Pharmacokogical Principles in Dermatology Flashcards
Steps of drug delivery to the skin:
Absorption, distribution, metabolism, and elimination
____ drug delivery is applied right to the target area. No need to worry about bioavailability or first pass. There is less systemic ____ of the drug
Topical
Circulation
____ dosing has more systemic circulation and delivery to more tissues beyond the skin. Need to consider first pass effect, plasma protein binding
Oral
Layers of the skin:
Topical drugs need to make it to the ___ to have full effect
Dermis
Skin ___ varies by location which results in differences in drug absorption. Drugs are more readily absorbed in ___ layers of skin.
Structure
Thin
Stratum corneum: lipids and dead cells
_____ delivery is when the drug moves around the cells. ____ delivery is when the drug moves through the cells. Both are considered ___ delivery.
Intercellular
Transcellular
Transepidermal
____ is when drugs gain access to the dermis through a gland. ___ is when drugs gain access to the dermis through the hair follicle. Both are considered ____ delivery.
Transglandular
Transfollicular
Transappendageal
Other factors that affect topical drug absorption are ___ skin and ____ skin.
Aged
Damaged
Many factors effect the skin integrity and effect topical drug absorption:
Other factors affecting topical drug delivery to the skin:
Concentration of the topical drug is highest at the ___ ___. Burning to proteins will decrease concentration as it moves to the ___, where there are blood vessels.
Stratum corneum
Dermis
____ skin absorbs drugs better especially for polar drugs
Hydrated
Formulations and vehicles of topical drug delivery:
Moisturizers are sorted into 3 categories:
____ tend to dry the skin, have patients avoid use of this to optimize absorption.
Soaps
The main cellular pathways and systems that commonly targeted in skin pharmacology:
Inflammation, infection, cell devision
_____ play a major role in the treatment of many dermatologic conditions especially inflammation and itchy conditions.
Corticosteroids
____ are effective for conditions involving hyper-proliferation as well as immune and inflammatory dysfunctions
Corticosteroids
Mechanism of actions for corticosteroids: activate the ____ receptor (GR) which acts as a transcription factor that upregulates ____ genes and down regulates ____ genes. Allows thousands of genes to be targets.
Glucocorticoid
Anti-inflammatory
Pro-inflammatory
The immediate effects of corticosteroids involves there ability to effect ___ cells without requiring gene transcription
Immune
Examples of topical corticosteroids
Potency of corticosteroids is based on their ability to ____.
Vasoconstrict
Side effects of corticosteroids:
Skin atrophy, striae (stretch marks), acne, suppression of hypothalamus pituitary adrenal (HPA) axis.
Hypothalamus pituitary adrenal (HPA) axis is how regular ___ is regulated in the body. When someone uses corticosteroids medication, it shuts down this pathway because the drug is acting like ___. Not a problem for short term use.
Cortisol
Cortisol
____ ___ ____ can develop from long term use of highly potent corticosteroids. Presents as a rash at the target site. Caused by disregulation of HPA axis
Topical steroid withdrawal (TSW)
Non steroidal anti-inflammatory topical calcineurin inhibitors (TCI):
Table comparing tacrolimus versus hydrocortisone:
Tacrolimus and Pimecrolimus bind ____ and inhibits the ability of ___ to dephosphorylate the NFAT transcription factor which inhibits ____.
FKBP
Calcineurin
Inflammation
____ is approved to treat mild to moderate eczema in patients two years and older
Primecrolimus
Side effects of Topical Calcineurin Inhibitors (TCI):
____ is a non-steroidal anti inflammatory drug that inhibits PDE4. It can also be used to treat mild to moderate eczema.
Crisaborole
Crisaborole:
Other actions of PDE4 inhibition, other anti inflammatory effects:
Side effects of Crisaborole:
____ is a topical medication that is an immune response modifier that draws in immune system to attack the target. Approved for genetically warts, actinic keratosis, precancerous lesions.
Imiquimod
Imiquimod stimulates ___ and ___ immunity leading to inflammatory cell infiltration within the field of drug application, followed by apoptosis of diseased tissue. It is available in one use packets because it is not stable in ___ or ___.
Innate
Adaptive
Air
Light
Imiquimod is recognized by __ ___ and stimulates the activation of ____ transcription factor, release cytokines and draws in immune cells.
T cells
NFKB
Imiquimod stimulates innate and acquired immunity:
Side effects of Imiquimod:
Topical medications that do not regulate inflammatory response:
____ is derived from vitamin D, it is an analogue of vitamin D. It regulates the production and growth of skin cells. Used in eczema and psoriasis.
Calcipotriene
Calcipotriene:
The active metabolite ____ binds to the vitamin D receptor (VDR) which is a transcription factor. Vitamin D is synthesized in the lower layers of the epidermidis through a chemical reaction that is dependent on ___ ___. D has a significant role in ____ homeostasis and metabolism.
Calcitriol
Sun exposure
Calcium
Mechanism of action of Calcipotriene is somewhat unknown:
It does regulate ___ __ ___ which regulate cell proliferation and differentiation. It also affect the immune system.
Vitamin D Receptor
Side effects of Calcipotriene:
Should avoid if ___.
Pregnant
____ is another topical drug medication that inhibits abnormal cell growth and alerts the immune system. It stop cell division. Used for actinic keratosis. Comes in solution or cream
5-Fluorouracil (5-FU)
Mechanism of action of 5-Fluorouracil:
It inhibits ____ ____ which inhibits nucleotide synthesis.
Thymidylate synthase
Side effects of 5-Fluorouracil:
____ effects is side effects during development
Teratogenic
____ is an oral systemic medication that treats skin diseases that are rooted in the neutrophil being the primary issue (neutrophilic disease)
Dapsone
Dapsone inhibits ____ (MPO) which is a key element in the innate immune system and is released primarily by neutrophils for defense
Myeloperoxidase
Side effects of Dapsone:
Due to ___ and ___ of metabolites of the drug
Acetylation
Hydroxylation
_____ is an oral systemic medication that inhibits dihydrofolate reductase and disrupts ___ synthesis and cell division. Used to treat psoriasis, lupus, cutaneous T cell lymphoma but is starting to not be used as much.
Methotrexate
DNA
Methotrexate side effects:
____ is a systemic medication drug class that is the newest generation of drug design. They are bio genetically engineered proteins, which disrupt focused portions of the immune system involved in psoriasis. They often target ___ ___ or ___ ____. They need to be ___. Very ___ so very little side effects. They are expensive.
Biologics
Signal molecules
Immune cells
Injected
Specific
Generic drugs and branded drugs have the same ____.
Efficacy
Once the brand name drug ___ expires usually after 17 to 20 years, other drug companies can start making the ___ brand.
Patent
Generic
____ drugs are medications composed of sugars proteins, and or nucleic acids. Examples:
Biologic
Vaccines, therapeutic proteins, monoclonal antibodies
____ are not the same thing as generic drugs. Have a different chemical composition, and then namebrand drugs, but accomplish the same results.
Bio similar
____ drugs use the same molecule, same mechanism of action, and accomplish the same results as brand-name drugs but for cheaper
Generic
Biologics: the suffix denotes the drug class:
____ is a biologic drug that inhibits IL-4 and IL-13 which are both involved in BN T cell, activation and stimulation of humoral immunity, including IgE. Treats eczema not controlled by topicals. Subcutaneous shots every two weeks.
Dupilumab
____ refers to the damage of skin caused by UV light
Phototoxicity
___ is the most damaging, shorter waves. ___ is less damaging but penetrates deeper.
UV-B
UV-A
We need sunlight for:
Responses of sun exposure (phototoxicity)
If the air is ___ or ___ or higher elevation, UV index will be higher.
Thinner
Drier
Sunscreen is used to combat ___ and ____, meaning it is broad spectrum. Some contain ___ and ___ which as as reflectors.
UVA
UVB
zinc
Titanium
SPF sunscreen table:
____ is abnormal sensitivity to UV and visible light due to genetics, autoimmune diseases, or medication .
Photosensitivity
Phototoxcity versus photoallergy
Phototoxicity is a direct response to ___. Photoallergy (photosensitivity) is a delayed response that requires ___ ___ response.
Exposure
Immune system
___ ___ is the most common neoplasm. Minnesota has one of the higher rates.
Skin cancer
Sunlight induces ___ ___ that lead to neoplasia. It is also immunosuppressive and reduces immune surveillance
Thymidine dimers
Review:
Review:
Chemical burns are caused by ___ ___ with major tissue damage. Damage is a direct result of the chemical not dependent on tissue reaction to exposure.
Coagulative necrosis
___ ____ comprises 90% of all occupational skin diseases. Two types: ___ and ___
Contact dermatitis
Irritant
Allergic
Irritant contact dermatitis:
Allergic contact dermatitis:
Skin can be used as an indicator of the type of exposure:
