Octreotide long-acting formulation (LAR) in chronic loperamide-refractory diarrhea not related to cancer treatment.
(41/165)
OBJECTIVE: The effectiveness and improvement in quality of life (QOL) of a long-acting formulation of octreotide (LAR) administration for cancer patients, with chronic loperamide-refractory diarrhea not attributed to medical therapy, were investigated. PATIENTS AND METHODS: Twenty-nine patients with chronic loperamide-refractory diarrhea were enrolled to receive octreotide LAR at a starting dose of 30 mg i.m. every 28 days until resolution of the diarrhea for a period of 3 months. RESULTS: Twenty-three patients (79.3%) administered octreotide LAR achieved resolution of diarrhea, while six patients (20.7%) successfully controlled their diarrhea during the study. All patients experienced improved sodium, potassium, albumin and total protein values with improvement in their QOL, as assessed by the Linear Analog Scale Assessment (LASA) (mean values at baseline and at 3 months: energy: 3.2+/-1.1 vs. 6.2+/-1.4; function: 3.1+/-1.3 vs. 6.2+/-1.2; QOL: 3.2+/-0.9 vs. 6.1+/-1.4). No toxicities associated with the administration of octreotide LAR were noted. CONCLUSION: The administration of octreotide LAR at a starting dose of 30 mg i.m. every 28 days efficiently resolved or controlled chronic loperamide-refractory diarrhea, not caused by medical intervention, in cancer patients and improved their QOL. (+info)
Prevention and self-treatment of traveler's diarrhea.
(42/165)
Of the millions who travel from the industrialized world to developing countries every year, between 20% and 50% will develop at least one episode of diarrhea, making it the most common medical ailment afflicting travelers. Although usually a mild illness, traveler's diarrhea can result in significant morbidity and hardship overseas. Precautions can be taken to minimize the risk of developing traveler's diarrhea, either through avoidance of potentially contaminated food or drink or through various prophylactic measures, including both nonpharmacological and antimicrobial strategies. If diarrhea does develop despite the precautions taken, effective treatment-usually a combination of an antibiotic and an antimotility agent-can be brought by the traveler and initiated as soon as symptoms develop. In the future, vaccines-several of which are in the advanced stages of clinical testing-may be added to the list of prophylactic measures. (+info)
Investigation on the relationship between cannabinoid CB1 and opioid receptors in gastrointestinal motility in mice.
(43/165)
1. This study investigated whether (a) cannabinoid CB(1) receptor knockout (CB(1)(-/-)) mice displayed altered gastrointestinal transit and (b) cannabinoid CB(1) and opioid receptors functionally interact in the regulation of gastrointestinal transit. 2. Gastrointestinal transit was assessed by the Whole Gastrointestinal Transit, measuring the excretion time of an intragastrically administered marker (whole intestine), and the Upper Gastrointestinal Transit, measuring the distance covered by the marker in the small intestine. 3. CB(1)(-/-) and homozygous CB(1)(+/+) (CB(1)(+/+)) mice did not differ in both whole gut and small intestine transit. CB(1)(-/-) and CB(1)(+/+) mice were equally responsive to the inhibitory effect of morphine (10 mg kg(-1)) and loperamide (3 mg kg(-1)) on whole gut transit.4. Additionally, in CD1 mice the cannabinoid CB(1) receptor antagonist, rimonabant (0-0.5 mg kg(-1)), failed to block the inhibitory effect of morphine (0-1.25 mg kg(-1)) and loperamide (0-0.5 mg kg(-1)) on transit in small and whole intestine. Similarly, the opioid receptor antagonists, naloxone (0-1 mg kg(-1)) and naltrexone (0-10 mg kg(-1)), failed to block the inhibitory effect of the cannabinoid WIN 55,212-2 (0-3 mg kg(-1)) on transit in small and whole intestine.5. These results suggest that (a) compensatory mechanisms likely developed in CB(1)(-/-) mice to overcome the lack of inhibitory function of endocannabinoid system; (b) cannabinoid and opioid receptor systems did not interact in regulating gastrointestinal transit in mice. (+info)
Antihyperalgesic effects of loperamide in a model of rat neuropathic pain are mediated by peripheral delta-opioid receptors.
(44/165)
The possible antihyperalgesic and antiallodynic activity of loperamide, an opioid agonist which does not readily penetrate the blood-brain barrier, were examined in the spinal nerve ligation model of experimental neuropathic pain. Intraperitoneal (i.p.) injection of loperamide effectively reversed thermal hyperalgesia. In contrast, loperamide had minimal effects on cold allodynia and no effects on mechanical allodynia. The antihyperalgesic action of loperamide against noxious heat was antagonized by naltrindole, a delta-opioid receptor selective antagonist, but not by pretreatment with beta-funaltrexamine, a mu-opioid receptor selective antagonist, or administration of nor-binaltorphimine, a kappa-opioid receptor selective antagonist. Furthermore, i.p. injection of [d-Ala(2), Glu(4)]-deltorphin II, a delta-opioid receptor selective peptide agonist, also reversed thermal hyperalgesia. The present results suggest that thermal hyperalgesia in experimental neuropathic pain can be reduced through activation of peripheral delta-opioid receptors. The data suggest the possible application of peripherally restricted and delta-opioid receptor selective agonists in the treatment of some aspects of neuropathic pain without many of the side effects associated with centrally acting opioids and without the peripheral side effects of opioid agonists acting at mu-receptors. (+info)
Pharmacological modulation of gut mucosal and large vessel blood flow.
(45/165)
BACKGROUND: Constipation, diminished gut blood flow, ischaemic colitis and drug therapy may be associated. AIM: To study the effect of constipating medication on, and the regulation of, gut blood flow. METHODS: 24 healthy females (mean age 30) received, in a double-blind, three-way crossover study: (i) placebo, (ii) ipratropium 40 microg by inhalation (positive control known to reduce rectal mucosal blood flow) and (iii) oral loperamide 4 mg. Mucosal blood flow was measured at the splenic flexure and rectum using laser Doppler flowmetry. Blood flow in the superior and inferior mesenteric arteries was measured by trans-abdominal Doppler ultrasound. RESULTS: Ipratropium decreased rectal mucosal blood flow by 16% (P=0.009) and splenic flexure mucosal blood flow by 8% (P=0.075). Loperamide caused no change in rectal (P=0.40) or splenic flexure mucosal blood flow (P=0.73). Neither treatment changed superior or inferior mesenteric artery blood flow. Splenic flexure mucosal blood flow showed a positive correlation with rectal mucosal blood flow (r=0.69; P<0.0001). CONCLUSIONS: Vasoactive agents may reduce gut mucosal blood flow in the absence of reduced large vessel flow. Constipating drugs do not necessarily reduce gut blood flow. Rectal mucosal blood flow correlates with splenic flexure mucosal flow, and potentially may be used as a more convenient surrogate for studying splenic flexure blood flow. (+info)
Use of probiotics for prevention of radiation-induced diarrhea.
(46/165)
AIM: To investigate the efficacy of a high-potency probiotic preparation on prevention of radiation-induced diarrhea in cancer patients. METHODS: This was a double-blind, placebo-controlled trial. Four hundred and ninety patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer were assigned to either the high-potency probiotic preparation VSL#3 (one sachet t.i.d.,) or placebo starting from the first day of radiation therapy. Efficacy endpoints were incidence and severity of radiation-induced diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication. RESULTS: More placebo patients had radiation-induced diarrhea than VSL#3 patients (124 of 239 patients, 51.8%, and 77 of 243 patients, 31.6%; P<0.001) and more patients given placebo suffered grade 3 or 4 diarrhea compared with VSL#3 recipients (55.4% and 1.4%, P<0.001). Daily bowel movements were 14.7 +/- 6 and 5.1 +/- 3 among placebo and VSL#3 recipients (P<0.05), and the mean time to the use of loperamide was 86 +/- 6 h for placebo patients and 122 +/- 8 h for VSL#3 patients (P<0.001). CONCLUSION: Probiotic lactic acid-producing bacteria are an easy, safe, and feasible approach to protect cancer patients against the risk of radiation-induced diarrhea. (+info)
Loperamide therapy for acute diarrhea in children: systematic review and meta-analysis.
(47/165)
BACKGROUND: Loperamide is widely used in adults for acute diarrhea. However, its use in children has been discouraged by the World Health Organization and the American Academy of Pediatrics owing to concerns over safety and efficacy in young children. METHODS AND FINDINGS: To assess the efficacy and adverse effects of loperamide compared with placebo for acute diarrhea in children, we reviewed Medline, EMBase, the Cochrane Central Register of Controlled Trials, and bibliographies of known clinical trials and of review articles, and we also interviewed key investigators in the field. We undertook a systematic review and meta-analysis of randomized controlled trials of children younger than 12 y of age with acute diarrhea, comparing loperamide with placebo. Included trials reported data on diarrhea duration or severity, or provided data on adverse effects. Compared with patients who received placebo, patients allocated to loperamide were less likely to continue to have diarrhea at 24 h (prevalence ratio 0.66, 95% confidence interval [CI]: 0.57 to 0.78), had a shorter duration of diarrhea by 0.8 d (95% CI: 0.7 to 0.9 d), and had a lower count of stools at 24 h (0.84, 95% CI: 0.77 to 0.92). Results were similar when random-effects summaries were estimated. Serious adverse events, defined as ileus, lethargy, or death, were reported in eight out of 927 children allocated to loperamide (0.9%, 95% CI: 0.4% to 1.7%). Serious adverse events were not reported in any of the 764 children allocated to placebo (0%, 95% CI: 0% to 0.5%). Among the children allocated to loperamide, serious adverse events were reported only among children younger than 3 y. CONCLUSIONS: In children who are younger than 3 y, malnourished, moderately or severely dehydrated, systemically ill, or have bloody diarrhea, adverse events outweigh benefits even at doses +info)
Direct inhibition of Ih by analgesic loperamide in rat DRG neurons.
(48/165)
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are responsible for the functional hyperpolarization-activated current (I(h)) in dorsal root ganglion (DRG) neurons, playing an important role in pain processing. We found that the known analgesic loperamide inhibited I(h) channels in rat DRG neurons. Loperamide blocked I(h) in a concentration-dependent manner, with an IC(50) = 4.9 +/- 0.6 and 11.0 +/- 0.5 microM for large- and small-diameter neurons, respectively. Loperamide-induced I(h) inhibition was unrelated to the activation of opioid receptors and was reversible, voltage-dependent, use-independent, and was associated with a negative shift of V(1/2) for I(h) steady-state activation. Loperamide block of I(h) was voltage-dependent, gradually decreasing at more hyperpolarized membrane voltages from 89% at -60 mV to 4% at -120 mV in the presence of 3.7 microM loperamide. The voltage sensitivity of block can be explained by a loperamide-induced shift in the steady-state activation of I(h). Inclusion of 10 microM loperamide into the recording pipette did not affect I(h) voltage for half-maximal activation, activation kinetics, and the peak current amplitude, whereas concurrent application of equimolar external loperamide produced a rapid, reversible I(h) inhibition. The observed loperamide-induced I(h) inhibition was not caused by the activation of peripheral opioid receptors because the broad-spectrum opioid receptor antagonist naloxone did not reverse I(h) inhibition. Therefore we suggest that loperamide inhibits I(h) by direct binding to the extracellular region of the channel. Because I(h) channels are involved in pain processing, loperamide-induced inhibition of I(h) channels could provide an additional molecular mechanism for its analgesic action. (+info)