Psoriasis Treatment

Question 1

Adalimumab
• Administration
• Structure
• MOA

Answer 1

Question 2

Alefacept
• Administration
• Structure
​• MOA

Answer 2

Question 3

Apremilast
• Administration
• Structure
​• MOA

Answer 3

Question 4

Etanercept
• Administration
• Structure
​• MOA

Answer 4

Question 5

Infliximab
• Administration
• Structure
​• MOA

Answer 5

Question 6

Uztekinamab
• Administration
• Structure
​• MOA

Answer 6

Question 7

Psoriasis
• Retinoids used to treat
• Biologics used to treat
• Other drugs used

Answer 7

• *Psoriasis** is treated using…
• *retinoids** (Acitretin and Tazarotene)

Inhibitors of inflammatory mediators (adalimumab, alefacept, apremilast, etanecept, infliximab, ustekinumab)

Others include Calcipotriene and Calitriol.

Question 8

Acne drugs used to treat
• Retinoids
• Steriods
• Others

Answer 8

• *Acne** is treated using…
• *retinoids** (Adapalene, isotretinoin, tazarotene, and tretinoin, ATRA)

steroids (Hydrocortisone, betamethasone valerate, flucinonide, clobetasol proprionate)

Others include Benzoyl peroxide, Clindamycin/Erythromycin, Salicylic acid

Question 9

What is the potency of the corticosteriods used to treat acne?

Answer 9

Potency of corticosteroids

Clobetasol propionate > Budesonide > Betamethasone > Hydrocortisone

Question 10

What side effects are common to all biologics used in the treatment of psoriatic arthritis?
• what biologics are these especially common in?

Answer 10

• *SIDE EFFECTS COMMON TO ALL:**
• *• Immunosuppression** – don’t initiate with an active infection, report symptoms of infection (especially Respiratory)

• Malignancy – decreased immune surveillance = increased malignancy (adalimumab, etancercept, infliximab especially); lymphomas are most common

Question 11

Which biologics should not be given to people with heart problems?
• which cause lupus?

Answer 11

• CHF or HypoTN, angina, dysrthythmia – INFLIXIMAB, adalimumab, rituximab (actual contraindication with infliximab)

• Lupus Like Syndrome – Adalimumab, Etanercept, Infliximab

Question 12

Which biologics can cause injection site reactions?
• Which can cause an elevation of LFTs?

Answer 12

• LFTs – infliximab
• Injection Site rotation needed – Adalimumab, Alefacept, Etanercept

Question 13

What effects of the retinoids make them useful in the treatment of psoriasis?

Answer 13

Effects of Retinoids – Modulate proliferation and Differentiation, Stimulate Keratinization, and Alter cellular cohesiveness. Importantly, in the treatment of acne these can decrease sebum and reduce sebaceous gland size.

Question 14

In general how do retinoids work?

Answer 14

GENERAL MOA: Retinoids bind to the RXR/RARa receptors (nuclear transcriptional repressors that recruit co-repressors (NTCO1) in the absence of the retinoid ligand). This blocks cell differenentiation and proliferation. When Retinoids bind genes are transcribed at the appropriate rate. Drugs that preferentially bind RARa are better for correct differentiation and proliferation or cells, while retinoids targeting RXR tend to induce apoptosis.

Question 15

Why are retinoids beneficial in psoriasis?
• What drugs are used in psoriasis?

Answer 15

In the treatment of psoriasis RARa targeting drugs are preferred, these upregulate HB-EGF (heparin-binding epidermal growth factor receptor) and AR (amphiregulin) stimulate basal bell proliferation and cause thickening of the epidermis and flaking of tissue.

Acitretin and Tazarotene used in psoriasis

Question 16

What retinoids are used in the treatment of acne?

Answer 16

Adapalene
Isotretinoin
Tazarotene
Tretinoin

Question 17

How do the side effects of the RAR targeting drugs differ from those of the RXR targeting drugs?

Answer 17

RARa targeting drugs

• Side effects: mucocutaneous and musculoskeletal symptoms

RXR targeting drugs

• Side effects: Physiological changes

Question 18

How do the side effects of retinoids differ depending on the method of administration?
• what are these side effects?

Answer 18

GENERALIZED SIDE EFFECTS :
• Resemble vitamin A intoxication – dry skin, EPISTAXIS, CONJUNCTIVITIS, reduced night vision, ALOPECIA

• Topical: Erythema, desquamation, burning, stinging, PHOTOSENSITIVE SKIN

Question 19

What is the 1st line therapy in acne?
• what else are these used for?

Answer 19

Topical Retinoids:
• 1^st line therapy in inflammatory acne

• Wrinkle Therapy (UV responsive MMPs inhibited, Epidermal Hypeplasia)

Question 20

Calcipotriene
• Administration
• MOA
• Indication

Answer 20

Calcipotriene
Administration – topical

MOA
Binds to vit. D receptor and associates with RXR to binds DNA vit. D response elements this modulates epidermal differentiation and inflammation.

INDICATION
Psoriasis

Question 21

Calcipotriene
• Side effects

Answer 21

Calcipotriene

SIDE EFFECTS
High doses: Hypercalcemia and Hypercalciuria (Abdominal pain, constipation, depression, HTN, anorexia, polydipsia)
Topical Irritant – attenuate with Corticosteroids
Increased risk of skin cancer (UV induced)

Question 22

Calcitriol
• Administration
• MOA
• Indication

Answer 22

Calcitriol
Administration – topical

MOA
AKA active vitamin D3; Binds to vit. D receptor and associates with RXR to binds DNA vit. D response elements this modulates epidermal differentiation and inflammation.

INDICATION
Psoriasis; better for sensitive skin

Question 23

Calcitriol
• Side effects

Answer 23

Calcitriol

SIDE EFFECTS
High doses: Hypercalcemia and Hypercalciuria (Abdominal pain, constipation, depression, HTN, anorexia, polydipsia)

Increased risk of skin cancer (UV induced)

Question 24

What are the more potent corticosteroids used in ACNE treatment? where are they used?
• weak ones?

Answer 24

More potent drugs like Clobetasol and Budesonide should be used on more keratinized surfaces while the weaker drugs like betamethasone and hydrocortisone should be used on the face and more sensitive skin.

Question 25

Topical Corticosteroids generally do not have systemic effects except when applied to?

Answer 25

Topically applied steroids are typically not heavily absorbed systemically, but can be when applied to genitalia.

Question 26

What are some side effects of topical corticosteriods?

Answer 26

Side effects:
• Fluorinated steroids can cause DRUG INDUCED DERMATITIS when applied to the face
• Dermal Atrophy (cigarette paper skin) => susceptible to purpura
• Rosacea/Telangiectasia
• Cushing’s, etc.

Question 27

Benzoyl Peroxide
• Administration
• MOA
• Indication
• Side effects

Answer 27

Benzoyl Peroxide
Administration – topical

MOA
Pro-drug that is converted to benzoic acid and a free radical by the skin causing death of P. acnes and keratolytic effect.

INDICATION

Acne (kills P. acnes and causes desquamation), Decubitus Ulcers (stimulates epithelial growth)

SIDE EFFECTS
Erythema, irritation, peeling

Bleaches hair and fabric

Question 28

Salicylic Acid
• Administration
• MOA
• Indication

Answer 28

Salicylic Acid
Administration – topical

MOA
Keratolytic

INDICATION
Acne, Hyperkeratotic Skin disorders

Neonatal toxicity

Question 29

What biologics are used to treat Psoriasis?

Answer 29

Adalimumab
Alefacept
Apremilast
Etanercept
Infliximab
Ustekinumab

Question 30

What non-retinoid and non-biologic drugs are used to treat psoriasis?

Answer 30

Calcipotriene
Calcitriol

Question 31

What non-corticosteroids and non-retinoids are used to treat acne?

Answer 31

Benzoyl Peroxide (with or without clindamycin or erythromycin)

Salicylic acid