Pharmacology Flashcards
3 main skin layers
3 main layers
-epidermis
-dermis
-subdermis
Epidermis (5)
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
Dermis + Subdermis
-Papillary dermis
-Reticular dermis
Subdermis- subcutaneous layer
Epidermis- Stratum corneum
a “brick and mortar” structure, with the bricks being an insoluble keratin matrix (corneocytes) and the mortar being an intercellular lipid layer made of ceramides, cholesterol, and fatty acids.
Absorption routes through the skin + factors that affect it (4)
Most drugs absorbed thro intercellular route
FACTORS that affect ABSORPTION:
=WATER SOLUBILITY
=MOLECULAR WEIGHT
=OIL/WATER PARTITION COEFFICIENT
Water solubility (2)
Hydrophylic drugs (e.g. antiviral agents) are poorly absorbed when applied topically, due to low partitioning through the lipid matrix of the stratum corneum.
Water-soluble molecules tend to diffuse along the aqueous domains of the lipid matrix.
Molecular weight
100-500 Da is the optimal MW for skin penetration
Oil/ water partition coefficient
Substances with LogP ~ 2 are best absorbed across the skin
Small hydrophobic drugs - glucocorticoid’s
are readily absorbed through the stratum corneum as they can easily penetrate the intercellular lipid matrix.
Topical drug delivery- conditions (5)
Psoriasis
Eczema
Skin infections (viral, bacterial, fungal)
Itching
Dry skin
Topical drug delivery advantages
reduced systemic effects =
Immunosuppression (used in transplant patients)
- Muscle atrophy and weakness
- Hyperglycaemia and Cushing’s syndrome
- Salt and water retention (mineralocorticoid effect)
- GI bleeding and ulceration
- Insomnia
GLUCOCORTICOIDS: PHARMACODYNAMICS (6)
LYMPHOCYTOPENIA
-They suppress lymphocyte proliferation
SCAR TISSUE FORMATION
-They inhibit collagen synthesis and fibroblast proliferation
ANTI-INFLAMMATORY
-Glucocorticoids inhibit the synthesis and release of chemical mediators of inflammation, including histamine and prostaglandins.
Clinical application- glucocorticoids (3)
Suppression of inflammation are reduction in immune response are useful in an allergic responses and eczema
Suppression of fibroblast and lymphocyte proliferation are useful in psoriasis
Vasoconstriction helps reducing transport of inflammatory mediators to affected area
GLUCOCORTICOIDS: MECHANISM OF ACTION- transactivation mech
Upon binding with their glucocorticoid ligand, GCRs dimerise and translocate inside the nucleus, where they bind to specific DNA responsive elements (GREs) and upregulate the transcription of genes encoding for regulatory proteins responsible for metabolic, anti-inflammatory, and immunosuppressive effects
GLUCOCORTICOIDS: MECHANISM OF ACTION- transrepression mech
GCRs can repress gene expression (e.g. genes encoding for pro-inflammatory proteins) by binding negative DNA responsive elements (nGREs) or transcription factors that constitutively drive the expression of these genes
