Beta-Lactams and Cell wall inhibitors

Question 1

Name the First Line Cell Wall Inhibitors

Answer 1

Penicillin V and Penicillin G

Question 2

Name 2nd generation penicillins

Answer 2

• Nafcillin -Dicloxacillin - Methacillin (Not used anymore due to resistance)

Question 3

Name the third generation penicillin Beta-lactamase inhibitors What Aminopenicillins are they paired with to prevent resistance?

Answer 3

-Clavulanate: Amoxacillin -Sulbactam: Ampicillin -Tazobactum: Amoxacillin (also Piperacillin)

Question 4

How do penicillins work? What is the Range and possible adverse effects of first generation penicillin?

Answer 4

• Penicillins work via Beta-Lactams. Beta-Lactams inhibit a transpeptidase (Penicillin Binding Protein or PBP) so that peptidoglycan cannot be linked to make the bacterial wall - Range: Gram + & Syphillis, Streptococci, most Neisseria gonorrhea - AE: Hypersensitivity (this means possible reaction to other penicillins)

Question 5

What mechanism have bacteria developed to create strains that are resistant to penicillins

Answer 5

-Penicillinase: This cuts the beta-lactam ring so that it can no longer act as an inhibitor of PBP’s action

Question 6

How do we get around Penicillinase? What are the ranges of these second gen. Penicillins? Side Effects?

Answer 6

• Nafcillin and Dicloxacillin are both second line drugs that are resistant to Penicillinase. - Range: Narrow gram + - AE: Same as penicillin

Question 7

There were penicillinase-inhibitors that were developed to be paired with other penicillins. What are they? What medications are they paired with?

Answer 7

• Clavulanate (Amoxicillin, Ticarcillin “need Ammo for the Calvary”) - Sulbactam (Ampicillin, “Amp it up or people will be Sullen”) - Tazobactum (Piperacillin)

Question 8

We engineered another group of penicillins (3rd Gen.) to make a wider spectrum. What is the name of this family and it’s constituents? What are their range? Are they Penicillinase resistant?

Answer 8

Name: Aminopenicillins Constituents: Ampicillin, Amoxicillin Spectrum: Broad (Gram -, E. Coli, H. Influenza, Salmonella, Enterococci) They are still susceptible to penicillinase *Bonus: Associated with pseudomembranous colitis

Question 9

What is the name for 4th Gen. Penicillins? Spectrum? AE?

Answer 9

General Name: Antipseudomonals Names: Ticarcillin, Piperacillin Spectrum: Broad spectrum (Gram -) - Pseudomonas AE: Penicillin allergy -Urticaria, angiodedema, anaphalaxis

Question 10

If a patient is has an allergic response to a penicillin, what should you use?

Answer 10

Aztreonam -Specific for only Gram - rods

Question 11

How do cephalosporins work? Are they resistant to penicillinase? What resistance do bacteria have to them if any?

Answer 11

-Cephalosporins bind to another protein that is involved in cross linking peptidoglycans. - Less susceptible to penicillinase - Still susceptible to Cephalosporinase!

Question 12

What are the 1st Gen. Cephalosporins? Spectrum? Drawbacks? Special Uses?

Answer 12

Name: Cefazolin, Cephalexin Spectrum: Narrow (Gram + cocci) Drawbacks: Bad for crossing BB barrier - Don’t use for CNS infections Special Uses: Prophylactic prior to surgery

Question 13

For 2nd Gen. Cephalosporins: -Names? -Spectrum? -AE? -Other info?

Answer 13

Name: Cefoxitin, Cefuroxime, Cefotetan Spectrum: More Gram +/- activity AE: Can inhibit Vitamin K –> Longer bleeding - Creates a disulfuram reaction if administered with alcohol

Question 14

For 3rd Gen. Cephalosporins: -Names? -Spectrum? -AE? -Other info?

Answer 14

Names: Ceftriaxone, Cefotaxime, Ceftazidime Spectrum: More serious Gram - - Good for streptococci AE: Can precipitate crystals in kidneys - Highly associated with C. diff!!!!!!!!!!!!!

Question 15

For 4th Gen. Cephalosporins: -Names? -Spectrum? -AE? -Other info?

Answer 15

Name: Cefepime Spectrum: Broadest of cephalosporins AE: Somewhat associated with C. diff Other: Good as an empiric treatment

Question 16

For 5th Gen. Cephalosporins: -Names? -Spectrum? -AE? -Other info?

Answer 16

Name: Ceftaroline Spectrum: This can kill MRSA! (Methicillin Resistant Staph aureus)

Question 17

Name the different Carbapenems? What is their mechanism for killing bacteria? Are they susceptible to penicillinase? Spectrum? Other info?

Answer 17

Names: Imipenem, Cilastin, Meropenem Mechanism: Beta-lactam ring Resistance: Low resistance via penicillinase Spectrum: Broad (no good for MRSA though) Other: Imipenem is administered with cilastatin to prevent it’s breakdown in the kidneys. -This can lead to kidney damage -Too much of these drugs –> toxicity –> G.I. distress

Question 18

What similarities are shared between Penicillins, Carbapenems, and Cephalosporins? Is it wise to give more than one at the same time?

Answer 18

-They all are blocking the same target; Penicillin Binding Protein (PBP). - It would not be wise to give more than one at the same time because they will just compete with each other. -They share the same Beta-lactam ring too so there will probably be cross-allerginicity

Question 19

What are some draw backs to Penicillins, Carbapenems, and Cephalosporins? What are they poor use against?

Answer 19

• They all have a few drugs that can lead to a “super infection” of C. diff - Almost all Staphylococcus strains now resist beta-lactam drugs! - MRSA (methicillin resistant staph aureus) is pretty much left untouched by any of these drugs except 5th Gen. Cefepime (ceftaroline).

Question 20

What drug should you give if you think you have a super infection of C. diff?

Answer 20

Vancomycin! - Disrupts the synthesis of the cell wall in bacteria by binding to D-alanyl-D-alanine (DADA) –> Interruption of its release from bactoprenol carrier –> interruption of peptidoglycan synthesis. The interruption of the bactoprenol carrier prevents flipping of the peptidoglycan to the outer surface (i.e. it stays on the inside of the cell membrane and can’t be added to make a cell wall).

Question 21

For Vancomycin, what are the following? -Spectrum? - Should it be given orally? -Adverse Effects?

Answer 21

Spectrum: Broad for Gram + organsims (C. diff and MRSA)

• It should not be given orally because it has poor absorption in the gut. It should be given parenterally instead.

AE: -There is no cross-sensitivity (good thing!)

• It is excreted quickly by the kidneys, so you will have to adjust the dosage for renal uptake
• Toxicity: Nephrotoxicity, Ototoxicity

Question 22

What is Bacitracin? How does it work? Spectrum? AE? Other?

Answer 22

Bacitracin disrupts the insertion of peptidoglycan into the cell wall by dephosphorylating the bactoprenol carrier -Bactoprenol carrier is what is taking newly synthesized peptidoglycans out of the cell cytoplasm and to the site of incorporation into the peptidoglycan wall (which is done by PBP)

Spectrum: Gram +

AE: Nephrotoxic

Other: Used as a topical ointment

Question 23

For Polymyxin B: Mechanism? Spectrum? AE? Other?

Answer 23

Polymyxin-B disrupts the membrane instead of the cell wall by punching holes in the membrane –> contents spilling out Spectrum: Gram - -Multi-drug resistant Gram - - Great for almost all strains of: Pseudomonas aeruginosa, Haemophilus influenza AE: Blurred vision, Ataxia, numbness of extremities Other: You can combine it with Bacitracin in skin ointments –> broad spectrum Gram - and Gram +

Question 24

For Daptomycin Mechanism? Spectrum? AE? Other?

Answer 24

Mechanism: Disrupts the cell membrane –> depolarization of the cell resting membrane potential –> disruption of cell function and death Spectrum: Gram + and MRSA Resistance: The drug has a positive charge so any positively charged amino acid (Lysine) on the outer cell membrane will repel it.