The two layers of the skin consist of the epidermis and dermis. The epidermis is the uppermost part of the skin, which we can see all over our bodies. The epidermis and dermis are composed of their own layers, which we will discuss in a bit. Below the dermis is the hypodermis, which consists of adipose tissue. Below the hypodermis is the subcutaneous layer, which is the location site for many of our injectable drugs, such as insulin. Between the layers there are many hair follicles, which make up the pilosebaceous unit, consisting of hair, sebaceous gland, apocrine and eccrine sweat glands, and the arrector pili muscle. The pilosebaceous unit is particularly important in thermoregulation and electrolyte homeostasis - sweat glands function to release NaCl and H2O from the body, producing a cooling effect and maintaining electrolyte balance.
Before we get into the functions of the skin, I will go back and summarize the various layers in the epidermis and dermis. The epidermis is composed of 5 or 6 layers, depending on the type of skin. These layers include (from bottom up): Stratum basale, spinosum, granulosum, lucidem (only on thick skin - soles of feet, palms of hands), and the stratum corneum. These sit on the basement membrane, which connects the dermis to the epidermis. The stratum basale consists of merkel cells and cuboidal cells. The stratum spinosum contains melanocytes, responsible for color of the skin, and langerhans cells, which are antigen-presenting cells involved in the immune response. The stratum corneum, the uppermost layer, is also the thickest layer of the skin.
The dermis is made up of many types of cells: fibroblasts, which make up the extracellular matrix, including collagen, mast cells, sensory nerve fibers, and capillaries. The dermis is the area of the skin containing the nerves and blood supply for the skin. Different sensations which are felt on the skin are pressure, pain, and temperature.
The functions of the skin are as follows: 1)protection/barrier for the underlying tissues, 2)wound healing, 3)vitamin D synthesis, 4)sensation, 5)thermoregulation, and 6)secretion. The skin acts as a barrier for bacteria (by secreting its own antimicrobials), UV light, and injury. The skin is extremely efficient at wound healing, as evidenced by the quick healing of superficial cuts and scrapes. Vitamin D synthesis occurs when the sun causes the conversion of 7-dehydrocholesterol to cholecalciferol and eventually into active vitamin d, which is crucial in the regulation of calcium. The skin also detects sensations, as mentioned above, pain, temperature, and pressure. The skin also secretes sweat, antimicrobials, and sebum. Sweat helps to regulate temperature, antimicrobials help to prevent bacterial infection on the skin, and sebum acts as a lubricant and fat secretor.
Pharmacologically, the skin conditions which are included in NAPLEX prep are: acne, cold sores, dandruff, alopecia, eczema, hyperhidrosis, fungal infections, diaper rash, hemorrhoids, pinworm, lice/scabies, minor wounds, burns, poison ivy/oak/sumac, inflammation/rash, and sunscreens. I will be delving deeper into these subjects individually throughout the duration of this APPE rotation. Please refer to this GoogleDoc Folder for all NAPLEX review of skin:
https://drive.google.com/drive/folders/1fS5RbT9WIJHUFy1TrVuWnd4XeQHT7LOT?usp=sharing
Drug-induced skin discoloration is a well-documented adverse effect that can occur with chronic or high-dose use of certain medications. Although often benign from a clinical standpoint, the resulting pigmentary changes can lead to significant psychosocial distress and negatively impact medication adherence. Discoloration may present as hyperpigmentation, hypopigmentation, or nonmelanin-based alterations in skin tone. These effects can be caused by mechanisms such as increased melanin synthesis, direct deposition of drug or metabolites in the skin, hemosiderin or iron complex deposition, or post-inflammatory processes triggered by drug-induced cutaneous inflammation.
Hyperpigmentation is the most commonly encountered form of drug-induced discoloration. A classic example is minocycline, which can cause blue-gray pigmentation that may affect the face, limbs, or oral structures, particularly with prolonged use. This is believed to be due to iron-containing complexes deposited in dermal tissues. Amiodarone, another frequently implicated agent, can produce a slate-blue or dusky discoloration, often in photoexposed areas, as a result of lipofuscin accumulation. Hydroxychloroquine and chloroquine, typically used in autoimmune disorders, have also been associated with bluish-gray or black pigmentation, particularly on the face and lower legs. Other agents such as chemotherapeutic drugs (e.g., bleomycin, cyclophosphamide) and antiretroviral medications like zidovudine have also been implicated in cutaneous and mucosal pigmentation changes.
Although less frequently observed, hypopigmentation can occur as a result of melanocyte suppression or destruction. This is seen with prolonged topical corticosteroid use, as well as agents like imiquimod and phenol derivatives. Rarely, biologic agents such as tumor necrosis factor-alpha inhibitors have been reported to induce vitiligo-like depigmentation, which may reflect immune modulation of melanocytes.
Pharmacists play an important role in the early identification and management of drug-induced pigmentary changes. This includes recognizing the clinical presentation, correlating it with the patient’s medication history, and differentiating it from other causes such as melasma, post-inflammatory hyperpigmentation, or systemic disease. While some pigmentary changes may be reversible upon drug discontinuation, others—particularly those related to minocycline or amiodarone—can be persistent or even permanent. Patient counseling should include education on the expected course of discoloration, the potential for reversibility, and strategies for prevention such as sun protection. In some cases, referral to dermatology may be warranted for further evaluation or cosmetic management.
Although pigmentation changes may be viewed as cosmetic, they can significantly influence a patient's willingness to continue therapy. Addressing these effects through education, monitoring, and empathetic communication allows pharmacists to support both clinical safety and patient-centered care.
Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2(4):253–262. doi:10.2165/00128071-200102040-00005
Mishra K, Mahajan VK, Mehta KS, Chauhan PS. Drug-induced pigmentation: an updated review. Pigment Int. 2016;3(1):5–12. doi:10.4103/2349-5847.180577
Sharma V, Kaur I, Kumar B. Drug-induced pigmentation: review and case series. Indian J Dermatol Venereol Leprol. 2001;67(5):241–244.
Cohen PR. Slate-gray pigmentation from minocycline: a review of the literature and a case report. Cutis. 1995;56(5):285–287.
U.S. Food and Drug Administration. Amiodarone [prescribing information]. Updated 2023. Accessed April 2025. https://www.accessdata.fda.gov