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Penicillins are _____ compounds
beta lactam
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Beta-lactam compounds
- penicillins
- cephalosporins
- monobactams
- carbapenems
- beta lactamase inhibitos
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all beta lactam compounds are ___ membered rings
4
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lactams are cyclic
amides
-
a beta lactam ring consists of
three carbon atoms and one nitrogen atom
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Substitutions of the _____ moiety determine the essential pharmacologic and antibacterial properties of the resulting molecules.
6-aminopenicillanic acid
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Three groups of penicillins
- penicillins (penicillin G)
- Antistaphyulococcal Penicillins (nafcillin)
- extended-specturm penicillins (ampicillin and antipseudomonal penicillins)
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Penicillins have greatest activity against
- gram positive organisms
- gram negative cocci
- non B-lactamase producing anaerobes
-
Penicillins have little activity against
gram negative rods because of suceptibility to hydrolysis by beta lactamase
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Antistaphylococcal PCN
resistant to staphylococcal beta lactamase
-
Antistaphylococcal penicillins are active against
staphylococci and streptococci
-
Antistaphylococcal Penicillins not active against
- enterococci
- anaerobes
- gram negative cocci and rods
-
Extended spectrum PCN have improved activity against
- gram negative organisms
- relatively suceptible to hydrolysis by beta lactamase
-
MIC is usually has units of
mcg/ml
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Most penicillins are dispensed as
sodium or potassium salt of the free acid
-
In dry crystallin form PCN salts are stable for
years at 4 C
-
PCN mechanism of action
interfere with transpeptidation step of cell wall synthesis
-
Polysaccharide chains contain
- alternating amio sugars
- N-acetylclucosamine
- N-acetylmuramic acid
-
A five-amino-acid peptide is linked to the ____ sugar and terminates in ____.
- n-acetylmuamic acid
- d-alanyl-d-alanine
-
Penicillin binding protien acts by removing ____ to allow cross link formation that gives the cell wall rigidity.
terminal alanine on the 5 amino acid peptide
-
B-lactam antibiotics are structural analogs of ____ which inhibits ___.
- D-ala-D-ala
- transpeptidation
-
Beta lactam antibiotics kill bacterial cells only when
they are actively growing and synthesizing cell wall
-
4 mechanisms of PCN resistance
- inactivation by beta lactamase
- modification of target PBPs
- impaired penetration of drug to target PBPs
- efflux of drug
-
Most common mechanism of resistance to PCN
beta lactamase production
-
Mechanism of PCN resistance in pneumococci and enterococci
altered target PBPs that have low affinity for binding beta lactam antibiotics
-
PCN resistance mechanisms in gram negative species
- impared penetration of outer cell wall membrane due to reduction in the presence of proper channels
- efflux pumps
-
Acid stable PCNs (3)
- dicloxacillin
- ampicillin
- amoxicillin
-
Absorption of most oral PCNs is impaired by food except
amoxicillin
-
PCNs formulated to delay absorption to prolong blood and tissue concentrations_____ & ____. Used for treatment of _____.
- Benzathine
- Procaine
- beta-hemolytic strep
-
PCN concentrations in most tissue are ____ to those in the serum.
equal
-
PCN is excreted in these fluids
-
PCN has poor penetration into
-
PCN is excreted by
the kidneys
-
90% of renal excretion of PCN is through____ 10% through___.
- tubular secretion
- glomerular filtration
-
Normal half life of PCN
30 min
-
Ampicillin and extended spectrum PCNs have half lives of
1 hour
-
Doses of PCNs must be adjusted according to
renal function
-
If creatinine clearance is 10mL/min or less the dose of PCN will likely be
1/4 to 1/3 of the normal dose
-
Nafcillin is primarily cleared by
biliary excretion
-
PCNs that are eliminated by both the kidney and biliary excretion
- require no dosage change based on renal function
- oxacillin
- dicloxacillin
- cloxacillin
-
Clearance of PCN is ____ efficient in newborns
less
-
PCNs should be given
1-2 hours before a meal
-
Administration of PCNs with _____ can result in higher blood levels of PCN by inhibiting renal tubular secretion.
probenecid
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Drug of choice for infections caused by streptococci, meningococci, enterococci, PCN susceptible pneumococci, non beta-lactamase producing staphylococci, spirochetes, clostridiumk actinomyces, gram positive rods and gram negative anaerobes (non beta lactamase)
Penicillin G
-
Benzathine PCN and procaine PCNG IM injections result in
low but prolonged drug levels
-
Benzathine PCN(1.2 million units) may be given 1 time for treatment of beta strep and repeated once every ____ to prevent reinfection
3-4 weeks
-
Benzathine PCN G (2.4 million units) IM once is effective in the treatment of
syphilis
-
PCNs that are resistant to staphylococcal beta lactamase
- methicillin
- nafcillin
- isoxazoyl PCNs
-
Strains of staphylococcie that are resistant to beta lactamase resistant PCNs
- listeria
- enterococci
- methicillin resistant strains
-
Methicillin, Nafcillin and Isoxazolyl PCNs are considered drugs of choice for
methicillin susceptible strains of staph
-
Extended spectrum PCNs
- aminopenicillins
- carboxypenicillins
- ureidopenicillins
-
Extended spectrum PCNs have greater activity against gram negative bacteria because of
- enhanced ability to penetrate gram negative outter membrane
- still succeptible to beta-lactamase
-
Aminopenicillin, ampicillin and amoxicillin
- same spectrum of activity
- amoxicillin is better absorbed
- given orally to treat UTI, sinusitis, otitis and lower resp. infections
-
Most active oral beta lactams against PCN resistant pneumococci and prefered for this use
-
Most serious side effect of PCN
hypersensitivity
-
incidence of allergic reactions to PCN in children is
negligible
-
other ADRs associated with PCNs
- oral lesions
- fever
- interstitial nephritis
- eosinophilia
- hemolytic anemia
- vasculitis
-
In pt with renal failure,PCN can cause
seizures
-
Nafcillin is associated with
neutropenia
-
oxacillin can cause
hepatitis
-
Large doses of oral PCNs may lead to
-
Rashes resulting from ampicillin and amoxicillin frequently occur when
aminopenicillins are inappropriately prescribed for a viral illness
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