Modified Release Tizanidine in the Treatment of Spasticity

1988 ◽  
Vol 16 (6) ◽  
pp. 459-465 ◽  
Author(s):  
A. Chantraine ◽  
C. Van Ouwenaller
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Side Effects ◽  
Modified Release ◽  
Cerebral Lesions ◽  
Release Formulation ◽  
Once Daily ◽  
End Of Treatment ◽  
Severe Spasticity

A 6-week study of a modified release formulation of tizanidine designed for once daily administration was performed in 27 patients with spasticity due to cerebral lesions. The dosage of tizanidine used ranged from 6 to 18 mg/day. At the start of the study all patients had at least moderate spasticity and 20 (74%) patients had severe or very severe spasticity. All had a decrease in muscle strength. After 1 week of treatment 22 (81%) patients showed improvement in overall spastic state and, after 6 weeks, all 27 patients had improved. At the end of treatment 25 (93%) patients showed an improvement in overall disability. The drug was well tolerated. Side-effects were reported in only four patients, and these were minor and mostly mild. Tizanidine had no clinically important effects on blood pressure, heart rate, body weight or laboratory values. Overall, once daily treatment with modified release tizanidine is well tolerated and gives good clinical efficacy in patients with spasticity.

Abstract MP016: Innovation in Exercise: Increasing Capacity of Sedentary Obese Women with Cooling

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Stacy T Sims ◽  
Sandra Tsai ◽  
Marcia L Stefanick
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Waist Circumference ◽  
Body Mass ◽  
Exercise Tolerance ◽  
Thermal Strain ◽  
Walk Test ◽  
Obese Women ◽  
Thermal Discomfort

Background: Barriers to physical activity for obese women include overheating, sweating, fatigue, exhaustion, and rapid heart rate. Adipose tissue acts as a thermal insulator, promoting a greater heat load on the nonfat tissues, reducing heat tolerance; exercise causes a rise in body temperature with an inability to dissipate heat contributing to reduced exercise tolerance. With difficulties of thermoregulation in the sedentary obese population, the aspect of attenuating the discomfort thus associated may encourage continuation of exercise. A heat sink applied to palmar surfaces extracts heat and cools the venous blood, reducing thermal strain by enhancing the volume of cooled venous return. We hypothesized that palmar cooling using a rapid thermal exchange device (RTX) during exercise would attenuate the thermal discomfort of exercise of sedentary obese women, improving exercise tolerance. Methods: To examine whether palmar cooling would impact exercise tolerance in obese women, 24 healthy women aged 30–45 years, with no history of long term structured exercise, a body mass of 120–135% above ideal and/or BMI between 30 and 34.9 were recruited. Women were randomized into a cooling (RXT with 16°C water circulating) or a control (RTX with 37°C water circulating) group and attended 3 exercise sessions a week for 3-months (12 weeks). Each session was comprised of 10 min body weight exercises, 25–45 min treadmill walking at 70–85% HRR with the RTX device, and 10 min of core strengthening exercises. The performance marker was a 1.5 mi walk for time; conducted on the first and last days of the intervention. Mixed models were used to model each of the outcomes as a function of thermal strain, time and treatment with covariates of speed, heart rate, distance, and the interaction of the main effects included in the model. Results: Groups were matched at baseline for key variables (time for 1.5 mile walk test, resting and exercising heart rate [HR], blood pressure [BP], waist circumference [WC], body weight, body mass index [BMI]). Among the cooling group, time to complete the 1.5mile walk test was significantly faster (31.6 ± 2.3 vs. 24.6 ± 2.5 min, pre vs. post, P< 0.01). A greater average exercising HR was observed (136 vs. 154 bpm, pre vs. post, P <0.001), with a significant reduction in WC (41.8 ± 3.1 vs. 39.1 ± 2.2 inches, pre vs. post, P< 0.01) and resting BP (139/84 ± 124/70 mmHg, pre vs. post, P < 0.025). There were no significant differences observed in the control group. Conclusion: Results indicate that exercise tolerance in obese women improved with cooling during exercise, more so than those women who did not have cooling. An improvement in blood pressure, heart rate, waist circumference, and overall aerobic fitness was observed. These findings suggest that by reducing thermal discomfort during exercise, tolerance increases, thus improving cardiovascular parameters of obese women.

Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia

1999 ◽  
Vol 87 (6) ◽  
pp. 2025-2031 ◽  
Author(s):  
Holger Kraiczi ◽  
Jarkko Magga ◽  
Xiang Ying Sun ◽  
Heikki Ruskoaho ◽  
Xiaohe Zhao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Atrial Natriuretic Peptide ◽  
Right Ventricular ◽  
Natriuretic Peptide ◽  
Intermittent Hypoxia ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.

Rapid cardiovascular effects of dexamethasone in rabbits with meconium-induced acute lung injury

2008 ◽  
Vol 86 (11) ◽  
pp. 804-814 ◽  
Author(s):  
Daniela Mokra ◽  
Ingrid Tonhajzerova ◽  
Juraj Mokry ◽  
Anna Drgova ◽  
Maria Petraskova ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Side Effects ◽  
Rabbit Model ◽  
Intratracheal Instillation ◽  
Cardiovascular Effects ◽  
Meconium Aspiration Syndrome ◽  
Cardiovascular Side Effects ◽  
Acute Side Effects ◽  
Systemic Glucocorticoids

Glucocorticoids may improve lung function in newborns with meconium aspiration syndrome (MAS), but information on the acute side effects of glucocorticoids in infants is limited. In this study using a rabbit model of MAS, we addressed the hypothesis that systemic administration of dexamethasone causes acute cardiovascular changes. Adult rabbits were treated with 2 intravenous doses of dexamethasone (0.5 mg/kg each) or saline at 0.5 h and 2.5 h after intratracheal instillation of human meconium or saline. Animals were oxygen-ventilated for 5 h after the first dose of treatment. Blood pressure, heart rate, and short-term heart rate variability (HRV) were analyzed during treatment, for 5 min immediately after each dose, and for the 5 h of the experiment. In the meconium-instilled animals, dexamethasone increased blood pressure, decreased heart rate, increased HRV parameters, and caused cardiac arrhythmia during and immediately after administration. In the saline-instilled animals, the effect of dexamethasone was inconsistent. In these animals, the acute effects of dexamethasone on blood pressure and cardiac rhythm were reversed after 30 min, whereas heart rate continued to decrease and HRV parameters continued to increase for 5 h after the first dose of dexamethasone. These effects were more pronounced in meconium-instilled animals. If systemic glucocorticoids are used in the treatment of MAS, cardiovascular side effects of glucocorticoids should be considered.

scholarly journals Fentanyl Pretreatment Modifies Anaesthetic Induction with Etomidate

1988 ◽  
Vol 16 (2) ◽  
pp. 171-176 ◽  
Author(s):  
R. J. Stockham ◽  
T. H. Stanley ◽  
N. L. Pace ◽  
S. Gillmor ◽  
F. Groen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Side Effects ◽  
Linear Regression ◽  
Anaesthetic Induction ◽  
Arterial Blood ◽  
Group I ◽  
Haemodynamic Changes ◽  
Induction Of Anaesthesia ◽  
Fentanyl Group

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I= 2 ml normal saline; Group II= 100 μg of fentanyl; Group III= 250μg of fentanyl; Group IV = 500 μg of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P< 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P< 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 μg of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.

0744 Cardiac Safety Profile of Pitolisant in Patients with Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A283-A283
Author(s):  
W Winter ◽  
S P Wanaski ◽  
A Patroneva ◽  
J M Dayno
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pooled Analysis ◽  
Mean Difference ◽  
Qtc Interval ◽  
Cardiac Safety ◽  
Open Label ◽  
Long Term Study ◽  
End Of Treatment

Abstract Introduction Cardiovascular diseases are comorbid in patients with narcolepsy. Cardiovascular adverse effects are of concern with narcolepsy medications because of this comorbidity and most patients require lifelong pharmacotherapy. Pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist, increases histamine transmission in the brain. In a QT study of healthy volunteers, pitolisant (35.6 mg/day) led to a mean increase of 4.2 msec in QTc interval. This analysis further characterized the cardiac safety of pitolisant (maximum dose, 35.6 mg/day) in adults with narcolepsy. Methods Data were obtained from a pooled analysis of 2 randomized, placebo-controlled, 7- or 8-week studies and from a 12-month, open-label study. Results Pooled analysis included 166 patients (pitolisant, n=85; placebo, n=81). Mean change in heart rate from baseline to end-of-treatment was -0.5 beats/min with pitolisant and -0.2 beats/min with placebo (LS mean difference, -0.4; P=0.744). Mean change was also similar for pitolisant versus placebo in systolic (LS mean difference, 0.0; P=0.983) and diastolic (LS mean difference, -0.6; P=0.552) blood pressure, as was mean change in QTc interval (LS mean difference, 0.4; P=0.911). Cardiac adverse events with pitolisant included heart rate increase (n=4), right bundle branch block (n=1), sinus tachycardia (n=1), and palpitations (n=1), and with placebo included blood pressure increase (n=1). In the long-term study, mean change from baseline in QTc interval was 3.1 msec at Month 6 (n=70) and 6.1 msec at Month 12 (n=67); 3 patients had a postbaseline increase &gt;60 msec but none had QTc &gt;500 msec. Conclusion In this analysis, no cardiac safety signals were observed during treatment with pitolisant administered up to the maximum recommended dose. Because concomitant use of pitolisant with other drugs known to increase the QT interval may add to the QT effects of pitolisant, avoid use of pitolisant in combination with these medications. Support Bioprojet Pharma and Harmony Biosciences, LLC.

Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans 

1995 ◽  
Vol 82 (2) ◽  
pp. 331-343 ◽  
Author(s):  
David D. Hood ◽  
James C. Eisenach ◽  
Robin Tuttle
Keyword(s):  
Carbon Dioxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Side Effects ◽  
Healthy Volunteers ◽  
Nausea And Vomiting ◽  
Severe Nausea ◽  
End Tidal Carbon Dioxide ◽  
End Tidal ◽  
Ice Water

Background In dogs, sheep, and rats, spinal neostigmine produces analgesia alone and enhances analgesia from alpha 2-adrenergic agonists. This study assesses side effects and analgesia from intrathecal neostigmine in healthy volunteers. Methods After institutional review board approval and informed consent, 28 healthy volunteers were studied. The first 14 volunteers received neostigmine (50-750 micrograms) through a #19.5 spinal needle followed by insertion of a spinal catheter. The remaining 14 volunteers received neostigmine through a #25 or #27 spinal needle without a catheter. Safety measurements included blood pressure, heart rate, oxyhemoglobin saturation, end-tidal carbon dioxide, neurologic evaluation, and computer tests of vigilance and memory. Analgesia in response to ice water immersion was measured. Results Neostigmine (50 micrograms) through the #19.5 needle did not affect any measured variable. Neostigmine (150 micrograms) caused mild nausea, and 500-750 micrograms caused severe nausea and vomiting. Neostigmine (150-750 micrograms) produced subjective leg weakness, decreased deep tendon reflexes, and sedation. The 750-micrograms dose was associated with anxiety, increased blood pressure and heart rate, and decreased end-tidal carbon dioxide. Neostigmine (100-200 micrograms) in saline, injected through a #25 or #27 needle, caused protracted, severe nausea, and vomiting. This did not occur when dextrose was added to neostigmine. Neostigmine by either method of administration reduced visual analog pain scores to immersion of the foot in ice water. Conclusions The incidence and severity of these adverse events from intrathecal neostigmine appears to be affected by dose, method of administration, and baricity of solution. These effects in humans are consistent with studies in animals. Because no unexpected or dangerous side effects occurred, cautious examination of intrathecal neostigmine alone and in combination with other agents for analgesia is warranted.

Repeated daily injections and osmotic pump infusion of isoproterenol cause similar increases in cardiac mass but have different effects on blood pressure

2005 ◽  
Vol 83 (2) ◽  
pp. 191-197 ◽  
Author(s):  
A Roger Hohimer ◽  
Lowell E Davis ◽  
Daniel C Hatton
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Systemic Hemodynamic ◽  
Routes Of Administration ◽  
Arterial Blood ◽  
C57bl6 Mouse ◽  
Dose Dependent ◽  
Pump Infusion

We found in mice that repeated single daily subcutaneous (s.c.) isoproterenol (ISO) injections, like constant infusions using osmotic minipumps, caused increased biventricular mass or weight relative to body weight (VW/BW). We found that 5 (1/d) s.c. injections of 2, 10, or 20 µg/g body weight caused equivalent VW/BW increases as compared with 5-d infusions at 20 µg/(g·d)). While it is often presumed that ISO elicits hypertrophy by a direct effect on the myocytes, growth may also be secondary to systemic hemodynamic effects. The 2 modes of ISO administration had different effects on mean arterial blood pressure (MABP) and heart rate. Using telemetry we observed that single injections of ISO (0, 0.5, 2, and 10 µg/g) were associated with hypotension and tachycardia with a duration but not a magnitude that was dose dependent. MABP dropped rapidly to 60 mm Hg for more than 2 h at the highest dose. Constant s.c. infusion of ISO at 20 µg/(g·d) initially lowered MABP to about 70 mm Hg for 24 h. At 48 h MABP was normal, but rose 10 mm Hg higher than baseline by day 5. Thus, different routes of administration of ISO that cause comparable increases in VW/BW had different effects on MABP. Thus when evaluating mouse models of ISO-induced cardiac hypertrophy, both repeated daily injections or infusions can cause similar increases in VW/BW, but the daily doses that are required are not the same. Furthermore, these different routes of administration have different hemodynamic sequelae and could potentially evoke different cardiac phenotypes.Key words: C57BL6 mouse, hypotension, heart rate, cardiac hypertrophy, β-adrenergic.

Experiences with Metoprolol Durules®, A Slow-Release Formulation in Hypertension

1980 ◽  
Vol 8 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Jaakko Tuomilehto ◽  
Aulikki Nissinen
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Moderate Hypertension ◽  
Antihypertensive Effect ◽  
Slow Release ◽  
Final Dose ◽  
Release Formulation ◽  
Once Daily ◽  
Slow Release Formulation ◽  
The Mean

The antihypertensive effect and the tolerability of metoprolol Durules® have been studied in fifty-five patients with mild to moderate hypertension. The patients' diastolic blood pressure was ≥95 mm Hg in order to qualify for entry. Thirty-seven out of fifty-three patients completing the study (70%) were treated with metoprolol Durules® monotherapy throughout the study. The mean blood pressure was reduced from 153/101 to 138/92 mm Hg after metoprolol Durules® compared to placebo (p < 0.001). Twenty-seven patients received one Durules® daily and ten patients received two Durules® daily as the final dose. Of the sixteen patients not responding on metoprolol Durules®, six patients achieved satisfactory control, i.e. a diastolic blood pressure below 95 mm Hg, when given 200 mg metoprolol + 25 mg hydrochlorothiazide (HCT). The results indicate that most patients with, mild or moderate hypertension can be controlled with metoprolol Durules® monotherapy given once daily. The addition of HCT gives a significant benefit in moderate hypertension, where metoprolol monotherapy is not sufficient.

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