Compounded Topical Analgesics

Amode Tembhekar, BS

Christopher Migdal, BS

Martin AC Manoukian, BS

FAST FACTS

Topical analgesics and anesthetics may include patches, creams, ointments, or gels prepared for local delivery to the skin, targeting sensory nerve endings and tissues after dermal penetration.
Topical administration allows effective delivery of medications while reducing systemic side effects.
Topical analgesics can improve patient adherence and acceptance.

INTRODUCTION

The use of compounded pain medications has long been used in pain management to increase drug efficacy while simultaneously decreasing toxicity. Recently, this method of pharmaceutical delivery has gained increasing popularity owing to a greater understanding of the adverse effects, addiction potential, and abuse of currently prescribed oral analgesics. Many physicians prefer to use compounded topical medications owing to perceived improvements in efficacy and a resultant decreased narcotic prescribing.¹ In particular, compounded topical analgesics have been demonstrated to be effective tools for treating various types of pain, including musculoskeletal pain, fibromyalgia, peripheral neuropathic pain, diabetic neuropathy, postherpetic neuralgia, and vulvyodynia.² Although there are a plethora of options and formulations, this chapter will provide a concise summary of commonly used compounding medications and the principles behind their use. There are numerous advantages to using compounding medications, chief among them their ability to produce local, targeted effects while avoiding the undesirable systemic effects of oral dosing, thereby resulting in improved patient adherence²^,³.

DELIVERY TO TARGET TISSUE

To be effective, compounded topical analgesics must be able to traverse the skin to reach their site of action at the nerve endings located within the dermis. To do so they must either enter the dermis via the skin appendages or diffuse through the epidermis. Although entry via the skin appendages is less selective, these appendages are not uniformly distributed throughout the body, and the drug can be sequestered in the hair follicles.⁴ Drugs that reach the dermis via diffusion must first cross stratum corneum, a layer of dead keratinocytes that contains intracellular lipids and is covered by a lipid film.⁴ To effectively cross this lipophilic barrier, drugs must follow Lipinski’s rule of five, which states that drugs must weigh less than 500 daltons, must have a log P of less than 5 (a measure of lipophilicity), must have less than 5 hydrogen bond donors, and must have less than 10 hydrogen bond acceptors.⁵ Next, compound topical analgesics must cross the layers of the epidermis, which from superficial to deep are the stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale, each of which are aqueous layers of keratinocytes at successive stages of differentiation.⁶ The final barrier is the basement membrane, a charged layer of connective tissue, anchoring fibrils, and glycoproteins that is mostly permeable to cationic molecules.⁷ Upon traversing the basement membrane, drugs then enter the dermis, which contains the sensory nerve endings that are the targets for compounded analgesics. The dermis is also highly vascularized, allowing for the delivery of drug to local downstream tissue (Figure 35-1). However, if too much drug enters the dermal vasculature, it is possible for the drug to reach detectable levels systemically.⁸

FIGURE 35-1 The skin layers.

FORMULATIONS

Multiple formulations of compounded analgesics exist, and selection should be based on the etiology of a particular pain condition. For example, for a patient with neuropathic pain a regimen may include Ketamine 10%, Gabapentin 6%, and Clonidine 0.2%.⁹ Baclofen 2% and Amitriptyline 2% may be supplemented as deemed appropriate. For mechanical or inflammatory pain associated with muscle spasms, another analgesic compounded combination of Ketoprofen, Lidocaine, and Cyclobenzaprine would be favorable. Capsaicin is another promising topical analgesic that has been effective in treating postherpetic neurlagia.¹⁰ The mechanisms of action of these drugs are summarized in Table 35-1. These analgesics are delivered in the form of creams, gels, and ointments that may have limited efficacy when used alone. Thus, compounded topical analgesics are usually delivered with transdermal bases such as Pluronic lecithin organogel, Speed Gel, VanPen, DemiGel, Lipoderm, or LipodermActiveMax to enhance permeation and absorption.³^,¹¹^,¹² Keep in mind that multiple mechanisms and potential targets exist for therapeutic pharmacologic intervention for both acute and chronic pain. Careful assessment should guide treatment strategy.

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