Antibiotics - Cell Wall Inhibitors Flashcards
How do beta-lactams work?
Inhibit transpeptidation in cell wall formation and activate autolysins in cell walls.
They bind to PBPs (penicillin binding proteins), which are responsible for building the cell walls.
How can bacteria be resistant to beta-lactams?
- Beta-lactamases
- Lack of PBPs (penicillin binding proteins)
- Autolysin mutations
List some (broad category) classes of beta-lactams.
Penicillins, Cephalosporins, Monobactams, Carbapenems
The two natural penicillins are _______ and they are best again _____ bacteria.
penicillin G (IV) and penicillin V (oral); G+
Some examples of beta-lactamase resistant penicillins are (3) __________, but they have lower activity.
Nafcillin, oxacillin, cloxacillin
NOT effective against MRSA (methicillin-resistant Staph aureus)
Expanded/broad spectrum penicillins (effective against G+ and G-) are:
- Ampicillin
- Piperacillin
- Mezlocillin
- Ticarcillin (vs. Pseudomonas)
Acid resistant (oral) penicillins include:
Amoxycillin, Penicillin V, Oxacillin
Sometimes, penicillins are used together with beta-lactamase inhibitors. Some examples are (3):
- Augmentin (amoxicillin + clavulanic acid)
- ampicillin + sulbactam
- Zosyn, Taxomed (piperacillin + tazobactam)
Cephalosporins are _____ sensitive to beta-lactamases than penicillins.
Less!
Great work, guys.
1st Generation Cephalosporins:
List the types of bacteria they are effective against and some examples of 1st generation.
G+ action, for prophylaxis only
Cephalexin, cephalothin, cefazolin
2nd Generation Cephalosporins:
List the types of bacteria they are effective against and some examples of 2nd generation.
G+ and G- action (including Bacteroides, NOT Pseudomonas)
Cefaclor, cefuroxime, cefoxitin
3rd Generation Cephalosporins:
List the types of bacteria they are effective against and some examples of 3rd generation.
G+ and G-, including Pseudomonas. Used mostly for G- to avoid overuse; can penetrate CNS (meningitis treatment).
Ceftazidime, cephotaxime, cephtriaxone, cefdinir
Why are the 3rd generation cephalosporins special?
Because their mother said so.
Broad spectra!, G+/G-, Pseudomonas treatment, MRSA/VRE, can cross BBB
4th Generation Cephalosporins:
List the types of bacteria they are effective against and some examples of 4th generation.
Slightly expanded spectrum from 4th gen (broadest of all!)
Cefepime
5th Generation Cephalosporins:
List the types of bacteria they are effective against and some examples of 5th generation.
Still has a broad spectrum… Activity vs. MRSA, drug-resistant Staph pneumoniae (but not Pseudomonas)
Ceftaroline
Describe the structure of monobactams and why it is important.
Monocyclic beta-lactam ring; resistant to beta-lactamases.
What type of bacteria are monobactams effective against?
What is an example?
G- ONLY (not G+ or anaerobes)
Aztreonam
What type of bacteria are carbapenems effective against?
Broad spectrum (G+ and G-)
What is a potential problem with carbapenems? List some examples of carbapenems.
Can be toxic!
Imipenem, ertapenem, meropenem (reduced toxicity)
Beta-lactams have side effects. Sad, but true! Rank the severity of allergic reactions among a few beta-lactam drugs.
Penicillin > cephalosporins > monobactams
Beta-lactams have side effects. Sad, but true! Rank the severity of toxicity among a few beta-lactam drugs.
Carbapenems (seizures) > cephalosporins (thrombophlebitis) > penicillin > monobactams
How does Bacitracin work?
Blocks dephosphorylation of bactoprenol (a lipid important in synthesis of peptidoglycan for the cell wall).
What are uses of bacitracin?
Mainly topical vs. G+ (way too large in size for G-)
Often used in conjunction with others (triple antibiotic ointment: BAC, NEO, PMB)
What are some side effects of bacitracin?
Poorly absorbed, renal toxicity
How do glycopeptides work?
Bind to end of amino acid side chain in developing cell wall; block transglycosylation as well as transpeptidation
(in addition, telavancin inserts in membrane and collapses pH gradient…which sounds epic)
What are some examples of glycopeptides? (2)
Vancomycin, telavancin
How can bacteria develop resistance to glycopeptides?
Use -ala-lactate (rather than -ala-ala) to end pentapeptide side chain
Chromosomal (vanB) and plasmid (vanA) genes
What are uses of glyocpeptides?
Treatment of only G+ (Staphylococci, Enterococci)…NOT G- (can’t get through pores)
Drugs must be injected.
Other Drugs:
Cycloserine is a D-ala analong, so inhibits _______.
Alanine racemase
Neurotoxic - use carefully
Sometimes used for UTI
2nd line drug against TB
Other Drugs:
Fosfomycin inhibits synthesis of ________ from ________.
UDP-MurNAc; UDP-GlcNAc
Good against UTI
Resistance by loss of transporter
Resistance develops quickly; use in short-term in one large dose
What are some special drugs used to treat Mycobacterium?
INH, EMB, PZA, RMP, BDQ
Isoniazid/ethionamide Ethambutol Pyrazinamide Rifampicin Bedquiline
Mode of action for isoniazid, ethionamide:
Inhibit pyridoxine step in mycolic acid synthesis (often taken with pyridoxine)
Mode of action for ethambutol:
Inhibits arabinogalactan (mycolic acids in outer membrane) synthesis (rapid resistance, so use with other antibiotics)
Mode of action for pyrazinamide:
Activated by Mycobacteria enzyme; inhibits trans-translation (pathway necessary to restart stalled ribosomes during stress response)
Mode of action for rifampicin:
…he didn’t cover in this lecture. Sorry, team.
Mode of action for bedaquiline:
Blocks mycobacterial ATP synthase (c subunit) - used to treat mulit-drug-resistant TB
