Pharmacology Flashcards
Vehicle
The way in which a drug is delivered/administered
Choice of specific vehicle is determined by
- physiochemical properties of drug (hydrophobic/hydrophilic)
- the clinical condition
Drug administration through the skin
Topical
Subcutaneous
Transdermal
Topical
Mainly for local effect but also used to treat underlying tissues
Direct application to the skin
Most important barrier to drug penetration
Keratin layer (stratum corneum) - very hydrophobic
Keratin layer drug penetration
Bricks are corneocytes
Mortar is the multiple intracellular lipids
INTRACELLULAR ROUTE
- most common, highly torturous, move around the bricks
TRANSCELLULAR ROUTE
- drug diffuses into bricks and enters underlying bricks
Topical drug uses
Local effects in the treatment of
- superficial skin disorders
- skin infections
- itching
- dry skin
- warts
Topical drug vehicles (6)
Ointments Creams Gels Lotions Pastes Powders
Factors influencing the absorption of topically applied drugs: Vehicle
Influences rate and extent of absorption of a topically applied drug
Lipophilic drug in lipophilic base
Because vehicle is highly lipophilic, it will tend to retain the lipophilic drug so there will be limited diffusion of drug across the keratin layer
Lipophilic drug in hydrophilic base
Ideal combination for moving a lipophilic drug across the keratin layer. Will achieve optimum concentration of drug in the skin
Hydrophilic drug in lipophilic base
Lipophilic base pushes drug into skin but it will be difficult for drug to diffuse around the hydrophilic environment
Factors influencing the absorption of topically applied drugs: drug conc
Only the soluble fraction provides the driving force of absorption
Factors influencing the absorption of topically applied drugs: partition coefficient
Only a small fraction partitions into the keratin layer - so poor absorption.
Increased partitioning results from decreased barrier function of the keratin layer.
To improve hydration we need to:
- hydrate the skin by occlusion (prevention of water loss)
- inclusion of excipients which increase solubility
Factors influencing the absorption of topically applied drugs: Nature of the skin
Site of application is important as the thickness of the keratin layer varies at different body parts
For areas of thicker skin, use a high potency glucocorticoid
If skin is broken then movement of the drug across it will be faster
Factors influencing the absorption of topically applied drugs: drug preparation
Consider what the drug salt is (butyrate stronger vs acetate weaker)
Consider the vehicle in which the drug is administered
Subcutaneous route of administration
Delivered by a needle into the adipose tissue just beneath the surface of the skin
Subcutaneous route of administration - advantages
Slow absorption - can be used to deliver drug for slow release to circulation
Painless
Subcutaneous route of administration - disadvantages
Injection volume limited
Transdermal drug delivery
Drug incorporated into adhesive patch and applied to epidermis
Transdermal drug delivery - advantages
Steady rate of drug delivery
Decreased dosing frequency
Avoids first pass metabolism
Transdermal drug delivery - disadvantages
Relatively few drugs are available
Transdermal drug delivery - examples
Nicotine
GTN
Fentanyl
Topical vehicles - creams
Semi-solid emulsion of oil in water
Contains emulsifier and preservative
High water content, not greasy
Topical vehicles - ointments
Semi-solid oil/grease - so restrict water loss
No preservative
Topical vehicles - lotions
Liquid formation
Solution of medication in water, alcohol etc
Used to treat scalp
Topical vehicles - gels
Semi-solid
Thickened aqueous lotions
Topical vehicles - pastes
Semi-solid
Contains finely powdered material
Protective and occlusive
Often used in cooling, drying, soothing bandages
Topical vehicles - emollients
Enhance rehydration of epidermis
Used for dry and scaly skin conditions (eczema, psoriasis)
Topical vehicles - wet wraps
Used for very dry skin
Topical steroids - properties
Vasoconstrictive
Anti-inflammatory
Anti-proliferative
Immunosuppression
Topical steroids - mild
Hydrocortisone
Topical steroids - moderate
Modrasone, clobethasone, butyrate
Topical steroids - potent
Mometasone, betamethasone
Topical steroids - v potent
Clobetasol, Proprionate
Topical steroids - side effects
Thin skin Stretch marks (striae atrophica) Purpura Steroid rosacea Telangectasia Too much use can trigger pustular psoriasis
Calicneurin inhibitor properties
eg tacrolimus, pimercrolimus
Don’t cause thinning of skin
May cause burning sensation
Anti-septics
eg: Savlon (chlorhexidine)
Uses: recurrent infections, wound irrigation, antibiotic resistance
Anti-virals
Topical antiviral - herpes simplex (cold sore)
Oral antiviral - eczema herpeticum, herpes zoster (shingles)
Anti-prupritics
Menthol - added to lotions to create cooling sensation
Capsaicin - reduces substance P at nerve endings
Keratolytics
Used to soften hard skin
eg: salicylic acid
