Term
| penicillin history: isolating |
|
Definition
| 1959-set off development of future penicillins by isolating 6-aminopenicillanic acid (semisynthetic) |
|
|
Term
|
Definition
| 6-aminopenicillanic acid (penicillin) |
|
|
Term
| penicillin's mechanism of action |
|
Definition
| disrupts assembly of cell wall (interacts with enzymes that cross-link peptidoglycan) |
|
|
Term
| penicillin binding proteins (PBPs) |
|
Definition
found on cell membrane of bacteria
catalyze transnpeptidation and carboxylation reactions important in cell wall assembly (penicillins bind with PBPs, inhibiting their ability to catalyze cell wall assembly) |
|
|
Term
| mechanisms of resistance to beta-lactam antibiotics |
|
Definition
1. *destruction of the antibiotic by beta-lactamases*
2. failure to penetrate to PBP targets (gram -)
3. low affinity binding of antibiotic to PBP |
|
|
Term
|
Definition
covalently react with beta lactam antibiotic to form an acyl enzyme intermediate which undergoes rapid hydrolysis
beta lactam ring opened and microbiological activity lost |
|
|
Term
| classification of beta lactamases |
|
Definition
1. classified by affinity for beta-lactam compounds
2. classified by amino acid composition (ex. TEM-1, TEM-2)
3. encoding origin (ex. chromosomal or plasmid)
4. interactive characteristics (ex. constitutive or inducible) |
|
|
Term
| Staphlococcal beta-lactamases |
|
Definition
-plasmid encoded, inducible by beta lactam compounds
-penicillinase
-exoenzyme that is liberated into the surrounding medium
-hydrolyzes penicillin before it reaches its target PBPs |
|
|
Term
|
Definition
-concentrated and strategically located in the periplasmic space between the inner cytoplasmic membrane and the outer lipopolysaccharide membrane
-protect PBPs from exposure to beta lactam compounds
-encoded on chromosomes or plasmids
-constitutive or inducible
-affinity for penicillins, cephalosporins, or both |
|
|
Term
|
Definition
-stability at low pH
-slower renal elimination
-stability to beta-lactamases
-broader antimicrobial coverage
-better penetration into CSF
-no hypersensitivity reactions |
|
|
Term
| penicillin G spectrum of activity |
|
Definition
Gram + aerobic cocci: Group A Strep, Group B Strep, S. viridans
Gram - aerobes: N. meningiditis
anaerobes: Clostridia (not difficile), Bacteroides (not B. fragilis)
Spirochetes: Treponema pallidum |
|
|
Term
| penicillin history: Who discovered penicillin? |
|
Definition
| penicillin was discovered in 1929 by Sir Alexander Fleming |
|
|
Term
| penicillin history: Who determined the structure and properties of penicillin? |
|
Definition
| In 1939 Florey and Chain became interested in the clinical potential of penicillin and determined its structure and properties. |
|
|
Term
| penicillin history: experimentation on mice |
|
Definition
| in 1940 penicillin protected mice from streptococcus |
|
|
Term
| penicillin history: sufficient quantity to treat patients |
|
Definition
| in 1941 penicillin was used to treat patients (British policeman with strep. and staph.) |
|
|
Term
| penicillin history: journey to America |
|
Definition
| in 1941 Florey went to US to get penicillin mass produced |
|
|
Term
| penicillin history: clinical trials |
|
Definition
| in 1942 penicillin underwent clinical trials and then was used to treat soldiers |
|
|
Term
| penicillin history: resistance discovered |
|
Definition
| in 1942 Abraham and Chain reported resistance by E. coli and S. aureus to penicillin |
|
|
Term
| penicillin G formulations: parenteral |
|
Definition
penicillin usually combined with aqueous K
Pen GK parenteral standard: 1.7 mEq's of K per 1 million units given
rapid elimination so drug given q4h for serious infections |
|
|
Term
|
Definition
suspension (only IM)
not used anymore
procain is a local anesthetic
originally developed to try and lengthen the time the drug stays in the body
may cause worse allergic reactions than other penicillins |
|
|
Term
| benzathine penicillin G: type of drug, what it is effective against |
|
Definition
suspension (only IM)
very long acting (1 month)
effective for all stages of syphilis, rheumatic fever prophylaxis and sometimes Strep pharyngitis |
|
|
Term
|
Definition
po drug only
designed to resist acid hydrolysis
60-73% oral absorption
take on empty stomach |
|
|
Term
|
Definition
| non-penicillin compound used to block selective tubular secretion (kidney elimination) of penecillins, increasing their serum half-life |
|
|
Term
| What are the adverse reactions to penicillin G and V? |
|
Definition
penicillin allergy and hypersensitivity reactions
central nervous system toxicity
pregnancy risk factor: B |
|
|
Term
| What are the penicillin allergy and hypersensitivity reactions? |
|
Definition
anaphylaxis
drug fever
eosinophilia (increase in eosinophils)
interstitial nephritis |
|
|
Term
| Describe penicillins central nervous system toxicity |
|
Definition
| seizures with high doses/decreased renal function |
|
|
Term
| Name the penicillinase-resistant penicillins in the US market |
|
Definition
methicillin
nafcillin
oxacillin
cloxacillin
dicloxacillin |
|
|
Term
| What are penicillinase-resistant penicillins? |
|
Definition
specifically designed to resist beta-lactamase destruction by Staph aureus
also referred to as anti-staphlococcal pcn's or PRP's
uniquely eliminated by biliary excretion and renal excretion so no dosing adjustments necessary |
|
|
Term
|
Definition
the prototype of PRP's but is no longer used because of very high incidence of interstitial nephritis
"arm" protect beta-lactam ring from disruption
poorly absorbed from GI tract so IV drug
excreted via biliary and renal |
|
|
Term
|
Definition
a penicillinase-resistant penicillin
preferred over methicillin
poorly absorbed from GI tract (IV drug)
eliminated via biliary and renal excretion |
|
|
Term
| List the isoxazolyl penicillins |
|
Definition
oxacillin
cloxacillin
dicloxacillin |
|
|
Term
| What are isoxazolyl penicillins? |
|
Definition
penicillinase-resistant penicillins
specifically designed to resist hydrolysis by acid pH and Staph penicillinases (oral administration)
anti-Staph penicillin |
|
|
Term
|
Definition
a PRP--isoxazolyl penicillin
used interchangeably with methicillin
IV, IM, PO
fallen to wayside |
|
|
Term
|
Definition
PRP
isoxazolyl penicillin
PO |
|
|
Term
|
Definition
PRP
isoxazolyl penicillin
PO
1/2 dose of cloxacillin, improved absorption |
|
|
Term
| List the broad-spectrum penicillins |
|
Definition
2nd generation: ampicillin and amoxicillin
3rd generation: carbenicillin and ticarcillin
4th generation: azlocillin, mezlocillin, piperacillin |
|
|
Term
| List the penicillin/beta-lactamase combination inhibitors |
|
Definition
| augmentin, timentin, unasyn, zosyn |
|
|
Term
| broad spectrum penicillins |
|
Definition
variable activity against gram - bacilli
increased activity due to increasing ability to penetrate the gram - cell wall
generally they are hydrolyzed by gram - beta lactamases |
|
|
Term
|
Definition
2nd generation penicillin
broad-spectrum
spectrum of activity similar to penicillin
more active against Enterococci and H. influenzae
not active against S. aureus or M. catarrhalis (b/c beta-lactamase production)
active against non pcn'ase producing E.coli and P. mirabilis
effective against many strains of Salmonella and Shigella
*not active against P. aeruginosa or most nosocomial Enterobacteriaceae*
about 40% bioavailability
diarrhea a big side effect
beta-lactamase inhibitor (sulbactam) helps spectrum of activity |
|
|
Term
|
Definition
2nd generation penicillin
broad-spectrum
oral replacement for ampicillin due to better bioavailability and less diarrhea
used in the treatment of otitis media, bacterial sinusitis, bacterial exacerbations of chronic bronchitis, and some Salmonella infections
higher incidence of skin rashes
problems: diarrhea, N/V, C. difficile |
|
|
Term
|
Definition
3rd generation
broad-spectrum
historical interest only
1st penicillin with activity against P. aeruginosa
not active against beta lactamase producing strains
rapid development of resistance
very high doses needed, many toxicities |
|
|
Term
|
Definition
3rd generation penicillin
broad-spectrum
oral form for UTI's by pseudomonas only
concentrates in urine so you can get an effective amount of drug
for P. aeruginosa |
|
|
Term
|
Definition
3rd generation penicillin
broad-spectrum penicillin
mostly historical interest
replaced carbenicillin (twice as effective)
only IV drug
rapid resistance by Pseudomonas: must be combined with other agents like aminoglycosides
not active against Enterococci or Klebsiella
good against anaerobes including B. fragilis
salt required to make drug soluble (careful of sodium overload)
acquired platelet disfunction (platelets would not clot)
used for Pseudomonas infections w/ aminoglycoside, 2nd line agent against B. fragilis, and resistant UTI's |
|
|
Term
|
Definition
4th generation penicillin
broad-spectrum
monosodium salt
activity: Pseudomonas only
not mainstream anymore
too narrow |
|
|
Term
|
Definition
4th generation
broad-spectrum
monosodium salt
similar in spectrum to ticarcillin
not mainstream |
|
|
Term
|
Definition
4th generation
broad-spectrum
broader coverage with activity against Klebsiella, Pseudomonas, Serratia, Enterobacter, Enterococci and anaerobes
most active penicillin against Pseudomonas
mostly used with a beta-lactamase inhibitor
major empiric drug
not good against MSSA or MRSA |
|
|
Term
| piperacillin + tazobactam (zosyn) |
|
Definition
4th generation
broad-spectrum
widely used in hospitals for treatment of nosocomial infections
gram+aerobes: MSSA, Strep, Enterococci
gram-aerobes: enteric gram - rods, pseudomonas
gram+ and gram- anaerobes: especially B. fragilis
moderate activity against gram-rods producing "advanced" beta lactamases
poor activity against MRSA, ESBL's produced by gram-rods
very potent for empiric therapy
only for serious infections
only parentarel |
|
|
Term
| adverse gastrointestinal effects of penicillins |
|
Definition
most common side effect associated with oral agents
diarrhea (most common w/ampicillin, amoxicillin)
N/V
epigastric distress |
|
|
Term
| adverse skin effects caused by penicillin |
|
Definition
rash most common with ampicillin/amoxacillin 5-10%
patients with mononucleosis are at increased risk |
|
|
Term
| adverse hemotologic effects to penicillin |
|
Definition
neutropenia (decrease in WBCs)3-8% generally with high doses and longer therapies
platelet dysfunction: prolonged bleeding times, risk factor--thrombocytopenia and azotemia, mostly ticarcillin 73%, piperacillin 43%, mezlocillin 25%, cefotaxime 17% |
|
|
Term
|
Definition
high doses, high levels in CNS associated with seizures
risks: renal impairment, patient w/ history of seizure disorder, meningitis |
|
|
Term
| adverse metabolic effects |
|
Definition
hyperkalemia (high potassium), hypokalemia (low K), hypernatremia (high Na)
risks: renal impairment |
|
|
Term
|
Definition
transient elevations in hepatic transaminases
hepatitis (inflammation of hepatocyte)/cholestasis (bile slowed or stopped) |
|
|
Term
|
Definition
| hardening of vein/area where you gave the drug due to irritation (IV administration) |
|
|
Term
| Jarixch-Herxheimer reaction |
|
Definition
very specific
occurs with spirochete infections (usually syphilis)
dropped blood pressure, generalized inflammatory response, fever, chills, sweating, tachycardia, myalgias, hyperventilation
begins 2 hours after administration of dose and last about a day
give with antihistimine, corticosteroid |
|
|
Term
| drug interactions: increased effect |
|
Definition
anticoagulants: increases anticoagulant effect of coumadin
probenecid: increases amoxicillin levels
allopurinol: increases incidence of rash
methotrexate: increases exposure (effect) to methotrexate |
|
|
Term
| drug interactions: decreased effect |
|
Definition
antibiotics and oral contraceptives
patient counseling implications |
|
|
Term
| list the suicide inhibitors |
|
Definition
| tazobactam, sulbactam, clavulanic acid |
|
|
