Pharmacy Specialists Compounding Pharmacy

MISCELLANEOUS

Rectal Propranolol Controls Paroxysmal Sympathetic Hyperactivity Post Brain Injury

Paroxysmal sympathetic hyperactivity (PSH) affects approximately 10% of survivors of acquired brain injury and is associated with substantial morbidity. The most effective maintenance therapies include oral β-blockers and α-2 antagonists. May et al. of the University of Kentucky HealthCare reported the use of rectal propranolol for symptomatic control of PSH in a critically ill patient with an altered gastrointestinal tract for whom oral intake was contraindicated. This is the first case report to describe the successful use of propranolol suppositories in a clinical environment. This case supports the use of propranolol suppositories as a potential alternative route when oral administration is not possible.

Pharmacotherapy. 2015 Apr;35(4):e27-31.
Rectal propranolol controls paroxysmal sympathetic hyperactivity: a case report.
Click here to access the PubMed abstract of this article.

Propranolol Suspension

Propranolol hydrochloride is a beta-blocker used to treat high blood pressure, abnormal heart rhythms, heart disease, pheochromocytoma, and certain types of tremors. Propranolol is a drug of choice for many diseases such as infantile hemangioma occurring in neonates and infants, an age group for which oral suspensions are required almost exclusively. Many adult and elderly patients for whom propranolol is prescribed are also unable to swallow solid dosage forms, leading practitioners to seek alternative dosing options; specifically oral suspensions in the strength that is most appropriate for the patient, using a vehicle that will mask the bitter taste of propranolol powder, while remaining alcohol, sorbitol and sugar-free when required.

A recent study determined the stability of propranolol hydrochloride compounded into a 1-mg/mL suspension using SyrSpend SF and subsequently stored in a low-actinic plastic prescription bottle at room temperature conditions. Six samples were assayed at each specific time point extending to 90 days by a stability-indicating high-performance liquid chromatography method. Based on the data collected, when protected from light at room temperature, the beyond-use date of propranolol hydrochloride in SyrSpend SF was shown to be at least 90 days.

To evaluate the stability of more concentrated propranolol suspensions in a sugar-free, commercially available vehicle after storage at room temperature and under refrigeration for up to 120 days, suspensions of propranolol (2 and 5 mg/mL) were prepared in the sugar-free vehicle (Ora-Blend SF), placed in 100-mL amber plastic prescription bottles, and stored at 25°C and 4°C. Physical compatibility was evaluated in terms of color, taste, precipitation, and pH. Propranolol suspensions 2 mg/mL and 5 mg/mL stored at 25°C maintained at least 94.7% of their initial concentration for 120 days, and suspensions stored at 4°C maintained at least 93.9% of their initial concentration for 120 days. There were no notable changes in pH, and all samples remained physically unchanged except for a slight change in color, around day 70, of suspensions stored at room temperature.

Int J Pharm Compd. 2012 Nov-Dec;16(6):513-5.
Stability of propranolol hydrochloride in SyrSpend SF.
Click here to access the PubMed abstract of this article.

Can J Hosp Pharm. 2013 Mar;66(2):118-24.
Stability of propranolol in extemporaneously compounded suspensions.
Click here to access the PubMed abstract of this article.

Nasal Sprays

Aminocaproic acid and tranexamic acid are antifibrinolytic agents with differing potencies. When patients suffer from recurrent nosebleeds, a nasal spray can be customized to meet each patient’s specific needs.

The Indiana Hemophilia and Thrombosis Center recommends the use of compounded aminocaproic acid nasal spray 250 mg/ml, 1 spray to the affected nostril every 4 hours while awake for 7 days following a nosebleed.

For relief of severe epistaxis, tranexamic acid injection has been applied topically to the nasal mucosa, as a spray or by packing the nasal cavity with a gauze strip that has been soaked in the solution. The NIH is conducting a clinical trial known as North American Study of Epistaxis in HHT (NOSE) and is currently recruiting participants to carefully examine the efficacy and safety of 3 nasal sprays, compared to placebo, for the treatment of HHT (Hereditary Hemorrhagic Telangiectasia) related nosebleeds. As per this study, tranexamic acid can be compounded as a 10% nasal spray, used as 0.1 ml spray in each nostril twice daily for 12 weeks (total dose of tranexamic acid is 40 mg/day).

Read about this clinical study:

Epigallocatechin Gallate (EGCG) Offers Protection Against Multiple Pathologies

Arch Oral Biol. 2012 May;57(5):429-35.
Green tea: a promising natural product in oral health.
Click here to access the PubMed abstract of this article.

Clin Exp Pharmacol Physiol. 2012 Mar;39(3):265-73.
Potential role of green tea catechins in various disease therapies: progress and promise.
Click here to access the PubMed abstract of this article.

PLoS One. 2011;6(10):e25224. Epub 2011 Oct 13.
Green tea catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE2 receptors and epithelial-to-mesenchymal transition.
Click here to access the PubMed abstract of this article.

Skin Pharmacol Physiol. 2009;22(3):137-41.
Effects of oral epigallocatechin gallate supplementation on the minimal erythema dose and UV-induced skin damage.
Click here to access the PubMed abstract of this article.

Basic Clin Pharmacol Toxicol. 2010 Aug;107(2):669-75.
(-)-epigallocatechin gallate inhibits endothelin-1-induced C-reactive protein production in vascular smooth muscle cells.Click here to access the PubMed abstract of this article.

Curr Mol Med. 2012 February; 12(2): 163–176.
Anti-Cancer Activities of Tea Epigallocatechin-3-Gallate in Breast Cancer Patients under Radiotherapy
Click here to access this article.

Topical Therapy to Reduce Infantile Hemangiomas

Infantile hemangiomas (IH), also known as “strawberry marks,” are collections of blood vessels caused by increased cell division and growth. A compounded topical “gel-forming solution” containing the medication timolol maleate has been reported as a potentially effective treatment for superficial IH. The best response was achieved with the superficial type of hemangioma, using a solution of 0.5% timolol applied topically twice daily for longer than 3 months. The major advantages of topical timolol are ready availability, cost, ease of administration, and minimal risk of drug-related adverse events.

Pediatr Dermatol. 2012 Jan-Feb;29(1):28-31.
Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study.
Click here to access the PubMed abstract of this article.

Zinc stimulates the immune system and zinc deficiency increases the risk of infections. An analysis of 13 placebo-controlled studies showed strong evidence that adequate doses of zinc may reduce the duration and intensity of the common cold. Three trials used zinc acetate in daily doses of over 75 mg; the pooled results indicated a 42% reduction in the duration of colds. Contradictory results in various studies can largely be explained by the formulation of the lozenges or the variation in the total daily dose of zinc that the person obtained from the lozenges. Zinc lozenges have caused side effects such as bad taste and constipation that stopped when lozenge use was discontinued, and there is no evidence that short-term occasional use would cause long-term harm. Ask our compounding pharmacist about the most appropriate preparations.

Open Respir Med J. 2011; 5: 51–58.
Zinc Lozenges May Shorten the Duration of Colds: A Systematic Review
Click here to access the PubMed abstract of this article.

Sildenafil Cream versus Nifedipine Cream for Patients with Secondary Raynaud’s Disease

Raynaud’s disease affects 5 to 10 percent of people, but only 1 in 10 seek treatment. Females are about nine times more likely to be affected than males. Vasospasm causes fingers or toes to turn white then blue and, as the blood returns, they flush red. Raynaud’s disease can also affect other areas of the body, such as the nose, lips, ears, and even nipples. After warming, it can take 15 minutes for normal blood flow to return to the area.

Secondary Raynaud’s, also called Raynaud’s phenomenon (RP), is caused by an underlying problem such as autoimmune disease, lupus, rheumatoid arthritis, or Sjogren’s syndrome. Some of these diseases reduce blood flow to the fingers and toes by causing the blood vessel walls to thicken and the vessels to constrict too easily. Although secondary Raynaud’s is less common than the primary form, it tends to be more serious. Signs and symptoms of secondary Raynaud’s usually appear around age 40, later than for primary Raynaud’s.

Secondary RP is often refractory to standard therapies and is a therapeutic challenge. Topical vasodilators may act as an adjuvant therapy for RP. A small prospective study of patients with secondary RP associated with connective tissue disease found that compounded 5% sildenafil cream improved arterial blood flow to the fingers, suggesting local vasodilatation.

Another study compared the vasodilator efficacy of topical 10% nifedipine versus 5% sildenafil. Tobacco smokers and patients with primary RP, hypotension, hypertension, myocardial infarction, stroke, or arrhythmia were excluded. Patients who were being treated with a vasodilator were required to discontinue use for at least 24 hours before randomization. Patients’ hands were randomized to treatment with 5g of 10% nifedipine cream on one hand and 5g of 5% sildenafil cream to the opposite hand. Vinyl gloves were supplied to improve topical absorption, leaving the thumbs out of the gloves without any cream (control group). All patients underwent a high-frequency color Doppler ultrasound examination before and 1 hour after topical application. For each hand, researchers obtained the differences of digital artery blood flows and diameters at baseline and after 60 minutes. Topical sildenafil significantly increased blood flow by 9.2 mm/second, while a trend toward improvement was observed for diameter. After topical nifedipine, there was no significant improvement in blood flow or diameter. Five of 10 hands using nifedipine experienced sensation of heat and 6 of 10 hands with sildenafil developed a tingling sensation. No serious adverse effects were detected. Additional studies are required to determine if 5% sildenafil cream can reduce the frequency of RP flares.

J Am Acad Dermatol. 2018 Jan;78(1):189-190.
Nifedipine cream versus sildenafil cream for patients with secondary Raynaud phenomenon: A randomized, double-blind, controlled pilot study
Click here to access the PubMed abstract of this article.

This study finds that modified-release sildenafil reduced attack frequency in patients with Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis and was well tolerated.

Arthritis Rheum. 2011 Mar;63(3):775-82.
Modified-release sildenafil reduces Raynaud’s phenomenon attack frequency in limited cutaneous systemic sclerosis.
Click here to access the PubMed abstract of this article.

Lidocaine 8% Intranasal Spray for Trigeminal Neuralgia

Intranasal lidocaine 8% administered by a metered-dose spray produced prompt but temporary analgesia without serious adverse reactions in patients with second-division trigeminal neuralgia.

Br J Anaesth. 2007 Feb;98(2):275
Lidocaine intranasal spray for treatment of trigeminal neuralgia.
Click here to access the PubMed abstract of this article.

Topical Treatment for Chronic Venous Leg Ulcers, Irritation around Stomas, and Diaper Rash

Daily application of sucralfate gel to non-infected post-phlebitis/vascular ulcers for 42 days led to complete healing in 95.6% of patients compared to only 10.9% of cases that used placebo.

Int J Mol Med. 2008 Jul;22(1):17-23.
Topical treatment of chronic venous ulcers with sucralfate: a placebo-controlled randomized study.
Click here to access the PubMed abstract of this article.

A 10% aqueous solution of sucralfate, administered twice daily as a rectal enema or vaginal douche, was also used successfully to treat radiation-induced rectal and vaginal ulcers.

Arch Dermatol. 2000 Oct;136(10):1199-200.
Topical sucralfate for erosive irritant diaper dermatitis.
Click here to access the PubMed abstract of this article.

Ann Pharmacother. 1999 Dec;33(12):1274-6
Treatment of radiation-induced proctitis with sucralfate enemas.
Click here to access the PubMed abstract of this article.

Topical sucralfate represents a safe, inexpensive, and effective therapeutic intervention, particularly for those patients with high output or short stomas where repeated stoma leakage may be unavoidable.

Clin Exp Dermatol. 2000 Nov;25(8):584-8.
Topical sucralfate in the management of peristomal skin disease: an open study.
Click here to access the PubMed abstract of this article.

Women's Health

Hormonal, metabolic, and endometrial safety of testosterone vaginal cream versus estrogens for the treatment of vulvovaginal atrophy in postmenopausal women: a randomized, placebo-controlled study

The aim of the study was to evaluate the laboratory and endometrial safety of topical testosterone versus topical estrogen for the treatment of vaginal atrophy in postmenopausal women. This was a randomized, placebo-controlled trial of 60 postmenopausal women aged 40 to 70 years at the Menopause Clinic of CAISM UNICAMP (Brazil). The authors concluded that 12 weeks of treatment with topical testosterone or estrogen in postmenopausal women with symptoms of vaginal atrophy demonstrated laboratory and endometrial safety when compared with placebo.

Menopause. 2018 Jun;25(6):641-647.
Click here to access the PubMed abstract of this article.

Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer

The use of aromatase inhibitors (AI such as anastrozole, letrozole, and exemestane) for the treatment of breast cancer is associated with significant urogenital atrophy, affecting the quality of life and compliance with therapy. A randomized clinical trial evaluated the safety of intravaginal testosterone cream (IVT) or an estradiol-releasing vaginal ring (7.5 microgram/day) in postmenopausal women with hormone receptor-positive stage I to III breast cancer taking AIs with self-reported vaginal dryness, dyspareunia, or decreased libido. Overall, 76 women signed consent (mean [range] age, 56 [37-78] years), and 69 completed 12 weeks of treatment. The trial concluded that in postmenopausal women with early-stage breast cancer receiving AIs, treatment with an estradiol vaginal ring or intravaginal testosterone over 12 weeks met the primary safety end point. Baseline elevation in E2 was common. Vaginal atrophy, sexual interest, and sexual dysfunction were improved.

JAMA Oncol. 2017 Mar 1;3(3):313-319.
Click here to access the PubMed abstract of this article.

Vaginal Dehydroepiandosterone for Vaginal Symptoms in Postmenopausal Cancer Survivors: Efficacy, Local and Systemic Effects Vaginal Dehydroepiandosterone for Vaginal Symptoms in Postmenopausal Cancer Survivors: Efficacy, Local and Systemic Effects

Women with estrogen deficiencies can suffer from vaginal symptoms that negatively impact sexual health. This study evaluated vaginal dehydroepiandrosterone (DHEA) for alleviation of vaginal symptoms.

DHEA resulted in increased hormone concentrations, though still in the lowest half or quartile of the postmenopausal range, and provided more favorable effects on vaginal cytology, compared to plain moisturizer. Estrogen concentrations in women on AIs were not changed. Vaginal DHEA 6.5 mg/day significantly improved sexual health. Further research on the benefit of vaginal DHEA is warranted in women with a history of hormone-dependent cancers.

Support Care Cancer. 2018 Feb;26(2):643-650.
Click here to access the PubMed abstract of this article.

Support Care Cancer. 2018 Apr;26(4):1335-1343.
Click here to access the PubMed abstract of this article.

Treatment for Vulvovaginal Atrophy

Despite its frequency, recognition and therapy of vulvovaginal atrophy (VVA) remains suboptimal. Wet mount microscopy, or vaginal pH testing, allows VVA diagnosis in menopausal or postpartum women, but also in young contraception users or after breast cancer. The basis of good treatment is a correct and complete diagnosis, using a microscope to study the maturity index of the vaginal fluid. Many experts believe that minimal doses of estriol with or without lactobacilli can be used intravaginally after breast cancer and in women with a history of thromboembolic disease. Ultra-low-dose vaginal estriol is beneficial in most cases, even in breast cancer patients.

A literature review was conducted to evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women and confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 hour. At the 6-month follow-up, there was no increase in serum estriol in treated women. The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations may be considered as a treatment option for women who have risk factors related to systemic estrogen therapy.

An Italian study evaluated the effectiveness of the application of 0.005% estriol gel to the vulvar vestibule to relieve sexual pain. Postmenopausal women with dyspareunia were enrolled in the study and instructed to use a fingertip to apply estriol vaginal gel to the vulvar vestibule daily for three weeks and then twice weekly for up to 12 weeks. Assessment of symptoms and signs of vestibular atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. A total of 63 women were included. Fifty-nine women completed the 12-week treatment period, and four dropped out for vestibular burning (which may have been a result of the base used for this particular preparation). Dyspareunia improved or resolved by week 12 in 81.4% of patients. The women also showed a statistically significant reduction in vestibular atrophy at the end of treatment.

Hyaluronic acid therapy may help women who cannot or do not want to use hormones. The use of a hyaluronic acid topical liquid preparation for vaginal use (Justgin®, Just Pharma, Rome, Italy) three times per week for 8 weeks produced statistically significant improvements in symptoms, both objectively via the use of the Vaginal health Index (VHI) and subjectively with a Visual Analogic Scale (VAS). The most significant improvements concerned vaginal dryness and painful intercourse, therefore strongly improving the Quality of Life of these women. The patients’ degree of satisfaction at the end of the trial was high (95%).

In contrast, laser therapy requires validation and safety data, as it can potentially cause vaginal fibrosis and stenosis.

Expert Opin Pharmacother. 2019 Mar 21:1-15.
Pharmacotherapy for the treatment of vaginal atrophy
Click here to access the full article.

Eur J Obstet Gynecol Reprod Biol. 2016 Dec;207:121-124.
Coital pain in the elderly: could a low dose estriol gel thrill the vulvar vestibule?
Click here to access the PubMed abstract of this article.

Climacteric. 2017 Aug;20(4):321-330.
The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review
Click here to access the PubMed abstract of this article.

https://www.europeanreview.org/wp/wp-content/uploads/4190-4195-Hyaluronic-acid-improves-VVA-symptoms.pdf

Treating Dysbiosis of the Vaginal Microbiome

Maintaining homeostasis of the vaginal microbiome, which consists of both bacteria and fungi, is essential to the health of a woman’s reproductive system. Dysbiosis can be caused by behavioral (wearing tight clothing, use of vaginal lubricants, sexual activity, douching, smoking, hormone use) or biological variables (menstruation, lack of immune response). Pathologic bacteria and fungi flourish on the biofilms they create and affect conception, pregnancy, delivery, development of infections or sexually transmitted diseases, and the overall health of the woman.

If the cause of a vaginal infection is suspected to be bacterial or an azole-resistant fungus, then a boric acid suppository inserted vaginally at bedtime for 14-21 days may be prescribed to decrease the vaginal pH and inhibit the growth of pathogens. If the infection persists, treatment with a flucytosine vaginal cream for 14 days may be considered. “Treatment with a vaginal cream containing EDTA 0.5% and boric acid 30% for 14 to 21 days can also be effective because that compound binds calcium ions (in some pathogens, this inhibits the conversion to the [disease-causing] hyphal form) and disrupts fungal biofilms.” A combination of intravaginally-applied estriol and Lactobacillus acidophilus can benefit women with vaginal dryness and atrophy and repopulate the vaginal flora.

Int J Pharm Compd. 2018 Nov-Dec;22(6):456-465.
Compounding to Prevent and Treat Dysbiosis of the Human Vaginal Microbiome
Click here to access the PubMed abstract of this article.

Hot Flashes linked to Heart Disease and Diabetes

Hot flashes are the most common symptom of menopause. Not only are vasomotor symptoms inconvenient and uncomfortable, hot flashes may increase the risk of health problems including heart disease and diabetes. Data was analyzed from over 150,000 postmenopausal women who participated in the Women’s Health Initiative: 33% of the women had hot flashes, which was associated with an 18% increased risk of diabetes. The risk increased with greater duration and severity of hot flashes. When night sweats were factored in, the risk of health problems increased further, especially in cases where the onset of hot flashes developed late into the menopausal transition.

Compared to men with diabetes, women with diabetes have a higher risk of being hospitalized for or dying from diabetes and its complications, which makes the timely identification and management of diabetes through lifestyle intervention or medical management critical.

Dr. JoAnn Pinkerton, executive director of the North American Menopause Society, said: “This study showed that, after adjustment for obesity and race, women with more severe night sweats, with or without hot flashes, still had a higher risk of diabetes… For symptomatic women, hormone therapy started near menopause improves menopause symptoms and reduces the risk of diabetes.”

Menopause. 2018 May;25(5):520-530.
Vasomotor symptom characteristics: are they risk factors for incident diabetes?
Click here to access the PubMed abstract of this article.

Topical Metformin for Hirsutism

Metformin’s antiandrogenic properties may help with the management of hirsutism associated with polycystic ovarian syndrome (PCOS). Hirsutism refers to excess growth of pigmented hair in women, typically in androgen-sensitive areas such as the lips, chin, and chest. Although long-term treatment can involve balancing the hormones or treating metabolic disorders, women can appreciate a faster solution to this problem which can detract from their femininity and negatively impact their self-esteem.

In approximately 90% of hirsute females, the cause is idiopathic or there is underlying PCOS. It has been proposed that reduction in circulating insulin levels leads to a decrease in the concentration of free circulating levels of androgens which can decrease the occurrence of excess hair in women.

The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 9, 1 September 2003, Pages 4116–4123.

Metformin or Antiandrogen in the Treatment of Hirsutism in Polycystic Ovary Syndrome

Click here to access the full article.

JCI Insight. 2018;3(7):e98569.
17-β Estradiol regulates proglucagon-derived peptide secretion in mouse and human α- and L cells
Click here to access the full article.

Both members of a couple may experience age-related changes concurrently and interdependently. In such cases, it is unhelpful, and sometimes detrimental, to treat the symptoms for only one member of the couple without also treating the other. Therefore, the concept of “couplepause” has been introduced to address the sexual health needs of the aging couple as a whole rather than treating the individual patient in isolation.

Taking a couple-oriented approach to evaluate and manage couplepause in the latter half of life can dramatically and simultaneously help both members of the couple to improve sexual satisfaction and intimacy.

Sex Med Rev. 2018 Jul;6(3):384-395.
Couplepause: A New Paradigm in Treating Sexual Dysfunction During Menopause and Andropause.
Click here to access the full article.

Menopause. 2018 May;25(5):520-530.
Vasomotor symptom characteristics: are they risk factors for incident diabetes?
Click here to access the full article.

Current Treatment Options for Postmenopausal Vaginal Atrophy

Reduced circulating estrogen concentrations adversely affect the elasticity and the collagen synthesis in the vulvovaginal tissue and the growth of the vaginal epithelial lining, resulting in vaginal atrophy in postmenopausal women. About 40% of post-menopausal women experience severe symptoms with a subsequent reduction in quality of life and sexual performance, yet only 20–25% of women seek medical advice. However, there are now various options for treating this pathological condition, including systemic and topical hormone replacement therapy, selective estrogen receptor modulators, vaginal dehydroepiandrosterone, vaginal oxytocin, lubricants and moisturizers, as well as non-drug therapies. Timely diagnosis and appropriate therapy can lead to restoration and maintenance of the vaginal function and vaginal health.

Post Reprod Health. 2015 Sep; 21(3): 88–97.
Intravaginally applied oxytocin improves post-menopausal vaginal atrophy
Click here to access the PubMed abstract of this article.

Int J Womens Health. 2018 Jul 31;10:387-395.
Current treatment options for postmenopausal vaginal atrophy.
Click here to access the PubMed abstract of this article.

Topical Oxytocin for Postmenopausal Vaginal Atrophy

Oxytocin is a nanopeptide hormone that is synthesized in the hypothalamus and secreted by the posterior pituitary gland. Oxytocin is also produced locally in certain types of epithelial and endothelial cells.

Studies have shown that oxytocin stimulates cell proliferation, suggesting that it is one of the mechanisms of action by which local oxytocin increases vaginal thickness and relieves vaginal symptoms in postmenopausal vaginal atrophy.

A very important finding was that intravaginal application of oxytocin did not stimulate the growth of the endometrium. This is in contrast to intravaginally applied estrogen, which, following absorption into the circulation, may stimulate endometrial growth. Furthermore, oxytocin might be of value in women who have estrogen-dependent types of cancers, as oxytocin has not been shown to stimulate the growth of cancer cells.

Climacteric. 2018 Apr;21(2):174-178.
Role of topical oxytocin in improving vaginal atrophy in postmenopausal women: a randomized, controlled trial.
Click here to access the PubMed abstract of this article.

Topical Combination of 0.25% Finasteride and 3% Minoxidil Versus Minoxidil Alone in
Female Pattern Hair Loss

While androgenetic alopecia (AA) or female pattern hair loss (FPHL) can be seen in women with medical conditions such as PCOS that produce high androgen levels in the body, AA/FPHL is actually more common in postmenopausal women.

Finasteride, a 5α-reductase inhibitor works by preventing testosterone from binding to receptors on hair follicles. The use of a topical formulation has been proposed to minimize unwanted effects. A topical combination of 0.25% finasteride and 3% minoxidil has shown promise in the treatment of FPHL with an additional benefit of increasing hair diameter.

NOTE: It’s absolutely essential to avoid pregnancy when taking finasteride. Because this topical therapy may be absorbed percutaneously, it should be reserved for postmenopausal women or those using effective birth control.

Am J Clin Dermatol. 2019 Feb;20(1):147-153.
Efficacy of Topical Combination of 0.25% Finasteride and 3% Minoxidil Versus 3% Minoxidil Solution in Female Pattern Hair Loss: A Randomized, Double-Blind, Controlled Study.
Click here to access the PubMed abstract of this article.

Progesterone Therapy in Women with Intractable Catamenial Epilepsy

Catamenial epilepsy involves exacerbation of seizures in association with the menstrual cycle, and has been defined as the occurrence of 75% of the seizures during a 10-day period of the menstrual cycle starting 4 days before menstruation. Catamenial epilepsy can be due to progesterone deprivation and/or a relative increase in estradiol/progesterone ratio.

A double-blind randomized controlled trial examined the effectiveness of progesterone for treatment of women with intractable catamenial epilepsy. Age, BMI, epilepsy duration, types of drugs used, progesterone level, and the number of the seizures in 3 months before and after the study were compared. The number of the seizures after treatment significantly decreased in the study group.

Adv Biomed Res. 2013; 2: 8.
Progesterone therapy in women with intractable catamenial epilepsy
Click here to access the full article.

Effect of Local Estrogen Therapy on Urinary and Sexual Symptoms in Premenopausal Women

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvovaginal health. Researchers aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. The results of this open study indicate that 12 weeks of local treatment with an estrogen cream at the vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as improve sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment affected by low estrogen.

Gynecol Endocrinol. 2015 Oct;31(10):828-32.
Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS).
Click here to access the PubMed abstract of this article.

Topical Estradiol and Testosterone for Vestibulodynia

Vestibulodynia, also known as provoked localized vulvodynia and formerly termed the “vulvar vestibulitis syndrome,” is characterized by a severe, burning/sharp pain that occurs in response to pressure localized to the vulvar vestibule. Painful intercourse (dyspareunia), as well as pain with tampon insertion, are hallmarks of this condition. Although there are likely multiple causes of vestibular pain, the relationship to combined hormonal contraceptive (CHC) use is becoming increasingly recognized. Because CHCs inhibit luteinizing hormone, there is a decreased ovarian production of testosterone. In addition, both the synthetic estrogen and synthetic progestin component of CHCs, which are metabolized in the liver, leads to increased hepatic production of sex hormone-binding globulin (SHBG).

Results demonstrated that women with vestibulodynia who had no other identifiable cause of their pain that began while taking combined hormonal contraceptives achieved a positive treatment outcome by discontinuing the CHCs combined with the application of a compounded topical hormone therapy containing estradiol and testosterone. Furthermore, subjective improvement was accompanied by normalization of calculated free testosterone and SHBG values.

Sex Med 2013;1:30–33.
The Treatment of Vestibulodynia with Topical Estradiol and Testosterone
C lick here to access the PubMed abstract of this article.

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors

Controversy exists about whether vaginal estrogens interfere with the efficacy of aromatase inhibitors (AIs) in breast cancer patients. With the greater incidence of vaginal atrophy in patients on AIs, Witherby et al. of Warren Alpert School of Medicine at Brown University, Providence, Rhode Island, searched for a non-estrogen therapy. The physicians concluded that a 4-week course of vaginal testosterone was associated with improved signs and symptoms of vaginal atrophy related to AI therapy without increasing estradiol or testosterone levels. Longer-term trials are warranted.

Oncologist. 2011;16(4):424-31.
Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study.
Click here to access the PubMed abstract of this article.

Topical EGCG Ameliorates Radiation-Induced Acute Skin Damage in Breast Cancer Patients

There are few effective treatment options for radiation-induced dermatitis in breast cancer patients. Despite technological advances, acute radiation skin toxicity (ARST) is the most common side effect of breast cancer radiotherapy, occurring in more than 90% of patients. Complications such as pain, discomfort, irritation, itching, and burning feeling may cause restriction in movement, unplanned treatment interruptions, and a decreased chance of getting an effective dose. These issues might reduce patients’ survival rates, as well as their quality of life.

Epigallocatechin-3-gallate (EGCG) facilitates the healing process in ultraviolet radiation-induced erythema in human skin. It has been demonstrated that EGCG enhances the viability of human skin cells and decreases apoptosis induced by X-ray irradiation.

Zhu et al. conducted a phase I study which demonstrated that topical administration of EGCG is safe and that the recommended concentration is 660 μmol/L during skin radiation. They then did a prospective study as a single-institution phase II trial to assess the effectiveness of EGCG as a topical agent for the treatment of ARST, and to evaluate the radiation-induced dermatitis outcomes in women who underwent a mastectomy followed by adjuvant radiotherapy. Forty-nine patients participated in this study.

The treatment with EGCG solution was given to all patients undergoing RT immediately after grade I toxicity was documented. The EGCG solution (660 μmol/L) was sprayed by the same investigator three times a day at 0.05 ml/cm2 to the whole radiation field from a distance of 10-20 cm from the skin, for two weeks after radiation completion. The skin folds, such as armpits required full stretch and exposure before spraying. Patients were advised not to use deodorants, lotions, creams, perfumes, or any other products on the area during the course of radiation therapy

The maximum dermatitis observed during the EGCG treatment was as follows: Grade 1 toxicity, 71.4% (35 patients); grade 2 toxicity, 28.6% (14 patients); there were no patients with grade 3 or 4 toxicity. The majority of the radiation-induced dermatitis was observed 1 week after the end of radiotherapy. EGCG reduced the pain in 85.7% of patients, burning feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6%. These findings suggest topical EGCG may be an effective treatment for radiation-induced dermatitis and has acceptable toxicity.

Oncotarget. 2016 Jul 26;7(30):48607-48613.
Epigallocatechin-3-gallate ameliorates radiation-induced acute skin damage in breast cancer patients undergoing adjuvant radiotherapy
Click here to access the PubMed abstract of this article.

Hormone therapy using estradiol has been shown to improve nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered hormones are more effective at improving nasal function than transdermal hormone therapy.

Menopause. 2004 Jul-Aug;11(4):447-55.
Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women.
Click here to access the PubMed abstract of this article.

A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder.

Estrogen therapy may be effective in alleviating the symptoms suggestive of OAB. Local administration may be the most beneficial route of administration.

Acta Obstet Gynecol Scand. 2004 Oct;83(10):892-7
A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder.
Click here to access the PubMed abstract of this article.

Curr Opin Obstet Gynecol. 2004 Oct;16(5):405-9.
Anabolic effects of androgens on muscles of female pelvic floor and lower urinary tract.
Click here to access the PubMed abstract of this article.

Oxybutynin Rectal Suppositories for Treatment of Detrusor Instability

At the Evanston Continence Center, Northwestern University, a retrospective chart review of 25 women diagnosed with detrusor instability and treated with oxybutynin rectal suppositories was conducted to determine whether oxybutynin hydrochloride suppositories can be used as a treatment for detrusor instability in patients who have not been able to tolerate oral pharmacological agents. Patients were started on one suppository, containing 5 mg oxybutynin, twice daily and the dose was titrated as tolerated. The range of the total daily dose was 5-20 mg. Nine of 25 women (36%) had greater than a 50% overall subjective improvement and 3 (12%) had some improvement. Seven of the 12 responders (58%) continued to use the suppositories for a prolonged period of time (> 90 days). The most common side effects reported were dry mouth 48% and constipation 14.3%. One patient with polymyositis developed a serious anticholinergic reaction which required hospitalization. It was concluded that patients who are unable to tolerate oral anticholinergic and antispasmodic agents for the treatment of detrusor instability may benefit from oxybutynin rectal suppositories.

Int Urogynecol J Pelvic Floor Dysfunct. 1998;9(2):100-2.
Treatment of detrusor instability with oxybutynin rectal suppositories.
Click here to access the PubMed abstract of this article.

Progesterone Cream: Effects and Side-effects on Skin of Peri- and Postmenopausal Women

This study demonstrates that topical 2% progesterone increases elasticity and firmness in the skin of peri- and postmenopausal women. These effects in combination with good tolerability make progesterone a possible treatment agent for slowing down the aging process of female skin after the onset of menopause.

Br J Dermatol. 2005 Sep;153(3):626-34.
Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study.
Click here to access the PubMed abstract of this article.

Topical amitriptyline cream can be considered for first-line treatment of women with provoked vestibulodynia that causes painful intercourse. One study reported a response rate of 56%. Topical therapy can reduce side effects such as drowsiness associated with oral administration.

J Low Genit Tract Dis. 2012 Oct;16(4):394-7.
Use of amitriptyline cream in the management of entry dyspareunia due to provoked vestibulodynia.
Click here to access the PubMed abstract of this article.

Treatment for Vulvodynia

In 2002 and again in 2006, the National Institutes of Health characterized vulvodynia (defined as chronic, unexplained vulvar pain or discomfort, characterized by burning, stinging, irritation, or rawness) as a poorly understood and underresearched focal pain syndrome for which optimal treatment remained unclear. Nearly 14 million U.S. women may at some point in their lives experience the symptoms of chronic vulvar burning and pain, and a localized form of vulvodynia involving the vulvar vestibule is thought to be the leading cause of dyspareunia in premenopausal women. Treatment recommendations range from topical therapies to oral medications, physical therapy and biofeedback, and surgical excision, although the latter is reserved for women with localized pain only. Although many of these modalities demonstrate efficacy, many are also associated with adverse effects, require numerous visits to physicians, or are invasive. A 47% complete response to oral tricyclic antidepressants for the treatment of vulvodynia (both generalized and localized) was reported in 33 women attending a vulvar pain clinic. Amitriptyline is often used as a first-line agent, started at an oral dose of 5 mg to 25 mg nightly and increased by 10 to 25 mg weekly, generally not to exceed 150 mg daily. Gabapentin appears to be very effective in the treatment of unprovoked generalized vulvodynia and has a very low side effect profile. To evaluate the clinical efficacy and tolerability of topical gabapentin in the treatment of women with vulvodynia, between January 2001 and December 2006, fifty-one women with vulvodynia were treated with 2% to 6% gabapentin prepared by local compounding pharmacists. Patients were instructed to apply a small amount of cream (approximately 0.5 mL, equivalent to the size of a pea) three times daily. After a minimum of 8 weeks of therapy, the mean pain score among the 35 evaluable women was significantly reduced. Sexual function improved. Common adverse effects of oral gabapentin, including dizziness, somnolence, and peripheral edema, were not reported by any of the 50 patients studied. The conclusion: “Topical gabapentin seems to be well-tolerated and associated with significant pain relief in women with vulvodynia.”
Call our compounding professionals to discuss individualized treatments and non-irritating topical preparations.

Journal of Lower Genital Tract Disease 2005;9(1):40–51
The Vulvodynia Guideline.
Click here to access the abstract of this article.

J Reprod Med 2007 Feb;52(2):103-6
Evaluation of gabapentin in the treatment of generalized vulvodynia, unprovoked.
Click here to access the PubMed abstract of this article.

Obstet Gynecol. 2008 Sep;112(3):579-85
Topical gabapentin in the treatment of localized and generalized vulvodynia.
Click here to access the PubMed abstract of this article.

Boric Acid Therapy for Chronic Vaginitis

Recalcitrant vaginal trichomoniasis is extremely distressing for patients and frustrating for physicians. Numerous studies have shown that an increase in vaginal pH creates a better environment for the growth of Trichomonas vaginalis. Vaginal acidification using boric acid has resulted in the resolution of recalcitrant Trichomonas vaginalis. Patients with diabetes mellitus (DM) are at increased risk of vulvovaginal candidiasis (VVC) due to Candida glabrata. Observational studies indicate that diabetic patients with C. glabrata VVC respond poorly to azole drugs. Women with DM and VVC showed an overall superior mycological cure rate (74% versus 51%) at day 15 with boric acid suppositories given daily for 14 days as compared to fluconazole as a single oral dose of 150 mg.A study done at New York Hospital-Cornell University Medical Center reported the “ineffectiveness of conventional antifungal agents appeared to be the main reason for chronic mycotic infections. In contrast, boric acid was effective in curing 98% of the patients who had previously failed to respond to the most commonly used antifungal agents and was clearly indicated as the treatment of choice for prophylaxis.” “A double-blind comparison was made of the use of 14 daily intravaginal gelatin capsules containing 600 mg of boric acid powder versus the use of identical capsules containing 100,000 U nystatin… for the treatment of VVC… Cure rates for boric acid were 92% at 7 to 10 days after treatment and 72% at 30 days, whereas the nystatin cure rates were 64% at 7 to 10 days and 50% at 30 days.” Torulopsis glabrata is second only to Candida albicans in the frequency of isolation from the vagina in both asymptomatic women and those with yeast vaginitis. In sixty patients with T. glabrata vaginitis, for whom repeated courses of antimycotic therapy with azoles had previously failed, boric acid emerged as a promising modality.” Another study concluded, “in non-Candida albicans infections, boric acid suppositories achieved the best mycologic cure rate (85%).”

J Obstet Gynaecol Can. 2008 Jan;30(1):55-8
Recalcitrant Trichomonas vaginalis infections successfully treated with vaginal acidification.
Click here to access the PubMed abstract of this article.

J Infect. 2007 Oct;55(4):374-7
Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis.
Click here to access the PubMed abstract of this article.

Diabetes Care. 2007 Feb;30(2):312-7
Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis.
Click here to access the PubMed abstract of this article.

J Reprod Med. 1991 Aug;36(8):593-597
Antifungal agents vs. boric acid for treating chronic mycotic vulvovaginitis.
Click here to access the PubMed abstract of this article.

Am J Ob Gyn. 1981 Sep 15;141(2):145-148
Treatment of vulvovaginal candidiasis with boric acid powder.
Click here to access the PubMed abstract of this article.

Clin Infect Dis. 1997 Apr;24(4): 649-652
Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy.
Click here to access the PubMed abstract of this article.

Am J Ob Gyn. 1995 Sep;173(3 Pt 1):820-823
Chronic fungal vaginitis: the value of cultures.
Click here to access the PubMed abstract of this article.

Compound of Isoflavones, Primrose Oil and Vitamin E Reduces Menopausal Symptoms

More than 60% of women complain of hot flashes during menopause. The etiology of hot flashes is related to low estrogen levels. However, estrogen therapy cannot be used in some patients and it is rejected by others. Isoflavones, present in soy extracts, have demonstrated efficacy in diminishing vasomotor symptoms without serious contraindications or side-effects. Primrose oil and vitamin E have documented antioxidant properties and from a practical point of view, a combination of these substances with isoflavones seems desirable.An open, multicenter, randomized, efficacy and safety trial evaluated the effect of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg on menopausal complaints in a total of 1,080 postmenopausal women with climacteric symptoms. A significant reduction in symptom scores was observed and was more intense in the first 3 months. Increasing doses of the preparation add no beneficial effects.

J Obstet Gynaecol. 2006 May;26(4):344-7
Effect of a compound containing isoflavones, primrose oil and vitamin E in two different doses on climacteric symptoms.
Click here to access the PubMed abstract of this article.

Breastfeeding

Oxytocin nasal spray can be compounded to help women who have problems with milk letdown. Lactation failure may result from insufficient oxytocin. A rise in the concentration of oxytocin causes contraction of cells around the alveoli and milk ducts, in preparation for suckling. Oxytocin nasal solution (Syntocinon®) was formerly commercially available and indicated for use in stimulating lactation during the first week postpartum (not for continued use). Oxytocin nasal spray is contraindicated during pregnancy since it may provoke a uterotonic effect, precipitating contractions and abortion. The medication is still frequently requested and can be compounded per a prescription order.“All purpose nipple ointment” (APNO) is a combination of ingredients that seems to relieve many causes of sore nipples during breastfeeding. The presence of Candida albicans can cause nipple soreness and cracking, and cracks and erosions in the nipple harbor bacteria that can cause infection or delay healing, and can cause significant pain. APNO was originally developed by pediatrician Jack Newman, MD, who started the first hospital-based breastfeeding clinic in Canada in 1984. He noted, “It is always good, however, to try to assure the best latch possible, because improving the latch helps with any cause of pain.” Ointments often work better than creams to treat sore nipples, and Dr. Newman recommended a preparation containing mupirocin 2% ointment 15 grams, betamethasone 0.1% ointment 15 grams, with miconazole powder added so that the final concentration is 2% miconazole. Dr. Newman suggested that sometimes it is helpful to add ibuprofen powder as well so that the final concentration of ibuprofen is 2%. The combination is applied sparingly after each feeding.

Stretch Marks

Topical application of tretinoin (retinoic acid) has been shown to significantly improve the appearance of pregnancy-related stretch marks. In a double-blind, randomized, vehicle-controlled study, 22 women with early, clinically active stretch marks applied either 0.1% tretinoin or vehicle daily for 6 months to the affected areas. Patients were evaluated by physical exam monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin. After 2 months, patients treated with tretinoin had significant improvements in severity scores of stretch marks compared with patients who received vehicle. After 6 months, 8 of the 10 tretinoin-treated patients had definite or marked improvement compared with one of the 12 vehicle-treated patients. An open-label, multicenter, prospective study of 20 women found that tretinoin cream 0.1% applied daily for 3 months to pregnancy-related stretch marks in the abdominal area resulted in significantly improved clinical appearance.Another study reported that elastin content within the reticular and papillary dermis can increase with topical 20% glycolic acid combined with 0.05% tretinoin emollient cream therapy.This therapy should not be used while pregnant or breastfeeding.

Arch Dermatol. 1996 May;132(5):519-26
Topical tretinoin (retinoic acid) improves early stretch marks.
Click here to access the PubMed abstract of this article.

Adv Ther. 2001 Jul-Aug;18(4):181-6
Topical tretinoin 0.1% for pregnancy-related abdominal striae: an open-label, multicenter, prospective study.
Click here to access the PubMed abstract of this article.

Dermatol Surg. 1998 Aug;24(8):849-56
Comparison of topical therapy for striae alba (20% glycolic acid/0.05% tretinoin versus 20% glycolic acid/10% L-ascorbic acid).
Click here to access the PubMed abstract of this article.

Men's Health

Compounded Tadalafil

Tadalafil is a phosphodiesterase-5 (PDE5) inhibitor – the same class of drug as sildenafil (Viagra®) – and has been prescribed for erectile dysfunction (ED) and female sexual dysfunction. Daily low dose tadalafil has also been used for the treatment of male lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH), including in men with diabetes mellitus or following radical prostatectomy. Off-label uses include treatment of sexual dysfunction in males receiving antidepressant therapy. PDE5 inhibitors induce relaxation of smooth muscle cells in the urethra, prostate, bladder neck, and blood vessels. Researchers have investigated the use of tadalafil to increase semen quality, improve endothelial function, assist in the passage of distal ureteral stones, and for treatment of myocardial ischemia, heart failure, bladder ischemia, and aging bladder dysfunction.

Our compounding pharmacy can formulate customized medications containing tadalafil. We can compound tadalafil in dosage forms and/or strengths and combinations that are not commercially available, including oral capsules, sublingual/buccal drops, rapid dissolve tablets, and nasal sprays. We will work together with physicians and their patients to customize medications to meet each patient’s specific needs.

The Aging Male, 2018; 21(1): 77-82.
Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia
Click here to access the PubMed abstract of this article.

Ther Adv Urol. 2017 Jan; 9(1):11-27.
The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction
Click here to access the PubMed abstract of this article.

Mental Support

Posttraumatic stress disorder (PTSD)

Intranasal oxytocin administration early posttrauma may prevent PTSD symptom development, as oxytocin administration was previously found to beneficially impact neurobiological and socio-emotional PTSD vulnerability factors. A multicenter randomized, double-blind, placebo-controlled clinical trial (BONDS study) included 107 patients and showed that repeated intranasal oxytocin administration early post-trauma reduced subsequent PTSD symptom development in recently trauma-exposed emergency department patients with high acute PTSD symptoms.

Eur J Psychotraumatol. 2017 Apr 11;8(1):1302652.
Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals
Click here to access the PubMed abstract of this article.

Addiction/Substance Use Disorders

There is interest in the use of oxytocin as a potential treatment for alcohol and other substance-use disorders. Oxytocin is a neuropeptide that modulates adaptive processes associated with addiction including reward, tolerance, associative learning, memory, and stress responses. oxytocin exerts its effects through interactions with the hypothalamic-pituitary-adrenal (HPA) axis and multiple neurotransmitter systems. A review conducted by Johns Hopkins University School of Medicine summarizes the preclinical and clinical literature on the oxytocin system and its relevance to drug and alcohol addiction. In addition, findings from recent clinical trials conducted in participants with cocaine, cannabis, or alcohol use disorder are included. Evidence is summarized, noting that oxytocin may help to normalize blunted stress responses, and attenuate hypercortisolism associated with withdrawal, negative mood, and withdrawal symptoms.

Behav Pharmacol. 2016 Dec;27(8):640-648.
Oxytocin for the Treatment of Drug and Alcohol Use Disorders
Click here to access the PubMed abstract of this article.

Intranasal Ketamine for Treatment-Resistant Depression

Rakofsky and Rapaport of the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, discuss new therapies that are available as treatment options for major depressive disorder and bipolar disorder, such as intranasal ketamine. There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments.

Continuum (Minneap Minn). 2018 Jun;24(3, BEHAVIORAL NEUROLOGY AND PSYCHIATRY):804-827.
Mood Disorders.
Click here to access the PubMed abstract of this article.

Research demonstrated a rapid, non-sustained antidepressant response to a single infusion of ketamine, with controlled studies of intranasal therapy that appear promising.

Depress Anxiety. 2016 Aug;33(8):698-710.
Ketamine for Treatment-Resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice.
Click here to access the PubMed abstract of this article.

The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression and attenuate suicidal symptoms. Frequently repeated intravenous ketamine infusion is not a practical treatment strategy for maintenance therapy. And, the oral bioavailability of ketamine is only 8%–17% because of extensive first-pass metabolism so oral therapy is not a viable option. Therefore, the intranasal route has been investigated.

Gen Hosp Psychiatry. 2015;37(2):178–184.
Ketamine as a novel treatment for major depressive disorder and bipolar depression: a systematic review and quantitative meta-analysis.
Click here to access the PubMed abstract of this article.

Intranasal drug delivery (INDD) systems offer a route to the brain that bypasses problems related to gastrointestinal absorption, first-pass metabolism, and the blood-brain barrier; onset of therapeutic action is rapid, and the inconvenience and discomfort of parenteral administration are avoided. INDD has found several applications in neuropsychiatry, such as to treat migraine, acute and chronic pain, Parkinson disease, disorders of cognition, autism, schizophrenia, social phobia, and depression.

J Clin Psychiatry. 2015 May;76(5):e628-31.
Intranasal drug delivery in neuropsychiatry: focus on intranasal ketamine for refractory depression.
Click here to access the PubMed abstract of this article.

In a randomized, double-blind, placebo-controlled, crossover trial conducted in 20 patients with major depression, the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Anxiety ratings also decreased significantly more with ketamine. Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo. Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters.

Biol Psychiatry. 2014 Dec 15;76(12):970-6.
A randomized controlled trial of intranasal ketamine in major depressive disorder.
Click here to access the PubMed abstract of this article.

Growing evidence of the rapid antidepressant effects of intranasal ketamine represents a promising advance in treatment-resistant depression (TRD) therapeutics. Most studies report a duration of response up to 7 days and remission up to 3-5 days after a single dose.

More of the patients who received esketamine achieved remission. “Most adverse events … subsided spontaneously by 60 to 90 minutes post dose.” In addition, “there was no pushback” in regards to the nasal delivery system. “The route of administration was well received, and it was certainly more convenient than intravenous administration.”

American Psychiatric Association (APA) 2018. Abstracts P7-065 and P8-054, presented May 8, 2018.
Study Shows Fast-Acting Benefits of Ketamine for Depression and Suicidality; Caution on the Potential for Abuse and the Need for Effective Controls
https://www.psychiatry.org/newsroom/news-releases/study-shows-fast-acting-benefits-of-ketamine-for-depression-and-suicidality-caution-on-the-potential-for-abuse-and-the-need-for-effective-controls

Psychiatry Clin Neurosci. 2018 Aug;72(8):623.
Time until relapse after augmentation with single-dose ketamine in treatment-resistant depression.
Click here to access the PubMed abstract of this article.

Ketamine and esketamine are not currently approved treatments for depression, but the clinical use of ketamine is increasing in a variety of practice settings internationally.

CNS Drugs. 2018 May;32(5):411-420.
Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review.
Click here to access the PubMed abstract of this article.

A study by Galves et al. concluded that the drug formulation, the delivery device, the technique and individual patient factors play an important role in tolerability and efficacy when using intranasal ketamine for Treatment Resistant Depression.

J Psychopharmacol. 2018 Apr;32(4):397-407.
Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial.
Click here to access the PubMed abstract of this article.

Intranasal Ketamine for Treatment-Resistant Depression: Glutaminergic Inhibition for Patients who are Refractory to MAOI Antidepressants

Depressive disorders represent diverse psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities that can lead to severe disability. In spite of decades of research on the pathogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one-third to a half of patients respond partially or become refractory to MAO inhibitors, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission, which can be inhibited by ketamine.

Ketamine is approved by the FDA to be used as an anesthetic; however, recent reports have shown its success in the treatment of major depressive disorder (MDD). Studies have suggested that a sub-anesthetic dose produces rapid antidepressant activity, providing significant symptomatic relief, particularly in patients with a history of treatment-resistant depression (TRD). Many reports have been published on the intranasal efficacy of ketamine in the treatment of depression.

In a randomized, double-blind, placebo-controlled, crossover trial conducted in 20 patients with major depression, Lapidus et al. of the Icahn School of Medicine at Mount Sinai, New York, tested the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Eighteen patients completed 2 treatment days with intranasal ketamine hydrochloride or saline solution. The researchers found that a single intranasal dose of ketamine (50 mg) outperformed saline by 7.6 points on the Montgomery-Asberg Depression Rating Scale as assessed 24 hours after dosing; the response rate was 44% vs 6%, respectively. Anxiety ratings also decreased significantly more with ketamine. Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo. Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters.

J Psychiatr Res. 2019 May;112:7-11.
Estimating patient-specific treatment advantages in the ‘Treatment for Adolescents with Depression Study’
Click here to access the PubMed abstract of this article.

Curr Pharm Des. 2019;25(4):381-387.
Novel Pathways in the Treatment of Major Depression: Focus on the Glutamatergic System
Click here to access the PubMed abstract of this article.

PLoS One. 2019 Mar 13;14(3):e0213721.
Ketamine disrupts neuromodulatory control of glutamatergic synaptic transmission
Click here to access the PubMed abstract of this article.

Gastroenterology / Proctology

Ketotifen: Treating Irritable Bowel Syndrome with Diarrhea

A study investigated the use of ketotifen for the treatment of irritable bowel syndrome with diarrhea (IBS-D). A total of 108 IBS-D patients were randomly divided into a ketotifen group (n = 55) and a control (placebo) group (n = 53).

The patients in the ketotifen group received ketotifen 1 mg oral tablets two times daily; patients in the control group received oral placebo. Before and after 8 weeks of treatment, gastrointestinal symptoms, anorectal sensory function and the number and activity status of mast cells were assessed for both groups. The overall effective rate of gastrointestinal symptom improvement in the ketotifen group was significantly higher than that in the control group (76.4 vs. 37.7%). First sensation, defecation urgency and discomfort/pain threshold in the ketotifen group improved significantly after treatment; no significant changes were observed in the control group. Six patients (10.9%) in the ketotifen group experienced drowsiness and fatigue, but the symptoms disappeared after 1 week of treatment.

Ketotifen significantly alleviated gastrointestinal symptoms and improved visceral hypersensitivity in patients with IBS-D. The therapeutic effect of ketotifen is related to a reduced number and decreased activity of mast cells in the intestinal mucosa, especially in the terminal ileum.

Eur J Gastroenterol Hepatol. 2020 Jun; 32(6):706-712.
Clinical efficacy and safety of ketotifen in treating irritable bowel syndrome with diarrhea
Click here to access the PubMed abstract of this article.

Small Intestinal Bacterial Overgrowth Syndrome (SIBO): Treatment and Prevention of Recurrence, with a Focus on Patients with Parkinson’s Disease

Small intestinal bacterial overgrowth (SIBO) is defined as the presence of excessive bacteria in the small intestine. SIBO is frequently implicated as the cause of chronic diarrhea and malabsorption. Patients with SIBO may also suffer from unintentional weight loss, nutritional deficiencies, and osteoporosis. A common misconception is that SIBO affects only a limited number of patients, such as those with an anatomic abnormality of the upper gastrointestinal (GI) tract or those with a motility disorder. However, SIBO may be more prevalent than previously thought. This apparent increase in prevalence may have occurred, in part, because readily available diagnostic tests have improved the ability to diagnose SIBO.

SIBO can be caused by delayed small bowel motility, such as in patients with intestinal pseudoobstruction, GI surgery, GP, or medications such as steroids or opiates. Symptoms of SIBO are nonspecific and include bloating, abdominal distension, abdominal pain or discomfort, diarrhea, fatigue, and weakness. The frequency and severity of symptoms likely reflect both the degree of bacterial overgrowth along with the extent of mucosal inflammation.

SIBO can lead to nutritional deficiencies in fat-soluble vitamins and vitamin B12, and electrolyte abnormalities. Complications of SIBO range from mild, including diarrhea and minimal vitamin deficiencies, to severe, including malabsorption and neuropathies due to fat-soluble vitamin deficiencies. Therefore, deficiencies and the condition must be treated. Further studies are needed to define the role of probiotic therapy in SIBO.

Parkinson’s disease (PD) affects the nerves of the entire GI tract, causing GI dysfunction leading to poor patient outcomes. Common GI disturbances in patients with PD include gastroparesis (GP), constipation, and small intestinal bacterial overgrowth syndrome (SIBO). GI dysfunction, especially gastroparesis and SIBO, can cause fluctuations in the absorption of medications used to treat PD, which can further impair the treatment of PD. Patients with both SIBO and PD have longer off-time, defined as periods when the medication is not working well or does not kick in, and this may lead to worsening motor symptoms, delays in motor symptom improvement after medication intake, or no improvement after medications.

Recurrence rates as high as 43% can be seen in patients with SIBO at 6 and 9 months post-treatment. Pimentel et al. of Cedars-Sinai Medical Center tested whether low-dose nocturnal erythromycin can prevent the recurrence of IBS symptoms after successful antibiotic treatment. 203 patient charts were reviewed to find IBS patients with SIBO, and treatment cycles were assessed to identify subjects with clinical and breath test resolution. The charts of those who met the inclusion criteria were reviewed to determine the method of prevention of symptom recurrence and the length of remission. 64 patients met the inclusion criteria. Subjects receiving no prevention (n=6) after successful antibiotic treatment experienced symptom recurrence after 59.7±47.4 days. Prevention using erythromycin 50 mg orally at bedtime (n=42) demonstrated 138.5±132.2 symptom-free days (P=.08 vs no prevention). This study also evaluated tegaserod (Zelnorm®) which was removed from US, Canadian, and Australian markets in 2007 due to side effects.

Erythromycin 50 mg is not commercially available. This immediate-release preparation must be compounded.

Expert Opin Pharmacother. 2015;16(16):2449-64.
The treatment of gastroparesis, constipation, and small intestinal bacterial overgrowth syndrome in patients with Parkinson’s disease
Click here to access the PubMed abstract of this article.

Gastroenterol Hepatol (N Y). 2009 Jun; 5(6): 435–442.
Low-Dose Nocturnal Tegaserod or Erythromycin Delays Symptom Recurrence After Treatment of Irritable Bowel Syndrome Based on Presumed Bacterial Overgrowth
Click here to access the PubMed abstract of this article.

Gastroenterol Hepatol (N Y). 2007 Feb; 3(2): 112–122.
Small Intestinal Bacterial Overgrowth
Click here to access the PubMed abstract of this article.

Regression of GERD Symptoms with a Custom Dietary Supplement, Compared to Omeprazole

The prevalence of gastroesophageal reflux disease (GERD) is increasing. GERD is a chronic disease and presenting symptoms may include heartburn, regurgitation, dysphagia, coughing, hoarseness, or chest pain.

A single-blind randomized study included 176 patients aged 18 to 88 years and compared the benefits of 20 mg omeprazole (a “proton pump inhibitor”) to a dietary supplement containing melatonin 6 mg, methionine 100 mg, L-tryptophan 200 mg, hydroxocobalamin 50 micrograms, pyridoxine 25 mg, betaine 100 mg, and folic acid 10 mg. Patients in the supplement group experienced 24-hour relief from GERD symptoms in as little as 7 days, and 90.3% of the supplement group had significant improvements in sleep quality by the end of the study.

Conclusion: The customized supplement formulation promoted regression of GERD symptoms with no significant side effects.

J Pineal Res. 2006 Oct;41(3):195-200.
Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole.
Click here to access the PubMed abstract of this article.

Melatonin, B-Vitamins and Amino Acids Show Promise for Reflux Disease
https://www.naturalhealthresearch.org/34410-2/

Anal Fissure

Chronic anal fissures can be simply and effectively treated medically without the risk of incontinence associated with sphincterotomy. The American Gastroenterological Association (AGA) has noted: “In most cases, an initial trial of conservative care alone is appropriate, particularly for acute fissures. The timing and choice of additional treatment depend on the chronicity of the fissure, the severity of its symptoms, and the rate and completeness of its response to conservative care. Although lateral internal sphincterotomy (LIS) is the procedure of choice for anal fissures that do not resolve with conservative care or that are simply too painful for conservative care, in a minority of patients, LIS is associated with minor, but sometimes permanent, defects incontinence. Topical therapy is directed at reversibly decreasing resting anal pressure, with a goal of allowing fissure healing without permanent sphincter damage. Because a long interval of time between first symptoms and treatment negatively affects fissure healing and increases recurrence rate, treatment for anal fissure should be initiated early.

Tech Coloproctol. 2011 Jun;15(2):135-41. Epub 2011 May 3.
The management of patients with primary chronic anal fissure: a position paper.
Click here to access the PubMed abstract of this article.

Sodium Butyrate Enemas for Treatment of Acute Radiation-induced Proctitis in Patients with Prostate Cancer and the Impact on Late Proctitis

To evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis, 31 patients were treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. 23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistically significant difference was found between the incidence and the severity of proctitis before the start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptoms. Eleven patients suffered from grade I and two of these patients from grade II toxicity as well. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity.

Strahlenther Onkol. 2008 Dec;184(12):686-92. Epub 2008 Dec 24.
Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis. A prospective evaluation.
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Short Chain Fatty Acid Enemas for Short-Term Treatment of Chronic Radiation Proctitis

Radiation proctitis is a common complication of abdominal and pelvic radiotherapy. Short chain fatty acids are the main energy source of colonocytes and their use may be impaired in chronic radiation proctitis. A prospective, randomized, double-blind trial compared short chain fatty acid enemas with placebo in 19 patients with chronic radiation proctitis. Short chain fatty acid enemas contained 60 mM sodium acetate, 30 mM sodium propionate, and 40 mM sodium butyrate. The treatment period lasted five weeks and patients were followed up for six months. After five weeks, short chain fatty acid-treated patients showed a significant decrease in the number of days with rectal bleeding from the previous week and an improvement of endoscopic score. Hemoglobin values were also significantly higher in short chain fatty acid-treated patients. Although short chain fatty acid-treated patients did not get worse in the next six months, placebo-treated ones gradually improved, and at the end of six months, differences between the two groups were no longer observed. The study concluded that short chain fatty acid enemas can accelerate the process of healing in chronic radiation proctitis, but treatment has to be continuous if a complete and sustained clinical, endoscopic, and histologic response is to be obtained.

Dis Colon Rectum. 1999 Jun;42(6):788-95; discussion 795-6.
Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial.
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Am J Gastroenterol. 1996 Sep;91(9):1814-6.
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
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Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.

Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis. A double-blind, double-dummy, randomized, multicentre study compared the therapeutic efficacy, tolerability and safety, and patient’s preference of budesonide foam vs. budesonide enema. Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index > 4 and endoscopic index > or = 4) received 2mg/25mL budesonide foam and placebo enema (n=265), or 2mg/100mL budesonide enema and placebo foam (n=268) for 4 weeks. Clinical remission rates were 60% for budesonide foam and 66% for budesonide enema. Both formulations were safe and no drug-related serious adverse events were observed. Budesonide enemas can be compounded in a “patient-friendly” more concentrated volume such as 2 mg/60 ml.

Aliment Pharmacol Ther. 2006 Jan 15;23(2):303-12.
Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.
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Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis.

Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis (UC). With the introduction of budesonide, the risk of systemic side effects may be reduced. We investigated whether a 2 mg budesonide enema administered twice daily could increase the remission rate in comparison with the once daily standard regimen, and whether 2 mg budesonide enema, given twice weekly, could have a relapse preventing effect.149 patients with active distal UC were treated in a controlled, double-blind multicenter study with two parallel groups: placebo enema in the morning and budesonide enema in the evening (i.e. 2 mg/day) or budesonide enema b.i.d. (i.e. 4 mg/day) until remission (absence of clinical symptoms and endoscopic healing) or at most 8 weeks. Patients in remission were randomized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse.The remission rates at 4 weeks were 33% for daily and 41% for b.i.d. regimens and correspondingly 51% and 54% at 8 weeks. The b.i.d. group had an increased frequency of impaired adrenal function, 32% versus 4.8% (P = 0.001). The relapse rates during maintenance treatment with budesonide enema and placebo were 15% versus 24% after 8 weeks, 31% versus 27% after 16 weeks and 41% versus 51% after 24 weeks (NS).This study concluded that budesonide enema 2 mg daily appears to be the optimal dosage in active distal UC. We could not show that budesonide enema twice weekly is sufficient to maintain remission.

Scand J Gastroenterol. 2002 Jun;37(6):705-10.
Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis.
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Glyceryl Trinitrate Suppository For Anal Fissure: Safety and Efficacy

A double-blind placebo-controlled clinical trial concluded that the use of glyceryl trinitrate 0.2% suppositories represent a new, promising, and effective treatment for chronic anal fissure.

Dis Colon Rectum, 51 (7), 1079-83 Jul 2008
Safety and efficacy of new glyceryl trinitrate suppository formula: first double-blind placebo-controlled clinical trial.
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Topical Amitriptyline/Ketamine for Analgesia in Refractory Proctodynia

Idiopathic proctodynia, an enigmatic pain syndrome affecting the perianal region, can be persistent, relatively refractory to treatment, and associated with considerable psychological distress. Lehman and Sciallis of the Department of Dermatology, Mayo Clinic, presented the case of a patient with a long history of severe proctodynia that had been resistant to a range of topical and systemic treatments. With the use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% cream, the patient’s pain resolved rapidly, leading to a substantially improved quality of life.

J Drugs Dermatol. 2008 Sep;7(9):887-9.
Effective use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% for analgesia in refractory proctodynia.
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A separate double-blind, randomized trial evaluated the effect of topical metronidazole 10% versus placebo, applied to surgical site, in reducing postoperative and post-defecation pain after hemorrhoidectomy. Findings indicated that topical 10% metronidazole significantly reduces post-hemorrhoidectomy discomfort.

Dis Colon Rectum. 2008 Feb;51(2):235-8.
Topical Metronidazole can Reduce Pain after Surgery and Pain on Defecation in Postoperative Hemorrhoidectomy.
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Chronic Fatigue / Fibromyalgia

Fibromyalgia

Pharmacotherapy for fibromyalgia has become more prevalent in clinical practice as our understanding of the cellular, molecular and pathophysiologic mechanisms contributing to widespread musculoskeletal and neuropathic pain has evolved. Thus, several pain pathways including high-voltage activated Ca2+ channels and the Kv1 family of K+ ion channels appear related to the efficacy of pregabalin and amitriptyline, respectively. Serotonin and norepinephrine reuptake inhibitors – including mirtazapine, duloxetine and milnacipran – appear to be more efficacious in FMS than selective serotonin reuptake inhibitors.

Clin Exp Rheumatol. 2009 Sep-Oct;27(5 Suppl 56):S86-91.
Focus on pain mechanisms and pharmacotherapy in the treatment of fibromyalgia syndrome.
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Sublingual Cyclobenzaprine Improves Outcomes in Patients with Fibromyalgia

Disrupted and nonrestorative sleep is widely thought to play a role in the pathophysiology of FM, suggesting that treatments that improve sleep quality would address global symptoms that patients with FM experience. Researchers found that a rapidly absorbed proprietary eutectic sublingual tablet formulation of low-dose (2.8 mg) cyclobenzaprine HCl taken at bedtime for 12 weeks improved both sleep and patient outcomes related to pain and other measurements.

Topics in Pain Management. 2016 Feb. 31(7): 10-12.
BESTFIT Studies Analyze Sleep Medication’s Role in Improving Fibromyalgia Patient Outcomes
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Considering the refractory nature of fibromyalgia to conventional pain treatments, the IV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials.

J Pain. 2006 Jun;7(6):391-8.
The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients.
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Diabetes

Estrogen Therapy may reduce the risk of diabetes in postmenopausal women

It is known that younger women are less likely than men to develop type 2 diabetes. But after menopause, the trend reverses dramatically and women are at higher risk of diabetes due to declining levels of estrogens, specifically, estradiol, which exerts specific actions on the pancreas and insulin biosynthesis and secretion. Clinical and experimental data from research done at University Hospital/Diabetes Center and University of Geneva Medical School, Geneva, Switzerland indicate a beneficial effect of estrogens on energy and glucose homeostasis associated with improved insulin sensitivity. Dr. Sandra Handgraaf noted: “A number of scientists are working on the effect of estrogens on pancreatic insulin-producing cells. But its effect on glucagon-producing cells, another hormone regulating blood sugar, had never been explored before… Besides their pivotal role in sexual development and reproduction, estrogens prevent the occurrence of visceral obesity, insulin resistance, and glucose intolerance in women.” Study leader Jacques Philippe, MD, a Harvard University/Mass General Hospital-trained endocrinologist, said: “It is important to remember hormonal substitution, when taken at the beginning of menopause and for a few years only, does not cause any particular risk of cardiovascular events.” The study concluded that a woman receiving hormone replacement therapy is up to 35 percent less likely to develop type 2 diabetes.

JCI Insight. 2018;3(7):e98569.
17-β Estradiol regulates proglucagon-derived peptide secretion in mouse and human α- and L cells
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Metformin Transdermal for Diabetic Patients Unable to Tolerate Oral Metformin

Transdermal metformin has been studied as an alternative treatment in patients with insulin resistance who are unable to tolerate oral medications. One advantage of using transdermal metformin is that it bypasses the gastrointestinal system, and therefore does not produce the gastrointestinal side effects associated with oral metformin. Transdermal metformin is dosed at only 5-10% of the typical oral dose, and this significantly reduced actual dose has achieved effects that are clinically comparable to the typical oral dose. Reduced incidence of adverse effects has improved compliance and tolerability for patients who have difficulty swallowing oral agents.In clinical use of transdermal delivery of metformin formulated with Pluronic Lecithin Organogel (PLO), it was observed that approximately 5-10% of the amount of the usual oral dose elicited a therapeutic response in terms of decreased blood-glucose levels. Transdermal metformin is recommended only for patients with stable, controlled blood sugar and optimized HgA1C levels.

Int J Pharm Pharm Sci, Vol 4, Suppl 3, 297-302
Preparation and evaluation of transdermal patches of metformin hydrochloride using natural polymer for sustained release
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“Psychological stress decreases insulin sensitivity and increases insulin resistance and may hence be important in the development/onset of type I diabetes.”

Neuroimmunomodulation. 2006;13(5-6):301-8.
Psychological stress and the risk of diabetes-related autoimmunity: a review article.
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“In patients with glucose intolerance, cortisol secretion, although normal, is inappropriately high given enhanced central and peripheral sensitivity to glucocorticoids……thus altered cortisol action occurs not only in obesity and hypertension but also in glucose intolerance and could therefore contribute to the link between these multiple cardiovascular risk factors.”

J Clin Endocrinol Metab. 2002 Dec;87(12):5587-93.
Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance.
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Otolaryngology

Ketotifen and Budesonide Nasal Spray for Treatment of Allergic Rhinitis

A total of 96 allergic rhinitis patients were treated with ketotifen fumarate and budesonide administered as a combination nasal spray. Results indicated that the combination of these two drugs can rapidly relieve allergic symptoms. After treatment, the symptoms of nasal obstruction, nasal itching, sneezing, and runny nose significantly improved, and the score of these symptoms was significantly lower when compared to that before treatment.

Int J Clin Pharmacol Ther. 2020 Apr; 58(4):195-197.
Combination treatment of allergic rhinitis using ketotifen fumarate and budesonide administered as nasal sprays
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Antifungal Therapy to Prevent Recurrent Allergic Fungal Rhinosinusitis After Surgery

Allergic fungal rhinosinusitis (AFRS) is the most common form of fungal sinus disease. Its recurrence rate is high despite numerous strategies to prevent it. A study assessed the effect of systemic and topical antifungal agents-both separately and in combination- in preventing recurrence of AFRS following functional endoscopic sinus surgery (FESS). It was concluded that treatment with topical fluconazole as either a nasal spray (0.5mg in each nostril twice daily for 3 months) or an irrigation solution (once a week for 6 consecutive weeks) can significantly reduce the rate of recurrence of AFRS after FESS.

Ear Nose Throat J. 2011 Aug;90(8):E1-7.
The role of antifungal therapy in the prevention of recurrent allergic fungal rhinosinusitis after functional endoscopic sinus surgery: a randomized, controlled study.
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Hemostatic Effect of Tranexamic Acid in Elective Nasal Surgery

Bleeding is the most frequent complication of nasal surgery. A prospective study evaluated the effectiveness of tranexamic acid (TA), an antifibrinolytic agent, in reducing bleeding during and after nasal surgery. The study concluded tranexamic acid “is a safe and effective drug for the reduction of bleeding in nasal surgery. It may be recommended for routine use.”

Am J Rhinol. 2006 Mar-Apr;20(2):227-9.
Hemostatic effect of tranexamic acid in elective nasal surgery.
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Capsaicin Nasal Spray for Idiopathic/Perennial Rhinitis

Capsaicin nasal spray has been shown to reduce nasal complaints in patients with non-allergic non-infectious perennial rhinitis. Blom et al. hypothesized that the beneficial effect of capsaicin might be the result of a down-regulation of inflammation, and showed that intranasal capsaicin spray gives a significant and long-term reduction of symptoms. In a double-blind parallel groups trial, 30 patients were randomized into two different treatment regimens: group A received capsaicin five times on the first day at one-hour intervals. This was followed by a placebo once every second or third day for a total of five treatments within 2 weeks after the initial capsaicin application. Group B received the placebo five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in smell, blood pressure, or heart rate were found. They concluded that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.In a separate trial, a total of 208 patients affected by idiopathic rhinitis (IR) were enrolled in a randomized placebo-controlled trial. Diagnosis of IR was made on the basis of history of nasal obstruction, sneezing and/or rhinorrhoea and after exclusion of other nasal/paranasal anatomic disorders. IR patients were randomized into four groups receiving increasing doses of capsaicin (Capsicum) or placebo. A significant reduction in the frequency of IR symptom was noticed in the group that received capsaicin 4 micrograms/puff, three times a day for 3 consecutive days. No significant difference in side effects was recorded in patients receiving capsaicin therapy when compared to controls.

Acta Otolaryngol. 2009 Apr;129(4):367-71.
Intranasal Capsicum spray in idiopathic rhinitis: a randomized prospective application regimen trial.
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Allergy. 2003 Aug;58(8):754-61.
Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study.
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Clin Exp Allergy. 1998 Nov;28(11):1351-8
The long-term effects of capsaicin aqueous spray on the nasal mucosa.
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Otitis Media

Treatment protocols have evolved considerably and will continue to change as new data continue to emerge regarding the bacteriology of chronic suppurative otitis media, bacterial resistance, and ototoxicity. Continuous surveillance is necessary to monitor antimicrobial resistance and to guide antibacterial therapy.

Clin Otolaryngol Allied Sci. 2004 Aug;29(4):321-3.
Emergence of ciprofloxacin-resistant pseudomonas in chronic suppurative otitis media.
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David S. Haynes, MD, director of otology and neurotology at the Vanderbilt University Medical Center and the St. Thomas Hospital Neuroscience Institute in Nashville, and associate professor in the Department of Otolaryngology and the Department of Hearing and Speech Sciences, notes that at Vanderbilt, physicians use a powder made up of amphotericin B, sulfanilamide, chloramphenicol, hydrocortisone, and corn starch to successfully treat refractory draining mastoid cavities and external ear infections. Powders have a mechanical drying effect and can be used to deliver antibiotics and other agents (i.e., antifungals) that are not commercially available as ototopical agents.

Ear Nose Throat J. 2002 Aug;81(8 Suppl 1):13-5.
Perioperative antibiotics in chronic suppurative otitis media.
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Xylitol for Otitis Media

In two clinical trials (of three months duration), oral xylitol in a daily dose of 8.4-10 g given in five divided doses was found to reduce the incidence of acute otitis media (AOM) by 35-40% in young children. The need for antimicrobials decreased markedly when using xylitol. Xylitol appears to be an attractive alternative to prevent AOM. However, in a high-risk group of children with tympanostomy tubes, xylitol was ineffective in preventing otitis.

Vaccine. 2000 Dec 8;19 Suppl 1:S144-7.
Xylitol in preventing acute otitis media.
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This study found that “Oral xylitol solution at dosages of 5g TID and 7.5g QD is well-tolerated by young children.”

Int J Pediatr Otorhinolaryngol. 2007 Jan;71(1):89-94. Epub 2006 Nov 9.
Tolerability of oral xylitol solution in young children: implications for otitis media prophylaxis.
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Xylitol inhibits the growth of Streptococcus pneumoniae and inhibits the attachment of both pneumococci and Haemophilus influenzae to the nasopharyngeal cells.

Vaccine. 2000 Dec 8;19 Suppl 1:S144-7.
Xylitol in preventing acute otitis media.
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The Cleveland Clinic Foundation, Head and Neck Institute, reports that mupirocin nasal irrigations may avoid the need for intravenous antibiotics, which often provide temporary benefits and entail greater cost and morbidity. Thus, mupirocin nasal irrigations may provide a relatively simple means for the management of MRSA exacerbations of CRS.

Am J Otolaryngol. 2006 May-Jun;27(3):161-5.
Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant Staphylococcus aureus with mupirocin irrigations.
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Nasal lavage with 0.05% mupirocin was well tolerated and may represent an effective alternative treatment for postsurgical recalcitrant chronic rhinosinusitis.

Laryngoscope. 2008 Sep;118(9):1677-80.
Nasal lavage with mupirocin for the treatment of surgically recalcitrant chronic rhinosinusitis.
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Results of this study indicate that topical fluconazole application may help patients with allergic fungal sinusitis.

Ear Nose Throat J. 2004 Oct;83(10):692, 694-5.
Fluconazole nasal spray in the treatment of allergic fungal sinusitis: a pilot study.
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Betahistine for Treatment of Acute Vestibular Vertigo & Meniere’s Disease

Betahistine at oral doses of 16 mg tid and 24 mg bid provides similar efficacy and tolerability in the treatment of vertigo in patients with Meniere’s disease. The efficacy and safety profile of betahistine in the treatment of vertigo due to peripheral vestibular disorders was confirmed.

Acta Otolaryngol. 2008 Jul 10:1-6.
Effects of semicircular canal electrode implantation on hearing in chinchillas.
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Acta Otorhinolaryngol Ital. 2001 Jun;21(3 Suppl 66):1-7
Betahistine in the treatment of vertigo. History and clinical implications of recent pharmacological researches.
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Eur Arch Otorhinolaryngol. 2003 Feb;260(2):73-7.
Betahistine dihydrochloride in the treatment of peripheral vestibular vertigo.
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Acta Otolaryngol Suppl. 2000;544:34-9
A review of medical treatment for Ménière’s disease.
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Otolaryngol Head Neck Surg 1999 Mar;120(3):400-5
Betahistine increases vestibular blood flow.
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Acta Otolaryngol Suppl 1991;479, pp. 44-47
Treatment of acute vestibular vertigo.
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