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PubMed1988

Nonresponsiveness to antianginal therapy--a frequent problem?

Nonresponsiveness to anginal treatment varies greatly and may be due to either the pathophysiology of the patients or the special pharmacology of different antianginal drugs. Therefore, individualized therapy, taking all aspects of patient and drug into account to improve responsiveness, seems desirable. Patients may vary--thus influencing the outcome of antianginal therapy--with respect to the severity of the disease, vasospastic components, and the pattern of organic vessel involvement. Drugs differ with respect to the ease of dose-finding, tolerance, the extent of spasmolytic activity, side effects, and paradoxical effects. In no patient with coronary artery disease is the outcome to treatment predictable, even if a full diagnostic evaluation of the patient has been performed. For example, the individual relevance of angiographically documented vasospastic components in patients with underlying organic multivessel disease can hardly be predicted, and therefore the appropriate choice of an antianginal drug is difficult. In addition, a full invasive evaluation of all coronary patients, only to find arguments for the optimal drug therapy, is not feasible. Therefore, the empiric approach is recommended for daily routine. Drugs are preferred that usually provide a high response rate and the smallest cause for concern.

Angina Pectoris↗
PubMed1994

Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain.

To investigate the combined analgesic and spasmolytic effect of dipyrone, 104 patients suffering from "severe" or "excruciating" colic pain due to a confirmed calculus in the upper urinary tract were randomized to receive i.v. either 2.5 g dipyrone (36 patients), 100 mg tramadol (35 patients), or 20 mg butylscopolamine (33 patients) in a multicentre, observer-blind, parallel-group study conducted in 8 German centres. The three treatment groups were homogeneous when analyzed by age, sex, height, and baseline pain intensity. Dipyrone was significantly more effective than tramadol in reducing pain for the primary endpoint, pain intensity differences (PID) at 20, 30, and 50 min after drug administration, and was significantly more effective than butylscopolamine at 30 and 50 min for the secondary efficacy endpoint, pain intensity differences on a categorical scale. Dipyrone had the highest SPID0-2 h of the three drugs (P < 0.05). Only 5 patients receiving dipyrone needed "rescue" medication as compared with 13 patients given tramadol and 11 patients receiving butylscopolamine. Adverse events were observed in 4 patients receiving butylscopolamine and in 1 patient each given dipyrone and tramadol. "Distinct" pain relief as assessed on a visual analogue scale (VAS) is a reliable method of determining the onset of analgesic action in the colic pain model.

Acute Disease↗
PubMed1986

Calcium antagonism by the antioestrogen tamoxifen.

Tamoxifen, an oestrogen receptor antagonist and an effective treatment for breast carcinoma, has recently been shown to possess spasmolytic activity in smooth muscle. Tamoxifen in vitro inhibited the contraction of smooth muscle from rat myometrium and aorta produced by exogenous calcium. At the same concentration tamoxifen did not affect the uptake of calcium into the muscle. The importance of calcium in cell proliferation suggests that some of the unexplained antitumor activity of the oestrogen antagonists may be accounted for by intracellular calcium antagonism.

Animals↗
PubMed1989

Analgesic-induced chronic headache: long-term results of withdrawal therapy.

Headache characteristics are described in 139 patients with chronic daily or almost daily headaches due to regular intake of analgesics and the short- and long-term results of drug withdrawal. Drug-induced headache was described as dull, diffuse, and band-like, and usually started in the early morning. The mean duration of the original headache (migraine or tension headache) was 25 years; regular intake of drugs and chronic daily headache had started 10 and 6 years prior to withdrawal therapy, respectively. Patients took an average of 34.6 tablets or analgesic suppositories or antimigraine drugs per week containing 5.8 different substances. The drugs most often used were caffeine (95%), ergotalkaloids (89%), barbiturates (64%), and spasmolytics, paracetamol, and pyrazolone derivates (45%-46%). A total of 103 patients (68 migraine, 35 tension or combination headache) were available for interviews at a mean time interval of 2.9 years after an inpatient drug withdrawal programme. Chronic headache had disappeared or was reduced by more than 50% in two-thirds of the patients. Positive predictors for successful treatment were migraine as primary headache, chronic headache lasting less than 10 years, and regular intake of ergotamine. Drug intake was significantly reduced and patients used single substances more often. Patients who originally suffered from migraine, superimposed on the daily headache, also experienced a significant improvement in the frequency of the migraines and their intensity. Migraine prophylaxis through beta-blocking agents and calcium channel antagonists was more efficient after drug-withdrawal therapy.

Adult↗
PubMed1986

Cold-induced Raynaud's phenomenon ameliorated by intravenous administration of ketanserin: a double-blind cross-over study.

Fifteen patients suffering from Raynaud's phenomenon (RP) were examined. They were placed in a "climate chamber" (a small room in which the temperature and humidity could be varied). The temperature was gradually decreased, while the humidity was kept constant. After 60-90 min, distinct RP was induced and intravenous medication was administered. The whole trial was performed in a double-blind, cross-over fashion. Every patient participated in two experiments performed 2 days apart. Either ketanserin or placebo was given during the first experiment. In the second experiment, the medication (or placebo) which had not been given was administered. The effects of ketanserin were highly significant: the bluish pallor changed into bright erythema and the skin temperature rose significantly. This was interpreted as a spasmolytic effect. Intravenously administered ketanserin has a place in the clinical treatment of acutely deteriorating RP of diverse etiologies.

Adult↗
PubMed1985

Protective effect by UCB JO28 against histamine and methacholine induced bronchial hyperreactivity.

UCB JO28 [( 2-[2-[4-(diphenylmethylene)-1-piperidinyl] ethoxy] ethoxy] acetic acid, hydrochloride) is derived from diphenylmethylene piperidine. Animal experiments have shown that it has spasmolytic properties for smooth muscle, particularly in the bronchi, as well as anti-Hl, anticholinergic and anti-serotonin activities. The degree of protection by JO28 against histamine and methacholine-induced bronchospasm has been investigated in 20 asthmatic patients with serious airways hyper-reactivity. Protection against histamine-induced bronchospasm was almost complete in 11 out of 12 patients, whereas protection against methacholine-induced bronchospasm, although clearly present in seven of eight patients, was less marked.

Adolescent↗
PubMed1990

Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage.

The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibition of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120-180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo-controlled double-blind trial (which is currently being carried out).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Effect of intravenous glucagon and glucagon-(1-21)-peptide on motor activity of sphincter of Oddi in humans.

Glucagon-(1-21)-peptide, the peptide containing the amino acid sequence (1-21) of glucagon, has the same spasmolytic effect as the complete molecule, without its metabolic action. The effect of glucagon and glucagon-(1-21)-peptide on sphincter of Oddi motor activity was evaluated in 20 patients undergoing ERCP and endoscopic biliary manometry. Glucagon produced a nonsignificant decrease in basal pressure, but significantly reduced both frequency and amplitude of phasic activity of the sphincter of Oddi. Glucagon-(1-21)-peptide showed no effect on basal pressure and amplitude of phasic activity, but provoked a significant reduction of frequency of phasic contraction.

Adult↗
PubMed1978

Effects of cholecystokinin-pancreozymin on bile flow and biliary bile salt secretion in the cholecystectomized animal.

The effects of an intravenous infusion of cholecystokinin-pancreozymin on bile secretion were studied in 13 unanesthetized and cholecystectomized piglets. The results demonstrate that CCK-PZ induces a significant increase of bile flow and bile salt excretion. The excretion patterns for bilirubin and Ioglycamide, however, showed a slight but not significant decrease. Peripheral hemodynamic parameters remained unchanged. A detailed analysis of these results suggests that CCK-PZ induces an increase of biliary bile salt secretion by stimulation of intestinal motility and enhancement of bile salt circulation within the enterohepatic circulation (EHC). In combination with previous studies on the effects of spasmolytics on biliary bile salt excretion these results therefore emphasize, that the intestinal motility and transit time might play a role in the physiology and pathophysiology of biliary bile salt secretion.

Animals↗
PubMed1988

[Sex- or symptom-specific behavior of male residents? An analysis of diagnosis and therapy of ambulatory female and male patients with abdominal pain].

We investigated the influence of the patient's gender for diagnostic and therapeutic approach of physicians at the outpatient clinic of the university hospital of Basle. In a prospective study 13 male residents in their second and third year of medical training were observed in their management of 25 female and 25 male patients presenting with the leading complaint of abdominal pain with regard to taking of the medical history, the physical examination and the performed diagnostic and therapeutic procedures, without informing the participating physicians. The time spent for the first consultation and the number of follow ups performed were registered. Following differences in the management of female and male patients were observed: The time spent at the first consultation was 59 +/- 5 minutes in female and 45 +/- 3.5 in male patients (p less than 0.03). Fundoscopic examination was three times more often performed in female patients. Endoscopic examinations were more often observed in male patients (p less than 0.01). Antacids and H2-antagonists were more frequently prescribed in male (p less than 0.01). Spasmolytics and laxatives more frequently in female (p less than 0.01). In summary in male patients the diagnosis of functional disease was predominantly made after exclusion of an organic disease what does explain the use of more diagnostic procedures and the induction of a more specific therapy.

Abdomen↗
PubMed1991

Coumarin compounds in cassava diets: 2 health implications of scopoletin in gari.

Scopoletin has been isolated and identified in gari, a cassava food consumed in Nigeria (West Africa). Its levels in gari and cassava flour is not altered by post processing treatments such as sundrying, refrigeration and storage. Scopoletin has also been identified as an active principle in the traditional herbal infusion of the fruit of Tetrapleura tetraptera TAUB used in the ethnopharmacology of West Africa. It is a potent hypotensive and non-specific spasmolytic agent. These pharmacological effects of Scopoletin are probably the underlying factors in the slowly developing tropical neuropathy characterised by optic atrophy, nerve deafness and ataxia endemic among populations subsisting on cassava diets such as gari. Hitherto, these toxicities were attributed to cyanogenic glucosides (cyanide) present in cassava.

Coumarins↗
PubMed1996

Effects of metamizol on nociceptive responses to stimulation of the ureter and on ureter motility in anaesthetised rats.

In this study, we have examined the effects of metamizol (dipyrone), a non-opioid analgesic which is effective in relieving renal colic pain, on nociceptive responses evoked by stimulation of the ureter, on pyeloureteral motility and on intraureter pressure after ureter obstruction in anaesthetised rats. Metamizol (5- 50 mg/kg i.v.) dose-dependently inhibited reflex pressor responses evoked by distensions of the ureter to pressures of 30, 55 and 75 mmHg for 30 s (ID50 = 8 +/- 1 mg/kg). Metamizol also dose-dependently reduced intraureter pressure during total ureter occlusion (25 mg/kg produced a reduction of 25% in 10 min). However, metamizol at doses up to 50 mg/kg had no effect on pyleoureteric motility (contraction amplitude, rate or intraureter pressure) under normal pressure conditions. We conclude that metamizol has a direct antinociceptive action on pain of ureteric origin, and spasmolytic effects after ureter obstruction (but not under normal conditions) which may also contribute to pain relief.

Analgesics, Non-Narcotic↗
PubMed1991

Foreign bodies in the esophagus. A study of causative factors.

Two hundred and twenty-nine patients were studied in an attempt to determine the main causative factors behind their having a residual foreign body in the esophagus. Strictures were present in 13%. Fifty-two percent of the patients with stricture had been hospitalized more than once for treatment of foreign body impaction; this was the case in only 8.5% of the rest of the patients (p less than 0.001). More than half of the patients aged 15 years or younger had a foreign body in the hypopharynx. This location was extremely uncommon in adults (p less than 0.001). The hypothesis of spasm distal to an esophageal foreign body as the cause for obstruction in patients without esophageal stricture was supported by the following findings: spontaneous disimpaction occurred in more than one-third of the patients and became more frequent as time progressed; 63% of 16 patients given spasmolytic drugs experienced spontaneous disimpaction of the foreign body; half of the patients had the foreign body in the proximal esophagus distal to the narrower passage of the upper esophageal sphincter; foreign body impaction in the esophagus turned out to be a once-only event in 86% of the patients; and 21% of the patients had a disorder of the central nervous system and had been hospitalized significantly more often because of food impaction than the other patients. The findings indicate that adults with a history of impaction of foodstuff lacking sharp bones and who do not have stricture suffer food impaction because of spasm of the esophageal smooth muscle, and can be treated accordingly.

Adolescent↗
PubMed1988

A new method for the management of ureteral colic after extracorporeal shock wave lithotripsy.

In ten patients, who underwent ESWL of renal calculi and had severe ureteral colic due to acute obturation of the ureteral lumen by larger stone fragments, i.v. glucagon injections combined with laevulose infusion were applied. All patients reported relief of pain and discomfort within 15-20 minutes after glucagon injection. Position of the stones in the ureter was regularly checked. No particular adverse effects of glucagon were noted. Glucagon increases GFR and diuresis and exhibits spasmolytic effect on the smooth muscle of the ureteral wall, thus facilitating the passage of stone fragments after ESWL. In certain cases and with certain indications we recommend the method as highly effective.

Adult↗
PubMed1990

Idiopathic bladder hyperactivity treated with Ditropan (oxybutynin chloride).

Ditropan (oxybutynin chloride), a tertiary amine with slight anticholinergic and marked "papaverine-like" direct spasmolytic effects has been administered to 25 patients with idiopathic hyperactive bladder function. The drug reduced voiding frequency and abolished urgency. Control cystometry confirmed a significant increase in bladder capacity. Oral dryness was a tolerable side effect.

Drug Evaluation↗
PubMed1998

Synthesis and biological evaluation of novel 2-[substituted acetyl]-amino-5-alkyl-1,3,4-thiadiazoles [corrected].

Sixteen novel 2-substituted acetyl amino-5-alkyl-1,3,4-thiadiazole were synthesized and screened for their pharmacological activities. A few of the compounds namely 11, 12 and 16 showed anti-inflammatory activities comparable to phenylbutazone. Compound 12 also showed significant non-specific spasmolytic activity. Diuretic activity of compound 15 at a dose level of 90 mg/kg p.o. was two fold higher compared to 50 mg/kg p.o. of furosemide. Comparable diuresis was also produced by compounds 9, 10 and 16.

Animals↗
PubMed1997

Midazolam reverses histamine-induced bronchoconstriction in dogs.

PURPOSE: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. METHODS: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. RESULTS: Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. CONCLUSION: Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.

Anesthetics, Intravenous↗
PubMed1998

Antinociceptive activity of metamizol in rats with experimental ureteric calculosis: central and peripheral components.

OBJECTIVE AND DESIGN: To study the antinociceptive effects of metamizol in a rat model of ureteric calculosis. SUBJECTS: Adult female Wistar rats (n = 40). TREATMENT: Metamizol was given i.p. 50-100 mg/kg, 3 times daily for 4 days for behavioural testing, and 25-100 mg/kg i.v. whilst recording peristalsis or dorsal horn neurons. METHODS: An artificial stone was induced in one ureter. In 3 separate groups of stone-implanted rats, behaviour was recorded continuously on video tape, ureteric peristalsis or the electrical activity of single nociceptive dorsal horn neurons with ureteric input was recorded under anaesthesia. Data were compared with analysis of variance. RESULTS: Metamizol inhibited the behavioural visceral crises, the abnormal ureteric peristalsis and the activity of nociceptive dorsal horn neurons. CONCLUSIONS: Metamizol has central antinociceptive effects on the pain produced by a ureteric stone, and an additional spasmolytic effect on the hyperperistalsis produced by the stone.

Abdominal Pain↗