daniels penicillins

natural penicillins — which can they not get into

gram neg

• bc can’t get into cell well

what is unique in carbapenems that allow them to bind tighter and to more types of PBPs

trans config on c5 and c6 is unique

why are most carbapenems not available PO

too polar and poorly absorbed through the intestinal membrane.

• zwitterions!

what does ionizable group a to the amide of a penicillin or a urea in that same spot do

increases gram negative coverage

describe ceph salt vs free acid solublity

Cephalosporin salts are generally water-soluble. Their free-acid forms are comparatively water-insoluble or poorly soluble.

which is more potent of the bezylpeniclilns

pen G

whicj ntal pen is better orally absorbed and why

acid-stability

(its PO my guys)

• lasts longer in teh stomach

WHY pen V more acid stable

more E with drawing gorups

what feature of anti staphs slows destruction of beta-lactamase

(naf, ox, meth, d) the bulky side chain

• prevent access of beta lactamase to the beta lactam ring

what enzyme (beta lactamase) are the anti staphs most resistant to

penicillinase

how are the anti-staphs given (ALL Of them)— naf/methic/ox etc

parental (never PO)

spec for pen-ressit parenteral penicillins

narrow— staphs

why does MRSA not get worked on by anti staphs

bc it has its own different PBP called PBP2a so the beta lactams can’t even bind it

are the antistaphs more or less potent than pen G?

LESS

why would you use the antistaphs if they are less potent than pen G?

bc they have better staph coverage

• steric group less bothered by beta lactamases

another word for the anti-staphs

Semisynthetic Penicillinase-Resistant pennies

what is another word for amidopenicillins

newly approved penase-resist oral penicilin (pivmecillinam)

what are the IV anti staphs

naf, methi

what are the PO anti staphs

oxacili, diclox

what Pivmecillinam used for

UTIs

what Pivmecillinam target

pbp2 by aidino c6 side chain

beta lactamse senstive need to be combined with what?

b-lac INHIBITOR

which inhibitors react irreversibly with OH nucleophile of b-lac?

Clavulanate, sulbactam, and tazobactam (these all fake b-lactams)

what are the DBOs

avibactam, durlobactam, relebactam,

zidebactam)

cyclic boronate what is it

vaborbactam

what are the pen-sens IV penicllins

ticarcilin, piperacillin

piperacillin what combined with and what is that combo

tazobactam (b-lac) inhib

• Zosyn

charged or urea addition, what does that help spec cover

gram NEGATIVE

what are the pen-sen PO penicillins

ampicillins, amoxicilllin

why we THINK ticarcillin has more gram - action

ionization allows for more porin penetration into the pleural spcae where b-lac-ases are

what does a-amino group on amp/amox do

increase oral stability

• makes it more acid stable

• BY its protonation

why does a-amino group on the amp/amox help with acid stable

becomes charged in the body and acts e w/d group

does amox or amp have better PO absorption and what does that mean in terms of ad eff

Better oral absorption with Amoxicillin therefore

less GI flora disturbance and less diarrhea

what reduces reactivity in ceph vs penicillins

reduced ring strain bc the ring is bigger

what INCREASES reactivity in cephs vs pen

double bond at C-2,3

leaving group capable to carrying away negative charge

• both these increase reactivity to bind b-l-ases

are salt forms of cephs hydrophob or phil

phil— soluble

are free acid (not salt form) of cephs hydro phob or phil

phob— insolubl e

where are salts formed on cephs

C-2 carbonyl

what is the OTHER place besides hte c-7 (c-6 analog to pens) that you can have subs in cephs?

c-3 (the “z” group)

what is perk of being less reactive antibiotic

it could destory stomach flora instead— “blows up in teh stomach”

what sub on the c-3 of cephs can ultiamtely form lactone? what is the mech

• acetyl group — elminates ability to bind to PBPs— rendered ineffective

• happensy by hydrolysis

what do better leaving gorups on c-3 do for cephs? what would better leaving groups be?

INCREASE reactivity bc you got that carbonyl and double bond

• more electronegative ?

does an amine a to the amide side chian on c-7 increase PO activity in cephs, liek c-6 in pens?

YES— electron withdrawing

• increase acid stability

what does 7-alkloxy group to do ceph activity

increases b-l-ase resistance

is z or e oxime ceph mroe stable

z is more stable towards b-l-ase

what does oxime at a position do to reactivity of cephs

more stable towards b-l-ase (so less destroyed by cephalosporinase)

if sulfur atom of ceph (in the ring) is changed to oxygen does ceph becomremore or less table to b-l-ase

MORE— less broken down

if sulfur atom of ceph (in the ring) is changed to oxygen how is antibac acitivty changed?

LESS reactive with bacteria (trade off for less destruction by b-l-ases)

where is the substitution on cephs that can form orally active prodrugs ? how are they activated?

c-2 carb A

• activated by hydrolysis

is ceph allergy more or less common than pen

less

when can pen allergy be ok to use cephs

pts with mild or delayed pen allergy

what is keflex (1) like

ampicillin

what is cefedaroxil (duricef— 1) like

amoxicillin like

what is the IV frist gen cep

cefazolin

what unqiue abotu cefazolin (1, iv)

thio-linked leaving group at c-3

• when leaves bceomes activiated

what first gen needs renal adjust? handling?

cefazolin

• unstable— no heat/light

  • think thio

name two oral ceph

cephalexain

cefadroxil

which 1st gen longest

cefadroxil

• amox like

2 gen cep IV

cefurozime

cefoxitin

cefotetan

cefotetan (2) what kind of rxn with OH and whta group causes

• MTT

  • disulfiram

what can mtt on cefotetan cause

prothrombin deficiency and bleeding problems (inhibits

vitamin K epoxide reductase)

what does cefoxitin have to be stable aginst b-l-ase

methoxy at c-7

what gives cefuroxime stabilite ot most b-l-ases

oxime group

what rehteh PO 2nd gen

cefaclor, cefprozil

what unqiue to make cefaclor stable

chloride

• less effective than others

IV 3 gen agents

cefotaxime

ceftizozime

ceftriazone

ceftazidime w/ avibactam

ceftolazoe with tazobactam

why cefotaxime no longer on market

c-3 acetoxy group can become inactive by that lactone mech

what do all iv 3 cephs have

oxime on a position

• Ceftazidime w/avibactam what does c-3 pyridinum sub do to b-lactam reactivity ? water sol?

more stable— bigger/bulk

more h2o-phil

po 3 gen ceph

cefixime

ceftibuten

cefdinir

Cefpodoxime proxetil

Cefditoren pivoxil

what happens to activity if taken with food for the two 3 gen ceph

increased (more bioavialb)

why no carinitine def for ceditoren pivoxil

bc has pivoxil ester (t-butyl group is a problem)

which class isolated form Steptomyces cattleya

carbapen

which broadest spec fo these antibios

carbpen

what is DOC for esbl producers

carbpen

how is sulfur dif in carbpe

OUTSIDE the ring— “replaced with CARBon”

what does sulfur outside ring do to carbp stability

increases ring strain

• more reactive

are more carbp PO acitive or not? why?

• FEWER are PO actiive

  • bc “blow up” too easily

when are carbp soluble (ph wise)

when pH is basic

how is sterochem dif in carbp and where

inverted

• c-6

bind PBPs dif

why carbp susceptible to b-lases

ring strain!

• lit main rxn to desotry is just the ring opening (“β-lactam bond hydrolysis”)

what happens when r2 is a hydrogen? what blows it up (carbap)

hydrolysis of b-lactam

• dhp-1

what stops dhp for carbp

cilastatin

what group on r2 makes it not substrate for dph-1 (carbp)

methyl group

what is PO carbp and how does that work

• slide 72

• tebipenem pivoxil 2025,

  sulopenem etzadroxil

• bc they are ester prodrugs

imipenem is it dhp

YES inactivated

what should imipenem be given with

cilastatin

does imipenem penetrate well or no

YES but not into CNS (cerebro/spin fluid)

what drug really bad (out of carbp) for inducing seizures

imipenem

meropenem brand

merrem

what does methyl-group at c-4 in meropenem do

makes it resistant to hydrolysis

• lets it be given as single agent

what is meropenem and vaborbactam given for

complicated urinary tract infections

what is doripenem? what active against? can you get it now?

carbp with mehtyl gorup at c-4

• active against psuedomonas

  • discontinued

ertapenem brand

invanz

ertapenem is it dhp-1 resist

YES bc has c-4 methyl group

where is the prodrug ester on tebipenem (one fo the PO ones) and what is the ester

on c-2

• pivolxil ester

which are some drugs for no carnitine

• cefditoren

• tebipenem

both have pivoxil

which is technicallye d a thiopeneme not carbapenem (has sulfur in the ring durp)

sulopeneme etrazdroxil

what does probenecid do

a renal tubular inhibitor that blocks the kidneys

from clearing sulopenem too quickly

what Sulopenem given with

probenecid (renal tube inhibitor so not cleared out quick)