Transcript Nursing 3703 Pharmacology

Nursing 3703
Pharmacology
Antimicrobials
By Linda Self
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
Age-Related ConsiderationsChildren
 Penicillins and Cephalosporins
generally safe
 Fewer clinical trials on children
 Erythromycin, Zithromax
(azithromycin) and Biaxin
(clarithromycin) considered safe
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
Antimicrobials and Children
 Fluoroquinolones contraindicated in
children under 18 yo. May have
effects on weight bearing joints.
 Bactrim (trimethoprimsulfamethoxazole) no longer 1st line
due to resistance
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
Antimicrobials and Older Adults
 Aminoglycosides can also cause
ototoxicity
 Cleocin (clindamycin)-diarrhea, colitis
 Bactrim (trimethoprimsulfamethoxazole) may be associated
with impaired liver or kidney function
Antimicrobials and Older Adults
 Tetracyclines (except doxycycline)
and Macrodantin (nitrofurantoin) are
contraindicated in impaired renal
function
In General
 With most oral antibiotics, liberal fluid
intake is recommended
 Always be aware of pregnancy
category before administering
medication
Bacteria
 Aerobic
 Anaerobic
 Gram’s Stain-microscopic appearance
and color
 Pathogenic
 Normal flora
Lab ID of Pathogens
 Culture and sensitivity
 Serology-measures antibody levels
 Polymerase Chain Reaction (PCR)
detects the specific DNA for a specific
organism
Common Human Pathogens
 Viruses
 Gram+ enterococci, streptococci and
staphylococci
 Gram- organisms: E.coli, Bacteroides,
Klebsiella, Proteus, Pseudomonas
 Opportunistic
 Community-acquired vs. nosocomial
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
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
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
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
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)
Host Defense Mechanisms
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Breaks in skin and mucous membranes
Impaired blood supply
Neutropenia
Malnutrition
Poor personal hygiene
Suppression of normal flora
Diabetes, advanced age or
immunosuppression
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)
Mechanisms of Action cont.
 Disruption of microbial cell
membranes (anti-fungals)
 Inhibition of organism reproduction
by interfering w/nucleic acid synthesis
(fluoroquinolones, HIV antiretrovirals)
 Inhibition of cell metabolism and
growth (sulfonamides)
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
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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
Drug Selection cont.
 Knowledge of organisms likely to
infect particular body tissues
Other Selection Considerations
 Drug’s ability to penetrate infected
tissues (prostate, sinuses)
 Drug’s toxicity and the risk-to-benefit
ratio
 Drug costs
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)
Antibiotic Combination Therapy
cont.
 Likely emergence of drug resistant
organisms
 In those who are immunosuppressed
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
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
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.
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)
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)
Examples
 Antistaphylococcal—dicloxacillin,
nafcillin
 Anti-pseudomonals—carbenicillin,
ticaracillin
 Beta lactamase inhibition
combinations: Unasyn
(ampicillin/sulbactam), Augmentin
(amoxicillin/clavulate), Timentin
(ticaricillin/clavulanate)
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
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
Cephalosporins
 Contraindicated in anaphylaxis to a
penicillin
 May develop a delayed reaction
Examples
 Oral—Keflex (cephalexin); Ceclor
(cefaclor), Lorabid (lorcarbef);
Omnicef (cefdinir)
 Parenteral—Ancef (kefzol); Mefoxin
(cefoxitin); Claforan (cefotaxime),
Fortaz (ceftazidime), Rocephin
(ceftriaxone); Maxipime (cefepime)
Carbapenems
 Broad spectrum, bactericidal, betalactam anti-microbials. Inhibit
synthesis of cell walls.
 All are parenteral
 Indicated for organisms resistant to
other drugs
 Examples: Merrem (meropenem) and
Primaxin (imipenem-cilastatin)
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
Indications for Monobactams
Infections of the:
 Urinary tract
 Lower respiratory tract
 Skin and skin structures
 Intra-abdominal and gynecologic
infections
 Septicemia
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
FYI
 Need to adjust dosages of all beta
lactams in the presence of renal
impairment whether PCN,
cephalosporins, carbapenems and
monobactams
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
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
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
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
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
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.
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
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
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.
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
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
Macrolides
 Include: Zithromax (azithromycin),
Biaxin (clarithromycin), EES
(erythromycin) and Dynabac
(dirithromycin)
 Effective against gram positive cocci,
Neisseria, Treponema,
Mycoplasma,Bacteroides, Clostridia
and Corynebacterium
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.
Macrolides
 Mechanism of action is by entering
microbial cells and attaching to 50S
ribosomes, thereby inhibiting
microbial protein synthesis
 EES is PCN alternative
Indications for Macrolides
 Respiratory tract infections
 Skin and soft tissue infections caused
by Staph and Strep
 For Legionnaire’s and GU infections
caused by Chlamydia
 Clarithromycin is indicated for tx of
MAC and for H. pylori
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)
Macrolides
 Contraindicated in liver disease
 Contraindicated in hypersensitivity
Miscellaneous Antibacterials
 Chloramphenicol—broad 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
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
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
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
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
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
Drug Interactions cont.
 Chloramphenicol and Streptomycin
increase the effects of EES
 Tagamet increases the action of Flagyl
 Others, see text
Syndercid (quinupristindalfopristin)
 Effective in vancomycin resistant
strains MRSA
 Strong inhibitor of cytochrome P450
 Belong to a class called
streptogramins
 Caustic to veins
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)
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
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)
Indications for use on tetracyclines
cont.
 May be used as substitute for
penicillin
 Doxycycline may be used for
Traveller’s diarrhea
 Declomycin (demeclocycline) may be
used to inhibit ADH in management of
chronic SIADH
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
Sulfonamides
 Bacteriostatic against both gram
positive and gram negative bacteria
 Resistance is mounting
 Combination of Bactrim
(trimethoprim-sulfamethoxazole) is
useful in the treatment of urinary
tract infections and in Pneumocystis
carinii
Sulfonamide preparaions
 Azulfidine (sulfasalazine) is used in
tx of ulcerative colitis and in RA
 May cause crystalluria. Liberal fluids
needed.
Sulfonamides cont.
 Sulfamylon used in burns—especially
w/Pseudomonas—can cause
metabolic acidosis, is painful
w/application
 Silver sulfadiazine—useful in burns
Miscellaneous Drugs for UTIs
 Macrodantin (nitrofurantoin)
 Pyridium (phenazopyridine)-no
antibacterial activity, acts as urinary
antiseptic
Questions?
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