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