EXAM #5: TOPICAL AGENTS Flashcards
What are the layers of the epidermis?
1) Stratum corneum
2) Stratum granulosum
3) Stratum spinosum
4) Stratum basale
*All of which rest on a basal lamina
What is the stratum corneum?
Layer of dead keratinocytes
What are the living layers of the epidermis?
1) Stratum granulosum
2) Stratum spinosum (synthesis of epidermal proteins)
3) Stratum basale (cell division)
What is the major barrier to percutaneous absorption of drugs?
Stratum corneum i.e. the layer of dead keratinocytes
Why is the stratum corneum the major barrier to percutaneous absorption of drugs?
Contains corneyocytes that are:
- Flattened and lipid depleted keratinocytes
- Plasma membrane has been replaced with protein
- Secrete lipids that are hydrophobic
What is the rule of thumb for choosing a vehicle for delivering drugs via the skin?
If it is wet, dry it; if it is dry, wet it.
What types of vehicles should be used in the scalp and hairy areas?
Lotion Gels Solution Foams Aerosols
What types of vehicles are good for intertriginious areas (two skin areas rubbing together)?
Creams
Lotion
Solutions
What vehicles are best for wetting?
Ointment
Creams
Gels
Lotions/solutions
What vehicles are good for drying?
Aerosols
Pastes
Powders
Tinctures
What is PCA?
Percutaneous Absorption
What factors affect PCA?
1) Concentration of drug in the vehicle
2) Drug diffusion coefficient/ molecular size (less MW gets absorbed faster)
3) Lipophilicity
4) Thickness of the stratum corneum
5) Cutaneous vasculature
6) SA of absorptive surface
7) Mucosal surface
How will skin inflammation affect PCA?
Inflammation will increase systemic absorption
How does skin hydration alter PCA?
Increased hydration increases PCA
How will occlusion of a topical medication i.e. in plastic wrap alter PCA?
Increase PCA
Explain the basic pathophysiology of acne.
1) Follicular epidermal hyperproliferation causes the formation of a “plug” limits the exit of sebum from the follicle
- Plus = “comedome”
2) Keratin, sebum, and bacteria* accumulate and cause inflammation
*Propionibacterium acnes
What topical antibiotics are used to treat acne?
1) Erythromycin
2) Clindamycin
3) Metronidazole
4) Sodium sulfacetamide
5) Azelaic acid
6) Benzoyl Peroxide
What is the MOA of Erythromycin and Clindamycin to treat acne?
- Inhibit protein synthesis
- Directed against P. acnes bacteria
What is the MOA of Metronidazole to treat acne?
Kills bacteria by disrupting DNA
What is the MOA of Sodium Sulfacetamide?
Kills P. acnes by inhibiting dihydropteroate synthetase activity i.e. folic acid
What bacteria are treated with Azelaic acid?
P. acnes and S. epidermidis
What is the MOA of Azelaic acid?
1) Reduces inflammation (free radical scavenging)
2) Reduces keratinization
3) Keratolytic effects cause desquamation
What side effects are associated with Azelaic acid?
1) Lightening of the skin
2) Skin dryness
What is the MOA of benzoyl peroxide?
Releases oxygen that is bactericidal against anaerobic bacteria
*Note that benzoyl peroxide does not lead to resistance
How is benzoyl peroxide commonly administered?
In combination with erythromycin or clindamycin
What is the MOA of Salicylic acid?
Topical keratolytic agent that helps to clear comodomes
What are four indications for Retinoid drugs?
1) Acne
2) Psoriasis
3) Skin aging
4) Skin cancer
What side effects are associated with the Retinoids?
1) Photosensitivity and increased risk of sunburn
2) Teratogenic
What is the MOA of Tretinoin?
Activation of RAA receptors leads to:
1) Reduced cohesiveness of follicular epithelial cells that produce comodomes
2) Codemolytic via increasing mitotic activity of follicular epithelial cells to extrude comedomes
3) Reduces keratinization
What drug should NOT be used with Tretinoin?
Benzoyl peroxidase–will inactive the drug
What is the MOA of Adapalene?
Via activation of the RAR:
1) Reduced cellular proliferation
2) Reduced inflammation
2) Comedolysis
What is the MOA of Isotretinoin?
Suppresses sebum production by inducing apoptosis sebum producing cells in the sebaceous glands
What unique adverse effect is associated with Isotretoinoin?
Highly Teratogenic–must be on oral contraceptive to use
What is Isotretinoin used to treat?
Oral retinoid used to treat severe acne (this is accutane)
What is the MOA of Tazarotene?
This a topical retinoid prodrug. Activation of the RAR is thought to:
- Decreases inflammation
- Reduce epidermal proliferation
What are the clinical uses for Tazarotene?
Psoriasis and acne
What major adverse effect is associated with Tazarotene?
Teratogenic–must be on oral contraceptives to use
What is the clinical indication for Acitretin? What type of drug is this?
Severe, recalcitrant psoriasis
*Oral retinoid
What drug-drug interaction should you be aware of with Acitretin?
Alcohol use prolongs half-life for months
Women are advised to avoid pregnancy for 3x years
What is Calcipotriene used to treat?
Psoriasis
What is the MOA of Calcipotriene?
Binds to Vitamin D receptor to induce gene transcription changes that are beneficial in psoriasis
What are the side effects associated with Calcipotriene?
- Hypercalcemia
- Hypercalciuria
What is the strength of hydrocortisone?
Weak
What is the strength of mometasone furoate?
Intermediate
What is the strength of clobetasol propionate?
High
What potency corticosteroid should be applied to the face and intertriginous areas?
Low i.e. Hydrocortisone
What potency corticosteroid should be applied to palms and soles?
High i.e. clobetasol propionate
What type of corticosteroid should be avoided in kids?
High i.e. clobetasol propionate
What are the side effects of topical corticosteroids?
1) Epidermal atrophy
2) Acne
3) Enhanced fungal infection
4) Delayed wound healing
5) Hypopigmentation
What are the side effects of the systemic corticosteroids?
1) HPA-axis suppression
2) Cushing Syndrome
3) Growth retardation
What is atopic dermatitis?
Eczema i.e. chronic skin disorder with intense pruritus and dried flaking skin
How is eczema treated?
1) Corticosteroids for primary infection
2) Abx for secondary infection e.g. S. aureus
What are Psoralens?
- Topical or oral agents that are ACTIVATED BY LIGHT
- On activation they intercalate with DNA to mediate effects
List the two Psoralens.
1) Methoxsalen
2) Trioxsalen
List the conditions that the Psoralens are used to treat.
1) Alopecia
2) Cutaneous T-cell Lymphoma
3) Eczema
4) Psoriasis
What are the short-term toxicities associated with the Psoralens?
1) Nausea
2) Blistering
3) Painful erythema
What are the chronic effects of Psoralens?
1) Photoaging
2) Actinic keratoses
3) Nonmelanoma skin cancer
