2a. Dermatological Pharmacology Flashcards
What are the methods of drug administration via the skin?
Topical Transdermal Subcutaneous Airways Conjunctival sac Nasal mucosa Vaginal
Describe topical treatment…
Used for local effect by applying the treatment directly to the skin
Describe transdermal treatments…
Used for systemic effect by applying the treatment to the skin. It subsequently diffuses into the dermal capillaries and is carried to other areas of the body e.g. drug patches
Describe subcutaneous treatments…
Delivered via injection into the adipose fat under the skin
What are the two methods of drug diffusion across the skin?
Intracellular route
Transcellular route
Describe the intracellular route of drug diffusion…
The drug diffuses between the corneocytes. This is the method of HYDROPHOBIC drugs
Describe the transcellular route of drug diffusion…
The drug diffuses through the corneocytes. This is the method of HYDROPHILLIC drugs
What equation describe the rate of diffusion of topically applied drugs?
Fick’s law of diffusion
What factors are considered in Fick’s Law of Diffusion?
concentration of drug in the vehicle, length of the coefficient pathway, permeability coefficient, partition coefficient and diffusion coefficient.
What is the role of a vehicle in giving a topically applied drug?
This can affect the rate and extent of absorption rate and extent of absorption
What are the factors that can affect the rate and extent of absorption of a topically applied drug?
Fraction of drug dissolved in vehicle
Inclusion of excipients
What is the purpose of excipients in a drug vehicle?
Enhance drug solubility and absorption
What factors can be used to increase the absorption of topically applied dugs?
Hydration of the skin to prevent moisture loss
Increasing the solubility of hydrophobic drugs by including excipients
What causes an increase in the partitioning?
A reduction in the barrier function of the strateum corneum perhaps from the formation of pore pathways.
What does an increase in the thickness of the skin lead to?
Decrease in the absorption of drug e.g. it is harder for drugs to be absorbed across the nail than on the face.
What are the functions of glucocorticoids?
Anti-inflammatory
Immunosuppressant
Vasoconstricting
Antiproliferation action upon keratinocytes and fibroblasts
What are some side effects of long term use of glucocorticoids?
Steroid rebound
Skin atrophy
Systemic effects
Spread of infection due to immune suppression of the skin
Steroid rosacea
Stretch marks - striae atrophica
Superficial dilatation of small blood vessels - telangiactasia
What is the mechanism of glucocorticoids?
- They are lipophilic and diffuse across the plasma membrane.
- Combine with GRα in the cytoplasm.
- Produce a dissociation of inhibitory heat shock proteins and the activated receptor translocates to the nucleus aided by importins.
- The activated receptor monomers assemble homodimers and bind glucocorticoid response elements in the promotor regions of specific genes.
- Transcription of genes is then switched either on or off to alter mRNA and the rate of synthesis of mediator proteins.
How does subcutaneously injected drugs reach the systemic circulation?
Capillaries an lymphatic vessels
Why is the skin a good choice for drug administration?
Application is simple
Allows for steady state plasma concentration
Avoids first pass metabolism
Drug absorption can be terminated rapidly
What are the factors that make a drug a good candidate for transdermal drug delivery?
lipophilic, of a low molecular weight, moderately potent and have a relatively short half life.
What are enhancers in terms of transdermal drug delivery?
Chemicals that interact with the lipid matrix of the stratum corneum to increase its permeability.
What are some examples of enhancers?
Water
Solvents - ethanol
Surfactants - sodium dodecyl sulphate.
What are creams?
Semisolid emulsion of oil in water
High water content
Contain emulsifier and preservative
What is an ointment?
Semisolid grease in ointment
Restrict transepidermal water loss
What are lotion?
Liquid formulation
What are gels?
Thickened aquaeous lotions
What are pastes?
Semisolids containing finely powdered material
What are foams?
Colloid with two-three phases
Usually hydrophilic liquid in continuous phase with foaming agent dispersed in gaseous phase
Name some types of topical therapies…
Emollients Topical Steroids Antiinfective agents Antipruritics Keratolytics Psoriasis therapies Cytotoxic and antineoplastic agents
What are emollients?
Enhance the rehydration of epidermis in dry and scaly conditions
What is the mode of action of topical steroids?
Vasoconstrictive
Anti-inflammatory
Antiproliferative
Name a mild steroid
Hydrocortisone 1%
Name a moderate steroid…
Modrasone Clobetasone Butyrate 0.05%
Name a potent steroid…
Mometasone Betamethasone Valerate 0.1%
Name a very potent steroid
Colbetasol Proprionate 0.05%
What are some side effects of topical steroids?
May worsen or mask infection
Systemic absorption
Increased risk of tachyphylaxis, rebound flares, glaucoma and cataract
What are some examples of antiseptics?
Povidone Iodine
Chlorhexidine]Triclosan
Triclosan
Hydrigen Peroxide
What are the clinical uses of antiseptics?
Recurrent infections
Skin cleansing
Wound irrigation
What are possible side effects of topical steroids?
Burning or irritation
Contact allergic dermatitis
Local toxicity
Systemic toxicity
Name the different bases or vehicles used for topical skin therapeutics…
Gels Creams Ointments Pastes Lotions Foams
What are the different TYPES of topical skin therapeutics?
Emollients Topical Steroids Anti-infective agents - antiseptics, antibiotics, antivirals, antifungals Antipruritics Keratolytics Psoriasis therapies Cytotoxic and antineoplastic agents
What are anti-pruritics?
Anti-itch drugs
What are keratolytics?
Topical agents applied to the skin to soften the keratin
What are emollients?
Emollients are used for the rehydration of the epidermis. This can be prescribed for dry and scaly skin conditions e.g. eczema
What are topical corticosteroids?
Topical steroids are medicines that are applied directly to the skin to reduce inflammation and irritation and cause local immune suppression
What are the modes of action of topical steroids?
Vasoconstrictive
Anti-inflammatory
Antiproliferative
What are the side effects of topical steorids?
thinning of the skin, purpura, stretch marks, telangiectasia, steroid rosacea and perioral dermatitis.
Name some calineurin inhibitors…
TACROLIMUS, PIMECROLIMUS
What is the role of calcineurin inhibitors?
To supress lymphocyte activation. This can be used in the topical treatment of eczema.
What are some systemic effects fo topical skin treatments?
Salicylism - this can rarely lead to death
Hypercalcaemia and Hypercalcuris - fromvitamin d analogues
Suppression of the pituitary
Name some antiseptic agents…
POVIDONE IODINE, CHLORHEXIDINE, TRICLOSAN, HYDROGEN PEROXIDE.
What is the use of antiseptics?
These are used to prevent recurrent infections, for skin cleansing and for wound irrigation.
Name some antifungals…
CLOTRIMAZOLE, TERBINAFINE CREAM, KETOCONAZOLE
Name some anti-pruritics…
MENTHOL, CAPSAICIN, CAMPHOR, PHENOL, CROTAMITON
Name some keratolytics…
SALICYLIC ACID OINTMENT
Name some cytotoxic and antineoplastic drugs…
SALICYLIC ACID OINTMENT
What is the use of cytotoxic and antineoplastic drugs?
Used for solar damages, Bowen’s disease and the treatment of superficial basal cell carcinoma
