Gastroenterology/Proctology
Anal FissureChronic 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 in continence.
Topical therapy is directed at reversibly decreasing resting anal pressure, with a goal of allowing fissure healing without permanent sphincter damage. Several preparations have been used, including compounded nitroglycerin ointment 0.2% (glyceryl trinitrate; GTN). Studies have shown healing rates of 25-50%. Side effects, particularly headache with higher doses of nitroglycerin ointment such as found in the commercially available 2% product, have been reported, but only infrequently require cessation of therapy with the less concentrated preparations.
An Italian position statement aimed to identify the best treatment option for anal fissures by drawing on evidence-based medicine and the expert advice of 6 colorectal surgeons with extensive experience in this field. Altomare et al. noted that use of 0.4% glyceryl trinitrate in standardized fashion seems to have the best results despite a higher percentage of headache, while the use of botulinum toxin had inconsistent results. Nonresponding patients should undergo lateral internal sphincterotomy.
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.
Altomare DF, Binda GA, Canuti S, Landolfi V, Trompetto M, Villani RD.
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Can J Surg. 2006 Feb;49(1):41-5.
Nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin.
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Gastroenterology 2003;124:233–234
American Gastroenterological Association medical position statement: Diagnosis and care of patients with anal fissure, This document presents the official recommendations of the American Gastroenterological Association (AGA) on Anal Fissures. It was approved by the Clinical Practice Committee on May 19, 2002 and by the AGA Governing Board on July 27, 2002.
Click here to access the 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 statistical significant difference was found between the incidence and the severity of proctitis before 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 symptom. 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.
Hille A, Herrmann MK, Kertesz T, Christiansen H, Hermann RM, Pradier O, Schmidberger H, Hess CF.
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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.
Pinto A, Fidalgo P, Cravo M, Midões J, Chaves P, Rosa J, dos Anjos Brito M, Leitão CN.
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Am J Gastroenterol. 1996 Sep;91(9):1814-6.
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
al-Sabbagh R, Sinicrope FA, Sellin JH, Shen Y, Roubein L.
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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.
Gross V, Bar-Meir S, Lavy A, Mickisch O, Tulassay Z, Pronai L, Kupcinskas L, Kiudelis G, Pokrotnieks J, Kovács A, Faszczyk M, Razbadauskas A, Margus B, Stolte M, Müller R, Greinwald R; International Budesonide Foam Study Group.
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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.
Lindgren S, Löfberg R, Bergholm L, Hellblom M, Carling L, Ung KA, Schiöler R, Unge P, Wallin C, Ström M, Persson T, Suhr OB.
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Oral Naloxone to Prevent or Reverse Opioid-Induced Constipation
Opioid analgesics are the cornerstone of pain management for moderate-to-severe cancer pain and, increasingly, chronic non-cancer pain. The use of opioids is commonly associated with dose-limiting constipation that seriously impacts patients’ quality of life. Agents currently used to manage opioid-induced constipation (OIC), such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective. A novel approach for selectively and locally antagonizing the gastrointestinal effects of opioids involves the coadministration of a mu-opioid receptor antagonist with negligible systemic availability, such as oral naloxone. Combination therapy with prolonged-release (PR) oxycodone plus PR naloxone has been shown to provide effective analgesia while preventing or reducing constipation. This novel strategy has the potential to significantly improve the quality of life of patients suffering from chronic pain, affording patients the benefit of full analgesia, without the burden of OIC.
Pharmacology. 2009;83(1):10-7.
Meeting the challenges of opioid-induced constipation in chronic pain management – a novel approach
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In a controlled trial involving 202 patients with chronic pain under stable oral prolonged-release (PR) oxycodone therapy (40, 60 or 80mg/day), patients were randomized to receive PR oral naloxone (10, 20, 40mg/day) or placebo. No loss of analgesic efficacy with naloxone was observed; mean pain intensity scores were comparable for placebo and all doses of naloxone and remained unchanged during treatment. Naloxone 20 mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo. The 2:1 oxycodone/naloxone ratio was identified as the most suitable. The conclusion: co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.
Eur J Pain. 2009 Jan;13(1):56-64
A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.
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A small double-blind, randomized, placebo-controlled study of 9 patients evaluated the effects on constipation and analgesia of low doses of oral naloxone (4 mg, 2 mg, or placebo) given three times daily in patients taking stable doses of opioids with complaints of constipation. All the patients who received oral naloxone had some improvement in their bowel frequency. Two patients experienced partial reversal of analgesia, and one patient had complete reversal of analgesia. Patients using high doses of opioids appeared to be the most vulnerable to reversal of analgesia by oral naloxone.
J Pain Symptom Manage. 2002 Jan;23(1):48-53
Low-dose oral naloxone reverses opioid-induced constipation and analgesia.
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To prevent systemic opioid withdrawal symptoms, therapy should be started with low doses and patients carefully monitored during titration.4
Oral naloxone, particularly when formulated as an extended release preparation, may provide an option for relief of opioid-induced constipation in patients who desire to avoid subcutaneous injections of methylnaltrexone.
Pain 2000 Jan;84(1):105-9.
Oral naloxone reverses opioid-associated constipation.
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Glyceryl Trinitrate Suppository For Anal Fissure: Safety and Efficacy
A double-blind placebo-controlled clinical trial concluded that use of glyceryl trinitrate 0.2% suppositories represents a new, promising, and effective treatment for chronic anal fissure.
Dis Colon Rectum. 2008 May 10. [Epub ahead of print]
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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Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. Low-dose naltrexone (LDN) therapy appears effective and safe in subjects with active Crohn’s disease.
Am J Gastroenterol 2007;102:1-9
Low-dose naltrexone therapy improves active Crohn’s disease.
Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS.
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Topical Metronidazole 10% Decreases Posthemorrhoidectomy Pain and Improves Healing
Oral metronidazole has been demonstrated to decrease postoperative pain after open diathermy hemorrhoidectomy. A prospective, randomized trial at the Georgia Colon and Rectal Surgical Clinic in Atlanta, Georgia investigated the efficacy of topical metronidazole 10% vs. placebo, applied to the surgical site, in reducing postoperative pain and promoting wound healing after Harmonic Scalpel hemorrhoidectomy. In the metronidazole group, postoperative edema was ranked significantly lower and overall wound healing ranked significantly better than in controls. The study concluded that topical 10% metronidazole significantly reduces post-hemorrhoidectomy discomfort on postop days 7 and 14. Postoperative edema is reduced and overall healing is improved, compared with placebo.
Dis Colon Rectum 2004 May;47(5):711-6
Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing.
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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. Epub 2008 Jan 4
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.
Malemud CJ.
Division of Rheumatic Diseases, Case Western Reserve University School of Medicine.
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Low-dose naltrexone reduced the fibromyalgia symptoms in the entire cohort participating in the below study. In addition, side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Study writer conclude that LDN “may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.
Pain Med. 2009 May-Jun;10(4):663-72. Epub 2009 Apr 22.
Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.
Younger J, Mackey S.
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Dr. Ian Carroll, MD, MS, and Dr. Jarred Younger, PhD, of the Stanford Systems Neuroscience and Pain Lab are conducting a clinical trial to investigate the use of T3 and Low Dose Naltrexone (LDN) for the treatment of fibromyalgia. Hypothyroid patients who have been treated with T3 have experienced some improvement in symptoms of fibromyalgia.
http://snapl.stanford.edu/t3/
Accessed January 2012
LDN reduced fibromyalgia symptoms in ten women meeting criteria for fibromyalgia, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug while side effects were rare, and described as minor and transient.
Pain Med. 2009 May-Jun;10(4):663-72. Epub 2009 Apr 22.
Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.
Younger J, Mackey S.
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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.
Cohen SP, Verdolin MH, Chang AS, Kurihara C, Morlando BJ, Mao J.
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Heading
Diabetes
“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. Epub 2007 Aug 6.
Psychological stress and the risk of diabetes-related autoimmunity: a review article.
Sepa A, Ludvigsson J.
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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.
Andrews RC et al.
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Otolaryngology
Capsaicin Nasal Spray for Idiopathic/Perennial RhinitisCapsaicin 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.
Ciabatti PG, D’Ascanio L.
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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.
Van Rijswijk JB, Boeke EL, Keizer JM, Mulder PG, Blom HM, Fokkens WJ.
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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.
Blom HM, Severijnen LA, Van Rijswijk JB, Mulder PG, Van Wijk RG, Fokkens WJ.
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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.
Jang CH, Park SY.
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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.
Haynes DS.
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Xylitol for Otitis Media
Vaccine. 2000 Dec 8;19 Suppl 1:S144-7.
Xylitol in preventing acute otitis media.
Uhari M, Tapiainen T, Kontiokari T.
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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.
Vernacchio L, Vezina RM, Mitchell AA.
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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.
Uhari M, Tapiainen T, Kontiokari T.
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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.
Solares CA et al.
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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.
Uren B, Psaltis A, Wormald PJ.
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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.
Jen A, Kacker A, Huang C, Anand V.
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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. Epub 2002 Sep 11
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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Women’s Health
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.
Nappi C et al.
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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.
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Curr Opin Obstet Gynecol. 2004 Oct;16(5):405-9.
Anabolic effects of androgens on muscles of female pelvic floor and lower urinary tract.
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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.
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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.
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J Reprod Med 2007 Feb;52(2):103-6
Evaluation of gabapentin in the treatment of generalized vulvodynia, unprovoked.
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National Vulvodynia Association News, Winter 2005 (accessed 06/09)
Obstet Gynecol. 2008 Sep;112(3):579-85
Topical gabapentin in the treatment of localized and generalized vulvodynia.
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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 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 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.
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J Infect. 2007 Oct;55(4):374-7
Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis.
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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.
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J Reprod Med. 1991 Aug;36(8):593-597
Antifungal agents vs. boric acid for treating chronic mycotic vulvovaginitis.
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Am J Ob Gyn. 1981 Sep 15;141(2):145-148
Treatment of vulvovaginal candidiasis with boric acid powder.
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Clin Infect Dis. 1997 Apr;24(4): 649-652
Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy.
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Am J Ob Gyn. 1995 Sep;173(3 Pt 1):820-823
Chronic fungal vaginitis: the value of cultures.
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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.
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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 which 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 harbour 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.
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Adv Ther. 2001 Jul-Aug;18(4):181-6
Topical tretinoin 0.1% for pregnancy-related abdominal striae: an open-label, multicenter, prospective study.
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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).
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Non-surgical Treatment of Anal Fissure
Chronic anal fissures can be simply and effectively treated medically without the risk of incontinence associated with sphincterotomy. Topical nifedipine can be beneficial, alone or after botulinum toxin injections (“an excellent combination” associated with a low recurrence rate and minimal side effects).Can J Surg. 2006 Feb;49(1):41-5.
Nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin.
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Low-Dose Naltrexone
Accumulating evidence suggests that Low Dose Naltrexone can promote health supporting immune-modulation which may reduce various oncogenic and inflammatory autoimmune processes. Since LDN can upregulate endogenous opioid activity, LDN may also play a role in healing and repair of tissues, as well as promoting stress resilience, exercise, social bonding, and emotional well-being, and ameloriating psychiatric problems such as autism and depression.Med Hypotheses. 2009 Mar;72(3):333-7. Epub 2008 Nov 28.
Low-dose naltrexone for disease prevention and quality of life.
Brown N, Panksepp J.
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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.
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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.
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Ann Pharmacother. 1999 Dec;33(12):1274-6
Treatment of radiation-induced proctitis with sucralfate enemas.
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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.
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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.
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Topical Glycopyrrolate for Treatment of Hyperhidrosis
Excessive sweating, or hyperhidrosis, is a socially embarrassing disorder and may negatively impact the quality of life. In order of frequency, palmar-plantar, palmar-axillary, isolated axillary, and craniofacial hyperhidrosis are distinct disorders.Application of topical glycopyrrolate 2% “appears to be effective and safe for the treatment of excessive facial sweating in primary craniofacial and secondary gustatory hyperhidrosis following sympathectomy”.
Ten patients with compensatory sweating after sympathectomy applied one milliliter of a 2% water solution of topical glycopyrrolate once a day over the affected area and massaged for 30 seconds. Eight of the 10 treated patients dramatically improved with the topical application of glycopyrrolate. Two patients quit the treatment due to secondary effects (optical accommodative failure and dry mouth). The results of the study demonstrated that local application of glycopyrrolate might be the treatment of choice for compensatory hyperhidrosis.
“Glycopyrrolate iontophoresis is more effective than tap water iontophoresis in the treatment of palmoplantar hyperhidrosis” and “glycopyrrolate iontophoresis has both local and systemic effects on perspiration”.
Br J Dermatol. 2008 May;158(5):1094-7.
Topical glycopyrrolate for patients with facial hyperhidrosis.
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Dermatol Ther. 2008 Sep-Oct;21(5):406-8.
A medical alternative to the treatment of compensatory sweating.
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Australas J Dermatol. 2004 Nov;45(4):208-12.
Iontophoresis with glycopyrrolate for the treatment of palmoplantar hyperhidrosis.
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