Pharmacology-Ch43-Betalactamantibiotics-And Other Cell Wall Synthesis Inhibitors

Front 1

what are the major antibiotics that inhibit bacterial cell wall synthesis?

Back 1

penicillins and cephalosporins

Front 2

what are penicillins and cephalosporins called because of their 4 membered ring?

Back 2

beta lactams

Front 3

penicillins vary in their resistance to this GI secretion?

Back 3

gastric acid- and therefor vary in their oral bioavailability

Front 4

how are ampicillin and naficillin partly excreted?

Back 4

in the bile

Front 5

penicillins are polar compounds that are not metabolized extensively and are usually excreted unchanged in the urine via these two methods?

Back 5

glomerular filtration dn tubular secretion

Front 6

how are procain and benzathine (forms of penicillin G) administered?

Back 6

intramuscularly- and have a long plasma halflife because the active drug is released very slowly in the blood stream.

Front 7

when do most penicillins cross the blood brain barrier?

Back 7

only when the meninges are inflammed

Front 8

are beta lactam drugs bactericidal or bacteriostatic?

Back 8

bactericidal

Front 9

beta lactam antibiotics inhibit cell wall synthesis through these 3 steps?

Back 9

1. binding of drug to penicillin binding proteins PBPs located inteh bacterial cytoplasmic membrane. 2. inhibition of transpeptidase enzymes that act to cross link linear peptidoglycan chains which form part of teh cel wall and 3. activation fo autolytic enzymes that cause lesions in the bacterial cell wall

Front 10

if a bateria enzymatically hydrolyzes the beta lactam ring what effect does that have on the beta lactam antiobiotics effectiveness?

Back 10

inactivates it- making it ineffective

Front 11

most staphylococci and many gram neg bacteria have this enzyme that makes them resistant to beta lactam antibiotics?

Back 11

beta lactamases (penicillinases)

Front 12

there are inhibitors of beta lactamase enzymes that are often administered with a beta lactam antibiotic what are some examples?

Back 12

clavulanic acid, sulbactam, tazobactam

Front 13

what is the mechanism of resistance for staph's resistance ot methicillin?

Back 13

structural change in target PBPs

Front 14

what does bactericidal mean?

Back 14

an antimicrobial drug tat can eradicate an infection in the absence of host defense mechanisms; kills bacteria

Front 15

what does bacteriostatic mean?

Back 15

an antimicrobial drug that inhibits antimicrobial growth but requires host defense mechanisms to eradicate the infection; does NOT kill the bacteria

Front 16

what are beta lactam antibiotics?

Back 16

drugs with structures containing beta lactam ring; includes penicillins and cephalosporins, this ring must be intact for antimicrobial action

Front 17

what is meant be minimal inhibitory concentration (MIC)?

Back 17

lowest concentration of antimicrobial drug capable of inhibiting growth of an organism in a defined growth medium

Front 18

what does the term selective toxicity mean?

Back 18

more toxic to the invader than to the host; a property of useful antimicrobial drugs

Front 19

what are transpeptidases?

Back 19

bacterial enzymes involved in the cross linking of linear peptidoglycan chains, the final step in cell wall synthesis

Front 20

in some gram neg rods like pseudomonas aeruginosa changes in this structure may contribute to resistance by impeding access of penicillins to PBPs?

Back 20

changes in porin structures in the outer membrane

Front 21

what is the prototype of a subclass of penicillins that have a limited spectrum of antibacterial activity and are susceptible to beta lactamases?

Back 21

Penicillin G

Front 22

what are the clinical uses of penicillin G?

Back 22

common streptococci infections, menigococci, gram positive bacilli, and spirochetes.

Front 23

although no longer suitable for treatment of gonorrhea (because they have developed resistance), penicillin G remains the drug of choice for this STD?

Back 23

syphilis

Front 24

the activity of penicillin G against enterococci species is enhanced through concurrent use of this other antibiotic?

Back 24

aminoglycosides

Front 25

describe Penicillin V?

Back 25

it is an oral drug used mainly in oropharyngeal infections listed under the narrow spectrum penicillinase susceptible agents category

Front 26

list the drugs under the very narrow spectrum penicillinase RESISTANT drugs?

Back 26

methicillin (the prototype), nafcillin, and oxacillin

Front 27

what is the primary use of methicillin, nafcillin and oxacillin?

Back 27

treatment of known or suspected staphylococcal infections.

Front 28

what is one organism we know of from our discussions that is resistant to methicillin?

Back 28

MRSA and MRSE (methicillin resistant staph epidermidis)

Front 29

what are examples of drugs in the category of wider spectrum penicillinase SUSCEPTIBLE drugs?

Back 29

ampicillin and amoxicillin and piperacillin and ticarcillin

Front 30

ampicillin and amoxicillin have a wider spectrum of activity than what other drug?

Back 30

penicillin G

Front 31

what is the prototype of a subclass of penicillins that have a limited spectrum of antibacterial activity and are susceptible to beta lactamases?

Back 31

Penicillin G

Front 32

what are the clinical uses of penicillin G?

Back 32

common streptococci infections, menigococci, gram positive bacilli, and spirochetes.

Front 33

although no longer suitable for treatment of gonorrhea (because they have developed resistance), penicillin G remains the drug of choice for this STD?

Back 33

syphilis

Front 34

the activity of penicillin G against enterococci species is enhanced through concurrent use of this other antibiotic?

Back 34

aminoglycosides

Front 35

describe Penicillin V?

Back 35

it is an oral drug used mainly in oropharyngeal infections listed under the narrow spectrum penicillinase susceptible agents category

Front 36

list the drugs under the very narrow spectrum penicillinase RESISTANT drugs?

Back 36

methicillin (the prototype), nafcillin, and oxacillin

Front 37

what is the primary use of methicillin, nafcillin and oxacillin?

Back 37

treatment of known or suspected staphylococcal infections.

Front 38

what is one organism we know of from our discussions that is resistant to methicillin?

Back 38

MRSA and MRSE (methicillin resistant staph epidermidis)

Front 39

what are examples of drugs in the category of wider spectrum penicillinase SUSCEPTIBLE drugs?

Back 39

ampicillin and amoxicillin and piperacillin and ticarcillin

Front 40

ampicillin and amoxicillin have a wider spectrum of activity than what other drug?

Back 40

penicillin G- but still remains susceptible to penicillinases

Front 41

what are the clinical uses of ampicillin and amoxicillin?

Back 41

simialr to penicillin G as well as infections resulting form enterococci, listeria, E coli, proteus, H. influenzae, moraxella catarrhalis, although resistant strains do occur

Front 42

when ampicillin and amoxicillin are used with this their antibacterial acitivity is enhanced?

Back 42

inhibitors of penicillinases (eg clavulanic acid)

Front 43

in enterococcal and listerial infections ampicillin is synergistic with this other antibiotic class?

Back 43

aminoglycosides

Front 44

piperacillin and ticarcillin have activity against several gram neg robs including there 3?

Back 44

pseudomonas, enterobacter, and in some cases klebsiella species.

Front 45

what are the allergic reactions possible to penicililns?

Back 45

urticaria, severe pruritis, fever, joint swelling, hemolytic anemia, nephritis, and anaphylaxis.

Front 46

which of all the beta lactams listed in prior questions causes nephritis more than the others?

Back 46

methicillin

Front 47

nafcillin is associated with this allergic toxicity?

Back 47

neutropenia

Front 48

should complete cross allergenicity between different penicillins be assumed?

Back 48

yes!!

Front 49

what does ampicillin frequently cause?

Back 49

a maculopapular skin rash that does not appear to be an alergic reaction

Front 50

what GI problems arise from oral penicillins?

Back 50

nausea and diarrhea may occur, especially with ampicillin. GI upset may be caused by direct irritation or by overgrowth of gram positive organisms or yeasts.

Front 51

which penicillin drug has been implicated in pseudomembranous colitis?

Back 51

ampicillin

Front 52

do cephalosporins contain a beta lactam ring?

Back 52

yes

Front 53

several cephalosporins are available for oral use, but most are administered this way?

Back 53

parenterally

Front 54

cephalosporins with side chains may undergo hepatic metabolism, but the major elimination mechanism is this?

Back 54

renal excretion via active tubular secretion

Front 55

how are cefoperazone and ceftriaxone excreted mainly?

Back 55

in the bile

Front 56

do most 1st and 2nd generation enter the CSF?

Back 56

no not even when the meninges are inflammed

Front 57

what is the MOA of cephalosporins?

Back 57

bind to PBPs on bacterial cell membranes to inhibit bacterial cell wall synthesis by mechanisms similar to those of the penicillins.

Front 58

are cephalosporins bacterostatic or cidal?

Back 58

bacterocidal

Front 59

do the structural differences between penicillins and cephalosporins make cephalosporins more or less susceptible to penicillinases produced by staph?

Back 59

less

Front 60

are MRSA's also resistant to cephalosporins?

Back 60

yes

Front 61

give two examples of 1st generation cephalosporins

Back 61

cefazolin (parenteral) and cephalexin (oral)

Front 62

generation 1 cephalosporins are most effective against these organisms?

Back 62

gram positive cocci like staph and strep. many strains of E coli and klebsiella are also sensitive. they have minimal activity agains gam neg gocci, enterococci, and MRSA, and most gram neg rods.

Front 63

2nd generation cephalosporins have less activity against gram positive organisms than the first generation but have an extended coverage of this group?

Back 63

gram negatives-bacteroides (cefoetan, cefoxitin) and H influenzae or M catarrhalis (cefmandole, cefuroxime, ceaclor)

Front 64

what are the characteristic features of 3rd generation cephalosporins?

Back 64

(examples = ceftazidime, cefoperazone, cefotaxime) have increased activity against gram neg organisms resistant to other beta lactam drugs and ability to penetrate the blood brain barrier (except cefoperazone and cefixime).

Front 65

drugs in the 3rd generation cephalosporin subclass should be reserved for treatment of this type of infection?

Back 65

serious eg bacterial meningitis

Front 66

what is the example of a 4th generation cephalosporin and describe it?

Back 66

Cefepime- more resistant to beta lactamases produced by gram neg organisms like enterobacter, haemophilus, neisseria and some penicillin resistant pneumococci. Cefepime combines the gram positive activity of first generation agents with the wider gram negative spectrum of third generation cephalosporins

Front 67

are the frequency of allergic reactions to cephalosporins greater or less than to penicillins?

Back 67

less frequent

Front 68

what is the cross reactivity between penicillin allergy and cephalosporin allergy?

Back 68

incomplete between 5-10% so penicillin allergic patientc can sometimes be treated successfully with a cephalosporin, but should not be given a cephalosporin if they had anaphylaxis to penicillin!!

Front 69

cephalosporins may increase the nephrotoxicity of this other antibiotic if given together?

Back 69

aminoglycosides

Front 70

drugs containing a methylthiotetrazole group (eg cefamandole, cefoperazone, cefotetan) may cause this side effect?

Back 70

hypoprothrombinemia and disulfiram like reactions with ethanol

Front 71

azotreonam is a monobactam that is resistant to beta lactamases produced by certain gram neg rod such as?

Back 71

klebsiella, pseudomonas, and serratia. the drug ahs no activity against gram positives or anaerobes

Front 72

how is azetreonam administered?

Back 72

IV and i eliminated via renal tubular secretion

Front 73

is there any cross allergenicity with penicillins and aztreonam?

Back 73

no

Front 74

the carbapenems (imipenem, meropenem, and ertapenem) are chemically different from penicillins but retain the beta lactam ring. do they have the same susceptibility to beta lactamases?

Back 74

lower than penicllins

Front 75

what is the carbapenems range of activity?

Back 75

wide- against gram pos cocci (including penicillin resistant pneumococci), gram neg rods and anaerobes

Front 76

how are carbapenems administered?

Back 76

parenterally

Front 77

imipenem is rapidly inactivated by renal dehydropeptidase I and is administered in fixed combination with ___, an inhibitor of this enzyme

Back 77

cilastatin

Front 78

what are the beta lactamase inhibitors that are used in fixed combinaitons with certain hydrolyzable penicillins?

Back 78

clavulanic acis, sulbactam, and tazobactam

Front 79

these beta lactamase inhibitors are most active against____encoded beta lactamases

Back 79

plasmid - ie those form gonococci, streptococci, E coli, and H influenzae. they are NOT good inhibitors of inducible chromosomal beta lactamases formed by enterobacter, pseudomonas, and serratia

Front 80

what is vancomycin?

Back 80

a bactericidal glycoprotein that binds to the D-Ala-D-Ala terminal o fthe nascent peptidoglycan pantapeptide side chain and inhibits transglycosylaiton. this action prevents elongation o fthe peptidoglycan chain and interferes with cross linking.

Front 81

when is vancomycin used?

Back 81

it has a narrow spectrum of activity and is used for serious infectiosn caused by drug resistant gram positive organisms, including MRSA, penicillin resistant pneumococci, and C diff.

Front 82

is vancomycin absorbed from the GI tract?

Back 82

NO, so it can be given orally for bacterial enterocolitis.

Front 83

what does Fosfomycin do?

Back 83

it is an antimetabolite inhibitor of cytosolic enolpyruvate transferase. this aciton prevents the formation of N acetylmuramic acid, an essential precursor molecule for peptidoglycan chain formation.

Front 84

what does bacitracin do?

Back 84

it is a peptide antibiotic that interferes witha late stage in cell wall synthesis in gram positive organisms. - it has marked nephrotoxicity so its use is limited to topical

Front 85

what does cycloserine do?

Back 85

it is an antimetabolite that blocks the incorporation of D-Ala into the pentapeptide side chian of the peptidoglycan. because of its potential neurotoxicity (tremors, seizures, psychosis), cycloserine is only used to treat TB caused by organisms resistnat to first line anti-TB drugs

Front 86

what is the prototype limited spectrum penicillin?

Back 86

penicllin G

Front 87

what is the prototype beta-lactamase resistant penicillin?

Back 87

methicillin

Front 88

what is the prototype wider spectrum penicillin?

Back 88

ampicillin

Front 89

what is the prototype for first generation cephalosporin?

Back 89

cefazolin

Front 90

what is the prototype for 2nd generation cephalosporin?

Back 90

cefamandole

Front 91

what is the prototype for 3rd generation cephalosporin?

Back 91

cefoperazone

Front 92

what is the prototype for 4th generation cephalosporin?

Back 92

cefepime

Front 93

what is the prototype for cabapenems?

Back 93

imipenem

Front 94

what is the prototype for beta lactamase inhibitors?

Back 94

clavulanic acid