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Molecules (Basel, Switzerland) Mar 2018The 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,... (Review)
Review
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.
Topics: Administration, Cutaneous; Administration, Topical; Analgesics; Analgesics, Opioid; Animals; Humans; Pain
PubMed: 29562618
DOI: 10.3390/molecules23030681 -
International Journal of Pharmaceutics Sep 2020Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes... (Review)
Review
Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes the drug to acid and enzymes present in the stomach, leading to denaturation of the compound and resulting in poor bioavailability. Microneedle transdermal drug delivery addresses the problems linked to oral delivery and to relieves the discomfort of patients associated with injections to increase patient compliance. Microneedles can be broadly classified into five types: solid microneedles, coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. The materials used for the preparation of microneedles dictate the different applications and features present in the microneedle. Polymeric microneedle arrays present an improved method for transdermal administration of drugs as they penetrate the skin stratum corneum barrier with minimal invasiveness. The review summarizes the importance of polymeric microneedle and discussed some of the most important therapeutic drugs in research, mainly protein drugs, vaccines and small molecule drugs in regenerative medicine.
Topics: Administration, Cutaneous; Drug Delivery Systems; Humans; Microinjections; Needles; Pharmaceutical Preparations; Polymers; Skin
PubMed: 32739388
DOI: 10.1016/j.ijpharm.2020.119673 -
Brain Research Bulletin Oct 2018The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited... (Review)
Review
The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.
Topics: Administration, Intranasal; Animals; Blood-Brain Barrier; Brain; Drug Administration Routes; Drug Delivery Systems; Humans; Models, Animal; Nasal Cavity; Trigeminal Nerve
PubMed: 30449731
DOI: 10.1016/j.brainresbull.2018.10.009 -
Biomolecules Nov 2020The potential therapeutic use of some plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of... (Review)
Review
The potential therapeutic use of some plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments. Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC. In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CBr and CBr), 5-HT receptor and neurogenesis factors. Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.
Topics: Animals; Anxiety; Cannabidiol; Depression; Dose-Response Relationship, Drug; Drug Administration Routes; Humans; Psychotic Disorders; Treatment Outcome
PubMed: 33228239
DOI: 10.3390/biom10111575 -
Journal of the American Association For... Sep 2011Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential...
Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. For all species, many different routes are available for administration of substances. The research team and IACUC members should be aware of reasons for selecting specific routes and of training and competency necessary for personnel to use these routes effectively. Once a route is selected, issues such as volume of administration, site of delivery, pH of the substance, and other factors must be considered to refine the technique. Inadequate training or inattention to detail during this aspect of a study may result in unintentional adverse effects on experimental animals and confounded results.
Topics: Animal Care Committees; Animal Welfare; Animals; Animals, Laboratory; Drug Administration Routes; Laboratory Animal Science; Research Design
PubMed: 22330705
DOI: No ID Found -
The Journal of Clinical Psychiatry Jul 2017Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of... (Comparative Study)
Comparative Study Review
BACKGROUND
Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of studies across nearly 2 decades of research, there is no definitive guidance on matters related to core practice issues.
METHODS
This article presents a qualitative review and summary about what is known about ketamine dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions.
RESULTS
Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration. Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously. Whereas the intravenous route is the most commonly employed, safety and efficacy have been described with other routes of administration, as well; these include oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes. Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases. When so extended, the ideal frequency is perhaps best individualized wherein ketamine is dosed a little before the effect of the previous session is expected to wear off.
CONCLUSIONS
There is likely to be a complex interaction between ketamine dose, session duration, route of administration, frequency of administration, and related practice. Until definitive studies comparing different doses, rates of administration, routes of administration, and other considerations are conducted, firm recommendations are not possible. From the point of view of clinical practicability, subcutaneous, intranasal, and oral ketamine warrant further study. If domiciliary treatment is considered, the risk of abuse must be kept in mind.
Topics: Antidepressive Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Infusions, Intravenous; Injections, Intramuscular; Injections, Subcutaneous; Ketamine; Treatment Outcome
PubMed: 28749092
DOI: 10.4088/JCP.17f11738 -
Archives of Gynecology and Obstetrics Jun 2023To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women. (Review)
Review
PURPOSE
To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women.
METHODS
We performed a systematic review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer.
RESULTS
The systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route.
CONCLUSIONS
Available evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route.
Topics: Female; Humans; Postmenopause; Estrogen Replacement Therapy; Venous Thromboembolism; Administration, Cutaneous; Estrogens; Hormone Replacement Therapy; Breast Neoplasms; Administration, Oral; Lipids
PubMed: 35713694
DOI: 10.1007/s00404-022-06647-5 -
The Journal of Clinical Endocrinology... Apr 2021This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose,... (Review)
Review
CONTEXT
This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose, and route of delivery.
METHODS
This summary is based on authors' knowledge in the field of menopausal HT and supplemented by a PubMed search using the terms "menopause hormone therapy," "transdermal," "estradiol," "conjugated estrogens," "bioidentical," "cardiovascular disease," "lipoproteins," "glucose," "progestogens," "low dose."
RESULTS
Available evidence indicates that oral unopposed estrogens have a favorable effect on lipoprotein levels, glycemia, insulin, and CVD risk; however, the addition of progestogens blunts the lipid-related effects. The progestogen with the smallest attenuating effect is micronized progesterone. Transdermal estrogens have less effect on coagulation, inflammation, and lipids than oral estrogens and observational studies suggest they pose a lower risk of venous thromboembolism and stroke than oral estrogens. Clinical effects of hormones were not consistently dose dependent.
CONCLUSIONS
Although HT continues to have an important role in menopause management, it is not recommended for primary or secondary CVD prevention. Different formulations, doses, and routes of delivery of HT have different effects on cardiometabolic markers and risks of clinical CVD events. However, long-term trials evaluating clinical outcomes with transdermal and other alternate HT regimens are limited.
Topics: Administration, Cutaneous; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Compounding; Estradiol; Estrogen Replacement Therapy; Female; Humans; Menopause; Risk Factors
PubMed: 33506261
DOI: 10.1210/clinem/dgab042 -
Respiratory Care Mar 2005Inhalation is a very old method of drug delivery, and in the 20th century it became a mainstay of respiratory care, known as aerosol therapy. Use of inhaled epinephrine...
Inhalation is a very old method of drug delivery, and in the 20th century it became a mainstay of respiratory care, known as aerosol therapy. Use of inhaled epinephrine for relief of asthma was reported as early as 1929, in England. An early version of a dry powder inhaler (DPI) was the Aerohalor, used to administer penicillin dust to treat respiratory infections. In the 1950s, the Wright nebulizer was the precursor of the modern hand-held jet-venturi nebulizer. In 1956, the first metered-dose inhaler (MDI) was approved for clinical use, followed by the SpinHaler DPI for cromolyn sodium in 1971. The scientific basis for aerosol therapy developed relatively late, following the 1974 Sugarloaf Conference on the scientific basis of respiratory therapy. Early data on the drug-delivery efficiency of the common aerosol delivery devices (MDI, DPI, and nebulizer) showed lung deposition of approximately 10-15% of the total, nominal dose. Despite problems with low lung deposition with all of the early devices, evidence accumulated that supported the advantages of the inhalation route over other drug-administration routes. Inhaled drugs are localized to the target organ, which generally allows for a lower dose than is necessary with systemic delivery (oral or injection), and thus fewer and less severe adverse effects. The 3 types of aerosol device (MDI, DPI, and nebulizer) can be clinically equivalent. It may be necessary to increase the number of MDI puffs to achieve results equivalent to the larger nominal dose from a nebulizer. Design and lung-deposition improvement of MDIs, DPIs, and nebulizers are exemplified by the new hydrofluoroalkane-propelled MDI formulation of beclomethasone, the metered-dose liquid-spray Respimat, and the DPI system of the Spiros. Differences among aerosol delivery devices create challenges to patient use and caregiver instruction. Potential improvements in aerosol delivery include better standardization of function and patient use, greater reliability, and reduction of drug loss.
Topics: Administration, Inhalation; Aerosols; Drug Delivery Systems; Equipment Design; Evidence-Based Medicine; History, 20th Century; Humans; Metered Dose Inhalers; Nebulizers and Vaporizers; Powders; Respiratory System Agents; Respiratory Tract Diseases; United States
PubMed: 15737247
DOI: No ID Found -
Advanced Drug Delivery Reviews 2020The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care,... (Review)
Review
The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is particularly important in COVID-19, as patients can deteriorate rapidly. Despite the advantages, these routes of administration face challenges including a relatively small surface area for effective drug absorption, small volume of fluid for drug dissolution and the presence of a mucus barrier, thereby limiting the number of drugs that are suitable to be delivered through the transmucosal route. In this review, the merits, challenges and limitations of each of these transmucosal routes are discussed. The goals are to provide insights into using transmucosal drug delivery to bring about the best possible symptom management for patients at the end of life, and to inspire scientists to develop new delivery systems to provide effective symptom management for this group of patients.
Topics: Administration, Mucosal; COVID-19; Drug Delivery Systems; Humans; Palliative Care; Pandemics; Terminal Care; COVID-19 Drug Treatment
PubMed: 33137363
DOI: 10.1016/j.addr.2020.10.018