Cell wall synthesis inhibitors

Question 1

What are the drug classes that are cell wall synthesis inhibitors?

Question 2

What is the mechanism of action for penicillins?

Answer 2

interfere with formation of peptidoglycan layer and bacteriocidal

specifically bind to transpeptidase enzyme whose function cross-links NAM and NAG

Question 3

What are the penicillin binding proteins activated by penicillins?

Answer 3

transpeptidases

autolysins

carboxypeptidases/endopeptidases

Question 4

autolysisn is a penicillin binding protein. how does it work?

Question 5

Carboxypeptidases/endopeptidases are PBPs. How do they work?

Answer 5

break peptide bonds

Question 6

For penicillins to gain access to microbes, they must permeate the cell wall. What mechanisms of resistance do bacteria have for this?

Question 7

Penicillins that are combined with bacteriostatic drugs. What happens?

Answer 7

antagonism results

synergistic actions are not expected

Question 8

For penicillins to be effective inhibitors of cell wall synthesis, what must be taking place?

Answer 8

microbe must be actively growing and dividing

Question 9

How do penicillins inhibit synthesis of bacterial cell walls? and what are the 2 results?

Answer 9

binding to penicillin binding proteins

1. inhibits cell wall synthesis by blocking transpeptidation of peptidoglycan
2. activates autolytic enzymes in cell wall that cause lesions resulting in bacterial cell death

Question 10

What mechanism will allow bacteria to become resistant to penicillins?

Answer 10

actions of penicillins may be terminated by B-lactamase enzymes that reside in the periplasmic space

Question 11

What can penicillin be combined with to get syngeristic actions?

Answer 11

penicillins + aminoglycosides

combo is a cell wall synthesis inhibitor plus a protein synthesis inhibitor

Question 12

Why should antibiotics not be taken with oral contraceptives?

Answer 12

estrogens are recycled via the enterohepatic recirculation pathway and normally gut bacteria cleave estrogen-glucuronide allowing them to be reabsorbed

with antibioitcs, normal GI flora are disrupted that impairs enterohepatic recirculation of estrogenic compounds thus diminishing their half-life

use a backup for 7 days after finishing dose of antibiotics

Question 13

What are the 4 distinct subclassifications of penicillins?

Answer 13

1. natural penicillins
2. aminopenicillins
3. penicillinase-resistant penicillins
4. antipseudomonal penicillins

Question 14

What will coadministering penicillins with drugs that are irreversible inhibitors of B-lactamase do?

Answer 14

broaden the spectrum of coverage to include B-lactamase producing organisms

Question 15

Which classes of penicillins are used to treat gram + microbes?

Answer 15

natural penicillins and penicillinase-resistant penicillins

Question 16

Which classes of penicillins are used to treat gram (-) organisms?

Answer 16

aminopenicillins and antipseudomonal penicillins

Question 17

What are the natural penicillins?

Answer 17

penicillin G and V

Question 18

How should penicillin G be administered? why? and what indications are necessary?

Answer 18

administered via IV or IM because it is readily destroyed in acidic environments

treats rheumatic fever and syphilis

Question 19

When should penicillin V be administered? How? What indications?

Answer 19

it is more stable so can be given orally

should be given on empty stomach, or 1 hour before meals, or 2-3 hours after meals

treats streptococcal pharyngitis

Question 20

What drugs are amino penicillins?

Answer 20

ampicillin

amoxicillin

Question 21

How should ampicillin be administered?

amoxicillin?

Answer 21

ampicillin can be orally given but best on empty stomach

amoxicilin can be taken w/ or w/o food b/c it is stable in presence of gastric acid

Question 22

What are the penicillinase-resistant penicillins?

Answer 22

• dicloxacillin,
• methicillin,
• oxacillin,
• nafcillin

Question 23

What is the mechanism of action of the penicillinase-resistant penicillins?

Answer 23

contain sie groups that protect the drugs from being inactivated by bacterial B-lactamases

Question 24

Describe the different routes of administration for the penicillinase-resistant penicillins

Answer 24

methicillin, oxacillin, nafcillin => parenterally

dicloacillin => orally

Question 25

What are the antipseudomonal penicllins (extended-spectrum)?

Answer 25

* carbenicillin * ticarcillin * mezlocillin * piperacillin

Question 26

How are the antipseudomonal penicillins usually administered? are there any exceptions?

Answer 26

parenterally carbenicillin can be administered orally but therapeutic levels are only found in urinary tract

Question 27

Carbenicillin is an antipseudomonal penicillin. What indications provide use for this?

Answer 27

urinary tract and prostatic infections

Question 28

What are the irreversible inhibitors of B-lactamases?

Answer 28

clavulanic acid sulbactam tazobactam

Question 29

what is important about the administration of the irreversible B-lactamase inhibitors?

Answer 29

they have NO antimicrobial activity by themselves muse be combined with penicillins, expanded coverage against B-lactamase-producing microbes provided

Question 30

Describe the cephalosporins structure and when they should be taken and how

Answer 30

cephalosporins resemble penicillins they possess a B-lactam backbone unlike natural penicillins, they are stable to pH changes and may be taken w/ or w/o food

Question 31

If a patient has a penicllin allergy, would you prescribe cephalosporins?

Answer 31

no =\> possibility that penicillin-allergic patients may also be hypersensitive to cephalosporins

Question 32

When cephalosporins are given orally, what is an adverse side effect? what if parenterally?

Answer 32

orally=\> GI irritation but if taken with food then can be prevented parenterally=\> local irritation at site of injection

Question 33

WRT excretion, what adverse effect of cephalosporins should be monitored?

Answer 33

since many are excreted by kidneys, renal toxicity is possible caution for pre-existing renal disease or impaired creatinine clearance

Question 34

2nd and 3rd generation cephalosporins may cause what adverse side effects? what if they are given parenterally?

Answer 34

disulfiram-like reactions and hyprothrombinemia parenterally=\> may cause seizures especially those with impaired kidney function due to accumulation

Question 35

Cephalosporins disrupt normal flora. What is an adverse effect of this?

Answer 35

**secondary infections** pseudomembrnaous colitis vaginal yeast infections

Question 36

What are the drugs considered carbapenums?

Answer 36

imipenem/cilastatin, doripenem, ertapenem meropenem

Question 37

What is the mechanism of action for the carbapenems? what is there structure and how does this help them?

Answer 37

bactericidial and inhibit cell wall synthesis different stereochemical structure in B-lactam ring that renders them **resistant to B-lactamases**

Question 38

What are some other antibiotics that dirupt cell walls?

Answer 38

* telavancin * vancomycin * cycloserine * polymyxin B

Question 39

What is the general mechanism of action for tevavancin and vancomycin?

Answer 39

interfere with cell wall synthesis by blocking polymerization and cross-linking of peptidoglycan by binding to D-Ala-D-Ala portion of cell wall

Question 40

along with blocking polymerization and cross-linking of peptidoglycan by binding to D-Ala-D-Ala portion of the cell wall, what is the other mechanism in which **televancin** work?

Answer 40

disruption of membrane potential and changes in cell permeability because of presence of lipophilic side chain moiety

Question 41

What is the mechanism of action for cycloserine? What organisms does it work for? What is it mainly used for?

Answer 41

inhibits cell wall synthesis in gram (+) and gram (-) microbes reserved usually for treating Mycobacterium tuberculosis that are resistant to 1st-line antitubercular drugs

Question 42

What is the mechanism of action for polymyxin B? What does it fight well?

Answer 42

cationic detergent that disrupts lipoproteins in bacterial cell walls to increase the membrane permeability bactericidal to nearly all gram (-) bacilli (except proteus)