penicillins week 26 costello

Question 1

Penicillins are — agents which inhibit…

Answer 1

antibacterial

bacterial cell wall synthesis

Question 2

Side-chain of penicillin depends on the —/— present in the — medium

Answer 2

carboxylic acid

fermentation

Question 3

Name the 2 rings in penicillins:

Answer 3

B-lactam ring

Thiazolodine ring

Question 4

Penicillin G:
Active against…
Toxic or Non-toxic?
Limited range of —
In terms of administration, It is not — active, must be —.
It is sensitive to which bacterial enzyme?
Some patients cannot take as they are ….
Inactive vs …

Answer 4

Gram +ve bacilli
Non-toxic
activity
orally
injected
B-lactamase
allergic
Staphylococci

Question 5

3 drug development aims of penicillin G:

Answer 5

Increase stability for oral administration
Increase resistance to b-lactamases
increase range of activity

Question 6

Nutrient broth can generate the bulk of the penicillin structure which is called… /// — Can not be made this way, they are synthesised elsewhere. The — side chain, also referred to as the — differs with different —.

Answer 6

6-aminopenicillanic acid
R-groups
Acyl
R-group
Penicillins

Question 7

SAR conclusions for penicillins:
Amide + COOH groups involved in —
COOH binds as a — ion
Activity of the B-lactam ring is related to the — involved in the ring.
—/— system increases b-lactam ring —

Answer 7

binding
carboxylate
strain
Bicyclic system
strain

Question 8

Mechanism of bacterial cell-wall synthesis:

— catalyses the cross-linking between — and — in the cell wall for increased stability.

Answer 8

DD-Transpeptidase
Glycine
D-alanine

Question 9

penicillin binds — to transpeptidase active site leading to — inhibition. This inhibition causes — to enter the cell and eventually it — and — (bursts)

Answer 9

covalently
irreversible 
water
swells
lyses

Question 10

The bicyclic ring is called a — ring

Answer 10

Penam

Question 11

An alternative theory of penicillin mechanism is that it mimics the — portion of the cell wall

Answer 11

D-alanine D-alanine

Question 12

Penicillin may also act as an umbrella inhibitor. This means that it may bind somewhere close to the —/— of the enzyme which still enables it to stop the — of the cell wall

Answer 12

active site

catabolism

Question 13

Penicillin fermentation:
The —/— is varied in the — medium
Limited to — acids at the — position.
This process is tedious and —

Answer 13

carboxylic acid
fermentation
carboxylic
alpha
slow

Question 14

Analogue penicillin preparation by total synthesis:
Only yields about -%
This process is also very —

:

Answer 14

1

impractical

Question 15

Semi-synthetic procedures use — occurring structures as starting material for — synthesis

Answer 15

naturally

analogue

Question 16

How do you hydrolyse the side chain of a sensitive molecule without affecting the b-lactam ring?

Answer 16

Activate the side chain first to make it more reactive

Question 17

Antibiotic resistance:

Mechanisms:

• drug inactivation by —
• Alteration of —
• Alternative metabolic —
• Reduced drug — mechanisms

Exacerbating factors:

• Failure to — course of antibiotics; exposure of — to — concentrations of antibiotic increases — of bacteria.
• Veterinary use: exposure to — bacteria via —.

Answer 17

B-lactamases
target
pathway
accumulation
finish
bacteria
sub-optimal
resistance
resistant
meat

Question 18

3 problems with penicillin G:

Answer 18

Sensitive to stomach acid
not resistant to b-lactamase
limited range of activity

Question 19

Factors affecting acid sensitivity of Penicillin:
Ring strain- Because of position of —/— in beta-lactam ring, the amide is very weak because the lone-pair in b-lactam ring can not — itself in the same way it does in normal —. It can not rotate and — with empty —

Answer 19

lone-pair
reorientate
amides
overlap
orbitals

Question 20

Factors affecting acid sensitivity in penicillin:
A very reactive B-lactam — group.
Nitrogen in B-lactam ring does not behave like a — amide. Interaction of the lone-pair on the — is not possible with the — group, this results in the — group being very reactive

Answer 20

carbonyl
tertiary
nitrogen
carbonyl
carbonyl

Question 21

One factor affecting the acid sensitivity of penicillin is the participation of the —/—/—.

Answer 21

Acyl Side chain

Question 22

Strategy to defeat acid sensitivity:

Answer 22

Vary the Acyl side chain to make it electron-withdrawing to reduce the nucleophilicity of the carbonyl oxygen.

Question 23

Penicillin V:
Better acid ---
Is active when administered ---
Sensitive to ---
slightly less active than ---
Some patients have --- problems

Answer 23

stability
orally
b-lactamases
Penicillin G
allergy

Question 24

Name 2 semi-synthetic penicillins:

Answer 24

Ampicillin

Oxacillin

Question 25

Beta-Lactamases: Allows --- to become resistant to --- Mechanism for lactamases is identical to mechanism of inhibition for ---/---

Answer 25

bacteria penicillins target enzymes

Question 26

Sensitivity to B-lactamases: - Penicllins use --- shields. - Blocks access of penicillin to --- by adding ---/--- to the side chain. - --- of shield is crucial to inhibit reaction of penicillin with ---., but not with the target --- enzyme

Answer 26

``` steric B-lactamase bulky groups size B-lactamases transpeptidase ```

Question 27

Methicillin: The --- group blocks access to the ---, but not to the ---. It has a --- range of activity. It is acid sensitive because... Inactive when administered ---, it must be ---

Answer 27

``` methoxy b-lactamase transpeptidase poorer there is no electron withdrawing group orally injected ```

Question 28

Oxacillin: Orally active and --- resistant because of --- and ---/--- R-group. Resistant to most ---. Active vs ---/--- Less/more active than other penicillins?

Answer 28

``` Acid bulky electron withdrawing staphylococcus aureus Less ```

Question 29

Broad spectrum, class 1 penicillins have a --- group at the --- position. Give 2 examples of these..

Answer 29

NH2 alpha ampicillin amoxicillin

Question 30

``` Carbapenems: Originally developed from --- isolated from ---/--- found in soil last resort against ---/--- they have low --- High resistance to --- poor stability in --- has the opposite --- to penicillins in the ---/--- Have a --- nucleus The --- side chain in absent ```

Answer 30

``` Thienamycin streptomyces cattleya E.coli infections toxicity b-lactamases solution stereochemistry b-lactam ring carbapenem acylamino ```

Question 31

What is NDM-1? Which 2 types of antibiotics are effective against NDM-1? For antibiotic 1, why is it not ideal? For antibiotic 2, why is it not ideal?

Answer 31

``` New Delhi metallo Beta-lactamase Colistin Tigecycline quite toxic not effective against all infections. ```

Question 32

Monobactams: The b-lactam ring is --- moderately active in vitro against --- range of ---/--- Inactive vs --- bacteria Low --- thought to act by different --- than ---- Active vs ---

Answer 32

``` Monocyclic narrow gram -ve bacteria gram +ve toxicity mechanism, penicillins Pseusomonas aeruginosa ```

Question 33

``` Aztreonam: Administered how? can be used if patient is... No activity against --- or ---- Active against ---, --- bacteria The only commonly available --- ```

Answer 33

``` Intravenous allergic to penicillins gram +ve or anaerobic gram -ve aerobic monobactam ```

Question 34

B-lactamase inhibitors: CLAVULANIC ACID No --- side chain B-lactam ring still present, but with ---- ring which has --- instead of ---. A powerful and --- inhibitor of --- It is known as a ---/--- Used as a --- drug for --- What is the name for the ampicillin/clavulanic acid combo? Allows for less --- needed per dose and increases the spectrum for ---

Answer 34

``` acylamino oxazolidine oxygen sulphur irreversible b-lactamase suicide substrate sentry ampicillin Augmentin ampicillin activity ```

Question 35

Suicide inhibition: When an --- binds irreversibly to a --- analogue forming and irreversible --- . Inhibitor binds to ---/--- of enzyme where it's modified to produce a --- group that reacts --- to form a stable ---/--- complex

Answer 35

``` enzyme substrate complex active site reactive irreversibly inhibitor/enzyme ```