Actinic keratosis (AK) is one of the most common skin conditions seen in an outpatient setting, with approximately 10% of all dermatology visits having a primary diagnosis of Actinic Keratosis. AK is a pre-cancerous skin condition resulting mainly from chronic UV exposure, including tanning beds. With up to 60% of squamous cell carcinomas (SCC) arising from AKs, early and effective treatment can be imperative. Currently, there are multiple treatments available for AK – Including cryosurgery and light therapy to topical creams like 5-FU and imiquimod - with no current agreement on which is the most efficacious. Side effects beyond minor skin irritation are common with current regimens. Now there is Patented Transdermal Verapamil Gel. Transdermal Verapamil helps improve wound healing by enhancing matrix remodeling of damaged tissue and provides antioxidant and anti-inflammatory activity. In contrast to current treatments, the only side effect noted with Transdermal Verapamil Gel is localized minor skin irritation.
Introduction
Using Patented Transdermal Verapamil gel for hard-to-treat issues is not a new concept. Transdermal Verapamil Gel has been used to treat Plantar Fibromatosis and Dupuytren’s Contracture for many years. Studies have demonstrated Transdermal Verapamil Gel effective for the treatment of Peyronie's Disease. Transdermal Verapamil’s proposed mechanism of action shows promise in dermatology, specifically as an agent for the very common dermatological condition Actinic Keratosis (AK) or Actinic keratoses (plural, AKs). AKs are diagnosed at > 10% of all dermatology visits, making them one of the most common diagnoses seen in the outpatient setting.[1]
What is Actinic Keratosis?
Actinic keratosis (AKs), also known as solar keratosis, is a rough, scaly, pre-cancerious, epidermal, keratinocytic lesion that results from chronic sun and UV light exposure (including tanning beds).[2] The prevalence increases with age and declining immune health. AKs are thought to be carcinomas in situ, which can progress to squamous cell carcinomas if not managed early and appropriately.
The prevalence of Actinic kertatosis in the US is estimated at almost 40 million individuals and annual costs of > $1 billion. Most AKs do not progress to cancer, and as many as 26% regress spontaneously. But up to 60% of squamous cell carcinomas (SCC) arise from AKs.[3] After progression to SCC, the risk of metastasis is estimated to be 0.5-3.3%.[4]
No two cases of actinic keratosis will look the same, but they may share the following similar features:
AKs most often appear on sun-exposed areas such as the face, bald or balding scalp, ears, shoulders, neck and the back of the hands and forearms. However, they can also appear on the shins and other parts of the legs. AKs are often elevated, rough in texture and resemble warts, with most become red. Some are light colored or dark tan, white, pink and/or flesh-toned, OR a combination of these colors.
Data from a large Rotterdam Study in 2013 revealed that individuals with Fitzpatrick type I or II skin characteristics, such as fair skin, freckles, light-colored eyes (blue or green) and blonde or red hair, are more likely to develop AKs as they are more sensitive to damage from chronic sun exposure.[5]
This study also reported that lighter pigmentation and tendency to sunburn were associated with higher risk of AKs, along with male sex, baldness, age > 70 years, use of sun-protective measures, and history of melanoma or keratinocyte carcinoma (KC), particularly squamous cell carcinoma (SCC).[6]
What Causes AKs?
The main cause of Actinic Keratosis is UV radiation – chronic, unprotected exposure to the sun. Also, UV radiation from tanning “beds” can also cause AKs. Chronic X-Ray exposure and exposure to chemicals have also been reported to cause AKs.
There are several mechanisms for the formation of AKs, including:
Excessive UV-A and UV-B generate a cascade of structural damage to cell’s DNA and membrane lipids due to increased oxidative stress, which leads to chronic inflammation.[7] Sun damage to the skin is cumulative, so even a brief period in the sun adds to the lifetime total. Those that work outside have an increased risk. Cloudy days aren’t safe either, because 70-80% of the sun’s ultraviolet (UV) rays can pass through clouds. These harmful rays can also bounce off sand, snow and other reflective surfaces, giving the individual extra exposure.
Though some individuals can get AKs as young as in their 20s, AKs are more common in people over age 50, with almost everyone over 80 having AKs. The incidence of AKs is higher in men presumably due to spending more time in the sun. Also, the closer to the equator one lives, the higher the incidence of AKs. Those with autoimmune or immune problems, such as AIDS, those receiving cancer chemotherapy, organ transplants, are more likely to develop AKs.
A summary of factors contributing to AKs include:
Current Treatments
There are multiple reasons for treatment, and there is no current agreement on the most efficacious treatment. The decision to treat can be based on cosmetic reasons, symptom relief, or, most importantly, the prevention of malignancy and metastasis. The most compelling reason and primary goal of treating actinic keratoses is to prevent malignant transformation into invasive squamous cell carcinoma. Treatment options include:[8]
Practitioners may combine therapy modalities to treat AKs. Typically, treatment regimens combine cryosurgery with photodynamic therapy (PDT) or a topical agent (such as imiquimod, diclofenac, ingenol mebutate, 5-fluorouracil). The topical medications and PDT may also be used alternately every three months, six months or year, as determined by the practitioner at follow-up skin examinations.[13]
Surgical treatments such as cryotherapy, excision and laser resurfacing, while effective against discrete lesions, may not address subclinical lesions, and are painful and associated with risks of scarring, infection and pigmentary changes.[14],[15]
Many AK patients have multiple lesions, not all of which are distinct and obvious. Suggested treatments for those patients include therapeutic options that treat the entire affected area of skin such as topical treatments and photodynamic therapy. Topical treatments, inducing 5-FU, imiquimod, and dicolfenac, however, are less effective than surgical options against discrete lesions and have been associated with irritation, allergic reactions, and problems with patient compliance.[16] ,[17]
All AK cases should be treated because of their propensity to transform into malignancy and further complicate treatment. In addition to medical or surgical care, education about sun exposure prevention remains the best and most cost-effective method for AK prevention.
The bottom line is many options are available with variable success and patient compliance rates. Although decreased sun exposure is the best way to prevent AKs, there still is a need for an effective, topical product with limited side effects as compared to current treatment options. One such product that may fill such a void is a patented, transdermal formulation containing the calcium channel blocker verapamil.
Transdermal Verapamil – Rationale for Use
Verapamil, USP, is chemically a diphenylalkylamine, and is in the class of drugs called calcium channel blockers. Calcium channel blockers have been used as prescription drugs for decades for blood pressure and other cardiovascular indications.
Application of Transdermal Verapamil is reported to affect the extracellular matrix by increasing the proteolytic activity of collagenase, thereby enhancing matrix remodeling of fibroblasts and vascular smooth muscle cells.[18],[19],[20] Calcium plays a noticeable role in wound healing, such as effects on organization of F-actinin collagen bundles by fibroblasts at injury site. Verapamil acts to block the entry of divalent calcium into cells, resulting in hematuration of fibroblast collagenase and subsequent degradation or remodeling of the fibrotic tissue.
Calcium channel blockers such as verapamil also improve wound healing by providing antioxidant activity by increasing nitric oxide production, thereby promoting angiogenesis, proliferation of fibroblasts and endothelial cells in skin-regeneration processes.[21] Verapamil has also been reported in the literature to exhibit anti-tumor activity and to enhance the effectiveness of chemotherapy.[22],[23]
In addition, verapamil and other calcium channel blockers affect cytokine expression associated with the early phase of wound healing and inflammation, including platelet derived growth factor, interleukin-6 and interleukin-8. It is believed that the effect on the appearance of skin by transdermal application of calcium channel blockers is in part due to the remodeling of the epidermal and dermal tissues. Additionally, calcium channel blockers may modulate the innate and adaptive immune responses.[24]
A 2016 laboratory animal study reported the application of a topical verapamil gel promoted faster wound closure rate in comparison with other topical agents. The numerical density of fibroblasts, volume density of collagen bundles, mean diameter and volume densities of the blood vessels in the verapamil treated group were significantly higher than others treatments. The authors concluded that topical verapamil has the ability to improve wound healing by enhancing fibroblast proliferation, collage bundle synthesis and revascularization in skin injuries.[25]
Patented Transdermal Verapamil 15% Gel
Transdermal Verapamil 15% Gel is a painless, non-invasive, treatment for fibrotic tissue disorders including Peyronie's Disease, Plantar Fibromatosis, Dupuytren’s Contracture as well as hypertrophic scaring. Patented Transdermal Verapamil Gel was invented and developed by W. Jerry Easterling RPH and his team at Prescription Dispensing Laboratories. PDLabs is a nationally licensed compounding pharmacy that relocated from San Antonio to Cedar Park TX in 2016. Since 1998, PD Labs Transdermal Verapamil 15% Gel has been prescribed for over 13,000 patients. It is an original and patented compounded prescription that is applied directly to the affective area twice a day. The proprietary formula allows for minimal absorption into the circulatory system, while maximizing the concentration of verapamil in the damaged and surrounding tissue.
Studies using Patented Transdermal Verapamil Gel include:
Additional components of the gel include antioxidant agents to prevent oxidation of verapamil and penetration enhancers. A list of ingredients in the Patented Transdermal Verapamil 15% Gel include: *
* Note – Avoid Counterfeit Transdermal Verapamil Gels
When using the Patented Transdermal Verapamil Gel as a treatment, lesions should be evaluated monthly and include:
Dosage
Potential Side Effects/Contraindications
Conclusion
PD Lab’s Patented Transdermal Verapamil Gel 15% is an effective prescription treatment option for Actinic Keratosis. With fewer side effects than current regimens, including the most popular therapy 5-FU creams, Transdermal Verapamil Gel has been reported to improve AKs with 0.5ml applied twice daily for 8-12 weeks to affected area(s). Transdermal Verapamil 15% Gel is also a painless and non-invasive treatment for fibrotic tissue disorders including Peyronie's Disease, Plantar Fibromatosis and Dupuytren’s Disease. It has been used for these conditions for over 2 decades. Make sure to only use PD Lab’s Patented, Prescription Transdermal Verapamil Gel, as imitations may be available on the market.
The information contained in this paper is provided for educational purposes only and is not intended to replace discussions with your healthcare provider. All decisions regarding a patients' treatment must be made with a healthcare provider. |
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