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At least 469 records · Page 26Linked to original sources
PubMed2003

Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Administration, Oral↗
PubMed1998

An acute dose of nicotine enhances cue-induced cocaine craving.

The present study examined whether the active component in tobacco, nicotine, can modulate cocaine craving in patients with a history of smoking crack cocaine when exposed to crack cocaine related environmental cues. Twenty patients, all cigarette smokers, were randomly assigned to nicotine (two 22 mg transdermal patches) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance and skin temperature were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the pre-cue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was strongly enhanced by nicotine, while the increase in anxiety was slightly augmented. Cue-induced skin conductance and temperature responses were unaffected by nicotine. These findings show that cue-induced cocaine craving is enhanced by nicotine. This occurred in the absence of any tobacco smoking-related cues, suggesting that nicotine may have direct psychopharmacological effects on conditioned cocaine craving.

Adult↗
PubMed2004

Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis.

OBJECTIVES: Following spontaneous menopause women show a greater increase in systolic and diastolic blood pressure than men of the same age. The aim of the present study was to assess the effect of acute ovarian hormone withdrawal and replacement on blood pressure and forearm blood flow. METHODS: We studied 18 fertile middle-aged normotensive women (48 +/- 1.5 years, range 46-51 years) 1 week prior and 1 month subsequent to bilateral oophorectomy by means of 24-h blood pressure monitoring and strain-gauge venous occlusion plethysmography. Eighteen subjects who had undergone hysterectomy with ovarian sparing, matched for age and biophysical characteristics, were used as a control group. All women were free from cardiovascular risk factors or disease. RESULTS: Oophorectomy increased the mean values of 24 h (P < 0.001), daytime (P < 0.05), and nighttime (P < 0.01) diastolic blood pressure and nighttime systolic blood pressure (P < 0.01). Blood pressure increase was associated with a rise in forearm vascular resistance (P < 0.01). No significant changes in either blood pressure or forearm vascular resistance values were observed in hysterectomized women. In 16 oophorectomized women a 3-month estrogen replacement therapy (ERT) (17beta-estradiol, 100 mcg/day by transdermal patches) brought blood pressure and forearm vascular resistance values to a level comparable to that recorded before intervention. CONCLUSIONS: Surgically-induced menopause causes an increase in peripheral vascular resistance and blood pressure suggesting a role of ovarian hormones in the homeostatic pressure modulation. Recovery of the baseline condition after ERT suggests that the accelerated increase in blood pressure after menopause is due to ovarian and above all estrogen insufficiency.

Case-Control Studies↗
PubMed1999

OESCLIM: an advanced delivery system for HRT.

AIMS: Transdermal estradiol offers a number of advantages over traditional oral routes of hormone replacement therapy (HRT) because it is not subject to the hepatic first-pass effect. However, transdermal systems need to balance adhesion, tolerability, and flux if they are to be effective. OESCLIM is a transdermal 17-beta estradiol HRT system designed to address the problems of conventional transdermal patches and offer optimal adhesion and tolerability in an effective HRT system. This paper reviews some of the data on OESCLIM with reference to its delivery system. RESULTS: The innovative technology used in OESCLIM results in a smooth pharmacokinetic profile throughout the 3-4 day application period. In recent pharmacokinetic studies, OESCLIM 50 provided a more consistent release of hormone than Estraderm TTS 50 and higher mean estradiol levels than Systen and Vivelle. This smooth pharmacokinetic profile is also maintained whether OESCLIM is attached to different body sites. The local skin tolerability of OESCLIM is good. One study reported that OESCLIM 50 caused less than half the number of skin reactions as Estraderm TTS 50 (4.2% compared to 9.5%). OESCLIM has also been shown to have fewer detachments than Estraderm TTS (6% compared to 11%). Both differences were statistically significant (P < 0.001). A study has shown OESCLIM to be as effective as Estraderm TTS at reducing vasomotor symptoms even in highly symptomatic women. CONCLUSION: OESCLIM is a very good first-line choice for estrogen replacement therapy (ERT) or HRT providing effective therapy with optimum adhesion, flux and tolerability profiles.

Administration, Cutaneous↗
PubMed2000

Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol.

OBJECTIVE: Cardiovascular disease seems to increase after the menopause and is thought to be reduced by estrogen replacement therapy. Among the many studies which have tried to define the multifactorial mechanisms of estrogens cardiovascular prevention, very few have focused on their possible modulation of adrenergic activity. In the present study we investigated whether prolonged estradiol replacement via transdermal patches is able to modulate cardiovascular and adrenergic responses to stimuli. METHODS: Baseline and responses to a cold stimulus and to the upright position of catecholamines (epinephrine and norepinephrine), heart rate, systolic and diastolic blood pressure were investigated in 15 healthy volunteer postmenopausal women both prior to and after 2 months of treatment with patches rated to deliver 50 microg/day of estradiol. RESULTS: Basal norepinephrine levels (P<0.005), as well as their integrated responses to the cold stimulus (P<0.02) were lower during estradiol. By contrast, responses of norepinephrine to the upright test, as well as basal and responses to stimuli of epinephrine and circulatory parameters were not different before and during estradiol. CONCLUSIONS: Estradiol replacement at low doses significantly decreases overall sympathetic output, both in basal conditions and under specific stimuli. These effects whether maintained or magnified in the long term may play a role in the prevention of the postmenopausal cardiovascular risk.

Administration, Cutaneous↗
PubMed1998

A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain.

Fentanyl has been incorporated into a transdermal therapeutic system (TTS) containing a rate-limiting membrane that provides constant release of the opioid. TTS fentanyl provides continuous opioid delivery for up to 72 hr without the need for special equipment. After Institutional Review Board approval, 53 patients with cancer pain requiring 45 mg or more of oral morphine daily were admitted into an open-label, prospective, multicenter evaluation of TTS fentanyl for the relief of pain. After a 1-week stabilization on oral morphine, patients were transferred from morphine to an appropriate dose of TTS-fentanyl (25, 50, 75, or 100 micrograms/hr) administered as a transdermal patch every 3 days. TTS fentanyl was titrated to pain relief, and patients were followed up for as long as 3 months. Pain relief and the side effects of the medications were assessed daily. Twenty-six men and 27 women with a mean (+/- SD) age of 61 (+/- 12) years entered the study; 23 patients completed the full 84-day study. The mean duration of TTS fentanyl use was 58 +/- 32 days. The mean (+/- SEM) daily morphine dose during the last 2 days of stabilization was 189 (+/- 20) mg, and the mean initial fentanyl patch dose was 58 (+/- 6) micrograms/hr. The mean daily morphine dose taken "as needed" for breakthrough pain at study completion was 35 mg. The mean final fentanyl dosage at study completion was 169 (+/- 29) micrograms/hr. Pain relief was rated as good or excellent by 82% of patients during the treatment period. When asked to compare pain relief during the first month of TTS-fentanyl use to that provided by their last analgesic before study entry, 63% preferred TTS fentanyl. Side effects considered related to the fentanyl patch were nausea (13%), vomiting (8%), skin rash (8%), and drowsiness (4%). Thirty percent of patients reported adverse experiences related to the fentanyl patch, and 17% had to be discontinued from the study. We conclude that TTS fentanyl administered every 3 days for the treatment of cancer pain is effective, safe, and well tolerated by most patients.

Administration, Cutaneous↗
PubMedDate not supplied

The role of physical agents in modulating pain.

This article presents a review of the literature on the use of physical agents in modulating pain associated the hand and upper extremity musculoskeletal conditions. The physical agents presented include superficial heating agents, cryotherapy, ultrasound, and transcutaneous electrical nerve stimulation. There has been increased interest in modes of transdermal drug delivery, including iontophoresis, phonophoresis, and the application of transdermal patches. Treatment applications, parameters, and integration strategies are suggested. The purposes of this article are to review which physical agents are used to treat pain or inflammation and to discuss their relevant application to hand therapy practice. Today's health care climate requires therapists to select treatment strategies that are efficient, safe, and clinically effective. Although physical agents are widely used to manage pain in hand therapy, there is little scientific evidence to support their efficacy. Most information regarding the rationale for the use of physical agents in pain management is based on tradition, data extrapolated from basic science research, and uncontrolled randomized clinical trials. This paper discusses the need for additional research to establish clinical efficacy and determine optimal treatment parameters for the physical agents used most often to modulate pain in hand therapy.

Acute Disease↗
PubMed2003

Crystallisation of estradiol containing TDDS determined by isothermal microcalorimetry, X-ray diffraction, and optical microscopy.

Transdermal drug delivery systems (TDDS) enable a controlled delivery of drugs to the skin. However, it is still a problem to achieve a stable and prolonged constant drug release. To attain high permeation rates across the skin, the concentrations of the drug dissolved have to be high and often create supersaturated, thermodynamically metastable, or unstable systems that possess a high tendency to crystallise. In the present study, microcalorimetry as well as polarisation microscopy and X-ray powder diffraction (XRPD) were used to characterise the growing crystal germs of estradiol (E2) hemihydrate. Polarisation microscopy enabled the observation of crystals with two different morphologies of E2 in the polymeric acrylic transdermal patch matrix. Crystal formation and growth were also detected by XRPD. The diffraction pattern corresponded to estradiol hemihydrate. The intensity of the observed reflections was proportional to the crystal quantities and increased during storage. A high supersaturation resulted in high peak intensities caused by a high crystallisation rate. Since precipitation is generally accompanied by heat evolution, crystal germ formation, and crystal growth could easily be detected early by isothermal microcalorimetry. Much lower amounts of crystal were detected by this method than with the significantly less sensitive XRPD method. Microscopy was equally sensitive to but much more time-consuming than microcalorimetry.

Administration, Cutaneous↗
PubMed1997

New approaches to pain control in patients with cancer.

Pain affects most patients with malignant disease, and the prevalence of severe pain increases in the advanced stages of the condition. One in 5 patients with cancer has uncontrolled pain, even after 10 years of the use of the World Health Organization programme for cancer pain control and its 'three-step ladder' for the rational use of analgesics including morphine. Morphine has long been the 'gold standard' for the treatment of severe cancer pain. However, its side-effects, particularly sedation, cognitive impairment and myoclonus at high doses, have provoked the use of 'opioid rotation' to alternatives such as methadone and hydromorphone. The new 72-h transdermal patch for fentanyl also offers advantages of reduced side-effects and increased convenience over oral morphine. Intravenous strontium-89 and bisphosphonate therapy are effective for both short- and long-term control of metastatic bone pain. The spinal N-methyl-D-aspartate (NMDA) receptor is important in modulating the plasticity of the central nervous system and in aggravating chronic pain through the phenomenon of 'wind-up'. The NMDA antagonist ketamine, an anaesthetic, can be used at low doses for the management of refractory and neuropathic pains. Among adjuvant drugs, ketorolac has emerged as a potent non-steroidal anti-inflammatory drug. Palliative care is gaining acceptance as a new discipline in healthcare. Its strategic role is being reviewed as an adjunct to cancer therapy at all stages and its use is no longer confined to the terminal phase of disease after curative treatment has failed. Pain control and other aspects of symptom control are, therefore, viewed as an integral part of cancer management.

Humans↗
PubMed2003

Androgens in women.

The role of androgen treatment in women remains controversial. The proposed "Female Androgen Insufficiency Syndrome" (Fertility and Sterility, April 2002) describes a number of non-specific symptoms including unexplained fatigue, decreased well being/dysphoric mood and/or blunted motivation and diminished sexual function. An estimated 40% of women experience sexual dysfunction, highlighting the need for ongoing research into this field in order to fully define the possible contribution of androgen insufficiency. The increasing availability of products, such as dehydroepiandrosterone (DHEA) supplements also points to the need for controlled studies to assess the safety of these and other preparations. Measurement of androgens in women requires sensitive assays with the ability to detect low levels and a narrow range with precision. Normal ranges of androgens for women of reproductive and post-reproductive age remain poorly defined. Debate exists as per importance of measurement of free versus total testosterone, with the "free androgen index" offering an alternative method of assessment of testosterone availability. Testosterone treatment is being developed for women in the form of transdermal patches, gels or cream, with percutaneous implants in common usage in some countries. Recent research has highlighted alternative means of administration, such as oral inhalation or buccal lozenge. DHEA is widely available in some countries. Research to date has demonstrated improvements in libido and sexual function, mood and well being. Evidence points to other potential benefits of androgen treatment, including preservation of bone mass, a possible protective role in breast cancer and beneficial effects on cognition. Adverse effects of androgen treatment in women are dose-dependent and include virilisation, mood disturbance and acne. These are uncommon if appropriate doses are administered and highlight the need for treatment to be closely monitored clinically and biochemically. Beneficial effects of testosterone treatment in post-menopausal women with lowered androgen levels have been well documented, and preliminary evidence suggests a role for treatment in pre-menopausal women with symptoms and lowered testosterone levels.

Aging↗
PubMed1995

Fentanyl transdermal (durogesic, Janssen).

Fentanyl is a potent opioid analgesic with a characteristically brief duration of action. Its formulation in a transdermal patch provides a novel method of delivering continuous analgesia for patients with prolonged or chronic pain.

Administration, Cutaneous↗
PubMedDate not supplied

Unusually prolonged duration of spinal anesthesia following 2% mepivacaine.

BACKGROUND AND OBJECTIVES: Spinal mepivacaine has been reported as a reliable anesthetic for ambulatory anesthesia. Its pharmacologic properties are midway between those of bupivacaine and lidocaine, and it can be used in intermediate duration ambulatory surgical procedures. METHODS: A patient taking clonidine transdermal patches (TTS) to control high blood pressure received spinal mepivacaine for surgical repair of a ruptured meniscus with arthroscopy. RESULTS: The resulting duration of sensory and motor block were 12 and 8.5 hours, respectively. These are more than four times as long as the reported mean durations with this spinal local anesthetic. We hypothesized that the use of clonidine via TTS for the previous 16 months contributed to this unusual delay of recovery from spinal anesthesia. CONCLUSIONS: Clonidine can increase the duration of spinal anesthetics. Even though this well-known effect has been considered mostly beneficial, it can be an adverse effect when spinal ambulatory anesthesia is given to patients receiving clonidine TTS or clonidine in other forms for long-term treatment of hypertension or other diseases.

Administration, Cutaneous↗
PubMedDate not supplied

[Effectiveness of a pharmaceutical care unit for the control of severe chronic pain].

INTRODUCTION: The effectiveness of a pharmaceutical care unit was assessed within a staged program for non-malignant severe chronic pain control in a multidisciplinary pain management unit at Consorcio Hospital General Universitario, Valencia, Spain. MATERIALS AND METHODS: One hundred and fifty patients with clinical indication for a major opioid were included in WHO's third analgesic rung by our medical team following careful triage. The pharmaceutical care unit, or phase II, monitored dosage titration for pain stabilization with absence of side effects, as well as the onset of subsequent chronic therapy. RESULTS: Upon program completion 75% of patients had their pain under control, having required 22.7 days on average for opiate dose titration. Mean daily dose was 22.3 mg, and constipation was prophylactically managed from the start. Fifty-nine percent of patients received subsequent chronic therapy with fentanyl transdermal patches at 25 microg/h; 10% followed suit with oral morphine solution, and 6% with controlled-release morphine. Twenty-five percent of the remaining patients had relevant events during the therapy titration stage, which led to therapy discontinuation and discharge because of lack of therapeutic effectiveness. After 24 months 70% of patients were still on initial doses. CONCLUSIONS: The effectiveness of our unit was demonstrated by the achievement of the program objectives.

Chronic Disease↗
PubMed2005

Delivery options for contraceptives.

Although a steady increase in contraceptive use has been observed in developed and less-developed countries, the contraceptive needs of a significant proportion of couples have not yet been met, resulting in an increase in unplanned pregnancies. Several new contraceptive products have reached the market during the past few years. Among these are new implants, a medicated intrauterine device, contraceptive vaginal rings, transdermal patches and several new regimen of combined oral contraceptives. These new or improved methods have been developed to expand the contraceptive choices available to women and men as well as to respond to the unmet need for contraceptives with long-term activity. New targets are being identified both in the ovary and the testes for a more specific non-hormonal contraception. This futuristic approach still keeps in mind the need for better access to existing contraceptive methods, as well as the discovery of new contraceptives that are simple to use, safe, reversible and inexpensive. In recent years, there has been great interest in agents that provide dual protection against pregnancy and sexually transmitted infections (STI), especially human immunodeficiency virus (HIV). A contraceptive method providing dual medical benefits might increase motivation for consistent use, thus reducing contraceptive failures and unwanted pregnancies.

Contraception↗
PubMed1988

Pharmacokinetics and bioavailability of hydromorphone: effect of various routes of administration.

The pharmacokinetics and bioavailability of hydromorphone following various routes of administration, i.e., intravenous, oral, intranasal, and transdermal, were investigated in rabbits. Hydromorphone plasma concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC). Comparison of area under the concentration versus time curve (AUC) between intravenous and oral administrations showed a low bioavailability of hydromorphone after oral administration. The nasal absorption of hydromorphone was studied by the in situ nasal recirculation technique, and the results showed that hydromorphone is well absorbed from the nasal mucosa. The transdermal permeation of hydromorphone was also evaluated for 24 hr and a steady-state plasma concentration (0.135 micrograms/ml) was achieved during the 6- to 24-hr periods following the application of a transdermal patch on the inner pinna of the rabbit's ear.

Administration, Cutaneous↗
PubMed1994

Estimation of skin target site acyclovir concentrations following controlled (trans)dermal drug delivery in topical and systemic treatment of cutaneous HSV-1 infections in hairless mice.

The use of controlled transdermal delivery of acyclovir (ACV) in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice was investigated. Using an in vivo animal model (A. Gonsho, et al. Int. J. Pharm. 65:183-194 (1990)) made it possible to quantify both, the topical and the systemic antiviral efficacy of ACV transdermal patches as a function of the drug delivery rate of the patches. Drug delivery rates required to attain systemic efficacy were found to be higher than the rates required to attain the same magnitude of topical efficacy. The ACV concentrations in the basal cell layer of the epidermis for 50% topical efficacy and 50% systemic efficacy were estimated. The basal epidermis layer was considered to be the site of antiviral drug activity (skin target site). Systemic plasma levels were obtained from pharmacokinetic studies and were used to estimate the ACV concentration achieved systemically in the basal epidermis layer. A computational model for drug permeation across skin was employed to estimate the ACV concentration achieved topically in the basal epidermis layer. Equal topical and systemic efficacies were found to correspond to equal drug concentrations at the site of antiviral activity. The length of the effective diffusion pathway of drug molecules in the dermis prior to entering the blood circulation was assumed to be approximately equal to 1/20 of the anatomical dermis thickness because of dermis vascularization.

Acyclovir↗
PubMed1992

Smoking cessation: what have we learned over the past decade?

This article discusses developments in understanding smoking and smoking cessation, methodological issues, and intervention approaches over the past 10 years. Although effective multisession clinic interventions have been developed, such programs reach relatively few smokers. This has led to self-help, work site, health care setting, and community interventions aimed at delivering less intensive programs to larger populations. Conceptual and empirical developments and trends within these above delivery contexts are reviewed, and avenues of research are identified. Nicotine replacement strategies have benefited from technological advances (e.g., transdermal patches) and present continuing challenges with respect to integration with behavioral strategies and incorporation into primary care medical settings. Research over the next decade should focus on the development of cost-effective interventions that can reach representative and high-risk smokers.

Administration, Cutaneous↗