Transdermal and Topical Drug Administration in the Treatment of Pain

Abstract

The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review

“…α-Lipoic acid is a natural thiol with potent antioxidant properties, and is used as a dietary supplement. In studies evaluating this indication, it has been administered orally at doses between 600 and 1800 mg and intravenously at 600 mg per day for 3 weeks, excluding weekends [77][78][79][80][81][82]. Both formulas have been recently characterized by the FDA as safe and effective treatment options for painful DSPN [83].…”

“…No [32] 0.075% four times/d [31] Skin-site reactions [63] Equal efficacy to amitriptyline [62] Capsaicin 8% patch No [68] One application every 3 months [66] Skin-site reactions [66] Conflicting results in DSPN [66]; application can be painful [66]; monitor for transient blood pressure increase for at least one hour following application [66] 5% lidocaine plaster No [70] Maximum 3 lidocaine plasters 5% can be applied to intact skin once daily for a period of 12 h [70] Skin-site reactions [74] Comparable efficacy to pregabalin, amitriptyline, capsaicin, and gabapentin [72,73] Clonidine gel 0.1% No [75] Single doses of 0.65 g of gel, three times daily [76] Skin-site reactions [76] Pain relief in a small number of studies of low-to-moderate quality [75] Pathogenesis-oriented treatment α-Lipoic acid No [77] 600-1800 mg orally or 600 mg/d intravenously for 3 weeks, excluding weekends [77][78][79][80][81] Nausea, vomiting, abdominal discomfort, diarrhea [77] FDA statement: safe and effective treatment option for painful DSPN [82] Legend: FDA: Food and Drug Administration.…”

Efek Eutectic Mixture of Local Anesthetics (EMLA) terhadap Nyeri Penyuntikan Jarum Spinal

“…Jalur intraseluler yang berliku dapat berperan sebagai rute utama penyerapan obat dan penghalang utama dari sebagian besar obat-obatan. 10 Lidokain dan prilokain menstabilisasi membran neuron dengan cara menghambat aliran sodium yang menyebabkan peningkatan ambang batas eksitasi saraf hingga tidak terbentuk aksi potensial yang diperlukan untuk inisiasi dan konduksi impuls sehingga menciptakan efek lokal anestesi pada lapisan kulit. Waktu aplikasi EMLA minimal 120 menit membuat EMLA diserap secara maksimum sehingga mencapai kedalaman 5 mm pada lapisan epidermis yang paling banyak memiliki ujung saraf sehingga efek lokal anestesi saat dilakukan penyuntikan jarum spinal akan mencapai yang lapisan kulit lebih dalam.…”

“…Diharapkan dengan aplikasi yang lebih lama, penyerapan EMLA lebih maksimal. 1,4,10,13 Penelitian di Amerika Serikat tahun 2018 yang menggunakan EMLA sebagai adjuvan infiltrasi anestesi lokal menunjukkan EMLA memberikan efek analgetik selama kateterisasi arteri femoralis. Penelitian tahun 2017 di Iran yang membandingkan efek vapocoolant spray dengan EMLA untuk mengurangi nyeri pada saat kanulasi intravena didapatkan EMLA efektif untuk mengurangi kanulasi intravena.…”

Peripheral Sensitization

“…Therefore, these chemicals provide enormous options for pain intervention of peripheral origin. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, and creams containing antidepressants (i.e., doxepin and amitriptyline) act locally in tissues through specific receptors and/or ion channels [166]. Topical drug delivery focuses on peripheral mechanisms and not only reaches greater concentrations in the region where it is applied, but also produces fewer side-effects along with greatly enhanced efficacy.…”