Pharmacology & The Skin Flashcards
Describe the outer layer of the epidermis
The stratum corneum has a “brick and mortar” structure.
The bricks being an insoluble keratin matrix (corneocytes)
The mortar being an intercellular lipid layer made of ceramides, cholesterol, and fatty acids.
Name the three routes that medications can be absorbed through the skin
Intercellular route (most common)
Transappendageal route
Intracellular route
Name 3 factors that affect absorption through the skin
Water solubility
Molecular weight
Oil/water partition
Are hydrophilic drugs poorly or well absorbed through the skin? Why?
- Hydrophilic drugs are poorly absorbed
- As low partition through the lipid matrix of stratum corneum
What are benefits of topical medications for local use
Reduced systemic side effects
Why are glucocorticoids readily absorbed through the skin
They are small & hydrophobic drugs =>
Can easily penetrate intercellular lipid matrix
Topical glucocorticoids effects
- Lymphocytopenia - Suppress lymphocyte proliferation
- Reduced scar tissue - Inhibit collagen synthesis and fibroblast proliferation
- Anti-inflammatory - inhibit the synthesis and release of chemical mediators of inflammation, including histamine and prostaglandins.
Topical glucocorticoid indications
Allergic responses
Eczema
Psoriasis
Glucocorticoid MOA
Bind to intracellular receptors =>
Receptors dimerise & translocate inside the nucleus =>
Can bind to HRE & upregulate transcription OR
Can bind to negative HREs & down regulate transcription OR
Can bind to transcription factors & down regulate transcription
What influences the potency of topical glucocorticoids
Solubility of active ingredient & vehicle penetration
The composition of a topical vehicle can affect what two factors
Rate & extent of absorption
Gel vs cream vs lotion - which is typically more potent
Gel>cream>lotion
Describe transdermal drug delivery
Method of delivery that involves applying drug formulation directly onto intact & healthy skin for systemic use
Drug diffuses into the stratum corneum, epidermis, dermis & subcutaneous tissue, where it enters systemic circulation
name examples of drugs that can be sued as transdermal patches
Motion sickness
Analgesia
HRT & contraception
Smoking cessation
Name some advantages of TDD
Simple, convenient, painless
Excellent for steady & prolonged administration
No first pass metabolism in liver
Name some disadvantages of TDD
- Local irritation possible
- Drug must be lipophilic & able to penetrate skin
- Can only be used for low medication doses
- Slower delivery to site of action, longer time to reach steady state
Why is water classified as a penetration enhancer
Water (in liquid preparations) can accumulate in the stratum corneum resulting in swelling of the corneocytes and the formation of pores that increase permeability
Why is alcohol classified as a penetration enhancer
Alcohols (e.g. ethanol) disrupt the lipid bilayer in the stratum corneum and increase flux.
What else can be used in addition to water & alcohol to enhance TDD
Molecular groups can be added to drugs that make them more lipophilic and can be removed after absorption through the skin to release the active drug. These are known as prodrugs
Summarise chemical strategies to enhance TDD
Water (enhance penetration)
Alcohol (enhance penetration)
Prodrugs (make drug more lipophilic)
Name three physical strategies to enhance TDD
Electroporation - Creating new temporary pores in skin using electrical pulses
Iontophoresis -Applying a low voltage electric field to drive ionised drugs through the skin
Sonophoressis - Using US
