Med Chem - Acne

Question 1

why is acne more common at puberty?

Answer 1

there is an increase in androgens, which causes oil/sebum production

this can clog pores and form a comedone – causes acne

Question 2

name 2 things that androgens do that causes acne

Answer 2

increased sebum production
skin thickening

both can clog pores and cause acne

Question 3

briefly explain the pathology of acne

Answer 3

dead cells and sebum accumulate in the hair follicle, causing a clog

this is a great place for the commensal bacteria - cutibacterium acnes to feed on the sebum and proliferate

the acne in the skin invokes an inflammatory response as well

the result is filled with pus and reddened

Question 4

excessive ____ + ____ + ____ = acne

Answer 4

cell build up
oil
bacteria

Question 5

is cutibacterium acnes gram positive or negative?

Answer 5

positive

Question 6

name 3 treatment goals for acne

Answer 6

-decrease inflammation

-decrease sebum production and c. acnes proliferation

-correct the abnormalities of follicular maturation

Question 7

name 5 classes of drugs used for acne treatment

Answer 7

systemic antibiotics
retinoids
azelaic acid
benzoyl peroxide
salicylic acid

Question 8

name 4 retinoids used in acne

Answer 8

tretinoin
adapalene
isotretinoin
trifarotene

Question 9

name 4 systemic antibiotics used in acne

Answer 9

tetracycline
doxycycline
minocycline
sarecycline

Question 10

name the 3 dosage forms in which salicylic acid is available

Answer 10

cream
lotion
gel

Question 11

explain how salicylic acid works to treat acne

Answer 11

it’s a keratolytic agent with anti-inflammatory action

reduces acne by exfoliating the skin and keeping pores clear

Question 12

what kind of acne severity is salicylic acid indicated for

Answer 12

mild acne

Question 13

true or false

salicylic acid does not have anti inflammatory action

Answer 13

FALSE - it does

Question 14

benzoyl peroxide is applied topically in concentrations up to…..

Answer 14

10%

Question 15

how does benzoyl peroxide have antimicrobial actions?

Answer 15

has an oxidizing effect due to the production of benzoate free radicals

Question 16

what is azelaic acid indicated for?

Answer 16

mild-moderate inflammatory acne vulgaris

Question 17

true or false

azelaic acid is naturally occurring

Answer 17

TRUE

naturally occurring acid found in whole grain cereals and animal products

Question 18

how does azelaic acid work in acne

Answer 18

inhibits the growth of cutibacterum acnes

Question 19

chemical name azelaic acid

Answer 19

nonanedioic acid

“non” - 9 carbons
“di” - 2 COOH groups

Question 20

what are the 2 types of retinoid receptors

what are the subtypes?

Answer 20

RARs - retinoic acid receptors

RXRs - Retinoid X receptors

all have a,B,Y subtypes

Question 21

what kind of receptors are RARs and RXRs

Answer 21

nuclear receptors

Question 22

RARs and RXRs are activated by what?

Answer 22

natural (endogenous) or synthetic retinoid agonists

Question 23

true or false

RARs and RXRs are GPCRs involved with the modulation of gene transcription

Answer 23

FALSE

they are nuclear receptors involved with the modulation of gene transcription

Question 24

what is the dominant RAR subtype present in the skin?

Answer 24

GAMMA (Y)

Question 25

explain how RARs and RXRs function

Answer 25

RARs dimerize with RXRs to form HETERODIMER. this heterodimer goes to the nucleus where it recognizes RARE DNA sequence in the promoter region of target genes involved with regulation of cell growth, differentiation, and apoptosis HOWEVER, while RARs MUST form a HETERODIMER with RXR, RXR can function as a homodimer as well as a heterodimer

Question 26

true or false in order to be functional, RARs must form a HETERODIMER with RXR

Answer 26

true

Question 27

what does the "RARE" DNA sequence stand for

Answer 27

retinoic acid response element

Question 28

as mentioned, RARY is the most predominant subtype of retinoic acid receptors in the skin what is the significance of this?

Answer 28

want to have highly selective RARY agonists. this will lead to less side effects. also, RARY subtype is not present in the placenta. therefore, a highly selective RARY agonist will not be teratogenic like every other retinoid!!

Question 29

tretinoin is a _____ form of _____

Answer 29

oxidized (active) form of vitamin A (retinol)

Question 30

how is tretinoin an oxidized form of vitamin A?

Answer 30

it has exact same structure only difference is that the -CH2OH in vitamin A (retinol) has been oxidized to COOH in tretinoin

Question 31

what is retinol

Answer 31

vitamin A

Question 32

explain the receptor selectivity of tretinoin

Answer 32

NONSELECTIVE RAR agonist

Question 33

how does tretinoin work in acne

Answer 33

unplugs the hair follicles and keeps the pores clear also, increases speed that surface skin cells are replaced

Question 34

explain in detail the conversion of vitamin A to ATRA, as well as the inactivation of ATRA include all enzymes and whether the steps are reversible or irreversible

Answer 34

retinol <-> retinal by retinol dehydrogenase retinal -> ATRA (COOH) by retinal dehydrogenase ATRA inactivated by CYP2D6 into an inactive 4-oxometabolite

Question 35

as mentioned, CYP2D6 mediates the inactivation of ATRACOOH into an INACTIVE 4-oxometabolite what potential drugs may be used to block the action of CYP2D6, and thus prolong the action of retinoids by preventing their inactivation?

Answer 35

RAMBAS (retinoic acid metabolism blocking agents)

Question 36

where are RAR and RXR receptors located? what does this mean regarding the drug?

Answer 36

in the NUCELUS, bound to RARE regions on DNA this means the retinoic acid (drug) has to diffuse into the nucleus and bind to RAR to form the heterodimer and modulate gene transcription

Question 37

what effect does retinoic acid binding to RARs have

Answer 37

cell differentiation and proliferation apoptosis immune modulation beneficial acne effects

Question 38

chemical name for isotretinoin

Answer 38

13-cis-retinoic acid

Question 39

true or false isotretinoin is a selective RARY agonist

Answer 39

FALSE - non selective bc of rotation it is a result of ATRA isomerization

Question 40

retinoids are also called_______

Answer 40

diterpenes

Question 41

why are retinoids also called diterpenes?

Answer 41

bc they have 20 carbons

Question 42

true or false isotretinoin is a 13-cis isomer of ATRA

Answer 42

true

Question 43

what is isotretinoin indicated for

Answer 43

severe and recalcitrant (stubborn) cases of inflammatory acne

Question 44

how is isotretinoin useful in acne

Answer 44

inhibits sebaceous gland function and inhibits follicular keratinization

Question 45

true or false adapalene is a natural retinoid compound

Answer 45

FALSE it's a synthetic retinoid-like compound

Question 46

does adapalene have any selectivity? why or why not

Answer 46

YES - has selectivity for RARB and RARY subtypes found in the epidermis this is because the double bonds are locked into the aromatic ring - RIGID. cannot cis-trans isomerize. thus, able to have some selectivity

Question 47

what is a similarity between adapelene and ATRA

Answer 47

the distance between the C with the bulky group and COOH is ~TEN CARBONS APART

Question 48

How does adapalene work to reduce the formation of pimples

Answer 48

it affects the growth of skin cells, thus reducing formation of pimples bc clogs not as likely

Question 49

name of the bulky group on adapalene

Answer 49

adamantyl

Question 50

what is the retinoid that has RARY selectivity

Answer 50

trifarotene

Question 51

what group on trifarotene allows it to have RARY selectivity?

Answer 51

hydroxyethoxy group

Question 52

explain some benefits of trifatorene over other retinoids

Answer 52

1. RARY selective: safer than others for teratogenity bc RARY is not expressed in placenta. also less side effects bc RARY selective and its predominantly in the skin 2. has poor systemic absorption than other retinoids because of polar hydroxyethoxy group - less systemic side effects!!

Question 53

what is trifatorene indicated for

Answer 53

ages 9 and older for facial and truncal acne

Question 54

trifarotene belongs to ______ class of compounds explain

Answer 54

meta-terphenyl meaning 3 phenyl rings all meta to each other