Topical Timolol for Recalcitrant Wounds

Abstract

A woman in her 80s with a history of venous insufficiency based on clinical presentation and vascular studies presented with multiple painful ulcerations on the bilateral ankles. She developed wounds in 1972 with subsequent trauma that led to repetitive skin breakdown. Her current wounds began 1 year ago. The patient was initially treated with multilayered elastic compression bandages (Profore; Smith & Nephew), which were changed weekly, and various foam dressings (Allevyn; Smith & Nephew; Mepilex Ag; Molnlycke Health Care). When her wound failed to heal, adjuvant therapies, including serial applications of porcine small intestine submucosa (Oasis; Healthpoint Biotherapeutics), bilayered living skin equivalent (Apligraf; Organogenesis) and an autologous splitthickness graft from the thigh were used but did not result in complete closure. After 6 months, the wound was 3.2 cm 2 and a β 2-adrenergic receptor (B2AR) antagonist, topical timolol, 0.5% (Timoptic; Aton Pharma), was instilled, 1 drop every 2 cm of wound edge weekly, then covered with silicone foam and 3-layer compression. All wounds, including her target ulcer, were fully epithelialized after 8 weeks of treatment, and the patient was prescribed a compression apparatus (JuxtaCure;

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

“…Accordingly, fibroblast activity and migration were not enhanced. This is contrary to findings of Braun et al [8], who detected a strong local pro-healing effect of timolol, which definitely involved fibroblast proliferation at the wound base. Timolol is an unselective β-blocker, which might be a first hint for divergent effects of different β-blockers on wound healing, dependent on the β-receptor selectivity.…”

“…β-Receptor blockers seemed to slightly improve wound healing. The results after local timolol application were particularly noteworthy [8]. The influence of calcium channel blockers on wound repair processes displayed a more positive tendency.…”

“…Most analyses refer to β-receptor blockers like metoprolol or propranolol. The effects seemed to be mediated by activation of the keratinocytes and elevation of angiogenesis [8-10]. Especially timolol exerted a pro-proliferative effect after local application [8].…”

“…The effects seemed to be mediated by activation of the keratinocytes and elevation of angiogenesis [8-10]. Especially timolol exerted a pro-proliferative effect after local application [8]. Bhaskar et al [11] demonstrated that the calcium channel blocker amlodipine enhances the tensile strength of wounds, but not the epithelialization [12, 13].…”

Topical timolol for the treatment of pyoderma gangrenosum

“…β-adrenergic receptors are present on cells in multiple organ systems, including the skin, particularly on keratinocytes, fibroblasts and melanocytes. The mechanism of action of β2-AR antagonists appears to be related to enhancement of keratinocyte migration and promotion of wound healing 6. Neutrophils also express β2-AR, and reduction of neutrophil recruitment can represent another mechanism responsible for improvement of PG lesions 7…”