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Chapter 75: Dermatological Pharmacology

Matthew J. Sewell; Dean S. Morrell

ABBREVIATIONS

Abbreviations

APC: antigen-presenting cell

AUC: area under the curve

BCC: basal cell carcinoma

cAMP: 3′,5′-cyclic adenosine monophosphate (cyclic AMP)

CBC: complete blood cell count

CCR4: C-C chemokine receptor 4

CTCL: cutaneous T-cell lymphoma

CTLA4: cytotoxic T lymphocyte–associated protein 4

DEET: diethyltoluamide (N,N-diethyl-m-toluamide)

DHT: dihydrotestosterone

ECP: extracorporeal photopheresis

En1: engrailed-1

EMA: European Medicines Agency

FDA: U.S. Food and Drug Administration

5FU: 5-fluorouracil

GI: gastrointestinal

GM-CSF: granulocyte-macrophage colony-stimulating factor

G6PD: glucose-6-phosphate dehydrogenase

GRASE: generally recognized as safe and effective

HPV: human papillomavirus

HSV: herpes simplex virus

IFN: interferon

IL: interleukin

IVIG: intravenous immunoglobulin

JAK: Janus kinase

MRGPR: Mas-related G protein-coupled receptor

MRSA: methicillin-resistant Staphylococcus aureus

mTOR: mammalian (or mechanistic) target of rapamycin

NSAID: nonsteroidal anti-inflammatory drug

ODC: ornithine decarboxylase

OTC: over the counter

PABA: p-aminobenzoic acid

PD-1: programmed death-1

PDE: cyclic nucleotide phosphodiesterase

PDT: photodynamic therapy

PUVA: psoralen and UVA

RAR: retinoic acid receptor

REMS: risk evaluation and mitigation strategy

RXR: retinoid X receptor

S1PR1: sphingosine-1-phosphate receptor 1

SPF: sun protection factor

SSD: silver sulfadiazine

SSTI: skin and soft-tissue infection

STAT: signal transducer and activator of transcription

TNFα: tumor necrosis factor α

TPMT: thiopurine S-methyltransferase

TRPV1: transient receptor potential vanilloid type 1

TYK2: tyrosine kinase 2

UV: ultraviolet

VZV: varicella-zoster virus

PRINCIPLES OF DERMATOLOGICAL PHARMACOLOGY

The skin is a biologically active, multifunctional, and multicompartment organ. Medications can be applied to the skin for two purposes: to directly treat disorders of the skin and to deliver drugs to other tissues. Effective and safe use of topical pharmacological therapies requires an understanding of skin physiology and factors influencing percutaneous drug absorption and metabolism (Hwa et al., 2011; Wolff et al., 2008). General features of skin structure and percutaneous absorption pathways are outlined in Figure 75–1.

Figure 75–1

Cutaneous drug absorption. After application of a drug to the surface of the skin (stratum corneum), evaporation and structural/compositional alterations may occur that affect the drug’s ultimate bioavailability. The stratum corneum limits drug diffusion into the lower layers and thence into the body. A number of absorptive routes are possible, singly or in combination: between the cells of the stratum corneum (intercellular), across the corneal cellular layer (transcellular), and into the concavity of a hair follicle (follicular) with its associated sebaceous glandular cells and arrector pili muscle that is innervated by the sympathetic branch of the autonomic nervous system. Melanocytes and Langerhans cells are accessible in the lower epidermis. In the epidermal and dermal layers, drugs may also reach the eccrine glands (sweat glands) and their ducts. Permeation to the dermis brings a drug in contact with lymphatics (in green) and cutaneous vessels carrying arterial and venous blood (red and blue, respectively). These vessels provide an absorptive route into the general circulation. Deeper permeation to the hypodermis may also occur.

A diagram depicts the cutaneous drug absorption process in the human skin.
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