DEENT EPAW

What is the mechanism of action of Crisaborole?

PDE4 inhibitor → increases cAMP levels → reduces inflammation

What is the chemical class of Crisaborole?

Benzoxaborole and soft drug (predictable metabolism to inactive metabolite)

What metals does boron coordinate with in PDE4 active site when using Crisaborole?

Zinc (Zn) and Magnesium (Mg)

What are key ADMET features of Crisaborole?

Lipophilic (Log P = 3)

What are the major target goals in eczema treatment?

Suppress immune response and suppress inflammation

What is the mechanism of action of Ruxolitinib and Upadacitinib?

Janus Kinase (JAK) inhibitors → anti-inflammatory

What are the ADMET characteristics of Ruxolitinib?

t½ = 3h

What are the ADMET characteristics of Upadacitinib?

t½ = 8–16h

What are the three major components of Psoriasis?

Hyperproliferation, inflammation, autoimmune

What are the three primary treatment goals for Psoriasis?

Normalize proliferation

What wavelength range defines UVA?

320–400 nm

Which UV range causes sunburn and skin cancer?

UVB = 280–320 nm

What are the main functions of emollients?

Prevent loss of water from skin

What are examples of petroleum-based emollients?

Vaseline (mineral oil + waxes + water)

What are examples of lanolin-based emollients?

Wool wax composed of fatty acid esters

What are examples of silicone-based emollients?

Dimethicone and Cyclomethicone (hypoallergenic and noncomedogenic)

What is the suspected MOA of tars?

Unknown

What are the main types of tars used in dermatology?

Coal tar

What type of UV light is coal tar used with?

UVB (280–320 nm)

Is coal tar photosensitizing?

Yes

Is shale tar photosensitizing?

No

What are the components of Lassar’s paste?

Anthralin + ZnO + paraffin + salicylic acid

What is the mechanism of action of Anthralin?

Antiproliferative via formation of cytotoxic radicals (anthranyl + superoxide anion) → disrupts DNA synthesis

What are Psoralens used for?

PUVA therapy (Psoralens + UVA) to inhibit DNA synthesis

What is the mechanism of action of Psoralens?

Furanocoumarins that intercalate and covalently bind to DNA pyrimidines → inhibit DNA synthesis

What CYP enzyme do psoralens inhibit?

CYP3A4

What structural features enhance glucocorticoid anti-inflammatory activity?

Double bond between C1–C2, Alpha 6-F, and 11B-OH

What determines glucocorticoid potency?

Structure, delivery vehicle, and concentration

Which glucocorticoid is super-potent?

Clobetasol propionate 0.05%

Which glucocorticoid is potent?

Betamethasone dipropionate 0.05%

Which glucocorticoid is of medium potency?

Betamethasone valerate 0.1%

Which glucocorticoids are low potency?

Hydrocortisone acetate 0.5% and 1%

What is the oral bioavailability of hydrocortisone?

95%

What is the topical bioavailability of hydrocortisone on normal skin?

Less than 15%

What is the mechanism of inactivation of hydrocortisone?

Hydrocortisone → Cortisone via 11β-HSD

What enzyme converts hydrocortisone to urocortisol?

5β-reductase then 3α-HSD

What are the main Vitamin D analogs used for bone health?

Calcitriol and Calcipotriene

What are the effects of Vitamin D analogs?

Promote bone health and have antiproliferative effects but can cause hypercalcemia

What is the mechanism of action of macrolide/lactone immunosuppressants?

Decrease inflammatory cytokines

Which macrolide immunosuppressant stays mostly on the skin?

Pimecrolimus

Which macrolide immunosuppressant penetrates systemically?

Tacrolimus

What is the mechanism of action of retinoids in psoriasis?

Normalize keratinization and proliferation via RAR/RXR agonism

What are examples of oral retinoids?

Acitretin and Isotretinoin

What is the mechanism of Methotrexate?

Competitively inhibits dihydrofolate reductase → ↓ DNA/RNA synthesis → antiproliferative and immunosuppressive

What are key structural features of Methotrexate?

Pteridine ring

What happens to Methotrexate activity if the pteridine ring loses aromaticity?

Decreases activity

What effect does N-CH₃ substitution have on Methotrexate activity?

Essential for activity

What type of compound is Cyclosporin?

Cyclic 11-amino acid peptide “prodrug” immunosuppressant

What enzyme metabolizes Cyclosporin?

CYP3A4

What is the mechanism of Apremilast?

PDE4 inhibitor → ↑cAMP → ↓inflammation

What is the mechanism of Tofacitinib?

JAK inhibitor used adjunctively with Methotrexate

What are general ADME properties of monoclonal antibodies?

Poor oral bioavailability

What are the four major pathogenic components of acne?

Increased sebum production

What are the main treatment goals in acne?

Decrease sebum

What are examples of keratolytic agents?

Glycolic acid, salicylic acid, sulfur, benzoyl peroxide

What is the mechanism of benzoyl peroxide?

Decomposes to benzoic acid and benzoyl radicals → keratolytic + anti-inflammatory

What is the mechanism of sulfur in acne treatment?

Breaks disulfide bonds in keratin (thiolysis)

What are the characteristics of glycolic acid?

Alpha-hydroxy acid

What are the characteristics of salicylic acid?

More lipophilic than glycolic acid → penetrates deeper

What are first-generation retinoids?

Non-aromatic geometric isomers like tretinoin (all-trans) and isotretinoin (13-cis)

What are second-generation retinoids?

Mono-aromatic retinoids such as acitretin (active form of etretinate)

What are third-generation retinoids?

Poly-aromatic synthetic retinoids like adapalene

Which retinoid is an alkyne/acetylenic prodrug?

Tazarotene

What are general ADMET properties of topical retinoids?

Lipophilic

What hormones are used in acne therapy for females?

Ethinyl estradiol + norgestimate or drospirenone

What is the mechanism of spironolactone in acne?

Steroidal antiandrogen → decreases testosterone biosynthesis

What is the mechanism of flutamide?

blocks testosterone receptor binding

What is the mechanism of ketoconazole in acne?

Non-steroidal antiandrogen → inhibits testosterone biosynthesis via CYP3A4 inhibition

What is the structure of azelaic acid?

A C9 bi-carboxylic acid

What is the class of clindamycin?

Lincomycin antibiotic used topically

Why is oral erythromycin not preferred for acne?

Unstable at pH < 4 and causes GI toxicity

What are key absorption issues with tetracyclines?

Chelation with Ca²⁺

Which tetracyclines are unaffected by food?

Doxycycline and Minocycline

What are half-lives of doxycycline and minocycline?

Doxycycline = 11–13h

Minocycline = 14–22h

What are major causes of wrinkles?

UVR

What are inorganic sunblocks?

Zinc oxide and titanium dioxide → reflect/scatter light

What are organic sunscreens?

Chromophores that absorb UVA/B and convert to harmless heat

What compound class absorbs UVA?

Dibenzoylmethanes (Avobenzone)

What class absorbs UVB?

Cinnamates, PABAs, salicylates, benimidazoles

What is a limitation of avobenzone?

Photodegrades under UVA exposure

Which sunscreen class may cause sensitivity?

PABAs (p-aminobenzoic acids)

What are examples of salicylate sunscreens?

Homosalate

What is the role of hydroquinone?

Skin lightening

must be protected from light and O₂

What do alpha-hydroxy acids (AHAs) do for wrinkles?

Exfoliate dead skin cells and stimulate collagen production

Which acids are examples of AHAs?

Glycolic, Lactic, Tartartic, Malic, Citric

What are the two main biological targets in eczema?

The immune response and inflammation

What is the primary therapeutic goal in eczema?

Suppress both immune response and inflammation

Which drug class does Ruxolitinib belong to?

Pyrrolopyrimidine derivatives (Janus kinase inhibitor)

Which drug class does Upadacitinib belong to?

Imidazopyrrolopyridine derivatives (Janus kinase inhibitor)

How does PDE4 inhibition reduce inflammation?

Increases intracellular cAMP

What metabolic pathway is responsible for Crisaborole’s degradation?

Hydrolytic deboronation followed by alcohol and aldehyde oxidation

What are the wavelengths used in psoriasis treatment?

( UVA, UCB, UVC ) = UVR

Which tars are photosensitizing?

Coal tars

Which tars are non-photosensitizing?

Shale and wood tars

What are the key ingredients of Lassar’s paste?

Anthralin, Zinc oxide, paraffin, salicyclic acid

What causes Anthralin’s cytotoxic effects?

Formation of anthranyl radicals that damage DNA and disrupt proliferation

Why is anthralin sometimes formulated in nanodendrimers?

To improve pharmacokinetic properties and increase duration of action

What are the main adverse effects of Psoralens?

Photosensitivity and potential for hepatotoxicity