. Drug Selection cont. • Knowledge of organisms likely to infect particular body tissues

24. Other Selection Considerations • Drug’s ability to penetrate infected tissues (prostate, sinuses) • Drug’s toxicity and the risk-to-benefit ratio • Drug costs

25. Antibiotic Combination Therapy • Used when infection is caused by multiple microorganisms • Nosocomial infections • Serious infections in which a combination is synergistic (aminoglycoside and antipseudomonal PCN)

26. Antibiotic Combination Therapy cont. • Likely emergence of drug resistant organisms • In those who are immunosuppressed

27. Beta Lactams • Contain a beta-lactam ring that is part of their chemical structure • An intact beta-lactam ring is essential for antibacterial activity • Include: Penicillins, Cephalosporins, Carbapenems and Monobactams

28. Beta Lactam Mechanism of Action • Inhibit synthesis of bacterial cell walls by binding to proteins in bacterial cell membranes • Binding produces a defective cell wall that allows intracellular contents to leak out • Most effective when bacterial cells are dividing

29. Penicillins • Derived from a fungus • Prototype is Penicillin G • Widely distributed except in CSF (except if inflammation is present) and in intraocular fluid • Most serious complication is hypersensitivity. Can cause seizures and nephropathy.

30. Indications for Penicillins • More effective in treating gram+ infections • Used to treat infections of the skin, GU, GI, respiratory tract and soft tissues • Selection depends on the organism and severity of the infection—anti-staph vs. anti-pseudomonal • Combinations for beta lactamase inhibition (Augmentin)

31. Examples of Penicillins • Penicillins G and V (parenteral); dicloxacillin (antistaph); • Ampicillins—Principen, Amoxil • Antipseudomonals—Geocillin (carbenicillin), Ticar (ticaracillin), Pipracil (piperacillin) • Combinations for beta lactamase—Unasyn (ampicillin/sulbactam), Zosyn (piperacillin/taxobactam)

32. Examples • Antistaphylococcal—dicloxacillin, nafcillin • Anti-pseudomonals—carbenicillin, ticaracillin • Beta lactamase inhibition combinations: Unasyn (ampicillin/sulbactam), Augmentin (amoxicillin/clavulate), Timentin (ticaricillin/clavulanate)

33. Cephalosporins • Also derived from a fungus • Broad spectrum with activity against both gram positive and gram negative bacteria • Less active against gram positives than penicillins • Do not penetrate CSF well w/exception of Ceftin (cefuroxime) and 3rd generation agents

34. Cephalosporins • Progressively more effective against gram negative pathogens as progress generationally • indications-surgical prophy, tx infections of the respiratory tract, skin, bone and joints, urinary tract, brain and spinal cord and in septicemia

35. Cephalosporins • Contraindicated in anaphylaxis to a penicillin • May develop a delayed reaction

36. Examples • Oral—Keflex (cephalexin); Ceclor (cefaclor), Lorabid (lorcarbef); Omnicef (cefdinir) • Parenteral—Ancef (kefzol); Mefoxin (cefoxitin); Claforan (cefotaxime), Fortaz (ceftazidime), Rocephin (ceftriaxone); Maxipime (cefepime)

37. Carbapenems • Broad spectrum, bactericidal, beta-lactam anti-microbials. Inhibit synthesis of cell walls. • All are parenteral • Indicated for organisms resistant to other drugs • Examples: Merrem (meropenem) and Primaxin (imipenem-cilastatin)

38. Monobactams • Azactam (aztreonam) is active against gram-negative bacteria and to many resistant strains • Similar to aminoglycosides but no kidney damage nor hearing loss • Stable in presence of beta lactamase • Preserves normal gram positive and anaerobic flora

39. Indications for Monobactams Infections of the: • Urinary tract • Lower respiratory tract • Skin and skin structures • Intra-abdominal and gynecologic infections • Septicemia

40. FYI • Penicillins may be given with Probenecid or aminoglycosides for serious infections • PCN can cause nephropathies • Ticaracillin has been linked to hypernatremia • PCN G can cause hyperkalemia • Caution w/Augmentin in hepatic impairment

41. FYI • Need to adjust dosages of all beta lactams in the presence of renal impairment whether PCN, cephalosporins, carbapenems and monobactams

42. Aminoglycosides • Bactericidal agents to treat gram negative organisms such as: Proteus, Klebsiella, Enterobacter, Serratia, Escherichia coli, and Pseudomonas • Poorly absorbed fro the GI tract so cause local effects • Accumulate in kidneys and ears • Poorly distributed to CNS, respiratory tract and intraocular fluids • Oral forms excreted in feces, injectables by kidneys

43. Aminoglycosides cont. • Mechanism of action by penetrating cell walls of susceptible bacteria and bind to 30S ribosomes. Bottom line—prevent protein synthesis and replication. • Indicated for serious gram negative organisms • Most often affect the respiratory, GU, skin, wound, bowel and bloodstream

44. Aminoglycosides cont. • Penicillin facilitates entry of aminoglycosdie through the bacterial cell wall • Streptomycin is useful in tuberculosis • Synergism when used with vancomycin, ampicillin or penicillin G in tx of enterococcal infections • Used to suppress intestinal flora in those with hepatic failure

45. Aminoglycosides cont. • Contraindicated in infections for which less toxic drugs are effective • These drugs are nephrotoxic and ototoxic • Must use cautiously in Myasthenia Gravis or neuromuscular disorders because muscle weakness may be increased

46. Aminoglycosides cont. • Choice depends on local susceptibility patterns • Gentamycin generally chosen first, then Tobramycin or Amikacin • Dosing must be carefully regulated because therapeutic doses are close to toxic doses

47. Aminoglycosides—Management Considerations • Initial loading dose based on ideal weight • Are not distributed in body fat • Maintenance doses are based on serum drug concentrations. Peak levels should be assessed 30-60 minutes after administration.

48. Aminoglycoside—Management Considerations cont. • Measurement of peak and trough levels helps to maintain therapeutic serum levels w/o excessive toxicity • With impaired renal function, dosage of aminoglycosides must be reduced. Dosages or intervals may be reduced. • In UTIs, may use lower dosage as excreted by kidneys • Daily dosing

49. Fluoroquinolones • Synthetic bactericidal drugs with activity against gram positive and gram negative organisms • Most are given orally • Excreted via kidneys • Mechanism of action is by interfering with DNA gyrase, an enzyme necessary for synthesis of bacterial DNA

50. Fluoroquinolones • May be used to treat respiratory, GU, GI, bones, joints, skin and soft tissues. Useful in multi-drug resistant TB, Mycobacterium avium complex patients, for fever in neutropenic patients and in tx of gonorrhea.