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PubMed2006

Smoked cocaine self-administration by humans is not reduced by large gabapentin maintenance doses.

Previously, we reported that gabapentin, a lambda-aminobutyric acid (GABA) agonist, significantly reduced "positive" subjective effects of cocaine without reducing cocaine self-administration. We speculated that the gabapentin doses used in that study were too low to detect subtle shifts in the reinforcing effects of cocaine. Thus, the present study examined the effects of larger gabapentin maintenance doses on cocaine-related effects, including self-administration. During this 48-day double-blind, crossover design study, the effects of gabapentin maintenance (0, 2400, 3200 mg/day) on response to cocaine (0, 12, 25, 50 mg) were investigated in six cocaine-dependent individuals not seeking treatment for their cocaine use. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., "Good Drug Effect"), blood pressure, and heart rate. Gabapentin did not decrease cocaine self-administration, cardiovascular measures, or most subjective effects of cocaine. These data agree with findings from a clinical trial examining the effects of similar gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals and suggest that gabapentin does not show promise as a treatment medication for cocaine dependence.

Adult↗

PubMed2006

Inhaled carbon monoxide prevents graft-induced intimal hyperplasia in swine.

BACKGROUND: Arteriovenous grafts often fail due to stenosis caused by venous anastomotic intimal hyperplasia (IH) and vascular smooth muscle cell (VSMC) proliferation. We examined the effects of inhaled carbon monoxide (CO), a product of heme-oxygenase-1 degradation of heme, on IH in a porcine arteriovenous graft model. MATERIALS AND METHODS: Eighteen Yorkshire pigs were divided into three groups (N = 6/group): (1) CO 100 ppm preoperatively for 1 h; (2) CO 250 ppm preoperatively for 1 h and intraoperatively; and (3) air-treated controls. Animals underwent end-to-side placement of polytetrafluoroethylene grafts connecting the common femoral artery and vein in both groins. Intimal thickness of the venous anastomosis at 30 days was measured blinded. The effect of CO on pig VSMC proliferation was studied in cell culture using [(3)H]thymidine incorporation. RESULTS: Pigs in the group receiving CO 250 ppm showed significantly less IH compared to animals in the group receiving 100 ppm and the air-treated group (267.5 +/- 21.4, 824 +/- 145.8, and 914.8 +/- 133.7 pixels, respectively, P < 0.0001). This effect was not observed when comparing the 100 ppm group to the air-treated group. COHb levels were significantly elevated in the 100 ppm and 250 ppm compared to air-treated pigs (5.8 +/- 0.47, 13.2 +/- 1.0 versus 2.3 +/- 0.11%, respectively, P < 0.001). Oxygen saturation, respiratory rate, and hemodynamics were not significantly different between the groups. CO induced VSMC growth arrest compared to air in vitro (11.9 +/- 4 versus 20.3 +/- 5 10(3) counts/min/well, P < 0.01). CONCLUSION: A single exposure to a low concentration of inhaled CO (250 ppm) confers protection against intimal proliferation of VSMCs when given perioperatively in a clinically relevant model of arteriovenous grafts. These data are the first to suggest, in a clinically relevant model, the potential role for CO in clinical applications.

Administration, Inhalation↗

PubMed2004

Bronchodilating effects of salmeterol, theophylline and their combination in patients with moderate to severe asthma.

Ten patients with moderate to severe asthma (mean FEV1+/-SD: 57.3+/-5.8% of predicted) participated in this 4-day single-blind, placebo-controlled, crossover study, aimed to comparatively evaluate the bronchodilating effects of a single dose of inhaled salmeterol (50 microg) and oral slow-release theophylline (Theo-Dur, 600 mg tablets), used either alone or in combination. In particular, FEV1 was recorded at baseline and 2, 4, 6, 8, 10, and 12 h after drug administration; at the same times, with the exception of the 12 th h, theophylline plasma concentrations were also measured. When compared to theophylline, bronchodilation induced by salmeterol was characterized by an earlier onset, a greater magnitude, and a longer duration. Given in combination with salmeterol, theophylline elicited a further slight increase in airway calibre with respect to the bronchodilator action of the beta2-agonist alone, with FEV1 changes which resulted to be statistically significant at the 4th, 6th and 8th h after administration (p<0.05, p<0.03 and p<0.05, respectively). At the 4th h theophylline reached serum levels included within the therapeutic range, which were persistently maintained at least until the the 10th h. Therefore, our findings suggest that inhaled salmeterol and oral slow-release theophylline, the latter acting within the range of therapeutic plasma concentrations, exert additive bronchodilating effects in asthmatic patients with moderate to severe airflow limitation.

Administration, Oral↗

PubMed2001

Short-term hemodynamic performance of the mitral Carpentier-Edwards PERIMOUNT pericardial valve. Carpentier-Edwards PERIMOUNT Investigators.

BACKGROUND: Although long-term durability data exist, little data are available concerning the hemodynamic performance of the Carpentier-Edwards PERIMOUNT pericardial valve in the mitral position. METHODS: Sixty-nine patients who were implanted with mitral PERIMOUNT valves at seven international centers between January 1996 and February 1997 consented to participate in a short-term echocardiography follow-up. Echocardiographs were collected at a mean of 600+/-133 days after implantation (range, 110 to 889 days); all underwent blinded core lab analysis. RESULTS: At follow-up, peak gradients were 9.09+/-3.43 mm Hg (mean, 4.36+/-1.79 mm Hg) and varied inversely with valve size (p < 0.05). The effective orifice areas were 2.5+/-0.6 cm2 and tended to increase with valve size (p = 0.08). Trace mitral regurgitation (MR) was common (n = 48), 9 patients had mild MR, 1 had moderate MR, none had severe MR. All MR was central (n = 55) or indeterminate (n = 3). No paravalvular leaks were observed. Mitral regurgitation flow areas were 3.4+/-2.8 cm2 and were without significant volumes. CONCLUSIONS: In this multicenter study, these mitral valves are associated with trace, although physiologically insignificant, central MR. Despite known echocardiographic limitations, the PERIMOUNT mitral valves exhibit similar hemodynamics to other prosthetic valves.

Aged↗

PubMedDate not supplied

Octreotide decreases canine gastric mucosal blood flow: a controlled assessment by endoscopic reflectance spectrophotometry.

The aim of this study was to evaluate the effects of octreotide, a long-acting somatostatin analogue, on canine gastric mucosal blood flow and hemodynamics. We hypothesized that octreotide might decrease gastric mucosal blood flow without causing adverse hemodynamic effects. Two groups of dogs were anesthetized (six normal dogs and six dogs with prehepatic portal hypertension), and each dog was administered intravenous octreotide, normal saline solution, and vasopressin for 30 minutes on separate days in a blinded, randomized fashion. Vasopressin was included as treatment for a positive control. Gastric mucosal blood flow was assessed at the fundus, corpus, and antrum by endoscopic reflectance spectrophotometry. A femoral arterial catheter monitored systemic blood pressure and heart rate. Treatment responses for all observations were calculated for each dog as a percentage of baseline values. For mucosal blood flow, treatment responses did not differ significantly over time or between animal group or gastric location. Octreotide significantly decreased indices of hemoglobin concentration (-19%, p = 0.01) and oxygen saturation (-17%, p = 0.0002) compared to saline (-9% and -7%, respectively). The mean arterial pressure was increased after octreotide compared to saline (+23% versus +7%, p = 0.01), but octrotide had no effect on heart rate (+2% versus +1%). Vasopressin also decreased the indices of hemoglobin concentration (-34%) and oxygen saturation (-82%) significantly more than saline (p = 0.001). Vasopressin increased mean arterial pressure (+55%), but also caused reflex bradycardia (-22%) significantly more than saline (p = 0.001). We conclude that octreotide decreases canine gastric mucosal blood flow and appears to cause minimal hemodynamic changes.

Animals↗

PubMed1997

Meloxicam: selective COX-2 inhibition in clinical practice.

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their actions by inhibiting cyclooxygenase (COX). It has recently been postulated that NSAIDs' antiinflammatory efficacy arises from inhibition of the COX-2 isoform of cyclooxygenase, whereas inhibition of the COX-1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs. A relatively selective COX-2 inhibitor, such as meloxicam, may combine antiinflammatory efficacy with improved tolerability. In volunteers, indomethacin 75 mg, but not meloxicam 7.5 mg, inhibited renal prostaglandin E2 excretion and platelet aggregation (COX-1 mediated effects). Double-blind, randomized trials in osteoarthritis and rheumatoid arthritis patients have shown equivalent antiinflammatory efficacy among meloxicam 7.5 mg or 15 mg and diclofenac 100 mg, naproxen 750 mg, and piroxicam 20 mg. In a double-blind, placebo-controlled trial, meloxicam (7.5 or 15 mg) caused less endoscopically detected gastrointestinal (GI) damage (Lanza scale) than piroxicam 20 mg. The MELISSA study, a double-blind, randomized, 28-day trial in over 9,000 patients showed that meloxicam 7.5 mg caused statistically less total GI toxicity, dyspepsia, abdominal pain, nausea and vomiting, and diarrhea than diclofenac 100 mg, despite equivalent reductions in pain on movement for each treatment. A global safety analysis of clinical trials, representing over 5,600 patients and comprising 170 and 1,100 patient-years of exposure for meloxicam 7.5 mg and 15 mg, respectively, showed that meloxicam caused less GI toxicity and fewer peptic ulcers and GI bleeds than naproxen, diclofenac, or piroxicam. The renal safety profile and incidence of liver function abnormalities with meloxicam is equivalent to other NSAIDs available for clinical use. In conclusion, relatively selective COX-2 inhibition exemplified by meloxicam may offer effective symptom relief with an improved GI tolerability profile.

Animals↗

PubMed1990

Retrobulbar optic neuritis in a two-year-old boy.

We report a 2-year-4-month-old boy with retrobulbar optic neuritis. He had a sudden onset of impaired vision, which progressed to total blindness within a day. The visual evoked potential (VEP) showed no activity, but the electroretinogram was normal. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no abnormal findings in the visual tract. The cerebrospinal fluid (CSF) myelin basic protein (MBP) level was elevated and serum anti-myelin antibody was positive. These findings suggested that optic neuritis in our patient was induced by retrobulbar demyelination, perhaps as a result of an autoimmune process. His visual impairment recovered gradually, but not completely, following oral prednisolone therapy. We have followed him for one year since discharge and have found neither recurrence of optic neuritis nor any other neurological disorders. Optic neuritis in children is rare and, to our knowledge, this patient is one of the youngest to be reported. This case suggests that autoimmune mechanisms may induce optic neuritis even in early childhood. In addition to VEP and MRI studies, the CSF MBP and serum anti-myelin antibody can be useful in the diagnosis and follow-up the patients with optic neuritis.

Child, Preschool↗

PubMed2004

Multidetector row CT angiography of the abdominal aorta and lower extremities in patients with peripheral arterial occlusive disease: diagnostic accuracy and interobserver agreement.

PURPOSE: To evaluate the accuracy of four channel multidetector row CT angiography (MDCTA) of the abdominal aorta and lower extremities arteries compared with digital subtraction angiography (DSA). MATERIALS AND METHODS: In our prospective study 42 patients with peripheral vascular occlusive disease (27 M, 15 F, age range 40-79 years) underwent MDCTA and DSA within 5 days. Images were blindly interpreted by two radiologists. Maximum intensity projections (MIP), multiplanar (MPR) reformations, three-dimensional (3D) reconstructions as well as axial images were available for analysis of MDCTA. DSA were analyzed on hard copies. RESULTS: Overall sensitivity and specificity of MDCTA were 93 and 95%, respectively, with positive and negative predictive values of 90 and 97%. Overall diagnostic accuracy was 94%. Normal arterial segments and 100% occlusions were correctly identified in all cases by MDCTA. Moderately stenotic segments interpretation in the calves appeared to be more controversial, but no statistical difference in accuracy of MDCTA in the infrapopliteal district arteries was noted with respect to accuracy in the more proximal arterial bed. Good to excellent interobserver and intraobserver agreement were observed, with k values greater than 0.80. CONCLUSIONS: MDCTA of the abdominal aorta and lower extremities is an accurate imaging modality in clinical practice when compared with DSA.

Adult↗

PubMed1986

Effects of nifedipine on arterial oxygenation at rest and during exercise in patients with stable angina.

The effects of nifedipine on arterial oxygenation and hemodynamics were studied at rest and during bicycle exercise in 12 men (mean age 55 years, range 41 to 67) with stable exertional angina. The study was conducted double-blind on 2 days, 1 week apart, using a placebo-controlled crossover design. On each day, measurements at rest were made before and 20 minutes after 20 mg sublingual nifedipine or placebo and were followed by measurements made during exercise. Compared with placebo, nifedipine reduced mean arterial pressure, systemic vascular resistance and pulmonary vascular resistance, and increased heart rate and cardiac output at rest and during exercise. It did not alter mean pulmonary artery or pulmonary artery wedge pressures at rest, but decreased them during exercise. Nifedipine decreased arterial oxygen tension (PaO2) from 96 +/- 10 to 90 +/- 13 mm Hg (p less than 0.05) at rest and from 99 +/- 11 to 92 +/- 12 mm Hg (p less than 0.005) at submaximal exercise (33 +/- 21 W), but did not alter it (100 +/- 12 versus 100 +/- 16 mm Hg, p = NS) at maximal exercise (68 +/- 30 W). The reduction in PaO2 was not due to alveolar hypoventilation, because nifedipine did not alter arterial carbon dioxide tension, or to changes in mixed venous oxygen tension, which nifedipine increased at rest (39 +/- 2 versus 43 +/- 3 mm Hg, p less than 0.001) and during submaximal exercise (31 +/- 4 versus 33 +/- 4 mm Hg, p less than 0.03) and maximal exercise (27 +/- 3 versus 31 +/- 3 mm Hg, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2004

The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis.

Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. Delta-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that Delta-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.

Adult↗

PubMed1999

Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen.

BACKGROUND: Compared with currently available NSAIDs (which inhibit COX-1 and COX-2 isoforms of cyclooxygenase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity. AIM: To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin. METHODS: Healthy subjects (n = 170; age range 18-54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK-0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end-point was the percentage of subjects who developed a mucosal score >/= 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thromboxane B2 levels were determined in a subset of the population. RESULTS: The percentage of subjects who developed a mucosal score >/= 2 in the MK-0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated. CONCLUSIONS: In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.

Adolescent↗

PubMed2003

Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.

BACKGROUND: Smokers have a higher risk of complicated tissue and wound healing after surgery than nonsmokers. We tested the hypothesis that short-term pre-operative cessation of smoking in colorectal surgery decreases the incidence of postoperative tissue and wound complications. METHODS: From February 1998 to March 2001, 60 patients, who smoked daily, undergoing colorectal resection were randomly assigned 2-3 weeks before scheduled surgery to either abstinence from smoking, counselling and nicotine replacement therapy or maintenance of daily smoking habits. Postoperative tissue and wound complications necessitating surgical or medical treatment were evaluated at discharge and 30 days after surgery by blinded outcome assessment. RESULTS: In the pre-operative period of 15 days (8-24) (median, interquartile range (IQR)), 89% of the patients in the intervention group vs. 13% in the control group abstained from smoking or reduced by more than half (P < 0.05). In the postoperative period of 11 days (10-13), the corresponding figures were 92% and 50%, respectively (P < 0.05). Postoperative tissue and wound complications occurred in 33% (9 of 27) of the patients in the intervention group compared to 27% (8 of 30) in the control group (NS). Likewise, no difference in overall postoperative complication rate was found between the groups. CONCLUSION: Short-term cessation of smoking does not reduce the risk of complicated tissue and wound healing or other complications in colorectal surgery.

Adult↗

PubMed2000

Fat embolism syndrome after cementless total hip arthroplasty.

There are few reports in the literature of fat embolism syndrome after cementless total hip arthroplasty (THA). Most reported cases have occurred after fracture or cemented THA. We report a case of a healthy 51-year-old woman who underwent THA for osteoarthritis under spinal anesthesia. A press-fit cup and extensively porous-coated diaphyseal locking stem were used and inserted without cement. In the recovery room, the patient became hypoxemic and hypotensive and developed cortical blindness. The next day, a petechial rash was evident. Gurd's criteria for fat embolism syndrome were fulfilled. Her symptoms resolved over a 2-week period. Patients undergoing cementless THA are at risk for fat embolism syndrome, and this must be considered in the differential diagnosis for postoperative hypoxemia and neurologic deficits.

Arthroplasty, Replacement, Hip↗

PubMed1977

Healing of duodenal ulcer with an antacid regimen.

To determine whether a large-dose antacid regimen is effective in promoting healing of duodenal ulcer, 74 patients with endoscopically proved duodenal ulcer completed a 28-day double-blind clinical trial comparing such a regimen with an inert placebo. The ulcer healed completely in 28 of the 36 antacid-treated as compared to 17 of the 38 placebo-treated patients (P less than 0.005). The antacid regimen was not more effective than placebo in relieving ulcer symptoms. Presence or absence of symptoms during the fourth treatment week was a poor predictor of presence or absence of an ulcer crater. Ulcers of placebo-treated patients who smoked cigarettes were less likely to heal than those of nonsmokers (P = 0.03). Except for mild diarrhea, no side effects of the antacid regimen were observed. We conclude that a large-dose antacid regimen hastens the healing of duodenal ulcer.

Administration, Oral↗

PubMed2001

Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume.

Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.

Animals↗

PubMed1996

Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia.

BACKGROUND: There is considerable controversy regarding the role of subarachnoid 5% hyperbaric lidocaine in the syndrome transient radicular irritation (TRI). This randomized, double-blinded, prospective study was designed to determine the incidence of TRI and identify factors possibly contributing to its development. METHODS: One hundred fifty-nine ASA physical status 1 or 2 patients undergoing outpatient knee arthroscopy or unilateral inguinal hernia repair were prospectively randomized to receive spinal anesthesia with 5% hyperbaric lidocaine with epinephrine (60 mg with 0.2 mg epinephrine for arthroscopy or 75 mg with 0.2 mg epinephrine for hernia repair), 2% isobaric lidocaine without epinephrine (60 mg for arthroscopy or 75 mg for hernia repair), or 0.75% hyperbaric bupivacaine without epinephrine (7.5 mg for arthroscopy or 9.0 mg for hernia repair) in a double-blinded fashion. On the 3rd postoperative day, patients were contacted by a blinded investigator and questioned regarding the incidence of postoperative complications including TRI, defined as back pain with radiation down one or both buttocks or legs occurring within 24 h after surgery. Postoperatively, time from injection to block resolution, ambulation, voiding, and ready for discharge were recorded by a postanesthesia care unit nurse blinded to the group assignment. RESULTS: The incidence of TRI was greater in patients receiving lidocaine than in those receiving bupivacaine (16% vs. 0%; P = 0.003). There was no difference in the incidence of TRI between the patients receiving 5% hyperbaric lidocaine with epinephrine and those receiving 2% isobaric lidocaine without epinephrine (16% vs. 16%; P = 0.98). The incidence of TRI was greater in patients undergoing arthroscopy than in those undergoing hernia repair (13% vs. 5%; P = 0.04). There was no difference in discharge times in patients receiving bupivacaine versus those receiving hyperbaric lidocaine with epinephrine (292 vs. 322 min; P = 0.61). CONCLUSIONS: The incidence of TRI is greater with lidocaine than bupivacaine, decreasing the lidocaine concentration to 2% does not prevent TRI, and surgical position may be an important contributing factor. Discharge times at our institution are not different when equipotent doses of 0.75% hyperbaric bupivacaine or 5% hyperbaric lidocaine with 0.2 mg epinephrine are used in ambulatory patients undergoing spinal anesthesia.

Adult↗

PubMed1991

Naloxone partly counteracts apomorphine side effects.

The effects of naloxone on side effects provoked by apomorphine (APO) administration in patients with parkinsonian syndrome have been studied. The group under study included eight patients with Parkinson's disease and four with parkinsonism who received 100 micrograms/kg s.c. APO acutely to test dopaminergic responsiveness. All patients were treated with 20 mg domperidone tablets t.i.d. and then for 2 consecutive days (in double blind fashion) were given a 2-hour i.v. saline infusion alone or with naloxone (8 mg) starting 30 min before APO administration. In both groups, naloxone delayed the appearance of sleepiness, and reduced the intensity of yawning, sleepiness, nausea, and vomiting as compared with saline. These findings indicate a potential usefulness of naloxone and other opioid antagonists in preventing acute APO side effects.

Apomorphine↗

PubMed2002

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome.

OBJECTIVE: To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourette's syndrome (TS). METHOD: Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS: Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS: In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.

Adrenergic alpha-Agonists↗