CELL WALL SYNTHESIS INHIBITORS Flashcards Preview

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Flashcards in CELL WALL SYNTHESIS INHIBITORS Deck (49)
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1

Why do CW synthesis inhibitors work? 

-mammalian cells DO NOT have a cell well

--> these drugs require actively proliferating bacteria (CW synthesis must be occuring) in order for them to be effective

2

CELL WALL SYNTHESIS INHIBITORS

1) B-LACTAM ANTIBIOTICS = MP CC 

--> PENICILLINS, CEPHALOSPORINS, CARBAPENEMS, MONOBACTAMS

MISCELLANEOS:

1) VANCOMYCIN

2) DAPTOMYCIN

3) BACITRACIN

4) FOSFOMYCIN

 

3

PENICILLINS: B-LACTAM

B-LACTAM

-is widely effective, has little toxicity, but there has been to shown to be increasing levels of resistance 

-structure includes a B-lactam ring 

MOA: is BACTERICIDAL: --> inhibit the lAST STEP in peptidoglycan synthesis through binding to PBPs

Note: is INACTIVE against organisms w/o peptidoglycan CW (eg mycoplasma, protozoa, fungi, viruses)

4

PENICILLIN MOA

 

What are autolysins? 

-are BACTERICIDAL

--> inhibit last step in peptidoglycan synthesis through binding to PBPs

--> inactive against organisms w/o peptidoglycna CW

PBPs: 

--> are bacterial enzymes that get inactivated by penicillins

--> includes transpeptidases

--> number varies with type of organism

--> RESISTANCE CAN DEVELOP WITH PBP MUTATIONS

--> AUTOLYSIN PRODUCTION: is produced by bacteria and mediates cell lysis --> penicillins activate autolysins to initiate cell death --> BACTERIA EVENTUALLY LYSE D/T ACTIVITY OF AUTOLYSINS + INHIBITION OF CW ASSEMBLY!!! 

5

PENICILLIN G

IS AN IM DRUG!!! (T1/2 = 3-4 weeks)

 

-Benzylpenicillin

• Active against:

• most Gram-positive cocci (not staph)
• Gram-positive rods (eg, Listeria, C.perfringens) • Gram-negative cocci (eg, Neisseria sp)
• most anaerobes (not bacteroides)

DOC FOR

1) SYPHILLIS (benzathine penicllin G)

2) STREP INFECTIONS (especially in prevention of rheumatic fever) 

3) SUSCEPTIBLE PNEUMOCOCCI

 

6

PENICILLIN G PROCAINE

REPOSITORY PENICILLIN

IM, not IV (risk of procaine toxicity)

--> t1/2 = 12-24 hours

-is SELDOM USED (increased resistance) 

 

7

PENICILLIN G BENZATHINE

-IM

-t1/2 = 3-4 weeks

DOC FOR

1) SYPHILLUS

2) RHEUMATIC FEVER PROPHYLAXIS

8

PENICILLIN V

 

-similar antibacterial spectrum to Penicillin G (less active against Gram -ve bacteria)

-most are ACID STABLE than G (CAN GIVE ORALLY

DOC: for STREP THROAT

"like swallowing a sharp KniVe" when have strep throat --> give penicillin V 

--> employed mostly orally for mild-moderate infections eg) pharyngitis, tonsilitis, skin infectious (caused by Strep) 

9

ANTISTAPHYLOCOCCAL PENICILLINS

"NOD" that you know what to do with the STaff" --> used for Staph endocarditis and patients with artificial valves

1) METHICILLIN --> only used in the lab now (not in humans)

2) NAFCILLIN

3) OXACILLIN

4) DICLOXACILLIN

they are ALL B-LACTAMASE RESISTANT (inactive against MRSA)

--> is restricted to treatment of B-lactamase-producing staphylocci

DOC for 

1) STAPH ENDOCARDITIS

2) PTS WITH ARTIFICIAL HEART VALVES

10

EXTENDED SPECTRUM PENICILLINS

USE AMPS (blasting music, travels far) and AMO (can shoot far) for EXTENDED spectrum

1) AMPICILLIN:

2) AMOXICILLIN: has a HIGHER ORAL BIOAVAILABILITY than other penicillins (including ampicillin) 

--> is a common antibiotic prescribed for children and in pregancy 

 

-are both similar to penicilin G, but also ahve gram -ve activity

-susceptible to B-lactamases

-activity enhanced with B-lactamase inhibitor 

USES: 

1) ACUTE OTITIS MEDIA

2) STREP PHARYNGITIS

3) PNEUMONIA

4) SKIN INFECTIONS

5) UTIs, etc... 

6) WIDELY USED TO TREAT UPPER RESP INFECTIONS (H. influenza + Strep pneumonia)

7) AMOXICILLIN = STANDARD FOR ENDOCARDITIS PROPHYLAXIS during DENTAL/RESP TRACT PROCEDURES

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ENDOCARDITIS PROPHYLAXIS during DENTAL PROCEDURES

AMOXICILLIN

12

TX OF ENTEROCOCCI + LISTERIA INFECTIONS

-AMPICILLIN is used in COMBO with AMINOGLYCOSIDES to treat 

1) ENTEROCOCCI

2) LISTERIA 

13

ANTIPSEUDOMONAL PENICILLINS

she's eating grapes, so those are CARBS, she has a pet TIGER (dalmation), and the PIPERACILLIN piper player on the left

1) CARBENICILLIN

2) TICARCILLIN

3) PIPERACILLIN

-is effective against MANY gram -ve and gram +ve BACILLI

-is often combined with a B-LACTAMASE INHIBITOR

-is active against Pseudomonas Aeruginosa 

14

1) CARBENICILLIN

2) TICARCILLIN

3) PIPERACILLIN

-commonly used to treat PSUEDOMONAS AERUGINOSA

-main clincial use = an INJECTABLE TREATMENT of GRAM -VEs

-Treatment of moderate-severe infections of susceptible organisms (eg, uncomplicated & complicated skin, gynecologic and intra-abdominal infections, febrile neutropenia)

15

 

EFFECTIVE EMPIRIC TX FOR INFECTIVE ENDOCARDITIS

PENICILLIN + AMINOGLYCOSIDE

are SYNERGISTIC

-penicillins facilitate the movement of aminoglycosides through cell wall

--> should never be placed in same IV (form inactive complex) 

--> is an EFFECTIVE EMPIRIC TX FOR INFECTIVE ENDOCARDITIS

 

16

PENICILLINS - RESISTANCE

-one of 4 general mechanisms (primary or acquired):

1) INACTIVATION by B-lactamase

2) MODIFICATION of TARGET PBPs

3) IMPAIRED PENETRATINO of drug to target PBPs

4) INCREASED EFFLUX

Note: MRSA --> have altered target PBPs (low affinity for B lactam antibiotics) 

17

PENICILLIN HALF LIFE AND ABSORPTION

Half-life

~30-60 min (except repository penicillins)

Oral absorption

• Absorption impaired by food

-EXCEPTIONS: amoxicillin --> high oral bioavailability)

Nafcillin = erratic (not suitable for oral admin.)

18

PENICILLINS = DISTRIBUTION

• All achieve therapeutic levels in pleural, pericardial, peritoneal, synovial fluids & urine

Nafcillin, ampicillin & piperacillin achieve high levels in bile, (PAN = high in the bile)

• Levels in prostate & eye = insufficient***


• CSF penetration = poor (except in meningitis)

19

PENICILLIN - ADVERSE EFFECTS:

 

1) HYPERSENSITIVITY: penicilloic acid = major antigenic determinant 

--> ~5% of patients claim to have some reaction (maculopapular rash --> anaphylaxis) 

--> • Cross-allergic reactions between B-lactam antibiotics can occur

2) GI disturbances (eg, diarrhea)
3) Pseudomembranous colitis (ampicillin)
4) Maculopapular rash (ampicillin, amoxicillin)

5) Interstitial nephritis (particularly methicillin)

6) Neurotoxicity (epileptic patients at risk)
7) Hematologic toxicities (ticarcillin)
8) Neutropenia (nafcillin)

9) Hepatitis (oxacillin)
10) Secondary infections (eg, vaginal candidiasis)

20

PENICILLIN - EXCRETION

-most excreted primarily via KIDNEY (beware of kidney failur)

NAFCILLIN = EXCEPTION --> is primarily excreted in the BILE 

OXACILLIN + DICLOXACILLIN = renal + biliary excretion

21

CLAVULANIC ACID

SULBACTAM

TAZOBACTAM

B-LACTAMASE INHIBITORS

-contain B-lactam ring but do not have signif antimicrobial activity 

--> bind to and inactivate most B-lactamases 

--> available only in fixed combinations with specific penicillins

22

WHAT ARE THE 3 B-LACTAMASE INHIBITORS?

 

1) CLAVULANIC ACID

2) SULBACTAM

3) TAZOBACTAM

23

CEPHALOSPORINS

• B-lactam antibiotics
• Bactericidal
• Same MOA as penicillin's
• Affected by similar resistance mechanisms

• Classified into generations

1ST GEN = "LIN is EXIN" us up 

CEFAZOLIN

CEPHALEXIN

2ND GEN = DOLE... TIN OR TAN?

1) CEFOXITIN

2) CEFACLOR

3) CEFOTETAN

4) CEFAMANDOLE

3RD GEN: "DIME ZONE XIME" with the TRI-AX-ONE dude

1) CEFTRIAXONE

2) CEFOPERAZONE

3) CEFTAZIDIME

4) CEFIXIME

 

4) 4th GEN: "4th line rides the PINE" 

1) CEFEPIME

 

24

CEPHALOSPORIN ACTIBACTERIAL SPECTRUM

1st, 2nd, 3rd, 4th, and 5th generations based on: 

• 1) Order of introduction into clinical use

• 2) Spectrum of activity

CLASS 1 -----------------> CLASS 3

GRAM +VE GRAM -VE

In general, Gram positive activity diminishes while Gram- negative activity increases moving from the first-to third generations

4th generation demonstrate similar activity to first- generation agents against Gram-positive cocci and are also active against most Gram-negative bacilli. = BROAD SPECTRUM --> ie we should probably save this drug so we can use it when we have no damn clue what kind of bacteria is causing the illness

5th generation have a similar spectrum to the 3rd generation. They are unique in that they have activity against MRSA.

NOTE: 

-All 1st-4th generation cephalosporins are considered inactive against MRSA,

All cephalosporins are considered inactive against enterococci, Listeria, Legionella, Chlamydia, mycoplasma, and acinetobacter species. 

 

25

PENICILLIN used when kidney problems? 

NAFCILLIN

(b/c is excreted via BILE, not by kidney) 

26

ALL CEPHALOSPORINS ARE CONSIDERED INACTIVE AGAINST WHICH BACTERIA? 

"LA MEAL"

L= Legionella

A = actinomyces

 

M = MRSA

E = Enterococci

A = atypical bact (Chlamydia, Mycoplasma)

L = Listeria

 

 

 

Class notes: also include Legionella + Actinetobacter

27

CEFAZOLIN

CEPHALEXIN

1ST GENERATOIN CEPHALOSPORIN

are penicillin G substitutes

-are resistant to staphylococcal penicillinase

--> activity against gram +ve COCCI + P. mirabilis, E. coli, and K. pneumoniae

-is RARELY DOC FOR ANY INFECTIONS

CEFAZOLIN = DOC FOR SURGICAL PROPHYLAXIS

28

DRUG FOR SURGICAL PROPHYLAXIS AGINAST GRAM +VE INFECTION

CEFAZOLIN

 

29

CEFACLOR

CEFOXITIN

CEFOTETAN

CEFAMANDOLE

2nd GENERATION CEPHALOSPORINS

-extended gram -ve coverage

-greater activity against H. Influenze, Enterobacter aerogens, and some Neisseria species

"HEN PEcKS"

Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.

--> Weaker activity against Gram + ve organisms than 1st gen 

CLINICAL APPLICATIONS: 

1) Primarily used to treat sinusitis, otitis & LOWER respiratory tract infections

2) Cefotetan & cefoxitin = prophylaxis & therapy of abdominal and pelvic cavity infections

30

CEFTRIAXONE

CEFOPERAZONE

CEFOTAXIME

CEFTAZIDIME

CEFIXIME

3RD GENERATION CEPHALOSPORINS

• Enhanced activity against Gram-negative cocci
Highly active against enterobacteriacae, Neisseria, &

H.influenzae

• Less active against most Gram-positive organisms

• Cefotaxime & ceftriaxone = usually active against pneumococci