Pharmacology Flashcards
What are the main routes of drug administration in the skin?
Topical
Transdermal
Subcutaneous
Other than the skin, what other epithelial routes can be used for drug administration?
Airways Bladder Conjunctival sac Nasal mucosa Rectum Vagina
What is the single most important barrier to drug penetration?
The stratum corneum (keratin layer)
What makes up the stratum corneum?
corneocytes (hardened, dead, keratinocytes)
surrounded by intercellular lipids forming 10 - 30 sheets of tissue (these are constantly shed and renewed)
What are the two routes by which drugs can travel through the stratum corneum?
Transcellular
Intercellular
What holds adjacent corneocytes together?
corneodesmosomes
describe the structure of the intercellular route
multiple bilayers of lamellar structures of intercellular lipids
Highly hydrophobic and can act as a reservoir for lipid-soluble drugs (e.g. topical corticosteroids)
In what conditions are topical agents most likely to be used?
superficial skin disorders skin infections itching (pruritus) dry skin warts
What formula describes the factors which influence absorption of a topical drug?
Fick’s Law of Diffusion
J = KpCv
J = Rate of absorption Kp = permeability coefficient Cv = concentration of drug in the topical medication
What part of topical drugs provides the driving force for absorption?
soluble fraction
What substances can be added to topical drugs to aid solubility?
excipients (e.g. propylene glycol)
What factors can affect the absorption of topical drugs?
- Site of application (thickness of stratum corneum)
- hydration of the skin
- Integrity of the epidermis
- drug concentration / physicochemical properties
- drug salt (hydrocortisone butyrate far more potent than hydrocortisone acetate)
- vehicle (betamethasone valerate more active as an ointment than as a cream, or lotion)
How are subcutaneous drugs delivered to the body?
needle inserted into the fatty (adipose) tissue just beneath the surface of the skin
Drug reaches systemic circulation by diffusion into either:
- capillaries
- lymphatic vessels (particularly high molecular weight compounds)
What are the advantages of subcutaneous drugs?
Absorption = slow
Relatively simple and painless
Route of administration for many protein drugs (e.g. insulin)
Suitable for administration of oil-based drugs (e.g. steroids)
Used to introduce depot of drug under skin that is slowly released into the circulation:
- certain contraceptive steroids (medroxyprogesterone)
- antipsychotic drugs (fluphenazine decanoate)
What disadvantage do subcutaneous drugs have?
Injection volume is limited
Why is the skin an attractive route of drug administration for a systemic effect?
Application = simple and non-sterile
Allows steady-state plasma concentration (Cpss) of drug to be achieved over a prolonged period of time
Avoids first pass metabolism
Drug absorption can be terminated rapidly
What drugs are most suitable for transdermal delivery?
(i) low molecular weight
(ii) moderately lipophilic
(iii) potent
(iv) of relatively brief half-life (t½)
What are the advantages of transdermal drug delivery?
- Steady rate of drug delivery
- decreased dosing frequency,
- avoidance of first-pass metabolism
- rapid termination of action (if t½ is short)
- User friendly, convenient, painless
What are the disadvantages of transdermal drug delivery?
- Relatively few drugs suitable
- allergies
- cost
Give examples of drugs that can be administered transdermally?
nicotine
GTN
Fentanyl
estradiol
What do chemical enhancers do to improve transdermal drug delivery?
interact with the lipid matrix of the stratum corneum to increase permeability
(mainly to drugs that already cross the skin reasonably well)
What agents can be used to chemically enhance a transdermal patch?
Water – increased hydration of the stratum corneum and the formation of a ‘pore’ pathway
Variety of solvents (e.g. ethanol) and surfactants (e.g. sodium dodecyl sulphate)
