Acne Pharmacology

Question 1

Benzoyl Peroxide Products

Answer 1

Acne: Clearasil, Fostex, Oxy-10

Question 2

Benzoyl Peroxide MOA

Answer 2

Keratolytic

Converted to benzoic acid which is a potent oxidizing agent in the skin

Question 3

Benzoyl Peroxide Pharmacological effect

Answer 3

Loosens keratinocytes(reduces plugs)

Increases turnover rate of keratinocytes (fall off the skin faster)

Prevents closure of follicles

Antibacterial activity against P. acnes

Question 4

Benzoyl Peroxide Side Effects

Answer 4

Drying and peeling of the skin

Burning, blistering, scaling, and edema

Bleaching

No known systemic side effects – metabolized before it gets through the skin and becomes inactive

Question 5

Sulfur Products

Answer 5

Acne: Fostril, Liquimat, combination products

(can also be used for scabies0

Question 6

Sulfur MOA

Answer 6

Keratolytic

Forms hydrogen sulfide when applied to skin

Question 7

Sulfur Pharmacological Effect

Answer 7

Causes inflammation which promotes peeling and unblocking of plugs

*Has antibacterial properties due to inactivation of bacterial enzymes

Question 8

Sulfur Side Effects

Answer 8

Redness, skin irritation, peeling, odor (forms hydrogen sulfide) and comedogenic (may cause/worsen acne due to inflammatory action)

Question 9

Salicylic Acid MOA

Answer 9

Keratolytic
Lowers skin pH increasing hydration of keratin which facilitates the loosening and removal of the keratinized skin cells (keratinocytes that are stuck together loosen and fall off)

Question 10

Salicylic Acid Pharmacological Effect

Answer 10

Promote the shedding of the stratum corneum

The effects range from peeling to desquamation (removal of layers of skin)

Question 11

Salicylic Acid Concentrations

Answer 11

3 to 6% - skin conditions like dandruff, acne and psoriasis

6% - may cause skin damage

Up to 40% wart and corn removal(Compound W, Duofilm, Freezone)

For wart removal – must protect the skin around it (use vasoline around the area that you are trying to remove)

Question 12

Salicylic Acid Side Effects

Answer 12

Irritation and inflammation of normal skin

Bleaching

Salicylism (overdose – tinnitis or ringing in the ears, change in pH: acid/base imbalance, rapid breathing, psychological disorders: altered mental function)

Question 13

Keratolytics

Answer 13

Benzoyl Peroxide
Sulfur
Salicylic Acid

Question 14

Acne Antibiotics MOA

Answer 14

EXCEPT metronidazole

Reduces P. acnes by inhibiting protein synthesis in the bacterial cell

Question 15

Acne Antibiotics

Answer 15

Tetracycline
Minocycline
Doxycycline
Clindamycin
Erythromycin
Metronidazole
Azelaic Acid

Question 16

Acne Antibiotic Pharmacological Effect

Answer 16

Decreases the percentage of free fatty acids (by inhibition of lipases)

Question 17

Tetracycline unique MOA

Answer 17

Decreases keratin in the sebaceous pores (keratinocytes are less sticky and plugs are not formed)

Question 18

Tetracycline products

Answer 18

Achromycin
Sumycin
Topicycline

Was used for many different types of infections, now used almost exclusively for the skin

Question 19

Tetracycline Side Effects

Answer 19

NOT UNDER 16
-GI - N/V/D
-Pseudomembraneous colitis
-Bones and teeth are discolored and growth is impaired in the young
-Photosensitivity in fair skinned people (sunburn easier – use higher SPF or stay out of the sun)
-Increased incidence of superinfections (kill the fungus/yeast normally present, bad stuff grows, pseudomembranous colitis, thrush)
Little use of topical tetracycline (it phosfloreses – face will be bright yellow under blue-light conditions)

Question 20

Tetracycline special warnings

Answer 20

NOT under 16

Should not be given with metal-containing products (contain Ca, Mg, Fe) – milk, MV, antacids – ions bind to the tetracycline and inactivate them

Tetracycline likes the + ions so it binds to teeth

Will look like bone cancer on an X-ray

Question 21

Minocycline products

Answer 21

Minocin

Question 22

Doxycycline products

Answer 22

Vibramycin

Question 23

Minocycline and Doxycycline

Answer 23

May be more efficacious than tetracycline

-More lipid soluble

Question 24

Minocycline and Doxycycline Side Effects

Answer 24

Ototoxicity and darkening of skin and teeth

May cause hearing difficulty (ototoxicity)

Question 25

Clindamycin Products

Answer 25

Cleocin Cleocin T C/T/S

Question 26

Clindamycin Side Effects

Answer 26

Oral: (Mostly likely to cause) Pseudomembranous colitis – the worst diarrhea (bloody, pussy, smelly) – caused by Clostridium difficile; c dif can be lethal N/V/D Impaired liver function Neutropenia (fewer neutrophils produced) - rare Topical: (used topical more than oral) Dryness or peeling of the skin Contact dermatitis

Question 27

% of topical clindamycin dose absorbed systemically

Answer 27

10%

Question 28

Erythromycin products

Answer 28

``` E-mycin Ery-tab A/T/S Erycette T-Stat Ery-Sol Benzamycin ```

Question 29

Erythromycin Side Effects

Answer 29

Oral side effects: N/V/D epigastric pain **Orally has many drug interactions – inhibitor of CYP3A4 (main drug metabolizing enzyme) Topical side effects: Burning and drying especially when combined with benzoyl peroxide (used topically because it is hard on stomach)

Question 30

Metronidazole Products

Answer 30

Flagyl | Metrogel

Question 31

Metronidazole MOA

Answer 31

Antibiotic (rosacea) reduced by low-redox potential electron transport proteins The reduction product disrupts DNA by inhibition of nucleic acid used for rosacea

Question 32

Metronidazole Side Effects

Answer 32

- N/V/D - Peripheral neuropathy with prolonged use - Disulfuram reaction - headache, copious vomiting, hypotension and possible death - Local effects include burning, stinging and drying - Found to be carcinogenic in animals.

Question 33

Metronidazole Pharmacological Effects

Answer 33

- Inhibits growth of Demodex brevis - Suppression of skin bacteria does not appear to play a major role in the mechanism of action of the drug in treatment of inflammatory lesions of rosacea - Inactive in vitro against Propionibacterium acnes - Bactericidal, amebicidal, and trichomonacidal - Has direct anti-inflammatory effects and effects on neutrophil motility, lymphocyte transformation, and some aspects of cell-mediated immunity

Question 34

Azelaic Acid Products

Answer 34

Azelex

Question 35

Azelaic Acid MOA

Answer 35

Antibiotic: inhibits bacterial protein synthesis And keratolytic

Question 36

Azelaic Acid Pharmacological Effect

Answer 36

--Antimicrobial action | Reduction in the thickness of the stratum corneum (less chance of producing a plug, also good for wrinkles)

Question 37

Azelaic Acid Side Effects

Answer 37

Pruritis, burning, stinging and tingling Erythema, dryness and rash Many side effects go away with continued use

Question 38

Retinoids

Answer 38

Vitamin A derivatives Retinoids combines Retinol, Retinal, Retinic Acid The “GOLD STANDARD” Necessary for cell growth, differentiation and homeostasis of epithelial cells, the reproduction system and vision Deficiency results in hyperplastic and keratotic skin (toad skin) High and low doses give the same effect on skin, eyes and birth defects

Question 39

Retinoids include

Answer 39

Tretinoin Isotretinoin Adapalene

Question 40

Tretinoin products

Answer 40

Retin-A, Renova, Avita, Retin-A Micro

Question 41

Tretinoin MOA

Answer 41

Direct mechanism: Homo- or heterodimer retinoid-receptor complexes bind to RARE and alter protein transcription (affects the growth of the skin cells) Indirect mechanism: One receptor complex binds a transcription factors preventing it from binding to TRE on the DNA (reduced inflammation)

Question 42

Tertinoin Pharmacological Effects

Answer 42

Effects on keratinocytes: - Decreases proliferation (decrease in the number of cells) - Promotes differentiation (goes through the life cylce faster = maturation) - Increases the turnover (the skin cells fall off) - Reduces the cohesiveness (reduced stickiness = reduced plugs) - The change in protein transcription has anti-inflammatory and anti-proliferative activity - Reduces the thickness of the stratum corneum (reduce the amount of wrinkles)

Question 43

Tretinoin Side Effects

Answer 43

-Blistering, peeling, crusting, burning and edema of the skin – highly likely Will go away with use - Can increase photosensitivity – use sunblock - There are no known systemic side effects, but they are teratogenic Note: Acne will get worse before it gets better (and it will get better…good drug) stick with it Do not give to patients with eczema Do not give in pregnancy-teratogenic

Question 44

Adapalene products

Answer 44

Differin

Question 45

Adapalene MOA

Answer 45

Same as other retinoids except: Specifically, binds to RAR beta and gamma (most prominent) receptors only Binds to 2 of the subtypes instead of 3 Gamma is predominant in skin (but no gamma only drug exists yet)

Question 46

Adapalene Pharmacological Effects

Answer 46

Same as Tretinoin: Effects on keratinocytes: - Decreases proliferation (decrease in the number of cells) - Promotes differentiation (goes through the life cylce faster = maturation) - Increases the turnover (the skin cells fall off) - Reduces the cohesiveness (reduced stickiness = reduced plugs) - The change in protein transcription has anti-inflammatory and anti-proliferative activity - Reduces the thickness of the stratum corneum (reduce the amount of wrinkles)

Question 47

Adapalene Side Effects

Answer 47

erythema, scaling, dryness, pruritis and burning

Question 48

Isotretinoin Products

Answer 48

Accutane

Question 49

Isotretinoin MOA

Answer 49

Same as others

Question 50

Isotretinoin Pharmacological Effects

Answer 50

Decreases sebaceous gland size – less sebum produced Decreases sebum production – less blockage, less food for P. acnes Reduces inflammation – inhibits the release of prostaglandins from macrophages Reduces keratinization – less sticky = less likely to form plug Superb acne drug – one course can lead to long term or permanent remission of acne

Question 51

Isoretinoin Side Effects

Answer 51

Dermatological: Common - Inflammation of the lips (90%), epitaxis – bloody nose (80%), itching of the skin and nose (80%), xerosis (dry mouth), conjunctivitis xerophthalmia (dry eyes – may be unable to wear contact lenses) Less common (3 – 8 weeks after therapy) - Skin rash, peeling of skin from palms and soles, photosensitization and alopecia (hair loss) Really hard to take Will look worse before it looks better

Question 52

Isotretinoin Other Side Effects

Answer 52

Arthralgia (15%) Pain or stiffness of muscles, bones & joints as a result of calcification and hyperostoses (bones grow) Closure of epiphyses plate causing premature stoppage in growth (Not as much of an effect in people) Persistent headache ***Pseudotumor cerebri*** (benign increase in intracranial pressure) – check eyes Drug should be discontinued and patient should be checked for papilledema with retinal hemorrhages - permanent CNS Lethargy and fatigue Depression, psychosis and suicidal ideation with attempts(especially in teenagers – major reason why people want it removed from the market) Ophthalmic effects Conjunctivitis Burred or tunnel vision, diplopia (double vision) Reduction of night vision with sudden onset (rare) Optic neuritis, cataracts, papilledema (rare) Blood lipids Increased triglycerides and plasma cholesterol levels occurring in 25% of patients – worry about this in older patients  can cause pancreatitis Reduces HDL levels Use cautiously in obese, diabetic or alcoholic patients (already have high triglycerides; at risk for developing pancreatitis)

Question 53

Retinoids in pregnancy

Answer 53

Contraindicated: Teratogenic Mechanism of action: Retinoids are called morphogens which are signaling molecules that control the spatial pattern of differentiation *Birth defects included hydrocephalus, microcephaly, facial malformation, cleft palate, abnormal formation of outer ear, facial dysmorphia, microphthalmia and cardiovascular defects (FYI) iPledge system: must have neg. pregnancy test every month before getting drug Cannot donate blood while on this medication (1 month from stopping drug) – due to potential that the blood could be given to a female who is pregnant Birth defects are most common in 1st trimester Women start med on 2nd day of menstrual cycle to ensure they are not pregnant

Question 54

Retinoid potential market removal

Answer 54

Birth defects Teen suicide 50% greater risk of Crohn’s Disease