Pharmacotherapy of Skin disease Flashcards
Is there gender bias in the prevalence of acne vulgaris?
No
Onset during puberty occurs earlier in girls than boys, but may be more severe in boys during puberty
Does adult acne occur more frequently in males or females?
Females
In the first stage of acne vulgaris pathophysiology, there is increased proliferation of these in the follicle
Keratinocytes
In the first stage of acne vulgaris pathophysiology, there is reduced clearance of these
Corneocytes
What therapy is used to target the first stage of the pathophysiology of acne vulgaris (increased follicular keratinocyte proliferation/reduced corneocyte clearance)?
Exfoliant
(salicylic acid, topical retinoids, oral isotretinoin)
In the second stage of acne vulgaris pathophysiology, there is increased production of this
Sebum
What 3 therapies focus on the second stage of acne vulgaris pathophysiology (increased sebum production)?
Isotretinoin (oral)
Corticosteroids
Drugs that inhibit action of testosterone/androgens (antiandrogens, estrogens)
In the third stage of acne vulgaris pathophysiology, colonizing bacteria convert this to free fatty acids
Sebum triglycerides
In the third stage of acne vulgaris pathophysiology, colonizing bacteria convert sebum triglycerides to this
Free fatty acids
What therapy focuses on the third stage of acne vulgaris pathophysiology (colonizing bacteria convert sebum triglycerides to free fatty acids)?
Topical/oral antibiotics
In the fourth stage of acne vulgaris pathophysiology, these induce inflammation
Free fatty acids
In the fourth stage of acne vulgaris pathophysiology, free fatty acids induce this
Inflammation
What therapies focus on the fourth stage of acne vulgaris pathophysiology (free fatty acids induce inflammation)?
Intralesional and oral corticosteroids
Topical/oral antibiotics
Exfoliants (salicylic acid, topical retinoids, oral isotretinoin) treat this stage of acne vulgaris pathophysiology
1st stage
Increased follicular keratinocyte proliferation/reduced corneocyte clearance
Isotretinoin (oral), corticosteroids, and drugs that inhibit action of testosterone/androgens treat this stage of acne vulgaris pathophysiology
2nd stage
Increased sebum production
Topical/oral antibiotics treat this stage of acne vulgaris pathophysiology
3rd stage
Colonizing bacteria convert sebum triglycerides to free fatty acids
Intralesional corticosteroids, oral corticosteroids, and topical/oral antibiotics treat this stage of acne vulgaris pathophysiology
4th stage
Free fatty acids induce inflammation
Exfoliant for acne that is a desmolytic agent
Salicylic acid
How does salicylic acid treat acne?
It degrades corneodesmosomes so corneocyte cohesion is lost, leading to exfoliation
Does Salicylic acid have anti-inflammatory action?
Slight
Tretinoin, adapalene and tazarotene topicals are this type of drug for acne
Topical retinoids
Topical retinoids (tretinoin, adapalene, tazarotene) are this type of acne treatment
Exfoliants
What is the OTC dose of adapalene topical?
0.1%
Retinoids are derived from this
Vitamin A
Retinoids are membrane permeable ligands for this type of receptor, and thus control gene expression
Nuclear receptors
How do retinoids treat acne?
Reduce sebum formation
Retinoids treat acne by reducing the formation of this
Sebum
How does Adapalene topical (0.1% OTC) treat acne?
Is a retinoid
Controls gene expression, reduces sebum formation
Retinoids promote gene expression that has these 2 effects
Inhibits sebum production
Controls keratinocyte proliferation
Approved OTC topical retinoid for mild-to-moderate acne
Adapalene
Is Adapalene stable in sunlight?
Yes
What severity of acne is Adapalene used for?
Mild-to-moderate
How does Adapalene react with benzoyl peroxide?
Is stable when combined with benzoyl peroxide
More potent topical retinoid that is a prescription for severe acne
Tretinoin
What severity of acne is tretinoin used to treat?
Severe
Is Adapalene OTC or prescription?
OTC
Is Tretinoin OTC or prescription?
Prescription
Is Tazarotene OTC or prescription?
Prescription
Is Tretinoin stable in sunlight?
No, should be applied at night
How does Tretinoin react with benzoyl peroxide?
Is inactivated by benzoyl peroxide
Prescription topical retinoid for moderate-to-severe acne
Tazarotene
What severity of acne is Tazarotene used for?
Moderate-to-severe
Topical retinoid with anti-aging properties
Tazarotene
The primary toxicity of topical exfoliants has to do with this
At site of application
Irritation, stinging, burning, pruritus, peeling
Benzoyl peroxide is this type of topical acne treatment
Antibacterial
Erythromycin, Clindamycin, Dapsone, Azelacid acid and Metronidazole are this type of topical acne treatment
Antibacterials
Azelaic acid is this type of acne treatment
Topical antibacterial
What is the MOA of benzoyl peroxide?
Slowly release free radical oxygen species to oxidize bacterial proteins, thus inhibiting bacterial growth and reducing production of inflammatory free fatty acids
Topical acne treatment that slowly releases free radical oxygen species to oxidize bacterial proteins
Benzoyl peroxide
Is benzoyl peroxide anti-inflammatory?
May INDIRECTLY suppress inflammation by inhibiting bacterial growth, thereby reducing production of inflammatory free fatty acids
Topical acne treatment that indirectly suppresses inflammation by inhibiting bacterial growth, thereby reducing production of inflammatory free fatty acids
Benzoyl peroxide
Patients with a cinnamon hypersensitivity should not use this topical acne treatment
Benzoyl peroxide
Topical acne treatment that may bleach hair and clothing
Body odor may also occur from degradation
Benzoyl peroxide
Pigmentation problems are observed with this topical antibacterial for acne
Azelaic acid
2 toxicities of Azelaic acid
Hypopigmentation
Hypersensitivity
This is the standard of care for moderate to severe acne and treatment of resistant acne
Oral antibacterials
Oral antibacterials are the standard of care for this severity of acne
Moderate to severe
3 systemic antibacterials for acne
Tetracycline, Doxycycline, Minocycline
Teeth discoloration if given to children <8 years and photosensitivity are adverse effects of these
Systemic antibacterials for acne - tetracycline, doxycycline, minocycline
Use of this should be avoided in lactating patients
Systemic antibacterials for acne - tetracycline, doxycycline, minocycline
These interact with metals, so avoid taking with calcium-rich foods or antacids
Systemic antibacterials for acne - tetracycline, doxycycline, minocycline
Systemic antibacterials for acne - tetracycline, doxycycline, minocycline - interact with these
Metals
Should avoid taking with calcium-rich foods or antacids
Do Systemic antibacterials for acne - tetracycline, doxycycline, minocycline - have anti-inflammatory activity?
Yes
Estrogen has antiandrogenic effect that reduces production of this
Sebum
Ethinyl estradiol is a form of this
Estrogen
How does estrogen treat acne?
Has an antiandrogenic effect that reduces sebum production
How do oral corticosteroids treat acne?
May inhibit serum production
Oral isotretinoin is a derivative of this
Vitamin A
Is thus a retinoid
Acne agent that inhibits sebum production by shrinking sebaceous glands, high doses may reduce P. acnes population
Oral isotretinoin
Does Oral isotretinoin have anti-inflammatory action?
Yes, inhibits follicular keratinization
Only acne treatment that provides prolonged remission
Oral isotretinoin
Oral isotretinoin increases the levels of this in the blood
Lipids (cholesterol, LDL)
Oral isotretinoin inhibits these 2 things
Sebum production
Follicular keratinization
Black box warning for Oral isotretinoin
No safe dose in pregnancy
Anti-sebum acne agent that should not be used in pregnancy or blood donation
Oral isotretinoin
Oral isotretinoin is this type of acne treatment
Retinoid
Oral isotretinoin toxicities are related to this
Too much vitamin A
Retinoid/vitamin A toxicity
What is cheilitis?
Inflammation of the lips
Cheilitis is an adverse effect of this acne anti-sebum agent
Oral isotretinoin
Xerosis, peeling, pruritus, and peeling of palms and soles are adverse effects of this acne anti-sebum agent
Oral isotretinoin
Incoordination, irritability, depression, headaches, suicide ideation, blurred vision and dizziness are adverse effects of this acne anti-sebum agent
Oral isotretinoin
Injections of anti-inflammatory doses of these are indicated for severe inflammatory acne
Steroids
Erythematous plaque with silvery white scale is seen in this condition
Psoriasis
Condition that is associated with comorbidities such as heart disease, diabetes and metabolic syndrome, screening is recommended
Psoriasis
Psoriasis is associated with comorbidities such as heart disease, diabetes, and this
Metabolic syndrome
Stress-reduction strategies, non-medicated moisturizers, oatmeal baths, skin protection, and avoiding harsh soap/detergents, fragranced cleansers and hot water are non-pharmacological therapies for this condition
Psoriasis
Topical agents are the standard of care for this condition
Psoriasis
This is the standard of care of psoriasis
Topical agents
These are typically used when comorbidities are present to treat psoriasis
Biological response modifiers
Biological response modifiers are typically used in psoriasis when:
When comorbidities are present
Calcipotriene is an analog of this
Vitamin D3
What is the MOA of Calcipotriene?
Binds to Vitamin D receptors to inhibit keratinocyte proliferation and modulate differentiation, and inhibits inflammatory cytokine expression and cytotoxic T cell function
Topical agent for psoriasis that binds to Vitamin D receptors to inhibit keratinocyte proliferation and modulate differentiation, and inhibits inflammatory cytokine expression and cytotoxic T cell function
Calcipotriene
What condition is Calcipotriene used to treat?
Psoriasis
Calcipotriene binds to Vitamin D receptor to inhibit proliferation of these
Keratinocytes
Psoriasis topical agent that inhibits inflammatory cytokine expression and cytotoxic T cell function
Calcipotriene
Hyperkalemia and hypercalciuria occur with high dose or long duration therapy are adverse effects of this topical agent
Calcipotriene
These 2 things occur with high dose or long duration therapy of Calcipotriene
Hyperkalemia and Hypercalciuria
Erythema, xerosis and exfoliative dermatitis may occur in up to 10% of patients and require discontinuation of drug therapy with this topical agent for psoriasis
Calcipotriene
Following topical application, tazarotene is hydrolyzed to this, which binds to specific nuclear retinoid receptors
Tazarotenic acid
Tazarotene MOA has these 3 effects
Normalize abnormal keratinocyte differentiation
Diminish keratinocyte hyperproliferation
Reduce inflammatory responses
Topical retinoid for psoriasis that has these 3 effects:
Normalize abnormal keratinocyte differentiate
Diminish keratinocyte hyperproliferation
Reduce inflammatory responses
Tazarotene
Absolute contraindication of tazarotene
Pregnancy
Topical agent for psoriasis that is a photosensitizer, and recommended not to be used with other photosensitizing agents
Coal tar
Topical agent for psoriasis that has some carcinogenic concern, although considered unlikely when used therapeutically
Coal tar
Coal tar is a topical agent for this condition
Psoriasis
Anthralin is a topical agent for this condition
Psoriasis
What is the MOA of anthralin?
Unknown
With use of this topical agent for psoriasis, it is recommended that protective zinc oxide or thick non-medicated paste (petroleum jelly) be applied around lesions to prevent irritation and burning of healthy tissue
Anthralin
With use of Anthralin, it is recommended that either of these be applied around lesions to prevent irritation and burning of healthy tissue
Protective zinc oxide or thick non-medicated paste (petroleum jelly)
What is the MOA of pimecrolimus and tacrolimus?
Inhibit calcineurin
Binds to FKBP-12, immunosuppression
Pimecrolimus and tacrolimus should not be used in these patients
Infants or children
Neoplastic disease
Type of phototherapy that is preferred as it is more efficacious in psoriasis
Narrowband (NB-UVB)
What is the MOA of UVB phototherapy for psoriasis?
Unclear
Decreases proliferation and induces apoptosis of multiple cell types, including keratinocytes and lymphocytes
Therapy for psoriasis with unclear MOA, decreases proliferation and induces apoptosis of multiple cell types, including keratinocytes and lymphocytes
UVB phototherapy
Therapy for psoriasis with these adverse effects:
Skin irritation, photo-aging, increased risk of skin cancer
UVB phototherapy
UVB phototherapy has adverse effects including skin irritation, photo-aging, and increased risk of this
Skin cancer
Photochemotherapy for psoriasis involves this wavelength of light
UVA (320-400 nm)
Most common oral photosensitizer used prior to UVA photochemotherapy
8-MOPS (8-methoxypsoralen)
Photochemotherapy is contraindicated in these patients
Children < 12 years
Photochemotherapy has adverse effects including GI intolerance, burn, cataracts, photo-aging, and increased risk of this
Skin cancer
Cyclosporine, methotrexate, acitretin and apremilast are non-biologic therapies for this condition
Psoriasis
Oral retinoid that is a non-biologic therapy for psoriasis
Acitretin
Acitretin is contraindicated in this
Pregnancy
2 forms of birth control and monthly pregnancy testing during treatment; regular pregnancy testing for 3 years after treatment (long biological half life)
What type of drug is Acitretin?
Oral retinoid
Acitretin is used to treat this condition
Psoriasis
Apremilast is used to treat this condition
Psoriasis
3 TNF alpha inhibitors used for psoriasis
Etanercept
Adalimumab
Infliximab
Etanercept, Adalimumab, Infliximab treat psoriasis through this MOA
Anti-inflammatory
Are TNF alpha inhibitors
Cytokine that is strongly associated with inflammation and is a target for biological response modifiers used to treat psoriasis
TNF alpha
Cyctokine produced by dermal dendritic cells that activates the pathogenic Th17 lymphocytes that produce IL-17 and are associated with psoriasis
IL-23
Cytokine that is strongly associated with inflammation, neutrophil accumulation and epidermal microabscesses and is a target for biological response modifiers used to treat psoriasis
IL-17
2 types of treatments for skin disorders involving inflammation with pruritus
Topical corticosteroids
Histamine type 1 receptor inhibitors (H1 blockers)
Most hypersensitivity symptoms can be elicited by activation of this
Histamine type 1 receptors (H1R)
Blockers of this histamine receptor are used to reduce stomach acid production
Histamine type 2 receptors
Are first or second generation H1R blockers more selective?
Second generation are more selective for peripheral H1R, polar drugs that do not cross into CNS, so less sedation than 1st gen
What is the MOA of bacitracin?
Blocks bacterial cell wall formation
Narrow gram+ spectrum
For cuts and scrapes
Polymyxin B and Neomycin are effective against this type of bacteria
Gram negative
Topical antifungals for skin that block ergosterol synthesis by inhibiting 14-a-demethylase (CYP51A1)
Azoles (miconazole, itraconazole, clotrimazole)
What is the MOA of Azoles?
Block ergosterol synthesis by inhibiting 14-a-demethylase (CYP51A1)
What is the MOA of Naftifine?
Block ergosterol synthesis by inhibiting squalene epoxidase
Melanoma tumor with this mutation is a good candidate for targeted therapy with vemurafenib +/- cobimetinib
BRAF mutation V600E
Competitive BRAF inhibitor (V600E mutation) used to treat melanoma
Vemurafenib
Vemurafenib is metabolized by this
CYP3A4
Expect drug interactions
What is the MOA of Vemurafenib?
Competitive BRAF inhibition (V600E mutation)
Common mutation in melanoma that is the target of Vemurafenib
BRAF (V600E)
Melanoma treatment that binds CTLA4 on T cells, preventing interaction with CD80/86 (B7) on tumor cells
Promotes co-stimulation needed to activate T cells
Ipilimumab
What is the MOA of Ipilimumab in the treatment of melanoma?
Binds CTLA4 on T cells
Prevents interaction with CD80/86 (B7) on tumor cells
Promotes co-stimulation needed to activate T cells
Melanoma treatment with severe immune-mediated reactions, mostly in colon, liver, skin
Ipilimumab
What is the black box warning for Ipilimumab?
Severe immune-mediated reaction, mostly in colon, liver, skin
Ipilimumab is a monoclonal antibody against this, and is indicated for melanoma
CTLA4