Topic Therapeutics in dermatology Flashcards
Topical Treatment
What are some disadvantages?
Why topical treatment?
-Medicationis applied directly into the skin.
- Focus on area of need.
- Increased concentration
- Less systemic toxicity (topical steroid vs oral prednisone)
Can combine more complicated regimens without multiple orals
Disadvantages include compliance, can be messy, variable application, time consuming.
Vehicles for topical medications:
The art of using topical medications often revolves around selecting the appropriate vehicle. Overall, the appropriate vehicle is as important as selecting the concentration or the active ingredient. The table below summarizes composition of the most frequently used vehicles:
Ointments: Water in oil emulsion
Creams: Oil in water emulsion
Gels: Semisolid emulsion in alcohol base
Lotions/Solutions: Powder in water (some oil in water)
Foams: pressurized collections of gaseous bubbles in a matrix of liquid film
Mechanisms of Penetration of Topical Medication through Stratum Corneum
- Passive diffusion (moving across stratum corneum)
- Through channels or pores within a lacunar system in the stratum corneum
- Through appendageal structures (such as sweat gland and hair follicles).
What are the drug factors affecting the absoprtion of topical drugs?
Diffusion of a compound is _______ proportional to the molecular size of the drug.
1- Active drug concentration
2- Absorption is directly proportional to the _concentration of the active ingredien_t in the medication.
3- Molecular size of the drug or prodrug (_diffusion coefficien_t*)
4- Diffusion of a compound is inversely proportional to the molecular size of the drug
5- Lipophilicity of the drug (partition coefficient*)
–>Lipophilic topical agents are more likely to permeate the skin than hydrophilic agents.
6- Composition of the vehicle (effect on stratum corneum)
What are some patient factors affecting perctaneous absorption?
-Presence of barrier disruption
-Anatomic location (including thickness of the stratum corneum).
- Skin hydration and temperature
- Occlusion
- Amount applied
- Frequency (compliance)
The vehicle
Classification of vehicles:
_______–> Water in oil emulsion (80+% oil)
________-> Oil in water emulsion (~50/50)
_______–> Semisolid emulsion in alcohol base
_________–> Powder in water, some oil in water.
Solutions: Powder in water, some oil in water, powder in oil, alcohol base
Foams: pressurized collections of gaseous bubbles in a matrix of liquid film
What are some consideration for choosing an appropiate vehicle?
Water-based vehicles (such as creams, lotions, and solutions) contain preservatives that may increase the risk of contact allergy and sensitization.
Irritancy is associated with _______ and other types of alcohols.
Consider anatomic location, contact allergy/sensitization, and irritancy.
**Water-based vehicles (such as creams, lotions, and solutions) contain preservatives that may increase the risk of contact allergy and sensitization.
Irritancy is associated with high concentrations of propylene glycol, other types of alcohols, and certain acidic vehicle ingredients.
Ointments
_____ risk for sensitization and irritation.
Active ingredient delivered with _____ potency.
Best for _______ sites.
Patient may not like the ______.
Creams
Gels
-Drying (for alcohol based, not for aqueous)
-Delivers active ingredient with strong potency
- Carries **significant sensitization risk and relatively high irritation risk
- Best for oral mucosal surfaces and scalp
-Avoid gels on fissures, erosions, or macerated areas.
- Patient preference variable
Lotions/solutions
Foams
QUANTITY OF APPLICATION FOR TOPICAL MEDICATIONS
-One fingertip unit is the amount of cream or ointment, squeezed out of a tube, from the tip of an adult’s index finger to the first crease in the finger
One fingertip unit is enough to cover an area of skin twice the size of a flat adult hand with the fingers together.
-For example, if the area of skin to be treated is the size of four flat adult hands, two fingertip units of cream or ointment should be applied each time.
4 hand areas = 2 FTU = 1 gm
◦When diameter of the tube nozzle is 5mm
Other Notable
Quantities
–>1 gram of cream covers approximately 10 cm x 10 cm area of skin
–> 1 gram of ointment spreads 10% further than the same amount of cream
–>Approximately 20g are necessary to treat the entire body of an adult man, or roughly 280g per week if the medication were applied twice daily for 1 week (TAC 454g)
–> Quantities of ointment to dispense in children differ according to age due to different body surface areas.
Glucocorticoids
Instrinsic activity of the particular corticosteroid:
◦Modifying the structure of a corticosteroid molecule to make it relatively more fat soluble than water soluble facilitates the absorption into the skin.
–The concentration of the corticosteroid (the more concentrated the greater the absorption)
–The characteristics of the base (vehicle) in which it is formulated.
Instrinsic characteristics of skin
◦Greater thickness – less absorption
◦Less thickness – more absorption
Classification of topical steroids:
Superpotent belong to class ____ and the very low potency belong to class _____.
Clases were developed based on __________ assays.
–>Seven classes have been proposed based on potency.
-The **superpotent topical glucocorticosteroids belong to class 1, and the very low-potency topical glucocorticosteroids belong to class 7 (OTC hydrocortisone 1%)
These classes were developed based on **vasoconstrictor assays.
The three clinically useful and cost-effective steroids:
What class is Hydrocortisone 2.5%?
Used for ______ in children and adults.
Used in what parts of the body?
“The Gentle Touch”: Hydrocortisone 2.5% (cream or ointment)
Class 7 (low-potency)
–> Efficacious for mild eczema in children and adults
–>Treatment of inflammatory dermatoses involving anatomic regions such as the face/eyelids, intertriginous areas, or groin
“The Almost All-Purpose Weapon” Triamcinolone Acetonide 0.1% (cream or ointment)
It is a class _____.
Effective against most moderate________.
Where is it most commonly used?
Class 4 (cream formulation, mid-potency)
–>Effective against most moderate spongiotic dermatoses (including eczematous dermatitis, atopic dermatitis, allergic contact dermatitis, arthropod bite**)
–>Use on trunk and extremities
–>Long-term use not recommended for facial, intertriginous, and groin regions.
The Clobetasol Propionate 0.05% (cream or ointment)
Class ___.
Treats ______.
Avoid use in the ____.
Class 1 (high-potency)
-Treatment for acute eruptions that necessitate relatively rapid amelioration, such as contact dermatitis or acute drug eruptions
-Avoid use on the face, intertriginous areas, or the groin
-Longer-term use of clobetasol requires monitoring of development of adverse effects
General considerations for selecting a topical steroid?
Consider severity of the condition, location of the lesion, and need for hydration or drying effect
–>Consider potential for sensitization or irritation of certain types of vehicles
–>The same active glucocorticosteroid ingredient in an ointment vehicle may be more potent than the same ingredient in a cream, lotion, or solution vehicle
Side effects of steroids:
What is Tachyphylaxis?
common in what type of corticosteroids?
After how long can it happen?
How to avoid this?
Defined as a ***diminished pharmacologic response after repeated drug administration.
-Can be due to down regulation or receptor sequestration
——>Transiently unavailable to the drug, no effects
–>Common with high potency (class I) corticosteroids
◦Happens after 2 to 4 weeks of continuous therapy
◦Need to employ intermittent therapy to avoid this
Topical calcineurin inhibitors
What are they?
They inhibit______, to impair transcription of cytokines.
- Tacrolimus
- Pimecrolimus
- Non steroidal immunomodulating agents
- Selectively inhibit calcineurin, thereby impairing transcription of cytokines.
- Inhibitory effect on proinflammatory cytokine production in skin
Alter epidermal antigen presenting cells (langerhan) which results in decreased immune response to antigen.
Side effects from topical Calcineurin inhibitors
Cause what sensation?
Which one stings more?
Which ones has a greater affinity for FKBP12?
-Stinging or “tingling” sensation in about 10% of patients
**Tacrolimus stings more than pimecrolimus.
◦Tacrolimus has a 3-fold greater affinity for the cytoplasmic immunophilin FKBP12 than does pimecrolimus.
◦These molecules may trigger release of Substance P and/or calcitonin-gene related peptide that may be relevant to stinging sensation.
–Systemic absorption
◦Greater when applied to inflamed skin than to intact skin
