Nursing 3703 Pharmacology

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Nursing 3703Pharmacology

• Antimicrobials
• By Linda Self

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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

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Age-Related Considerations-Children

• Penicillins and Cephalosporins generally safe
• Fewer clinical trials on children
• Erythromycin, Zithromax (azithromycin) and
  Biaxin (clarithromycin) considered safe

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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

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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

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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

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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

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Antimicrobials and Older Adults

• Tetracyclines (except doxycycline) and
  Macrodantin (nitrofurantoin) are contraindicated
  in impaired renal function

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In General

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

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Bacteria

• Aerobic
• Anaerobic
• Grams Stain-microscopic appearance and color
• Pathogenic
• Normal flora

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Lab ID of Pathogens

• Culture and sensitivity
• Serology-measures antibody levels
• Polymerase Chain Reaction (PCR) detects the
  specific DNA for a specific organism

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Common Human Pathogens

• Viruses
• Gram enterococci, streptococci and staphylococci
• Gram- organisms E.coli, Bacteroides, Klebsiella,
  Proteus, Pseudomonas
• Opportunistic
• Community-acquired vs. nosocomial

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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

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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

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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

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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

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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)

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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

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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)

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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)

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Prophylactic Therapy or Empiric Therapy

• STD exposure
• Recurrent UTIs
• TB
• Perioperative infections in high risk patients or
  high risk surgeries
• Bacterial endocarditisw/cardiac valvular disease
  undergoing dental, surgical or other invasive
  procedures

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Drug Selection

• Best if based on culture and sensitivitymatch
  the drug to the bug
• MICminimum inhibitory concentrationlowest
  concentration of a drug that prevents visible
  growth of microorganisms

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Drug Selection cont.

• Knowledge of organisms likely to infect
  particular body tissues

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Other Selection Considerations

• Drugs ability to penetrate infected tissues
  (prostate, sinuses)
• Drugs toxicity and the risk-to-benefit ratio
• Drug costs

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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)

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Antibiotic Combination Therapy cont.

• Likely emergence of drug resistant organisms
• In those who are immunosuppressed

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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

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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

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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.

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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 infectionanti-staph vs. anti-pseudomonal
• Combinations for beta lactamase inhibition
  (Augmentin)

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Examples of Penicillins

• Penicillins G and V (parenteral) dicloxacillin
  (antistaph)
• AmpicillinsPrincipen, Amoxil
• AntipseudomonalsGeocillin (carbenicillin), Ticar
  (ticaracillin), Pipracil (piperacillin)
• Combinations for beta lactamaseUnasyn
  (ampicillin/sulbactam), Zosyn (piperacillin/taxoba
  ctam)

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Examples

• Antistaphylococcaldicloxacillin, nafcillin
• Anti-pseudomonalscarbenicillin, ticaracillin
• Beta lactamase inhibition combinations Unasyn
  (ampicillin/sulbactam), Augmentin
  (amoxicillin/clavulate), Timentin
  (ticaricillin/clavulanate)

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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

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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

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Cephalosporins

• Contraindicated in anaphylaxis to a penicillin
• May develop a delayed reaction

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Examples

• OralKeflex (cephalexin) Ceclor (cefaclor),
  Lorabid (lorcarbef) Omnicef (cefdinir)
• ParenteralAncef (kefzol) Mefoxin (cefoxitin)
  Claforan (cefotaxime), Fortaz (ceftazidime),
  Rocephin (ceftriaxone) Maxipime (cefepime)

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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)

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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

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Indications for Monobactams

• Infections of the
• Urinary tract
• Lower respiratory tract
• Skin and skin structures
• Intra-abdominal and gynecologic infections
• Septicemia

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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

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FYI

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

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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

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Aminoglycosides cont.

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

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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

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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

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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

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AminoglycosidesManagement 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.

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AminoglycosideManagement 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

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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

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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.

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Fluoroquinolones cont.

• Contraindicated in hypersensitivity reactions
• In children under 18 years of age
• In pregnant or lactating women
• Examples of quinolones Cipro (ciprofloxacin),
  Levaquin (levofloxacin), Floxin (ofloxacin)
• Pregnancy category C

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Fluoroquinolones cont.

• Monitor renal and liver function
• Ensure adequate fluid intake to prevent
  crystalluria
• Assess current medications for drugs that
  interact with
• Avoid exposure to sunlight

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Macrolides

• Include Zithromax (azithromycin), Biaxin
  (clarithromycin), EES (erythromycin) and Dynabac
  (dirithromycin)
• Effective against gram positive cocci, Neisseria,
  Treponema, Mycoplasma,Bacteroides, Clostridia and
  Corynebacterium

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Macrolides

• Erythromycin is the prototype
• Food can have an effect on absorption
• New relative, Ketek (telithromycin) called
  ketolides. Will offer better activity against
  multi-drug resistant strains of Streptococcus.

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Macrolides

• Mechanism of action is by entering microbial
  cells and attaching to 50S ribosomes, thereby
  inhibiting microbial protein synthesis
• EES is PCN alternative

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Indications for Macrolides

• Respiratory tract infections
• Skin and soft tissue infections caused by Staph
  and Strep
• For Legionnaires and GU infections caused by
  Chlamydia
• Clarithromycin is indicated for tx of MAC and for
  H. pylori

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Macrolide Management Considerations

• EES interferes with the elimination of drugs
  metabolized by the cytochrome P450 enzymes
• Interacting drugs include Coumadin,
  Theophylline, Prednisone, Norpace, Lanoxin,
  Tegretol, Alfenta and Parlodel (dopamine agonist)

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Macrolides

• Contraindicated in liver disease
• Contraindicated in hypersensitivity

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Miscellaneous Antibacterials

• Chloramphenicolbroad spectrum bacteriostatic
  used for gram negative and positive bacterial
  infections
• More toxic than others that can do equally well
  for gram positives
• Indicated in meningococcal, pneumococcal,
  rickettsial infections and in Haemophilus and
  Klebsiella

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Miscellaneous

• Cleocin (clindamycin)similar in actio to
  macrolides is effective against gram positive
  cocci and pneumococci
• Effective in treating mixed infections
• Great for acne and bacterial vaginosis
• Can cause pseudomembranous colitis

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Miscellaneous

• Zyvox (linezolid) is a member of the oxalodinone
  class
• Active against aerobic gram positive bacteria
• Indicated for septicemia
• Can cause myelosuppression and psedomembranous
  colitis

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Miscellaneous

• Flagyl (metronidazole)
• Effective against anaerobic bacteria, gram
  positive bacilli such as clostridium and protozoa
  such as Giardia, amebiasis, trichomoniasis
• Useful topically for rosacea
• Used for bacterial vaginosis
• Disulfiram-like reaction if taken w/alcohol

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Miscellaneous--Vancomycin

• Active against gram positives only
• Frequently used to treat MRSA
• Can cause hypotension, flushing and skin rash if
  given too quickly
• Resistance is mounting
• Can cause red man sydrome if given too quickly
• Caution in patients w/myasthenia gravis

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Drug interactions

• Amphotericin B, vancomycin, cephalosporins, loop
  diuretics, neuromuscular blocking agents can
  increase the effects of aminoglycosides
• Tagamet (cimetidine) and Probenecid increase the
  effects of the fluoroquinolones

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Drug Interactions cont.

• Chloramphenicol and Streptomycin increase the
  effects of EES
• Tagamet increases the action of Flagyl
• Others, see text

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Syndercid (quinupristin-dalfopristin)

• Effective in vancomycin resistant strains MRSA
• Strong inhibitor of cytochrome P450
• Belong to a class called streptogramins
• Caustic to veins

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Tetracyclines

• Broad spectrum bacteriostatic
• Microbial resistance emerging
• Newer options less toxic
• Still very effective against rickettsiae (e.g.
  Rocky Mountain Spotted Fever)
• Effective against Chlamydia, Mycoplasma, protozoa
  (e.g. Malaria, Giardia, Leishmaniasis)

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Tetracyclines

• Most are excreted in urine
• Examples include Minocin (minocycline),
  Vibramycin (doxycycline), Achromycin
  (tetracycline)

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Tetracyclines

• Work by passive diffusion and an active transport
  system
• Bind to 30S ribosomes and inhibit micorbial
  protein synthesis
• Drugs of choice in Brucellosis, Chancroid,
  Cholera, Granuloma Inguinale, Trachoma, H. pylori

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Indications for use

• Treatment of uncomplicated urethral, endocervical
  or rectal infections caused by chlamydia
• Adjunt in the treatment of PID and STDs
• Long term treatment of acne (interfere with
  production of free fatty acids and
  Corynebacterium in sebum)

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Indications for use on tetracyclines cont.

• May be used as substitute for penicillin
• Doxycycline may be used for Travellers diarrhea
• Declomycin (demeclocycline) may be used to
  inhibit ADH in management of chronic SIADH

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Tetracyclines cont.

• Contraindicated in renal failure except for doxy
  and minocycline
• Not indicated in children less than 8 years of
  age because can cause permanent discoloration of
  teeth and can depress bone growth
• Can cause photosensitivity
• Avoid taking within 2 hours of dairy products,
  w/iron or w/antacids

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Sulfonamides

• Bacteriostatic against both gram positive and
  gram negative bacteria
• Resistance is mounting
• Combination of Bactrim (trimethoprim-sulfamethoxaz
  ole) is useful in the treatment of urinary tract
  infections and in Pneumocystis carinii

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Sulfonamide preparaions

• Azulfidine (sulfasalazine) is used in tx of
  ulcerative colitis and in RA
• May cause crystalluria. Liberal fluids needed.

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Sulfonamides cont.

• Sulfamylon used in burnsespecially
  w/Pseudomonascan cause metabolic acidosis, is
  painful w/application
• Silver sulfadiazineuseful in burns

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Miscellaneous Drugs for UTIs

• Macrodantin (nitrofurantoin)
• Pyridium (phenazopyridine)-no antibacterial
  activity, acts as urinary antiseptic

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Questions?
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Sulfonamides

• Contraindicated in renal failure
• Can cause bone marrow depression, especially in
  elderly
• With Bactrim, can cause folic acid deficiency
• Can cause cholestatic jaundice in rare cases