Beyond the Bandage: How Common Medications Affect Wound Healing

Beyond the Bandage: How Common Medications Affect Wound Healing

By Alexis Tunnell and Nicole Brandt, PharmD, MBA

Chronic wounds affect about 1 in 6 Medicare beneficiaries in the United States, totaling approximately 10.5 million people.¹  Too often, consideration of prescription and over-the-counter medications are not factored into the plan of care for wound care.  The intent of this article is to draw attention to commonly used medications and their negative implications for wound healing.  

There are several classes of medications known to delay wound healing, but we will review anticoagulants, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and histamine-2 receptor antagonists (H2-RAs), as well as discuss implications of medications on nutrient deficiencies. 

Anticoagulants

Anticoagulant use, including warfarin and direct oral anticoagulants (DOACs), increases with age due to conditions such as atrial fibrillation and venous thromboembolism. Warfarin can impact skin health and wound healing by causing cutaneous necrosis.² Cutaneous necrosis is attributable to transient hypercoagulability owing to altered protein C and S levels that impair blood vessels, especially those supplying body areas with abundant subcutaneous fat, such as the breast, thigh, and buttocks.³ Additionally, patients on warfarin should be monitored for bleeding through routine International Normalized Ratio (INR) blood tests to measure how quickly the blood clots.⁴

DOACs are increasingly prescribed preferentially over warfarin due to their direct impact inhibition on factor Xa as well as a lower risk of bleeding and drug interactions.⁵  Despite these advantages, they still can impact wound healing due to the bleeding risk. Examples of skin wounds affected by DOACs are skin incisions and biopsies, which may bleed persistently if clot formation is impaired. Profuse bleeding, hematoma formation, and infection risk are possible if hemostasis is not achieved.⁶ While blood tests are not required to monitor DOACs, it is important to regularly assess for signs of bleeding and be aware of enhanced measures needed for injuries.

Corticosteroids

Corticosteroids are commonly used as topical treatments for various skin conditions by binding and blocking specific proinflammatory genes, interleukin 1-alpha, and interleukin 1-beta.⁶ Proinflammatory genes are responsible for promoting the inflammatory response of the immune system to help fight infections and heal wounds. Disruptions to perfusion, oxygenation, and inflammatory signaling processes result in insufficient wound reparation.⁷ Corticosteroids specifically disrupt the body’s inflammatory response, especially in skin and soft tissue infections. Additionally, prolonged use of corticosteroids can cause skin atrophy. Chronic steroid use thins the dermis, weakens barrier functions, and increases corticosteroid absorption. Atrophic skin more readily absorbs topical medications, leading to a significant increase in systemic corticosteroid plasma concentrations.⁸ Substantial levels of corticosteroid in the body will continue to decrease the immune system's anti-inflammatory response, which can cause slower healing. Meanwhile, corticosteroid-induced skin atrophy results in fragile, injury-susceptible skin, adding an additional challenge for wound healing in older adults.^9,10

NSAIDs

NSAIDs work by inhibiting cyclooxygenase (COX) enzymes 1 and 2. COX-1 is expressed in most tissues for normal cellular processes, including platelet aggregation, while COX-2 is expressed in response to inflammatory stimuli.¹¹ Nonselective NSAIDs (e.g., ibuprofen, naproxen, diclofenac) inhibit both enzymes, leading to an increased bleeding risk and decreased inflammatory response.

Diclofenac gel is a topical NSAID used for pain and osteoarthritis. Patients taking this medication have an increased risk of bleeding due to the lack of platelet formation.¹² This bleeding risk causes delayed wound healing. Most skin wounds have damaged blood vessels that require rapid platelet recruitment. The clot that forms acts as a shield to protect the wounded tissue and allows a matrix for cells to begin the repair process.^13,14

Additionally, further systemic absorption of the topical medication when applied to broken skin or open wounds can lead to other adverse effects. Skin wounds that heal slowly may have poor tissue quality, allowing medications to be absorbed more readily into systemic circulation. Rapid absorption of the drug through the skin to the bloodstream can lead to adverse reactions. NSAID application to open skin should be avoided, and current wounds should be monitored for proper healing.

Medication Related Nutrient Deficiencies

Wound healing is dependent on hemostasis, inflammation, remodeling, and proliferation. These factors are influenced by proper nutrients such as magnesium, copper, zinc, and iron. Magnesium aids in the synthesis of protein and collagen, whereas copper impacts the cross-linkage of collagen.¹³ Cross-linkage is important for structural support, re-epithelialization, and inflammation during the healing process.¹⁴ Iron and zinc also impact collagen synthesis. Zinc is a co-factor for RNA and DNA polymerase, which is responsible for tissue regeneration.^10,15

Recognizing the role nutrients play in the proper healing of skin wounds is essential to understanding the impact medications have on nutrient depletion. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H-2 RAs) are commonly prescribed medications that can alter the balance and absorption of these nutrients in the body.¹⁶ Once protonated by the stomach acid in the gastrointestinal tract, PPIs act by binding to the proton pump and blocking acid secretion. Most nutrients require an acidic environment for solubility and absorption. Without the proper absorption of these nutrients, patients can experience delayed and ineffective wound healing. H2-RAs can impair nutrient absorption, like PPIs. Although they do not directly block acid production, H2-RAs inhibit histamine receptors, thereby reducing gastric acid secretion. Nutrient availability is vital to the wound-healing process, and proper acidity levels play a significant role. However, H2-RAs have also been shown to accelerate skin repair by blocking histamine production in inflamed skin, so the effects are mixed.¹⁷

Organizations such as the Post-Acute Wound & Skin Integrity Council provide education and resources for the interdisciplinary team.¹⁸  

Find the references for this article here.

Alexis Tunnell is a 3rd-year PharmD student training at the University of Maryland, Baltimore (UMB). Dr. Nicole Brandt is a Professor, Executive Director & Endowed Parke-Davis Chair in Geriatric Pharmacotherapy at UMB, as well as a practicing pharmacist.