Multidrug resistance
-bacteria that efflux any xenobiotic substances; causing the medication to not take effect.
Beta-lactamase
-the enzyme responsible for inactivating the pharmacophore present in penicillin by hydrolyzing the peptide bond of the characteristic four-membered ring.
b-lactamase production, modification of PBPs, reduces number of porins, multidrug efflux
What are the 4 types of Penicillin resistance mechanisms?
Benemid/Probalan
What drug is co-administered with Penicillin G to decrease urinary excretion?
binds to and inactivates transpeptidase; gram + not including MRSA; long term use; beta-lactamase; potential for allergy, serum sickness, caution in kidney failure (can lead to seizures)
Penicillin G
MOA:
Spectrum:
Uses:
Resistance:
Chemistry:
Adverse Effects:
IV/IM or SC; only stable at pH 5-7, not bioavailable PO
How is Pen G administered? Any specific reasons why?
D-Ala-D-Ala
What is the specific amino acid sequence that penicillin and cephalosporins target?
Penicillin G Procaine
- a penicillin G formulation
-can only be administered via IM
-may cause a temporary increase in BP
Penicillin G Benzathine
-penicillin G formulation
-can be administered IM or PO
-delayed-release that lasts a long time
What gram + bacteria is resistant to Pen G?
Staph
sulbactam, tazobactam, clavulanic acid
What are our Beta-lactamase inhibitors?
A
Which formulation has the highest serum concentration?
a) Pen G
b) Pen G procaine
c) Pen G Benzathine
B
Which formulation offers moderate serum concentrations?
a) Pen G
b) Pen G procaine
c) Pen G Benzathine
C
Which formulation offers the longest duration?
a) Pen G
b) Pen G procaine
c) Pen G Benzathine
contains electron-withdrawing side chain which prevents catalytic intramolecular reaction; leading to acid stability via oral route
What is special about Penicillin V's chemistry?
targets transpeptidase in bacterial cell wall, Gm + w/ activity against staph (MRSA), mild-severe staph infections, active against beta-lactamase, bulky r-group blocks beta-lactamase, rash
Anti-Staph Penicillins
MOA:
Spectrum:
Uses:
Resistance:
Chemistry:
Adverse Effects:
anti-staph pens, gm + methicillin-sensitive strains, none, not used in US
Methicillin
class:
spectrum:
side effects:
special facts:
IV/IM; anti-staph pens; neutropenia, rash; severe staph infections
Nafcillin
administration:
class:
side effects:
uses:
IV/IM; anti-staph pens; rash; severe staph infections
Oxacillin
administration:
class:
side effects:
uses:
oral (capsule), anti-staph pens; abdominal pain, GI bleeding, rash; mild-moderate infection & impetigo
Dicloxacillin
administration:
class:
side effects:
uses:
penetrates into Gm - outer membranes pbp; gm -; blocks formation of a positive charge reaction intermediate required for hydrolysis reaction
Aminopenicillin
MOA:
Spectrum:
Uses:
Chemistry:
IV/IM; aminopenicillin; Gm + & some G (-); diarrhea, monno, CLL; moderate-severe RTI, pneumonia, s/ssi, gi, uti
Ampicillin
administration:
class:
spectrum:
side effects:
uses:
IV/IM; aminopenicillins; rash, diarrhea; severe infection (including Pen'ase+)
Unasyn (ampicillin + sulbactam sodium)
administration:
class:
side effects:
uses:
strep, e coli, H flu, salmonella
What gram - bacteria is Ampicillin effective against?
contains positive charge in side chain
Aminopenicillins- extended spectrum chemistry?
amoxicillin, augmentin
What are our aminopenicillins-extended spectrum drugs?
oral; aminopen es; Gm + & Gm-; rash, diarrhea; less severe RTI, otis media, h.flu, strep
Amoxicillin
administration:
class:
spectrum:
side effects:
uses:
oral (liquid & tab); aminopen es; Pen'ase + H.flu, Morexella catarrhalis
Augmentin
administration:
class:
spectrum:
side effects:
uses:
enteric KES, mycoplasma pneumoniae
Aminopenicillins are not active against _______
timentin, piperacillin, mezlocillin
What are our broad spectrum antipseudomonal penicillins?
hydroxylation of phenyl group improves GI absorption
How do we improve Amoxicillin's bioavailability?
Borrelia
What gram - bacteria is Amoxicillin used for?
bind to PBP; Gm - Enterobacteria, KES; side chain increases gm - penetration and PBP binding
Carboxypenicillins
MOA:
Spectrum:
Chemistry:
low acid stability; penicillinase degradation
Carboxypenicillins have ______ & are susceptible to ______
IV; antipseud pens; Gm -; severe Gm - infections (2nd line)
Ticarcillin
administration:
class:
spectrum:
side effects:
uses:
IV/IM; similar to piperacillin; gm-, KES
Mezlin
administration:
Tx:
IV/IM; antipseud pens; Pseudomonas + AGs; nosocomial pneumonia, sepsis, wounds, appendicitis, periontitis, pelvic inflammatory disease, complicated UTI
Piperacillin
administration:
class:
spectrum:
uses:
Piperacillin
Which antipseudomonal should you never admix?