DEENT EXAM 1

What do nuclear receptor binders modulate?

Protein synthesis via DNA transcription regulation.

Direct nuclear receptor action requires how many receptor complexes?

Two — they dimerize and bind to DNA response elements.

Example of a drug that acts via glucocorticoid response element (GRE)?

Prednisone.

Indirect nuclear receptor action involves binding to what?

One transcription factor, thus preventing it from binding to DNA

Name three main nuclear receptors.

GRE, RARE, TRE

Main therapeutic uses of corticosteroids?

Autoimmune diseases, allergic reaction, transplant rejection, block first-dose cytokine storm

Glucocorticoid mechanism of action summary?

Steroid binds receptor → complex enters nucleus → binds GRE → alters gene transcription.

Common corticosteroid side effects?

Hyperglycemia, risk of infections, cataracts, glaucoma

Low-potency topical corticosteroid example?

Hydrocortisone 1%.

What increases topical steroid absorption?

Application to dry skin.

Retinoid mechanism of action?

Bind to RAR/RXR receptors → affect gene transcription via RARE.

RAR receptor effects?

Cell differentiation and proliferation.

RXR receptor effects?

Apoptosis induction.

Topical retinoids are used for?

Acne

Oral retinoid used for severe cystic acne?

Isotretinoin.

Isotretinoin major risk?

Teratogenicity (iPLEDGE program required).

Oral retinoid used for psoriasis with long half-life?

Acitretin.

What must be avoided while on acitretin?

Pregnancy (3 years post-treatment) and alcohol.

Vitamin D analog used in psoriasis?

Calcipotriene.

Calcipotriene mechanism?

Binds VDR → heterodimerizes with RXR → binds VDRE → promotes differentiation

Calcineurin inhibitors target what?

T-cell and mast cell activation.

Cyclosporine binds to what protein?

Cyclophilin.

Tacrolimus binds to what protein?

FKBP.

Result of calcineurin inhibition?

↓ NFAT activation → ↓ IL-2 transcription → ↓ T-cell proliferation.

Topical calcineurin inhibitors are used for?

Atopic dermatitis and psoriasis.

Key adverse effect of calcineurin inhibitors?

Burning

Cyclosporine black box warning?

Lymphoma and severe infections.

Cyclosporine-specific side effect?

Gingival hyperplasia.

Tacrolimus-specific side effect?

Tremors.

PDE-4 inhibitor mechanism?

Inhibits PDE4 → ↑ cAMP → ↓ pro-inflammatory cytokines.

Topical PDE-4 inhibitor for AD?

Crisaborole 2% ointment.

Oral PDE-4 inhibitor for psoriasis?

Apremilast.

Apremilast key caution?

Avoid in depressed patients

Benzoyl peroxide mechanism?

Antimicrobial against P. Acnes, penetrate stratum corneum, loosens keratinocytes

Benzoyl peroxide main caution?

Can bleach hair and clothing.

Sulfur pharmacologic effect?

Reduced to hydrogen sulfide, causes inflammation, which leads to peeling and unclogging of plugs

Salicylic acid mechanism?

Solubilizes skin surface → promotes shedding of stratum corneum.

Salicylic acid toxicity name?

Salicylism.

Avoid strong salicylic acid on which patients?

Diabetics or those with peripheral vascular disease.

Tetracycline(-CYCLINE) antibiotics mechanism?

Inhibit protein synthesis by binding irreversibly to 30S, blocking aminoacyl-tRNA binding to the acceptor site

Clindamycin mechanism?

Binds 50S subunit → inhibits translocation.

Major oral side effect of clindamycin?

Pseudomembranous colitis.

Macrolide mechanism?

Bind 50S → prevent bacterial translocation.

Dapsone use?

Leprosy and acne.

Dapsone mechanism in acne?

Anti-inflammatory (exact MOA unknown).

Metronidazole mechanism?

Inhibits Demodex brevis and neutrophil activity.

Coal tar mechanism?

Cross-links DNA → antiproliferative + anti-inflammatory.

Coal tar key risk?

Photosensitizing, potentially carcinogenic, unpleasant odor, contact dermatitis

Anthralin mechanism?

Direct antiproliferative by affecting the mitochondria, and prevent t-lymphocyte activation

Anthralin special use regimen?

Short-contact anthralin therapy (SCAT).

Methotrexate mechanism?

Inhibits DHFR → ↓ THF → ↓ purine synthesis → ↓ cell proliferation.

Methotrexate notable toxicity?

Hepatotoxicity (dose-dependent)

Abatacept mechanism?

Blocks CD80/86 from binding CD28 → inhibits T-cell activation.

Dupilumab mechanism?

IL-4Ra/IL-13Ra1 antagonist, blocks IL-4Ra → inhibits IL-4 and IL-13 signaling.

Dupilumab treatment?

Moderate-to-severe atopic dermatitis.

IL-17 inhibitors

Secukinumab, Ixekizumab, and brodalumab

IL-17 inhibitors common precaution?

Test for TB prior to therapy.

Ustekinumab mechanism?

FULLY HUMAN, Blocks p40 subunit of IL-12 and IL-23 → ↓ proinflammatory Th1/Th17 cells.

Guselkumab mechanism?

selective binding at p19 subunit of IL-23 → prevents binding to IL-23 receptor

TNF-alpha inhibitors mechanism?

Bind TNF-α → prevent receptor interaction → ↓ inflammation.

TNF-alpha inhibitors black box warning?

Serious infection and lymphoma risk.

Etanercept mechanism type?

Fusion protein, with two p75-soluble TNF receptors + IgG Fc. —> prevents interaction with TNF receptor —> inhibits cell activation

Infliximab MOA?

Chimeric (mouse/human) monoclonal antibody; Binds to TNF and prevents interaction with TNF receptor

Adalimumab type?

Fully Human IgG1 antibody to TNF

Certolizumab pegol unique feature?

Pegylated Fab fragment (no Fc region), anti-TFA attached to a polyethylene glycol

JAK inhibitor mechanism?

Inhibits JAK enzymes → blocks cytokine signaling.

Tofacitinib warning?

BBW: severe infection, and lymphoma

Ruxolitinib inhibits which JAKs?

JAK1 and JAK2.

Upadacitinib inhibits which kinases?

JAK1

Psoralen + UVA therapy (PUVA) mechanism?

Psoralen intercalates DNA → UVA activates → antiproliferative

Methoxsalen risks?

Skin aging

Which biologic is contraindicated in MS?

Etanercept.

What monoclonal can cause lupus-like syndrome?

Infliximab.

Which topical retinoid is photochemically stable?

Adapalene.

Which retinoid is contraindicated in pregnancy?

Tazarotene and isotretinoin.

What enhances topical corticosteroid systemic absorption?

Occlusion and dry skin application.

What reduces irritation from calcipotriene?

Combine with topical corticosteroids.

What should you monitor with methotrexate use?

Cumulative liver dose/toxicity.

What is NF-κB?

A transcription factor affected by glucocorticoid action.

What do PDE-4 inhibitors increase intracellularly?

cAMP.

Key side effect of oral PDE-4 inhibitors?

GI upset and depression risk.

What effect does vitamin D analog have on keratinocytes?

Inhibits proliferation

What is the primary mechanism of corticosteroid immunosuppression?

Inhibition of cytokine transcription via GRE activation.

Which calcineurin inhibitor causes nephrotoxicity?

Both cyclosporine and tacrolimus.

What are common topical retinoid adverse effects?

Peeling

What is the onset of improvement with topical retinoids?

8–12 weeks.

What enzyme do folate antagonists inhibit?

Dihydrofolate reductase (DHFR).

What does JAK inhibition do?

Inhibit the production inflammatory cytokines (ILs) through the inhibition of JAK which inhibit inflammation

Common infection risk across biologics?

Tuberculosis reactivation.

Which drugs block IL-23 only?

Guselkumab

Which IL inhibitor acts on both IL-12 and IL-23?

Ustekinumab.

Main cytokine target for psoriasis?

IL-17 and IL-23.

What kind of drug is dupilumab?

Fully human monoclonal antibody; IL-4Ra and IL-13Ra1 antagonist

Which antibiotics discolor teeth?

Tetracyclines.

What receptor complex is needed for retinoid action?

RAR-RXR heterodimer.

What key protein activates IL-2 transcription in T-cells?

NFAT.

Inhibition of calcineurin prevents activation of which factor?

NFAT.

Which drugs have photosensitivity risk?

Retinoids

What is the therapeutic target of methoxsalen therapy?

Melanocyte stimulation and T-cell suppression.

What are the main topical antibiotics for acne?

Clindamycin