Antibacterial drugs

Question 1

what color are G+

Answer 1

dark purple

Question 2

what color are G-

Answer 2

light pink

Question 3

difference between G+ and G- bacteria

Answer 3

G+ have one bacterial cell membrane

G- have cell membrane-> inner and outer

Question 4

can drugs penetrate G+ bacteria?

Answer 4

yes

Question 5

can drugs penetrate G- bacteria?

Answer 5

Not readily

-must go through channels called porins

Question 6

is the peptigoglycan layer thick or thin in G+

Answer 6

thick

-G- is thin

Question 7

where are the beta-lactamases in G-?

Answer 7

in the periplasmic layer

-in G+, free

Question 8

what is the difference between peptidogylcan structure in G+ and G-

Answer 8

G - have meso-diaminopimetic acid

G+ that group is a lysiene

Question 9

in G- cells, what happens to peptidogylcan?

Answer 9

cross-linking by a bridge between the DAP residue of one strand and the terminal D-Ala of another

Question 10

what is the cross-linking done by?

Answer 10

transpeptidase

• attacks carbonyl-> forms tetrahedral intermediate (unstable)
• peptidogylcan is linked via an ester bond-> then attacked by amine-> another tetrahedral intermediate-> linked peptidogylcan

Question 11

beta-lactam MOA

Answer 11

acylate the transpeptidase ser residue in the enzyme active site to form a stable product-> inactivates enzyme, inhibiting peptidoglycan cross-linking-> results in a defective bacterial cell wall-> osmotic cell stress-> cell lysis and cell death.

Question 12

why is beta-lactam so reactive?

Answer 12

1. ) ring strain, carbonyl angle is 90 degrees
2. ) folded ring structure N lone pair does not overlap with C=O, more reactive carbonyl because more like ketone than an amide carbonyl

Question 13

resistance mechanism

Answer 13

mutation of penicillin binding protein
antibiotics are pumped out of cell
production of beta-lactamases
decreased cellular uptake of drug

Question 14

what is an important characteristic of beta-lactamases activity?

Answer 14

hydrolysis of acylated beta-lactamase intermediate is very fast
-enzyme can hydrolyze many drug molecules quickly

Question 15

where does the beta-lactam act for those who are allergic?

Answer 15

drug acts as a hapten

-acylates host cell proteins, which then raise antibiotics and results in an allergic reaction

Question 16

test for penicillin allergy

Answer 16

topical flare and wheal test

Question 17

how is penicillin degraded?

Answer 17

in acidic conditions and basic conditions

Question 18

how do you determine if penicillin will be degraded in acidic or basic conditions

Answer 18

electronegativity of R group on penicillin
-Pen G->has carbon-> carbonyl is more reaction
Pen V: has an O-> pulls electron density away from the carbonyl-> less reactive in stomach

Question 19

what should penicillin solutions be kept away from

Answer 19

heavy metal ions (catalyze penicillin degradation)

Question 20

serum protein binding: Penicillin

Answer 20

more lipophilic side chains-> more highly protein bound

Question 21

what does protein binding do to penicillin bioavailablity?

Answer 21

decreases it

-reduces effective concentration of free drug

Question 22

what is co-administered with penicillin to prolong half life?

Answer 22

probenecid

-competes for tubular secretion with penicillin-> increases its half-life, both are anionic

Question 23

is Benzylpenicillin (Pen G) beta-lactamase sensitive?

Answer 23

yes
Drug of choice for treating infections
-neisseria, hem. Influenza
- acute allergic reactions

Question 24

is Methicillin beta-lactamase sensitive?

Answer 24

No

-b/c of steric hinderance of nucleophilic attack by the enzyme on the beta-lactam carbonyl

Question 25

why doesn't methicillin administered orally?

Answer 25

unstable in acid stomach-> must be injected -instability due to electron donation toward the amide carbonyl oxygen by the methoxy groups-> makes amide carbonyl oxygen more reactive

Question 26

Cephapirin

Answer 26

cephalosporin antibiotic - six membered sulfur containing ring fused with beta-lactam - same MOA of penicillin - beta-lactamase sensitive

Question 27

how are Cephalosporins made inactive?

Answer 27

if have an acetate in 3-position are metabolically inactivated by hydrolysis of acetate by host esterase-> hydroxymethyl acid that lactonizes

Question 28

imipenem

Answer 28

carbapenems, carbon analogs of penicillin - inhitbit beta-lactamase - used for G+ and G-

Question 29

why is ring strain greater in carbapenems like impenem

Answer 29

sulfur is present in thiazolidine ring is a methylene group-> increases reactivity b/c methylene is smaller than sulfur

Question 30

what is imipenem co-administered with?

Answer 30

cilastatin sodium | -imipenem is hydrolyzed by renal dehydropeptiase-1 and this blocks that

Question 31

how is imipenem and cilastatin sodium administered?

Answer 31

parenterally | -infections of gut, GU tract, bone, skin and endocardium

Question 32

Aztreonam

Answer 32

synthetic | -inspired by monocyclic beta-lactam natural products called monobactams

Question 33

what is aztreonam used for?

Answer 33

G- bacteria, especially those by penicillin resistant organisms acquired in hospitals

Question 34

cross allergenicity has been seen with penicillins and cephalosporins with what antibiotic?

Answer 34

ceftazidime

Question 35

what is the main difference between aztreonam and penicillins/cephalosporins?

Answer 35

has a sulfamic acid group instead of carboxyl group

Question 36

Penicillin V

Answer 36

more stable to hydrolysis in stomach than Pen G because electronegativity of the ether oxygen decreases the nucleophilicity of the amide carbonyl

Question 37

What does protein binding do for penicillin

Answer 37

Protects from degradation

Question 38

Why aren't the half life's of penicillin affected by protein binding?

Answer 38

1. Dissociate from protein fast | 2. Renal excretion rates are rate limiting

Question 39

More lipophilic side chains mew what for penicillin

Answer 39

More highly protein bound

Question 40

Who should avoid taking Pen G

Answer 40

Histories of significant allergies or asthma

Question 41

Methicillin can treat

Answer 41

Staph aureus | Not MRSA tho

Question 42

What causes aztreonam to be more reactive with penicillin binding proteins?

Answer 42

Electro negativity of sulfamic acid activates the beta-lactam ring toward hydrolysis and to reaction with penicillin binding proteins