Pharmacology and Skin Flashcards
Major routes of drug administration through skin?
Topical
Transdermal
Subcutaneous
Single most important barrier to drug penetration?
Stratum Corneum
What does the stratum corneum consist of?
Corneocytes (hardened dead keratinocytes)
Surrounded by intercellular lipids
Brick and Mortar model of the stratum corneum?
Bricks: corneocytes embedded in a filaggrin matrix
Surrounded by cornified cell envelope
Mortar: Multiple lamellar structure of intercellular lipids, cholesterol, free fatty acids
How do corneocytes have tensile strength?
Highly cross-linked by protein rivets
Drug delivery into stratum corneum process when applied topically?
Passive process
Mediated by diffusion when a drug is applied topically
When is topical application most commonly used?
- Superficial skin disorders (eczema, psoriasis)
- Skin infections
- Itching
- Dry skin
- Warts
Choices of type of topical treatment are decided by?
Physiochemical properties of drug
Clinical condition
What law does the rate of absorption of topical creams follow?
Fick’s law of diffusion
Kp=?
Permeability coefficient
Cv=?
Concentration of a drug in the vehicle
What are Cv and Kp highly dependent on?
The vehicle of transmission (ointment, paste, cream)
Important factors of the vehicle that can affect extent of absorption of drug and rate of absorption?
Dissolved concentration of drug in vehicle
Movement of the drug from vehicle into stratum corneum and deeper
What is the driving force for skin penetration in topical drugs?
The fraction within the vehicle that is solubilized
What factors can improve topical drug absorption?
- Hydration of the skin
- Site of application
- Integrity of the epidermis
Side effects of long term use of higher potency steroids?
- Steroid rebound
- Skin atrophy
- Systemic effects
- Steroid rosacea
- Production of stretch marks
How do glucocorticoids signal?
Via nuclear receptors specifically GRa
How do glucocorticoids enter cells?
By diffusion across plasma membrane
Journey of glucocorticoids?
- Diffuse across plasma membrane
- -Within cytoplasm they combine with GRa, producing dissociation of inhibitory heat shock proteins
- Within the nucleus activated receptor monomers assemble into homodimers and bind to glucocorticoid response elements
- Transcription of specific genes either switched on or switched off to alter mRNA levels
How are drugs delivered sub cutaneously?
Needle inserted into fatty tissue
How does a subcutaneous drug reach systemic circulation?
Diffusion into either capillaries or lymphatic vessels
Advantages of subcutaneous administration?
- Absorption is relatively slow due to poor vascular supply (pro & con)
- Can be used to introduce a depot of drug or drug under the skin that is very slowly released into circulation
- Relatively simple, not very painful
Disadvantages of sub cutaneous administration?
Injection volume is limited
Why the skin is an attractive route for a lack of systemic side effect?
Avoids first pass metabolism - to liver and intestine and potential toxicity to those organs
-Potentially allows for steady state plasma concentration of drug to be achieved over prolonged period of time
