Pharmacology Of Topical Drugs Flashcards
5 components of transdermal delivery systems/patches
1) plastic backing or support layer that protects the patch
2) drug layer (solid gel reservoir in a matrix or adhesive membrane)
3) membrane itself
4) pressure sensitive adhesive layer
5) release linear or protective strip
4 basic configuration of transdermal drug systems
1) matrix
- can be cut*
2) reservoir
- stores a lot of drug and leaks out overtime
- CANT be cut**
3) multi laminate
- two matrix patches stacked onto each other
- can be cut*
4) drug in adhesive
- can be cut*
Disadvantages to patches
Skin irritation or contact dermatitis
Variation of drug absorption at different sites of skin
CANT be used for drugs requiring high blood levels for therapeutic effect
CANT be used to deliver ionic drugs or large molecular drugs
Are more expensive than oral
Topical glucocorticoids
Fluocinonide, fluticasone, hydrocortisone, desonide, etc.
MOA
- inhibits numerous inflammatory steps
Indications:
- inflammatory skin diseases
PK:
- initially start with more potent agent and then follow up with less potent agent to “ween dose”
- ONLY use for 14 consecutive days MAX(must allow for a week in between to allow for recovery
- must use nonflourinated glucocorticoids on face or groin if going to use
ADRs:
- chronic use of potent class 1/2 = skin atrophy/striae/acneiform and purpura on the skin
- fluoridated = perioral dermatitis
- increased risk of hypothalamus pituitary axis suppression
Topical retinoids
1st gen = retinol, tretrinoin (RAR), alitretinoin (RXR), isotretinoin (RAR)
2nd = acitretrin
3rd = tazarotene (RAR), bexarotene (RXR), Adapalene (RAR)
MOA: activates steroid, retinoic acid (RAR) and retinoid X receptors (RXR). Upregulates cell division (epidermal hyperplasia and RAR only) and exfoliates dead skin cells. RXRs also induce apoptosis.
- RAR’s = upregulated cellular differentiation and proliferation. treats acne and psoriasis
- RXR’x = induces apoptosis of cells. treat cancerous malignant cells
ADRs: ALL ARE TERATOGENIC
- **isotretinoin (accutane) requires enrollment in the REMS program
- erythema, desquamation, burning and staining
- photosensitivity (high risk of sunburns)
REMS program
Required legally if patient is put on isotretinoin (accutane)
- females = need to be on two different birth control methods
- males = must use condoms or male birth control
- Both sexes = NO BLOOD DONATIONS
Vitamin D analogue
Calcipotriene
MOA: binds to vitamin D receptors and forms a complex that binds to retinoid X receptors which creates its own complex.
- this complex binds to vitamin D on DNA and increases gene expression and cell differentiate as well as inflammation on epiderminal cells
- improves psoriatic plaques
- **often dosed with a corticosteroid to reduce inflammatory effects
ADRs:
- hypercalcemia and hypercalciuria if dose is above 100g/week
- mild photosensitivity
- perilesional also irritation
Sunscreen products
Organic UVA agents: “chemical blockers”
- benxophenones, dibenzoylmethanes
Organic UVB
- aminobenzoates, cinnamates, salicylates, octocrylene
Inorganic agents: “physical blockers”
- zinc oxide and titanium dioxide
4 modalities for treating acne vulgaris
1) inhibiting the activity of sebaceous hypertrophy
2) control keratinocyte differentiation
3) treatment of anti-inflammatory effects
4) treatment with antibacterial effects
Common antibiotic treatment for acne vulgaris
Most commonly used = benzoyl peroxide
Macrolides (clindamycin/erythromycin)
Dapsone
Tetracyclines
Etanercept (TNF inhibitor)
MOA:
- fusion protein that chelates TNF-a ligands
Pregnancy = B
Indications:
- RA
- Plaque psoriasis
- psoriatic arthritis
ADRs
- injection site reaction and URIs
- autoimmune hepatitis and reactivate of tuberculosis or HBV
- BLACK BOX = TB reactivating and serious infections
**dont give live vaccinations with this drug
Infliximab and adalimumab
TNF-a inhibitors
MOA: chelates TNF-a by binding to its receptors
Pregnancy = B
Indications = RA and psoriasis
ADRs = same as etanercept
Ustekinumab
MOA: human IGg1k MAB that binds to IL-12/23
Indications = psoriasis
ADRs:
- nasopharyngitis
- URIs
- headache
- fatigue
Tofacitinib
JAK inhibitor
MOA:
- inhibits JAK tyrosine kinase and STAT proteins = no inflammation
Indications = RA and psoriasis
Pregnancy = C
ADRs:
- increases in LDL/HDL***
- anemia
- headaches
- skin cancer risks
- BLACK BOX = reactivate TB and invasive opportunist pathogens
**must monitor cholesterol and dont give live vaccines
PDE4 inhibitors
apremilast
MOA: inhibts phosphodiesterase 4 (PDE4)
- decreases infalammatory cytokines and increases anti-inflammatory cytokines
Pregnancy = C
Indications: psoriasis and Behçet’s disease
ADRs:
- diarrhea
- nausea
- URIs
- headaches
- increases depression
- weight loss
**dont give with rifampin (reduces load)
