Penicillins Lecture 13

Question 1

Structure and chemistry

Answer 1

House with garage

betalactam ring

betalactamase inhibitor irreversibly binds to a beta lactamase

Question 2

MoA

Answer 2

inhibit bacterial cell wall synthesis by blocking crosslinking of adjacent peptidoglycan strands with subsequent lysis.

penicillin binding proteins (PBPs) are target of B lactam antibiotics and include transpeptidases, transglycolases, and D alanine carboxykinase.

peptido glycan transpeptidase is on PBP that is inhibiited

bactericidal

Question 3

MoR

Answer 3

betalactamse production: staph, H. Flu

failure of antibiotic to penetrate to PBP target: gram negative organisms only (porin channel penetration)

low affinity binding of antibiotic to PBPs: pneumococcus, MRSA, enterococcus

Question 4

Absorption

Answer 4

Some are acid stable and others not.

peak levels 1-2 hours after ingestion

food delays and decreases absorption. Absorption not deceased with Pen V, Amoxicillin, and carbenicillin

Question 5

distribution

Answer 5

well distributed

insoluble in lipid; therefore unless inflammation is present there is poor distirbution to brain, CSF, and prostate

Question 6

metabolism

Answer 6

metabolized to some degree based on agent

Question 7

excretion

Answer 7

renal excretion is the most important route of elimination: adjustment for renal insufficiency is a must. Infants excrete penicillins at a slower rate due to immature transport systems

biliary excretion occurs with ampicillin, nafcillin, and the antipseduomonal penicillins

Question 8

AE

Answer 8

hypersensitivity reactions: most common adverse effect. All penicillins have equal potential for inducing allergic reaction. Hypersensitivity to one means probable hypersensitivity to all penicillins. Hypersensitivity may not occur on reexposure or may occur without previous reaction. Immediate reaction (anaphylaxis)- IgE mediated. Delayed reaction (rash)- IgM or IgG mediated. Maculopapular rash is most common

hematologic (eosinophilia, thrombocytopenia, neutropenia), interstitial nephritis, pseudomembranous colitis

Question 9

penicillin G

Answer 9

Spectrum of activity: gram positive organisms (streptococcus and some entercoccus)

staph. produce B lactamase: 995 resistant.

Warning: strep. pneumonia resistance prevalent in some areas.

Question 10

aminopeniciilins

Answer 10

amino group allows for penetration into gram negative cell wall

SoA: streptococcus, enterococcus, haemophilus (non b lactamase producing), proteus mirabilis (watch sensitivity), e coli (watch sensitivity, esp if GI is the source of E coli), Klebsiella (watch sensitivity

AE: diarrhea (take with food amoxicillin absorption not impaired). Ampicillin > amoxicillin

Question 11

Penicillanse resistant Penicillins

Answer 11

antistaphylococcal penicillins

cover streptococcus and beta lactamase positive staph.

IV: methacillin, oxacillin, nafcillin (hepatic elimin)

PO: cloxacillin, dicloxacillin

Question 12

carboxypenicillins

Answer 12

Carbenicillin/Ticarcillin

increased permeability to cell wall

SOA: streptococcus, proteus, e. coli, klebsiella, SPACE. First group in PCN. Enterbacter spp,

carbenicillin: indanyl salt: stable oral form. High urine concentrations. Body normally cannot tolerate high dosages necessary for concentrations to treat systemic infections
ticarcillin: 2-4 x more active than carbenicillin against pseudomonas

NA load = 5.2 MEQ/GM

adverse effects: hypersensitivity. carboxy group can cause platelet dysfunction (dose dependent). Na overload (hypernatremia, severe CHF, and renal failure)

Question 13

ureidopenicillins

Answer 13

piperacillin (low Na Load)

SOA: streptoccus, enterococcus (more potent than carboxypenicillins), proteus, e coli, klebsiella, space bugs

Question 14

Betalactamase inhibitor/penicillin combination

Answer 14

augmentin (amox and clavulanic acid) PO

unasyn (ampicillin and sulbactam) IV

timentin (tacarcillin and clavulanic acid) IV

sozyn (piperacillin and tazobactam) IV