CELL WALL SYNTHESIS INHIBITORS Flashcards
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
CELL WALL SYNTHESIS INHIBITORS
1) B-LACTAM ANTIBIOTICS = MP CC
–> PENICILLINS, CEPHALOSPORINS, CARBAPENEMS, MONOBACTAMS
MISCELLANEOS:
1) VANCOMYCIN
2) DAPTOMYCIN
3) BACITRACIN
4) FOSFOMYCIN
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)
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!!!
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
PENICILLIN G PROCAINE
REPOSITORY PENICILLIN
IM, not IV (risk of procaine toxicity)
–> t1/2 = 12-24 hours
-is SELDOM USED (increased resistance)
PENICILLIN G BENZATHINE
- IM
- t1/2 = 3-4 weeks
DOC FOR
1) SYPHILLUS
2) RHEUMATIC FEVER PROPHYLAXIS
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)
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
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
ENDOCARDITIS PROPHYLAXIS during DENTAL PROCEDURES
AMOXICILLIN
TX OF ENTEROCOCCI + LISTERIA INFECTIONS
- AMPICILLIN is used in COMBO with AMINOGLYCOSIDES to treat
1) ENTEROCOCCI
2) LISTERIA
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
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)
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
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)
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.)
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)
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)
PENICILLIN - EXCRETION
-most excreted primarily via KIDNEY (beware of kidney failur)
NAFCILLIN = EXCEPTION –> is primarily excreted in the BILE
OXACILLIN + DICLOXACILLIN = renal + biliary excretion
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
WHAT ARE THE 3 B-LACTAMASE INHIBITORS?
1) CLAVULANIC ACID
2) SULBACTAM
3) TAZOBACTAM
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
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.
