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99 Cards in this Set
- Front
- Back
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what is selective toxicity
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Antibiotics have the capacity to kill invading microorganisms without injuring the host, because toxicity is relative, and not
absolute, and based upon drug concentration |
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antibiotic therapy/selective therapy takes advantage of what?
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fundamental biochemical, anatomical, and physiological differences between the organism and the host
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what is the most widely used family of drugs? what percentage of all hospitalized pts receive them?
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antibiotics
30% |
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why is the cell wall a natural target for many classes of antibiotics?
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Since human beings are eukaryotic organisms, we have
no cell wall, must be antibiotics which attack the cell wall, exhibit a selective toxicity, against the bacteria, and not against human cells. |
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what is another important difference that exists btw bacteria and humans that could serve as a target for AB?
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Bacterial ribosomes are 70s
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what is an important difference that exists btw bacteria and humans regarding acquisition vs. the sythesis of vital compounds from the environment?
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Folic acid is a key requirement in the synthesis of DNA,
RNA, and selected proteins |
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what is a narrow spectrum antibiotic?
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A narrow spectrum antibiotic is one that is effective
against only a few microorganisms |
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what is a broad spectrum antibiotic?
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broad spectrum
antibiotics, as the name implies, are active against huge numbers of bacteria |
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why do we always use the narrowest spectrum of antibiotic against a microbe?
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We realize that in addition to killing the pathogenic
bacteria, we are also killing useful bacteria to body • In targeting just the pathogenic bacteria by using a narrow spectrum antibiotic, we minimize damage to the useful bacteria which we depend upon |
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See Table 83-1 "Classification of the Penicillins"
See table "Classification of Antimicrobial Drugs by Mechanism of Action" |
Make appropriate flashcards
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What is a C&S?
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Identification of bacteria that is causing infection is done by culture
and sensitivity (C&S) |
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Define Bactericidal
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this antibiotic is one that is directly legal to the
bacteria once clinically significant concentrations of antibiotic have accumulated |
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Define Bacteriostatic
When do we give a bacteriostatic AB? |
this antibiotic is an agent that merely slows
microbial growth, but does not cause direct bacterial that |
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what is the MIC
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minimum
inhibitory concentration (MIC), and this is different for every antibiotic • This is the lowest concentration of antibiotic that produces complete incubation of bacterial growth |
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what is MBC?
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minimum bactericidal concentration (MBC), which is the lowest concentration of drug that produces 99.9 percent decline in the number of bacterial colonies
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What variables does the duration of AB therapy depend upon?
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The status of the host defenses, e.g., immunocompromise? Elderly, neonate, the
infection site, and the identity of the infecting organism • Can the antibiotic actually get to the site of infection? Eg., pus pocket |
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what is the most common reasons for treatment failure, recurrent infection, and drug resisitance?
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early discontinuation
Antibiotics should be taken for their entire prescribed course |
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define "resistant" bacteria
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Bacteria are said to be resistant if their growth is not halted by maximum amounts of antibiotic that can be tolerated by the host
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Describe selection pressure as a mechanism of drug resistance
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Under normal conditions, bacteria compete with each other for living space and
available food |
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why are broad spectrum AB's more likely to produce resistance than narrow spectrum AB's?
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because broad spectrum antibiotics will kill off a greater
variety of bacteria, both harmful and beneficial, than the narrow spectrum antibiotics |
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why are the Penicillins collectively referred to as the beta-lactam antibiotics?
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because of a chemical structure known as a
beta-lactam ring, at the core of the molecule |
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How to the Penicillins work?
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This class of antibiotics works by inhibiting a key enzyme of cell wall synthesis,
transpeptidase |
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what are the advantages of Penicillin?
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Penicillin is almost the perfect antibiotic: it is
active against a broad spectrum of bacteria, it has low toxicity, and it’s very cheap |
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what are the disadvantages of Penicillins?
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10% of the population is allergic and doesn't know it. Many people have alleric reactions
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How do Penicillins kill bacteria?
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This class of antibiotics works by inhibiting a key enzyme of cell wall synthesis,
transpeptidase |
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what and where are penicillin binding proteins?
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penicillin binding proteins are present on the bacterial cell membrane, these proteins are responsible for the final steps to synthesis of transpeptidase-when Penicillin binds to the PBP, transpeptidase is inhibited.
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what type of bacteria is Penicillin primarily effective against: Gram - or Gram +?
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Gram +
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What are three common examples of Gram+ bacteria that Penicillin is effective against?
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Staph aureus, Strep pyogenes, Strep pneumoniae
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why aren't Penicillins typically effective against Gram- bacteria?
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G-negative bacteria have a cell wall, but also
are equipped with a special lipopolysaccharide coating that surrounds the cell wall, which acts as a barrier to entry |
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Are there exceptions to Penicillin being effective against primarily G+ bacteria?
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Some gram negative bacteria have special
channels called porins, which allow penicillin to enter; so even though they are gram negative, they are sensitive to penicillin (eg. |
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Complete linkage
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the inheritance patterns for 2 genes on the same chromosome when the observed frequency for crossover between the loci is 0.
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what are two diseases caused by Gram- spirochetes that are susceptible to Penicllin?
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Spirochetes, such as Treponema pallidum (syphilis) and Borrelia burgdorferi (Lyme disease) are sensitive to penicillin
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How do bacteria become resistant to Penicillin?
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Over time, bacteria have developed the capacity to produce beta-lactamase, which is an enzyme that has the capacity to dismantle the central beta-lactam ring of penicillin and cephalosporin molecules,
functionally inactivating the antibiotic |
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what is the second mechanism of action that Penicillin uses against bacteria?
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disinhibition (activation) of autolysins, which are bacterial enzymes that cleave bonds in the cell wall. Combined with disrupting the synthesis of the cell wall, autolysins further breadk down the cell wall, resulting in cell lysis and death
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What are the three mechanisms of resistance that bacteria employ agains penicillins?
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Bacterial resistance to Penicillin is determined primarily by:
1. inability of penicillins to reach their targets (PBP 2. inactivation of penicillins by bacterial enzymes 3. production of PBPs that have a low affinity for penicillins |
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what are the four antibiotics that are beta-lactam AB's and are considered Penicillin AB's?
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Penicillin, cephalosporins, azotrenam, imipenim
"I see a Pen" imipenim cephalosporins azotrenim Penicillin |
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what are the Penicillin prototypes you're responsible for knowing?
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PCN G
Depository PCN G Amoxicillin, Ampicillin, Pen VK, dicloxacillin, ticarcillin |
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Are most penicillins metabolized in the liver?
What is a major consideration when using Penicillins? |
Most penicillins are not metabolized by the liver, and are
excreted unchanged by the kidney—this makes renal function a major consideration |
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what are some side effects of penicillins?
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Hypersensitivity
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what are some important drug interactions regarding the use of Penicillins
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PCN + aminoglycoside together in the same IV line = ppt
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Which member of the Penicillin Family is:
Made from the fungus Penicillium chrysogenum, “natural penicillin” |
Penicllin G
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Which member of the Penicllin Family has:
Same spectrum as penicillin G but has better stability in the low pH of the stomach • Increased absorption on empty stomach, food decreases absorption |
Penicillin V or Pen VK
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Which member of the Penicillin Family is a long-acting formulation that
lasts for hours (15-24 hours) |
Procaine PCN-G
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Which member of the Penicillin Family is a long-acting formulation that
lasts for weeks (1-4 weeks) |
Benzathine PCN-G
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How are Procain and Benzathine PCN-G administered?
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IM only!!! Depot Formulations
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What Spectrum are Penicillins G's
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Narrow Spectrum?
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What spectrum are Penicillin V's
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Narrow spectrum?
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what bacteria are responsible for many skin and superficial structure infections? Is it Gram + or -?
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Staph aureus, G+ bacteria
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Which PCN have a specific site chain modification which makes them specific to Staph aureus infections?
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Methicillin, oxacillin, dicloxacillin, nafcillin
"My Ox Died (of staph) Naturally • Methicillin is off the market in US, almost total resistance |
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what does MRSA and VRSA stand for?
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methicillin resistant staph aureus
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Identify the bacteria:
G- rod, motile, pili (allows bacteria to “anchor itself” to a cell… serious infection!, common in ICUs |
Pseudomona aeruginosa
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what penicillins are effective against Pseudomonas aeruginosa?
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Carbenicillin, Piperacillin, Ticarcillin, Mezocillin
"the Carbon dioxide coming from the Pipe Ticked Me off." |
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How do Carbenilcillin, Piperacillin, Ticarcillin, and Mezocillin act against Pseudomonsa aeruginosa?
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Even though bug is G-, still inhibits Cell wall
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What beta-lactam type of AB is Very broad spectrum: good for mixed infections from anaerobes, G+ Staph, G- bacilli, Pseudomonas
• Very B-lactamase resistant |
Imipenem/cilastatin (Primaxin)
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Imipenem/cilastiatin (Primaxin) is considered what type of beta-lactam AB
What spectrum? |
Carbapenem
Very Broad |
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What is another name for penicillinase?
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Beta-lactamase
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what bacterial enzyme do penicillins and cephalosporins target?
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transpeptidase
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What enzyme do gram negative and positive bacteria make to inactive penicillins
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beta-lactamase
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How does MRSA protect itself from all classes of beta-lactams?
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Alters molecular structure of transpeptidase so beta-lactams can't bind at all
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What are the most common side effects of penicillins? What is the most dangerous effect
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Common = delayed rash, diarrhea (since kills normal GI flora C. dificile can grow in their place); Most dangerous = anaphylactic allergic reactions (mediated by preformed IgE molecules
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How can penicillin G be given?
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IV or IM only since will be destroyed in stomach
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what is the most common oral form of penicillin?
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penicillin V
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what is penicillin V usually given for
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strep throat from group A strep.
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what is the difference between ampicillin and amoxicillin?
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ampicillin is IV, amoxicillin is oral
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How are penicillin and cephalosporins similar and different?
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This class is closely related to penicillin in all structure and function, but
are more resistant to beta-lactamase, many different drugs in this class, sound a lot alike! Beware! |
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which antibiotic is notorious for causeing C. diff diarrhea
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cephalosporins
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adverse effects of cephalosporins:
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Notorious for causing C. dif diarrhea
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which Gram + organism is Penicillin G not effective against? Why?
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staphylococci
because staphylococci produce penicillinase |
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what is the most common indication for use of multiple antibiotics?
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initial therapy of severe infection of unkown etiology, especially in the neutropenic host (Low numbers of neutrophils in the blood). (until the infecting org has been ID'd, wide antimicrobial coverage is appropriate.
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what are other indications for antibiotic combinations?
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mixed infections
prevention of resistance in TB decreased toxicity risk enhanced antibacterial action |
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what are the generally accepted indications for prophylactic antibiotics (prescribing AB's to prevent infection rather than to treat infection)
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*prior to Surgery
*prior to dental procedures in individuals with gongenital or valvular heart desease and those with proshtetic heart valves. *Severe neutropenia *severe rheumatic endocarditis - lifelong prophylaxis *after exposure to STD's |
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penicillins and aminoglycosides should never __________? Why?
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Be mixed into the same IV solution.
Penicillins inactivate aminoglycosides when in high enough concentrations |
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what is the difference between Penicillin G and V?
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Penicillin V is stable in stomach acid wherease Penicillin G is not.
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what is the mechanism of action for cephalosporins
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sim to PCN, bind to PBPs and disrupt cell wall synthesis and activate autolysins, causing death by lysis
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describe first generation cephalosporins
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great G+ coverage, limited G-
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describe second generation cephalosporins
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Same G+ coverage as 1st gen., but more expanded G-
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describe third generation cephalosporins
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Less G+ coverage, more G- coverage, better anti-pseudomonal coverage
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describe 4th generation cephalosporins
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limited G+ coverage, much more Gram - coverage,
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As Cephalosporin generations increase from 1st to 4th, what two things increase?
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resistance to beta-lactamase destruction and
Gram - coverage |
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which generation(s) of cephalosporin would you use to treat an infection in the cerebrospinal fluid?
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3rd or 4th
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These antibiotics are used for only the
most serious G-infections, and their use this limited principally by their strong potential for toxicity |
Aminoglycosides
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how are aminoglycosides administered?
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At physiologic pH, these drugs carry multiple positive charges, which
means that they cannot readily cross cell membranes |
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what is the mechanism of action of aminoglycosides?
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These drugs disrupt protein synthesis, by binding to the bacterial ribosome
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what type of organisms do aminoglycosides destroy?
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Gram - only
(narrow spectrum) |
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what are the adverse effects of aminoglycosides?
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Aminoglycosides concentrate in renal tissue, achieving
levels in the kidney up to 50 times greater than in the serum, this makes for a high potential for renal toxicity |
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how do bacteria resist aminoglycosides/
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The principal cause of resistance is
production of enzymes that can inactivate the antibiotic; currently more than 20 different enzymes have been identified |
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How do you monitor aminoglycosides effects?
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Peak and trough
• Monitoring of serum drug levels provide the best basis for adjustment of the dosage, which means you’ll be drawing blood to measure antibiotic levels at various times • Peak levels are blood levels of the drug taken 30 minutes to one hour after administration • Trough levels are blood levels of drug taken just prior to the next dose of drug • Dosage needs to be adjusted so that peak levels are high enough to kill bacteria but not so high as to be toxic • Since excessive trough levels correlate with increased toxicity, high trough levels should be avoided • Peak and trough levels are determined by your individual institutions |
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what is the principal damage that aminoglycosides cause when in toxic amounts?
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Nephrotoxicity
• The principal damage is to the proximal convoluted tubules, the drug accumulates in high concentrations at this location, why is not clear, often causes acute tubular necrosis which manifests itself as acute renal failure, watch for proteinuria, an elevated BUN, creatinine |
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what does BUN stand for?
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Blood urea nitrogen
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what is the one key difference between humans and fungi that we exploit to kill fungi?
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One interesting difference between
fungal cell membranes and human cell membranes is the relative lipid content |
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What is the drug of choice for severe, systemic fungal infections, because it
is broad spectrum, very effective, but unfortunately carries toxicities that make it the agent of last choice (Nickname?) |
Amphotericin-B/Fungizone
"Amphoterrible" |
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what is the mechanism of action of amphotericin-B
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This agent works by binding to components in the fungal cell membrane,
and actually creating a pore in the cell membrane, which allows critical ions to leak out (K+, Mg+2) which eventually results in fungal death. • It is selective for ergosterol in the CM; since humans only have cholesterol in our cell membranes, this drug is selectively toxic |
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what are the adverse affects of amphotericin-B
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Common side effects
• Fevers, chills, rigors, HA often start 1-3 hours into administration, can be pretreated with Benadryl, tylenol, and demerol. • Can only be reconstituted with or diluted with D5W, NOT NS • Hypotension • Nephrotoxicity – some degree of renal impairment will happen with repeated doses of Ampho B • Check renal function frequently • pre-hydrate with 1L NS and post-hydrate with 1L NS • Watch administration of other renal toxic drugs, eg., aminoglycosides • Hypokalemia |
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how is ampotericin-B administered?
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Generally this is used exclusively IV, GI absorption is very poor
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This drug requires acidic activation by the gastric acid of the stomach, so a low pH is
important. • Any use of PPIs, antacids, or H2RAs will decrease activation and absorption |
Ketoconazole/Nizoral
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what is seen as the PO alternative to Ampho-B for treatment of severe fungal
infections, safer than ampho-B and is stable PO |
Ketoconazole
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What is the mechanism of action for ketoconazole?
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Inhibits ergosterol synthesis, which makes for a weaker membrane
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what are the adverse effects of Ketoconazole?
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Hepatotoxicity, rare but nasty when it happens
• Endocrine effects • Will inhibit the synthesis of selected steroids: in males = testosterone (gynecomastia) and in females = estrogen (menstrual irregularities) |
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which antifungal is very useful for fungal brain infections and has excellent covertage of vaginal candida and oral/esoph thrush
does not require acid activiation in stomach |
Flucaonazole/Diflucan
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