NMT150 Introduction to Dermatological Pharmacology (PDF)

INTRODUCTION TO DERMATOLOGICAL PHARMACOLOGY Dr. Adam Gratton NMT150 MSc ND January 26, 2023 LECTURE COMPETENCIES Describe the mechanism of action of topical corticosteroids Describe the adverse effects associated with topical corticosteroid use Describe the differences between the...

INTRODUCTION TO DERMATOLOGICAL PHARMACOLOGY Dr. Adam Gratton NMT150 MSc ND January 26, 2023 LECTURE COMPETENCIES Describe the mechanism of action of topical corticosteroids Describe the adverse effects associated with topical corticosteroid use Describe the differences between the vehicles used to deliver corticosteroids State the appropriate initial corticosteroid potencies based on the area of the body being treated Define a fingertip unit INTRODUCTION There are a large number of conditions that can cause a rash, pruritis, or both Treatment for rashes secondary to infectious etiologies generally focus on the infection itself Secondary infections are possible For conditions like atopic dermatitis (eczema) pruritis is the most important symptom to control CORTICOSTEROIDS Two main subclasses: glucocorticoids and mineralocorticoids Glucocorticoids affect carbohydrate, fat, and protein metabolism and also have anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive properties CORTICOSTEROIDS Mineralocorticoids are primarily involved in electrolyte regulation by modifying renal excretion mechanisms Both mineralocorticoid and glucocorticoid receptors are expressed in the skin TOPICAL CORTICOSTEROIDS The hydrocortisone backbone provides the basic structure from which all other topical corticosteroids (TCS) are derived Fluorinating or esterifying certain carbons in the four-ring backbone can increase the potency of the TCS MECHANISM OF ACTION Once absorbed, TCSs interact with an intracellular glucocorticoid receptor The TCS-receptor complex then translocates to the nucleus where a large number of gene transcription changes take place MECHANISM OF ACTION General upregulation of anti-inflammatory mediators and downregulation of inflammatory mediators Vasoconstrictive effect which reduces delivery of inflammatory mediators and improves erythema Anti-mitotic effect which inhibits cell proliferation and collagen synthesis Immunosuppressant effect MECHANISM OF ACTION More precise descriptions of their mechanism of action are usually discussed within the context of specific disorders, like atopic dermatitis, psoriasis, etc. ADVERSE EFFECT Many adverse effects are caused by overstimulation of glucocorticoid receptors Stimulation of mineralocorticoid receptors in the skin may reduce the severity of some of these adverse effects ADVERSE EFFECTS When used topically… Perioral dermatitis Stinging or burning Acne sensation Purpura Dermal atrophy Increased hair growth Striae Skin pigment changes Rosacea Delayed wound healing ADVERSE EFFECTS Many adverse effects are due to inappropriate use or using too high a potency for longer than is necessary Systemic suppression of the HPA axis is generally only seen when TCSs are applied to large body surface areas, particularly more so in children FINGERTIP UNITS Developed to help patients apply appropriate amounts of TCSs. One FTU is approximately 0.5 g The amount squeezed from a standard tube from the fingertip to the first crease of an adult finger One FTU should cover an area equal to 2 adult handprints with fingers together  FTUs required for one application by age group Body Area 3–6 1 -2 years 3 – 5 years 6 – 10 years Adults months Face and Neck 1 1.5 1.5 2 2.5 One arm and 1 1.5 2 2.5 4 hand One leg and 1.5 2 3 4.5 8 foot Trunk (front) 1 2 3 3.5 7 Trunk (back 1.5 3 3.5 5 7 incl. buttocks) TOPICAL DRUG VEHICLES Topically administered drugs need to be compounded in a base to stabilize the drug and permit it to be stored in a manner that allows for as-needed delivery There are many options each with their own pros and cons TOPICAL DRUG VEHICLES Creams Fairly standard and commonly used vehicle Generally preferred from a patient perspective because they tend to absorb quickly and leave minimal residue Tend to cause irritation due to additives Are the least effective vehicle to allow the drug to penetrate the skin TOPICAL DRUG VEHICLES Gel An alcohol-based vehicle that can cause stinging and irritation if used on open lesions Useful for hairy areas and oily skin TOPICAL DRUG VEHICLES Lotion Often an alcohol-based vehicle that can cause stinging and irritation if used on open lesions Evaporates well leaving minimal residue and is useful for larger areas or hairy skin areas TOPICAL DRUG VEHICLES Ointment Thick, greasy base like petroleum jelly Least preferred by patients but offers the best vehicle to allow the drug to permeate the skin Also has an emollient effect Causes little to no irritation TOPICAL DRUG VEHICLES Foam An aerosolized oil-based formulation Allows for application to hard-to-reach areas Tends to leave a greasy residue POTENCY TCSs are classified by potency and are often divided into seven classes. Class 1 is the highest potency also called the superpotent or ultra-high class. Class 2 – high, Class 3 – medium-high, Class 4/5 - medium Class 6/7 – low potency POTENCY Potency can change depending on vehicle used The same drug at the same concentration is a higher potency when compounded in an ointment versus a cream POTENCY Low potency drugs should be used on the face and within skin folds as the skin is thinner and more absorption takes place Medium potency drugs can be used on the body and scalp High potency drugs are needed to penetrate the palms and soles PRESCRIPTIONS TCS prescriptions require some additional information Drug name, concentration, base/vehicle In addition to instructions, refills, etc. Example: Halobetasol proprionate 0.05% ointment Most are standard concentrations and many are available prepackaged in commonly used vehicles. SAMPLE QUESTION A high-potency topical corticosteroid would be an appropriate initial recommendation for the treatment of which of the following body areas? A. Face B. Elbow C. Palm D. Scalp