Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm Exam 2 > Antibiotics 1 - Cell wall and Beta Lactams > Flashcards

Antibiotics 1 - Cell wall and Beta Lactams Flashcards

1
Q

Main barrier keeping drugs out of cell in gram positive

A

Bacterial membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Gram positives excrete…

A

B lactamase through the cell wall into the external environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Outer membrane barrier property in gram negative?

A

excludes drugs, but some may stil get in through porins in the OUTER cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

In gram negatives, where is the beta lactamase located?

A

in the periplasmic space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

type with thicker PG

A

gram positive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Gram negatives have an ____ that contains ____ which may facilitate entry

A

outer membrane

porins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

G- Peptidoglycan contains _______

A

meso-diaminopimelic acid residue

(DAP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

G+ peptidoglycan contains ____ instead of the ____ that gram negative contains

A

L-Lysine

DAP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Crosslinking occurs in G- between the ___ and ____

A

DAP and D-ala

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

G+ crosslinking occurs between…

A

L-Lys and terminal D-ala

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

S. aureus crosslink composition

A

5 glycine residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Transpeptidase mechanism:

The OH from ___ attacks the ___ carbon of peptide-d-ala-d-ala

A

OH from Transpeptidase attacks the amide carbon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Transpeptidase mechanism: ____ is formed as an intermediate which is more reactive

A

Ester linkage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

After the ester linkage is broken, a ____ intermediate is formed.

A

tetrahedral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Final products of transpeptidase mechanism

A

Peptide- D-Ala-Gly-Gly -Peptide

+

Transpeptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

B-lactam MOA

A

acylates the transpeptidase’s serine residue in the enzyme active site.

–> inactivates the enzymes and inhibits cross linking.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

reactivity of B lactam system is due to…

A

highly strained 4-membered ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

NCC bind of the B lactam is compressed to ___ from _____

A

compressed to 90 from normal 120 angle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Bond angle of a tetrahedral carbon

A

109

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Stress can be releived in beta lactam strain by conversion of…

A

carbonyl to the tetrahydral intermediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The beta lactal carbonyl is more reactive because…

A

its more like a ketone carbonyl than an amide carbonyl, because of the steric inhibition of overlap of the non-bonded electrons of the nitrogen with the adjacent carbonyl.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Penicillins assume a _____ structure with _____

A

folded ring structure with an sp3 hybridized nitrogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

There are many ____ which explains the heterogenecity of bacterial responses

A

penicillin binding proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

The bacterial transpeptidases do not catalyze rxns with host cell proteins because…

A

the bacterial substrate contains unnatural D-ala residues that arent found in host cell proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Four mechanisms of resistance to beta-lactam

A

decreased cellular uptake

mutation of the PBPs

Presence of efflux pump

**Induction/elaboration of B-lactamases**

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Four steps in B lactamase mechanism

A

[B lactamase + Penicillin] –>

Tetrahedral intermediate –>

Acylated B lactamase –>

[Regenerated enzyme + hydrolyzed penicillin]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Fast step in beta lactamase mechanism =

A

Hydrolysis of the acylated B-lactamase intermediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

__% of population has beta-lactam AB’s

A

6-8%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How are beta lactams allergenic?

A

Drug acts as hapten - acylates host cell proteins

(generates covalent products that are “foreign”)

30
Q

Why can’t the allergic reaction of beta lactam be overcome via structural manipulation of the compound?

A

the reaction originates from the pharmacore of the drug

31
Q

Can you use other penicillin-type drug on a penicillin-allergic person?

A

NO!

32
Q

____ tests for beta lactam allergy are recommended if there is doubt about allergy

A

Topical flare and wheal test

33
Q

Main degradation products of Pen G

A
  1. Benzylpenicillenic acid
  2. Benzylpenicillic acid
  3. Benzylpenicilloic acid
34
Q

Penicillin hydrolysis products have no _______

A

antibiotic activity

35
Q

Hydrolysis of B lactam is ___

A

irreversible

(once the ring is opened, no closure)

36
Q

Electronegative substituents have what effect when they’re on the side chain carbonyl?

A

They reduce the nucleophilicity of the side chain amide carbonyl oxygen atom.

  • Stabilizes the penicillin against hydrolysis under acidic conditions
  • Increases oral bioavailability
37
Q

Which is more stable, Pen G or Pen V?

A

Pen V is more stable to acid hydrolysis

*because the electronegativity of the ether oxygen decreases the nucleophilicity of the amide carbonyl

38
Q

Solutions of penicillins should be used promptly and stored how?

A

In refrigerator at pH 6.0-6.8

39
Q

_____ catalyze penicillin degradation

A

heavy metal ions

40
Q

Penicillins with ______ are more highly protein bound

A

lipophilic side chains

41
Q

Protein binding effects (2)

A
  1. Reduces BA
  2. Protects from degradation
42
Q

Why isn’t half life affected by protein binding?

A

dissociation rates from protein are fast,

and the renal excretion rates are the rate-limiting factor

43
Q

Highest and lowest penicillins protein bound

A

cloxacillin = >90% protein bound

Ampicillin = 25-30% protein bound

44
Q

Penicillin excretion routes

A

renal

biliary

45
Q

Glomerular vs tubular filtration of penicillins

A

10% glomerular

90% Tubular

46
Q

Effect of kidney disease on half life of penicillin

A

prolonged half life

47
Q

Two mechanisms for tubular excretion

A

anionic

cationinc

48
Q

Penicillins are anionic or cationic?

A

anionic.

Competition with probenecid (anion) for secretion when coadministered with penicillin

49
Q

Pen G

  1. a.k.a
  2. Spectrum
  3. Beta-lactamase sensitivity?
  4. Toxicity
A
  1. Benzylpenicillin
  2. Gram+ and N.gonorrhoeae and H. influenzae
  3. Yes, sensitive
  4. Acute allergy
50
Q

Methicillin has no beta lactamase sensitivity because

A

steric hindrance of nucleophilic attack by the enzyme on the beta lactam carbonyl.

methoxy groups are attached ortho to the amide–hinder nucleophilic attack on the lactam.

51
Q

Why must methicillin be injected?

A

Electron donation to the amide carbonyl oxygen by the methoxy groups = amide carbonyl oxygen more nucleophilic

= unstable in acidic conditions

52
Q

Methicillin is mainly used for

A

B-lactamase producing S. Aureus

53
Q

Methicillin is an effective…

A

inducer of beta lactamase

54
Q

What causes MRSA to be methicillin resistant

A

mutation in mecA in the penicillin binding protein gene (the protein is PBP2’)

55
Q

Cephapirin is a ___ AB

Structural difference?

A

cephalosporin

has a 6-membered sulfur containing ring instead of a 5 membered ring.

Some have an acetate in the 3 position = inactivated by hydrolysis by esterases (produces hydroxymethyl acid)

56
Q

Ceph’s MOA vs Pen MOA

A

same

57
Q

Carbapenems are ______

A

carbon analogs of penicillins

58
Q

Carbapenems have a ____ group instead of ____ that is present in penicillin’s thiazolidine ring

A

methylene

sulfur

59
Q

What does ring strain have to do with sulfur and carbapenems?

A

The methylene in Carbapenems instead of the sulfur causes increased ring strain because the methylene is smaller

60
Q

2 things imipenem reacts with

A

PBP’s

beta lactamases (inhibits them)

61
Q

imipenem is hydrolyzed by _____

But this can be overcome by ___________

A

dehydropeptidase-1

coadministration of cilastatin (dehydropeptidase-1 inhibitor)

62
Q

Imipenem and cilastatin is special because… (2)

A

it has broader spec than any other AB available

active against both gram + and -

63
Q

imipenem and cilastatin are used to treat

A

Infections of:

GI, GU, Bone, Skin, and Endocardium

64
Q

ROA for imipenem-cilastatin

A

parenterally

65
Q

Aztreonam disodium is a ____ drug that is inspired by _____

A

totally synthetic

monobactams

66
Q

In Aztreonam, a _______ group takes the place of the c2 carboxyl group (as in pen/ceph)

A

sulfamic acid

67
Q

Spectrum of Aztreonam

A

Almost all gram-

68
Q

What (Aztreonam) property activates the beta lactam ring to hydrolysis and to reaction with PBP’s?

A

The electronegativity of the sulfamic acid

69
Q

Aztreonam is used to treat…

A

severe Gram- infections, especially those by penicillin-resistant organisms acquired in hospitals

70
Q

Example of cross reactivity between pen and cephs

A

Ceftazidime

(has identical sidechain)

Pharm Exam 2 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions