EXAM L8

Question 1

How can hydrolysis of esters and lactones be prevented?

Answer 1

Protect from moisture
Protect from heat
Control pH in solution formulations

Question 2

Lactam properties

Answer 2

Cyclic amides
The size of the ring is indicated by a greek letter prefix
Ex. B-Lactam - 2 carbon atoms outside the carbonyl
y-lactam - 3 carbons
δ-lactam- 4 carbons
ɛ - lactam-5 carbons

Question 3

Lactam mechanism

Answer 3

Hydrolyze by mechanisms like those for amides
The product is a ring-opened compound with carboxylic acid and amine groups

Question 4

Penicillin hydrolysis

Answer 4

*Look at mechanism (55)
Penicillins are B lactam antibiotics
Several different “penicillins” with diff. R-grpups
Penicillin contains an amide as well as a lactam; hydrolysis of the lactam is usually faster than that of the amide

Question 5

*Auto-Oxidation of Captopril

Answer 5

Mechanism review, slides 63-64

Question 6

Captopril auto-oxidation

Answer 6

Captopril was the first angiotensin converting enzyme (ACE) inhibitor developed
Is used to treat hypertension and congestive heart failure (CHF)
Oxidation catalyzed by metal ions
Also undergoes amide hydrolysis, but this is QUITE slow

Question 7

Hydroquinone is used in

Answer 7

Sunscreens
topical medications for skin whitening

Question 8

T/F: Hydroquinone is a suspected carcinogen

Answer 8

True
(banned in the EU, FDA approved in USA)

Question 9

Concern with hydroquinone

Answer 9

Toxicity concerns often involve superoxide, and hydroxyl radical (HO) generated from it

Question 10

Photolysis Characteristics

Answer 10

Is drug degradation caused by exposure to light
Light often (not always) causes oxidative degradation
Light can serve as an initiator in chain oxidation

Question 11

*Review photolysis of hydroquinone

Answer 11

Mechanism 72

Question 12

Photolysis of hydroquinone

Answer 12

First steps in HQ photolysis are identical to metal catalyzed oxidation
Additional oxidation products are shown
Tetrahydroxy biphenyl is an oxidation product linking two HQ molecs
Polymeric products can be formed

Question 13

How can oxidation and photolysis be prevented?

Answer 13

Protect from oxygen (nitrogen fill)
Protect from heat
Protect from light (colored glass bottles)
Include anti-oxidants (e.g. ascorbic acid BUT these can sometime act as pro-oxidants)
Include metal chelators (e.g. EDTA)

Question 14

T/F: Oxidation is a common and complicated route of drug degradation

Answer 14

True

Question 15

Photolysis is drug degradation caused by

Answer 15

Exposure to light

Question 16

Oxidation can be minimized by

Answer 16

Protecting from air, light and metals
Excipients added to the formulation