Transdermal Medications


Transdermal Medications

Article Author:
Samara Khan
Article Editor:
Tariq Sharman
Updated:
10/1/2020 11:29:07 PM
For CME on this topic:
Transdermal Medications CME
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Transdermal Medications

Indications

Transdermal drugs are a vast category of drugs defined as vessels for the delivery of drugs for a local or systemic mechanism of action. Transdermal drug delivery has become increasingly popular due to the significant advantages they carry. For example, transdermal drugs bypass the firs-pass metabolism of the liver, protecting it from damage. Additionally, transdermal drugs decrease the risk of damage to the gastrointestinal system via the oral route, increase the likelihood of consistent patient use, and allows drug administration in a continuous stable-interval manner.[1][2]

The fundamental principle of transdermal drug delivery relies on the ability of the drug to pass through the skin into the systemic circulation. Therefore, there are limited drugs that meet the criteria required to be able to bypass the skin. These criteria include having a low molecular weight (less than 600 g/mol), having the ability to pass through the epidermis, and being able to be absorbed by the blood vessels and enter the circulation. Additionally, the active drug must be chemically and physically stable, the active substance must have a low daily dose for patient comfort and adhesive propensity, and the skin should metabolize the drug. With such specific properties, there have only been a limited number of successful transdermal drugs.[2][3]

Some indications that are addressed by transdermal medications since the 1970s include:

  • Hypertension
  • Local anesthesia
  • Angina pectoris
  • Motion sickness
  • Pain
  • Smoking control
  • Migraine
  • Major depression
  • Parkinson disease
  • Alzheimer disease
  • ADHD

Mechanism of Action

The greatest challenge for the success of transdermal drug delivery is diffusing active substances through the barrier function of the many layers of the skin. The outermost layer of the skin, the stratum corneum, is the thickest layer that includes numerous layers of keratin-heavy corneocytes. Additionally, the stratum corneum consists of two chemically different regions that need to be accounted for when creating transdermal drugs. There is an aqueous region at the outer surface of the keratin filaments and a lipid matrix between the filaments that active drugs need to have the ability to diffuse through both to be successful.[4]

However, there have been recent advancements in the development of enhancement delivery methods for active drugs through the transdermal route. These methods are listed below:

  • Microneedles: These are very small, painless needles that are either hollow or solid and filled with the desired drug. The microneedles pierce through the stratum corneum without causing a painful sensation. The advantages of this method are its painless nature and the ability to deliver compounds that have a higher molecular weight.
  • Iontophoresis: The main force used to drive substances across the stratum corneum is the electrical driving force, where there is charged particle movement via electrophoresis. This way, a persistent low-voltage current enables the diffusion of substances across the stratum corneum. The rate of drug delivery can be controlled by an electrical current that is under the control of either a microprocessor or the patient.
  • Thermal poration: The application of heat to the skin creates small pores in the skin for the easy diffusion of molecular substances across the stratum corneum.
  • Electroporation: The application of a high electrical voltage to the stratum corneum also creates small pores for molecular substances to diffuse through the stratum corneum.
  • Conventional enhancers: A chemical substance applied first to the skin to increase the permeability of the stratum corneum or change the thermodynamics of the active drug itself.
  • Ultrasound: The application of sound waves to disrupt the stratum corneum and increase its permeability.[1][2][5][6]

Administration

Transdermal patches administration should follow a proper physical examination of patients and considerations of any associated comorbidities. The following steps are a general overview for administering a transdermal patch:

  • Proper disinfecting and cleaning of skin where the patch is applied
  • Application of patch in the desired area
  • A follow-up appointment to ensure no adverse skin reactions
  • Proper adherence to the guidelines of the transdermal patch for future use

Administration of transdermal patches varies based on the drug administered via the patch. For example, a transdermal patch with 5% lidocaine for the treatment of pain involving conditions such as painful diabetic neuropathy, postherpetic neuralgia, etc. should follow these administration steps:

  • Clean and disinfect skin thoroughly of the desired area of application.
  • Apply the patch on the painful area of the skin once a day and take it off for at least 12 hours a day.
  • The area where the patch was applied should have a break for at least 12 hours in the day to prevent any adverse skin reactions.
  • With a single application, a maximum of three patches is permissible for use.[7]

Adverse Effects

The main adverse effects that can be caused by transdermal drug delivery are skin reactions. Transdermal patches are the most common method of delivery for active substances. Transdermal patches can irritate the skin and cause pruritis, burns, and redness of the surrounding area. Additionally, there are reported allergic reactions for all types of patches on the skin due to the active substance administered. The two most common types of skin reactions include irritant contact dermatitis and allergic contact dermatitis, both of which are usually caused by the drug or the patch, including adhesives and excipients.[3][8][9]

Contraindications

Transdermal drug delivery is contraindicated in patients with[10]:

  • Allergies to the active substance utilized in the transdermal patch
  • Essential fatty acid deficiency
  • Dry skin
  • Psoriasis
  • Ichthyosis
  • Atopic dermatitis
  • Increased ultraviolet radiation exposure
  • Premature neonate
  • Pregnant women (dependent on the drug administered)

Monitoring

The most significant issue associated with transdermal drug delivery is the likelihood of skin irritation caused by penetration enhancement techniques and the transdermal patch itself. Due to this, there have been models created to foresee the likelihood of skin irritation due to drug or vessel interaction using solubility as well as skin irritation studies using the PII test for detection of redness or swelling 24 hours after administering the patch.[4][11]

Toxicity

The toxicity of the transdermal patch depends on the selected drug/active substance administered through the use of transdermal drug delivery.

Enhancing Healthcare Team Outcomes

Managing proper drug administration in healthcare requires interprofessional effort from various healthcare professionals such as clinicians, pharmacists, nurses, residents, physician assistants, etc. Without appropriate regulation and administration techniques, numerous drug-related problems result in medication-related harm and low-quality healthcare for patients. To properly deliver a drug via transdermal patches, the following steps are necessary:

  • Proper physical examination and update on the medical history of the patient by the physician.
  • Consult with the pharmacist on the appropriate drug to be administered based on patient symptoms and history.
  • Consult with a clinician if there are any concerns about a transdermal patch.
  • If there is a life-threatening emergency related to the transdermal patch, the emergency department should be contacted immediately.

To enhance communication between healthcare professionals, techniques such as face-to-face interviews have proven to provide cohesiveness between pharmacists, primary care physicians, and surgical physicians for drug-related healthcare. Ultimately, these techniques allow for an amplified patient-centered approach.[12][13]


References

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[2] Walter JR,Xu S, Therapeutic transdermal drug innovation from 2000 to 2014: current status and outlook. Drug discovery today. 2015 Nov;     [PubMed PMID: 26116094]
[3] Hupfeld S,Gravem H, [Transdermal therapeutic systems for drug administration]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2009 Mar 12;     [PubMed PMID: 19282891]
[4] Benson HA, Transdermal drug delivery: penetration enhancement techniques. Current drug delivery. 2005 Jan;     [PubMed PMID: 16305405]
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[8] Pastore MN,Kalia YN,Horstmann M,Roberts MS, Transdermal patches: history, development and pharmacology. British journal of pharmacology. 2015 May;     [PubMed PMID: 25560046]
[9] Romita P,Foti C,Calogiuri G,Cantore S,Ballini A,Dipalma G,Inchingolo F, Contact dermatitis due to transdermal therapeutic systems: a clinical update. Acta bio-medica : Atenei Parmensis. 2018 Oct 26     [PubMed PMID: 30889148]
[10] Kalia YN,Merino V,Guy RH, Transdermal drug delivery. Clinical aspects. Dermatologic clinics. 1998 Apr;     [PubMed PMID: 9589202]
[11] Al Hanbali OA,Khan HMS,Sarfraz M,Arafat M,Ijaz S,Hameed A, Transdermal patches: Design and current approaches to painless drug delivery. Acta pharmaceutica (Zagreb, Croatia). 2019 Jun 1;     [PubMed PMID: 31259729]
[12] Foppe van Mil JW,Westerlund T,Brown L,Chen TF,Henman M,Hersberger K,McElnay J,Schulz M, Medical care and drug-related problems: Do doctors and pharmacists speak the same language? International journal of clinical pharmacy. 2016 Apr;     [PubMed PMID: 26797769]
[13] Foral PA,Anthone JM,Destache CJ,Vivekanandan R,Preheim LC,Gorby GL,Horne JM,Dobronski LA,Syed JJ,Mindru C,Ali MA,Ali KF,Neemann KA,Bittner MJ, Education and Communication in an Interprofessional Antimicrobial Stewardship Program. The Journal of the American Osteopathic Association. 2016 Sep 1;     [PubMed PMID: 27571295]