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PubMed2005

Manometric effect of topical glyceryl trinitrate and its impact on chronic anal fissure healing.

INTRODUCTION: The duration of physiologic action of topical glyceryl trinitrate in the management of anal fissure has been the source of some controversy. This study was designed to assess the manometric effect of glyceryl trinitrate on internal sphincter resting tone with continuous monitoring. METHODS: Twenty-seven patients with a chronic anal fissure were assessed with fissure, pain, bleeding, and continence scores. Twenty-two were randomized to 1 cm of topical 0.2 percent glyceryl trinitrate paste, applied to the lower anal canal. Five patients were randomized to 1 cm of water-soluble lubricating jelly to the lower anal canal. Continuous stationary six radial channel water perfusion anorectal manometry was performed for 5 minutes before treatment and then for a further 30 minutes. The 22 glyceryl trinitrate patients were then advised to apply topical 0.2 percent glyceryl trinitrate, three times daily, for eight weeks. Twenty-four hours after completing treatment, all baseline assessments were repeated. The lubricant jelly cohort was discharged from the study after the initial assessment. RESULTS: During the initial manometric assessment, 21 glyceryl trinitrate patients (95 percent) had 20 percent or more reduction in mean and maximum anal resting pressure after treatment. However, there was no statistical difference at 20 minutes compared with 0 minutes (P > 0.1). After eight-week treatment, 16 patients (73 percent) reported symptom resolution and 15 (67 percent) were found to be healed on examination. Clinical healing and resolution of symptoms positively correlated with a higher pretreatment maximum anal resting pressure in the mid anal canal (P < 0.0001), lower fissure score (P < 0.0001), and greater percentage reduction of the maximum resting pressure after application of glyceryl trinitrate (P < 0.001). The mean and maximum anal resting pressure at Week 8 was not significantly different from the baseline values (P > 0.05). During continuous manometry, the anal resting pressure did not significantly change in the patients treated with lubricating jelly. CONCLUSIONS: In those patients with a lower fissure score, a higher mid anal canal anal resting pressure, and a greater resting pressure reduction after glyceryl trinitrate application, a favorable clinical outcome can be expected with glyceryl trinitrate treatment. However, because the physiologic response has resolved in fewer than 20 minutes, the dosing regime should be reassessed.

Administration, Topical↗

PubMed2003

Transdermal glyceryl trinitrate for prevention of post-ERCP pancreatitis: A randomized double-blind trial.

BACKGROUND: Pancreatic sphincter hypertension increases the risk of pancreatitis in patients undergoing ERCP. Glyceryl trinitrate reduces sphincter of Oddi pressure. This study tested the hypothesis that transdermal glyceryl trinitrate could be effective in the prevention of post-ERCP pancreatitis. METHODS: One hundred forty-four patients undergoing ERCP were randomized: 71 received a 15-mg glyceryl trinitrate patch (glyceryl trinitrate group) and 73 a placebo patch (control group). RESULTS: In the control group, post-ERCP pancreatitis developed in 11 patients versus 3 in the glyceryl trinitrate group (p < 0.05). Twenty-four hour to baseline serum amylase and lipase ratios were lower in the glyceryl trinitrate group (respectively, 3.6 vs. 7.5, p < 0.05; and 5.3 vs. 27.7, p < 0.05). In a multivariate analysis, glyceryl trinitrate patch and the number of pancreatic injections, but not endoscopic sphincterotomy, were independent risk factors for post-ERCP pancreatitis. CONCLUSIONS: The results of this study suggest that use of a transdermal glyceryl trinitrate patch protects against post-ERCP pancreatitis.

Administration, Cutaneous↗

PubMed2002

The pharmacokinetics of glyceryl trinitrate with the use of the in vitro term human placental perfusion setup.

OBJECTIVE: The purpose of this study was to determine the pharmacokinetics of glyceryl trinitrate across the in vitro term human perfused placenta. STUDY DESIGN: Peripheral placental lobules (n = 6) were dually perfused. The maternal side was perfused with glyceryl trinitrate (100 nmol/L) for 90 minutes. Serial samples from the fetal venous and maternal venous catheters were collected and assayed for glyceryl trinitrate and its vasoactive metabolites (1,2- and 1,3-glyceryl dinitrate) with gas chromatography. Fetal arterial perfusion pressure was continuously measured throughout. Data are expressed as the mean +/- SEM, with 1-way analysis of variance followed by a Newman-Keuls post-hoc test (P <.05). RESULTS: The mean steady-state fetal venous:maternal side ratio of glyceryl trinitrate concentration was 18.5% +/- 3.7%. The 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate levels in the fetal venous samples and maternal venous samples were less than the lower end of the sensitivity range of the assay (<5 nmol/L). Fetal arterial perfusion pressure did not change with glyceryl trinitrate administration. CONCLUSION: The glyceryl trinitrate in the fetal venous sample was approximately 18.5% of the glyceryl trinitrate in the maternal side in this preparation. The presence of glyceryl dinitrates in the maternal venous samples and the fetal venous samples indicates the capacity for placental biotransformation of glyceryl trinitrate. The data demonstrate that glyceryl trinitrate, at a tocolytic concentration, has the ability to cross the placenta but was not found to affect fetal arterial perfusion pressure.

Culture Techniques↗

PubMed1988

Reflected pressure waves in the ascending aorta: effect of glyceryl trinitrate.

Reflected pressure waves returning to the ascending aorta are an important contribution to aortic systolic pressure and thus the load on the left ventricle. The effect of glyceryl trinitrate on pressure wave reflections in the ascending aorta was studied using the transmission of arterial pressure between two high fidelity pressure transducers. Glyceryl trinitrate 0.3 mg sublingually reduced systolic arterial pressure by 11 mmHg owing to a reduction of the late systolic pressure peak. Mean arterial pressure fell 2 mmHg, but heart rate and aortic flow did not change. The aortic input impedance was reduced at the first harmonic (control 18.4(4.1); glyceryl trinitrate 10.8(2.4) kPa.s.litre-1; p less than 0.005) but characteristic impedance was not changed (control 12.7(3.8); glyceryl trinitrate 14.2(3.3) kPa.s.litre-1). The first two harmonics of apparent phase velocity were reduced by glyceryl trinitrate (1.05 Hz: control 3314(798); glyceryl trinitrate 1772(495) cm.s-1; p less than 0.01; 2.1 Hz: control 1246(269); glyceryl trinitrate 754(127) cm.s-1; p less than 0.05), yet the foot to foot wave velocity was unchanged (control 688(112); glyceryl trinitrate 726(112) cm.s-1). There was a significant reduction in the amplitude of the global reflection coefficient at 1.05 Hz (control 0.70(0.09); glyceryl trinitrate 0.48(0.08); p less than 0.001) and at 2.1 Hz (control 0.48(0.07); glyceryl trinitrate 0.23(0.06); p less than 0.005) with no significant change in phase. Glyceryl trinitrate reduces cardiac pulsatile load by diminishing the amplitude of wave reflections arriving back in the aorta during systole yet has no effect on aortic compliance or arteriolar resistance. This study demonstrates a method of evaluating the effect of vasoactive drugs on cardiac pulsatile load.

Adult↗

PubMed1991

Glyceryl trinitrate increases platelet cyclic GMP after metabolism in fibroblasts.

Glyceryl trinitrate had no direct effect on cyclic GMP levels in platelets. However, in the presence of fibroblasts (RFL-6 cells), glyceryl trinitrate increased platelet cyclic GMP up to 7.8 fold (11.5 fold in the presence of superoxide dismutase). Fibroblasts alone had no effect. Endothelial cells alone increased platelet cyclic GMP up to 4.1 fold (9.6 fold in the presence of superoxide dismutase), but glyceryl trinitrate had no additional effect. Thus fibroblasts, but not endothelial cells, metabolize glyceryl trinitrate to a nitric oxide-like material that stimulates platelet soluble guanylyl cyclase.

Animals↗

PubMed1999

Glyceryl trinitrate and ritodrine in tocolysis: an international multicenter randomized study. GTN Preterm Labour Investigation Group.

OBJECTIVE: To compare the efficacy of transdermal glyceryl trinitrate and intravenous (IV) ritodrine as tocolytics. METHODS: Two hundred forty-five women with preterm labor and intact membranes between 24 and 36 weeks' gestation were randomized to transdermal glyceryl trinitrate or intravenous ritodrine. Treatment was continued until contractions stopped or a maximum of 7 days. Glyceryl trinitrate was administered as a 10- or 20-mg transdermal patch. Intravenous ritodrine was administered according to nationally available guidelines. The primary outcome was prolongation of gestation expressed as a percentage of the time from entry to 37 weeks. Secondary outcomes were proportion of women who delivered the same day, next day, or within 7 and 14 days of entry, and by 32, 34, and 37 weeks. Analysis was by intention to treat. RESULTS: Twelve women (5%) were lost to follow-up. Glyceryl trinitrate and ritodrine prolonged gestation by 74% of time to 37 weeks (difference glyceryl trinitrate-ritodrine 0%; 95% confidence interval (CI) -10%, +10%). There was no significant difference in the proportion of women receiving glyceryl trinitrate or ritodrine who delivered within the specified days from study entry or weeks of gestation; however, 42 women who received glyceryl trinitrate and 58 women who received ritodrine delivered by 37 weeks (difference -11%; 95% CI -24%, +2%). No serious maternal side effects were reported for ritodrine or glyceryl trinitrate. CONCLUSION: We found no overall difference between glyceryl trinitrate and ritodrine in the acute tocolysis of preterm labor but a suggested advantage of glyceryl trinitrate over ritodrine in reducing preterm delivery rate. The maternal side effect profile and treatment discontinuation rates were fewer for glyceryl trinitrate, suggesting it was a safer alternative to ritodrine.

Adolescent↗

PubMed1984

Potential deleterious haemodynamic effects of glyceryl trinitrate on myocardial ischaemia in man.

The potential adverse effects of glyceryl trinitrate on myocardial ischaemia were studied using low and high dose infusions in 10 patients with coronary heart disease. Cardiac venous flow was measured by the thermodilution technique and blood was sampled for metabolic studies. Angina pectoris was provoked by atrial pacing before drug infusion and the same heart rate was regained with low and high doses of glyceryl trinitrate. Both doses reduced myocardial ischaemia equally. The low dose of glyceryl trinitrate reduced mean systolic aortic pressure from 145(23) to 128(23) mm Hg and the high dose further to 103(9) mm Hg. Myocardial oxygen uptake decreased owing to a combined reduction in preload and afterload with the low dose and was substantially more reduced with the high dose owing to a further afterload reduction. Transmural perfusion gradient did not change with the low dose of glyceryl trinitrate but fell significantly with the high dose. This fall in myocardial perfusion probably accounts for the lack of further reduction in ischaemia with the high dose. Thus the adverse effects of glyceryl trinitrate infusion are small and do not increase myocardial ischaemia.

Adult↗

PubMed2001

Topical 0.2 percent glyceryl trinitrate ointment has a short-lived effect on resting anal pressure.

PURPOSE: Glyceryl trinitrate ointment applied to the anal verge lowers anal resting pressure, but its duration of action is uncertain. This study investigated the effect and duration of action of 0.2 percent glyceryl trinitrate on anal resting pressure and hemodynamic parameters. METHODS: A total of 15 volunteers, 9 male, with a median age of 30 (range, 20-71) years, underwent continuous static anal manometry using a solid state catheter for ten minutes before and two hours after applying 0.2 percent glyceryl trinitrate ointment to the anoderm with a gloved finger. Pulse and blood pressure were recorded every 15 minutes. RESULTS: A significant reduction in maximal anal resting pressure compared with preglyceryl trinitrate values was observed at 15, 30, 45, 60, and 90 minutes after application, but no significant difference thereafter. There was no significant change in pulse during the study. Systolic and diastolic blood pressures dropped significantly after application of glyceryl trinitrate, but had recovered and were not significantly different from original values after 90 minutes. A significant fall in blood pressure did not correlate with the onset or duration of side effects. CONCLUSIONS: Continuous static manometry (as opposed to interval measurements reported in previous studies) demonstrates that 0.2 percent glyceryl trinitrate ointment significantly lowers anal resting pressure, but only for 90 minutes. Twice daily application of topical 0.2 percent glyceryl trinitrate heals two-thirds of fissures after eight weeks, but its apparently short duration of action may indicate that more frequent application might heal more fissures, more rapidly.

Administration, Topical↗

PubMed2001

Comparison of topically applied 0.2% glyceryl trinitrate ointment, incision and excision in the treatment of perianal thrombosis.

BACKGROUND AND AIMS: Topically applied 0.2% glyceryl trinitrate ointment to the anal region, incision and excision were compared in the treatment of perianal thrombosis, in order to establish which method is the best in terms of pain relief, number of recurrences and the appearance of anal skin tags. PATIENTS AND METHODS: A total of 150 patients were randomly divided into three groups of 50, each group being treated by one of the above-mentioned methods. The results of the treatment were evaluated during the first 4 days, after one month and after one year. RESULTS: A statistically significant reduction of pain was achieved by excision if compared with incision or conservative treatment with glyceryl trinitrate (p<0.001), and by conservative treatment with glyceryl trinitrate if compared with incision (p<0.01 on the 4th day of follow-up. Comparison of patients treated by the three different methods did not reveal any significant difference between these methods after one month (p>0.05). After one year the number of recurrences was significantly reduced after excision if compared with incision (p<0.05) or conservative treatment with glyceryl trinitrate (p<0.05). The number of patients without symptoms was significantly greater after excision if compared with incision or conservative treatment with glyceryl trinitrate (p<0.001). The number of patients with anal skin tags was significantly reduced in patients treated by excision if compared with incision (p<0.001) or glyceryl trinitrate treatment (p<0.001). CONCLUSION: Excision is a significantly better method of treatment of perianal thrombosis than incision or topically applied 0.2% glyceryl trinitrate ointment.

Administration, Topical↗

PubMed1982

Topical glyceryl trinitrate as adjunctive treatment in Raynaud's disease.

The effects of topical glyceryl trinitrate in Raynaud's disease were compared with those of placebo in a double-blind, crossover trial in 17 patients with bilateral Raynaud's disease and an associated collagen disease, who were receiving oral sympatholytic agents at the maximum levels they could tolerate. 1% glyceryl trinitrate ointment or a placebo of lanolin was applied to one hand only for 6 weeks, then patients changed to the other preparation for 6 weeks. The results were evaluated every 2 weeks. The frequency of attacks, severity of attacks, and size of ulcers in the treated hand were significantly lower when the patients were using glyceryl trinitrate ointment than when they were using placebo. The treatment of Raynaud's disease may be improved by using topical glyceryl trinitrate ointment as an adjunct to a basic regimen of oral sympatholytic agents. Glyceryl trinitrate ointment may obviate the need for more aggressive treatment, such as intraarterial reserpine, in selected patients.

Administration, Topical↗

PubMed2001

Chemical colostomy irrigation with glyceryl trinitrate solution.

PURPOSE: Colostomy irrigation may improve patient quality of life, but is time consuming. This study tests the hypothesis that irrigation with glyceryl trinitrate solution, by inducing gastrointestinal smooth muscle relaxation, may accelerate expulsion of stool by passive emptying, thereby reducing irrigation time. METHODS: Fifteen colostomy irrigators(with more than 3 years' experience) performed washout with tap water compared with water containing 0.025 mg/kg glyceryl trinitrate. Fluid inflow time, total washout time, and hemodynamic changes occurring during glyceryl trinitrate irrigation were documented by an independent observer. Subjects recorded episodes of fecal leakage and overall satisfaction on a visual analog scale. Cramps, headaches, and whether or not a stoma bag was used were expressed as a percentage of number of irrigations. Comparison of fluid inflow time, total washout time, leakage, and satisfaction was by Wilcoxon's signed-rank test and headaches, cramps, and stoma bag use was by McNemar's test. Pulse rate (paired t-test), systolic and diastolic blood pressures (Wilcoxon's test) at 20 and 240 minutes after washout with glyceryl trinitrate solution were compared with baseline. RESULTS: Fifteen patients (9 female), with a mean age of 53 (31-73) years, provided 30 sessions (15 with water and 15 with glyceryl trinitrate). Medians (interquartile ranges) for water vs. glyceryl trinitrate were fluid inflow time 7 (4-10) vs. 4, (3-5; P = 0.001); total washout time 40 (30-55) vs. 21, (15-24; P < 0.001); leakage 0 (0-1) vs. 0, (0-0; P = 0.02), satisfaction 10 (8-10) vs. 10 (9-10; P = 0.31). The number (percentage) of stoma bags, cramps, and headaches with water vs. glyceryl trinitrate were 7 (47 percent) vs. 7 (47 percent), P = 1; 1 (7 percent) vs. 14 (93 percent), P < 0.001; and 0(0 percent) vs. 14 (93 percent), P < 0.001, respectively. Changes in pulse (increase) and systolic and diastolic blood pressures (decrease) from baseline were maximal at 20 minutes (P < 0.001, P = 0.001, and P = 0.002, respectively) and had returned to baseline by 240 minutes (P = 0.52, P = 0.08, and P = 1, respectively). CONCLUSION: Glyceryl trinitrate solution significantly reduces colostomy irrigation time compared with the generally recommended tap water. Patients suffer fewer leakages and are highly satisfied, but side effects are potential drawbacks. Other colonoplegic agent solutions should now be evaluated.

Adult↗

PubMed1997

Effect of glyceryl trinitrate on gastric accommodation and symptoms in functional dyspepsia.

The purpose of this study was to investigate whether sublingual glyceryl trinitrate influences the size of the proximal stomach and postprandial symptoms in patients with functional dyspepsia. Twenty patients with functional dyspepsia were included in a double-blind, placebo-controlled crossover study with sublingual glyceryl trinitrate. All patients were scanned twice on consecutive days, receiving either placebo or 0.5 mg glyceryl trinitrate randomly 5 min prior to ingestion of 500 ml meat soup. Total symptoms, pain, nausea, and bloating were scored on a visual analog scale before and after the meal. Standardized ultrasonograms were obtained 1, 10, and 20 min postprandially of the proximal and distal stomach. The proximal stomach was larger in the sagittal section at 1 min postcibally (26.5 +/- 3.9 vs 24.8 +/- 4.9 cm2, P = 0.036) and 10 min postprandially (22.0 +/- 5.1 vs 19.8 +/- 5.3 cm2, P = 0.009) after administration of glyceryl trinitrate compared with placebo, whereas a tendency was observed after 20 min (18.7 +/- 5.5 vs 17.3 +/- 5.7 cm2, P = 0.076). The corresponding changes in the frontal diameters were 8.3 +/- 1.1 vs 7.8 +/- 1.2 cm (P = 0.067) after 1 min, 7.2 +/- 0.9 vs 6.4 +/- 0.8 cm (P = 0.001) after 10 min, and 6.3 +/- 1.1 vs 5.6 +/- 1.2 cm (P = 0.016) after 20 min. The area of the distal stomach was not different (P > 0.31) in the two groups. After administration of glyceryl trinitrate, the patients reported less pain (P = 0.048) and nausea (P = 0.023) 5 min postprandially, but this effect was reduced 15 min later. Total symptom score was improved by glyceryl trinitrate treatment (P < 0.042). Sublingual glyceryl trinitrate improves accommodation of the proximal stomach to a meal and reduces postprandial symptoms in a group of patients with functional dyspepsia.

Administration, Sublingual↗

PubMed1985

Randomized crossover trial of isosorbide mononitrate (Elantan 20) and slow-release glyceryl trinitrate in the treatment of angina pectoris.

An open, randomized, comparative crossover clinical trial was carried out to compare the clinical efficacy of 20 mg isosorbide mononitrate 3-times daily and 6.4 mg sustained-release glyceryl trinitrate 3-times daily in the treatment of angina pectoris. Fifty patients entered the trial and 48 patients completed. Each treatment was given for 12 weeks followed by crossover to the alternative drug. Both treatments resulted in marked significant improvements relative to the pre-trial baseline, but isosorbide mononitrate was shown to be significantly (p less than 0.001) more efficacious than sustained-release glyceryl trinitrate in the reduction of the number of angina attacks and sub-lingual glyceryl trinitrate consumption. Angina frequency was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 33 (69%) of the patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 3 (6%) patients (p less than 0.001). Sub-lingual glyceryl trinitrate consumption was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 36 (75%) patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 5 (10%) patients. Examination of the effect of changing from isosorbide mononitrate to sustained-release glyceryl trinitrate therapy or vice versa confirmed the clinical superiority of isosorbide mononitrate. Physical exercise capacity was reported as improved in 20 (60%) patients with isosorbide mononitrate but in only 12 (25%) patients with sustained-release glyceryl trinitrate (p less than 0.02). Neither treatment showed any tendency for a reduction in effect during 12-weeks' continuous therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1987

Collateral function modified by glyceryl trinitrate and dipyridamole during coronary occlusion in conscious dogs.

The effects of glyceryl trinitrate and dipyridamole on induced ischaemia were studied in awake dogs during transient coronary occlusion before and after collateral development. Seventeen dogs were instrumented under sterile conditions with a miniature pressure gauge to measure left ventricular pressure, a cannula for aortic pressure, and pairs of piezoelectric crystals towards the subendocardium of the left ventricle for regional segment length measurements. A hydraulic cuff occluder and Doppler flow probe were placed around the left circumflex coronary artery. Collateral function was increased by repeated 2 min coronary occlusions at 32 min intervals for 2-9 days until regional wall motion returned to preocclusive values, despite the persistence of coronary occlusion. The effects of glyceryl trinitrate and dipyridamole were studied after the initial haemodynamic changes had subsided. Collateral function was quantified by integrating changes in end systolic length of the ischaemic area during coronary occlusion. Before collateral development the end systolic length area was 29.4(2.4) cm X s and was unchanged by glyceryl trinitrate or dipyridamole. After the development of collaterals the end systolic length area decreased from 4.1(1.1) to 2.2(1.0) cm X s (p less than 0.01) after glyceryl trinitrate and increased to 14.9(1.7) cm X s (p less than 0.01) after dipyridamole. Therefore, glyceryl trinitrate acted directly on collaterals and improved the induced ischaemia, whereas dipyridamole exaggerated the regional wall motion abnormality.

Animals↗

PubMedDate not supplied

Positive inotropic action of glyceryl trinitrate as observed in the blood-perfused papillary muscle preparation of the dog heart.

1. The effects of glyceryl trinitrate on the coronary vasculature and on the contractility of the ventricular myocardium were investigated by the use of papillary muscle preparations of the dog, and that on the sino-atrial node activity by the use of sino-atrial node preparations of the dog. The papillary muscle preparation was cross-circulated through the anterior septal artery and the sino-atrial node preparation through the sinus node artery from a donor dog. The papillary muscles were driven at a rate of 120 beats/min. Drugs were injected close-arterially. 2. Glyceryl trinitrate, in doses of 0-03-100 microgram, produced dose-related increases in blood flow and developed tension. An increase in developed tension caused by 100 microgram of glyceryl trinitrate amounted to about 24% of the basal developed tension. Large doses of glyceryl trinitrate (100-300 microgram) produced a negative inotropic effect after a positive one in some preparations. 3. The positive inotropic effect of glyceryl trinitrate was not modified by propranolol, excluding a possible participation of an adrenergic mechanism. 4. Glyceryl trinitrate in large doses failed to modify the positive inotropic effect of calcium chloride. 5. Glyceryl trinitrate in a wide range of doses (0-03-100 microgram) had virtually no effect on sino-atrial node activity.

Animals↗

PubMed1996

Heterogeneity of glyceryl trinitrate response in isolated bovine coronary arteries.

Factors determining heterogeneity of response to glyceryl trinitrate in coronary microvessels have been extensively documented in recent years, but determinants of heterogeneity between conduit and large resistance vessels are poorly understood. The current study has characterised heterogeneity to glyceryl trinitrate and other vasodilators in bovine isolated proximal (4.5 mm i.d.) and distal (0.5 mm i.d.) segments of left anterior descending artery. Compared with proximal segments, distal segments were less responsive to glyceryl trinitrate and sodium nitroprusside, equi-responsive to S-nitroso-N-acetylpenicillamine, and more responsive to isoprenaline. Heterogeneity to glyceryl trinitrate was unaffected by the presence of the thiols (cysteine or N-acetylcysteine, 100 microM). The results are interpreted as evidence that heterogeneity of vascular responsiveness to glyceryl trinitrate reflects impairment in the small artery of the cellular events which precede activation of the cyclic GMP pathway. An implication is that the impairment is not a consequence of limited thiol availability, and in this respect the cellular mechanism of heterogeneity differs from those proposed for the coronary microvasculature.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1984

Intravenous glyceryl trinitrate (nitroglycerin). A review of its pharmacological properties and therapeutic efficacy.

The recently introduced preparation of intravenous glyceryl trinitrate (nitroglycerin) provides a rapid steady therapeutic blood concentration of nitrates during continuous infusion. Intravenous glyceryl trinitrate causes venodilation at low doses, but at higher doses dilates both arteries and veins. Its principal haemodynamic effects at therapeutic dosages include a decrease in blood pressure in preload (left ventricular filling pressure) and in determinants of afterload, and a decrease in myocardial oxygen demand. Human pharmacokinetic data are few and difficult to interpret due to wide interstudy and interindividual variation. There is no close correlation between infusion rate, blood concentration and haemodynamic effects. The nature of the patient population treated with intravenous glyceryl trinitrate has largely precluded the use of a placebo, but in open trials the drug has been used successfully in the treatment of unstable angina, left ventricular failure accompanying acute myocardial infarction and in the control of hypertension associated with cardiac surgery at dosages titrated to achieve a specific end-point. Favourable haemodynamic responses have been achieved in very short term studies in congestive heart failure, and preliminary studies suggest that institution of intravenous glyceryl trinitrate early after acute myocardial infarction may limit ischaemic damage. However, use of the drug in acute myocardial infarction remains controversial. Intravenous glyceryl trinitrate is generally well tolerated, although hypotension and headache occur occasionally, and sinus tachycardia and bradycardia less frequently. Careful titration of dosage is required (beginning at 5 micrograms/min), and if the infusion sets contain polyvinylchloride, the delivered dose is lower than that calculated, because of adsorption of glyceryl trinitrate onto the plastic tubing.

Acute Disease↗

PubMed1999

Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo-controlled trial and long-term follow-up.

PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to test the effect of intra-anal glyceryl trinitrate ointment in patients with chronic anal fissures that would normally have been treated by sphincterotomy. Long-term follow-up was then performed to assess fissure healing. METHODS: Patients with chronic anal fissures were randomly assigned to 0.2 percent topical glyceryl trinitrate ointment or placebo. Anal manometry was performed before treatment, one week later, and 48 hours after treatment ceased at four weeks. Fissure healing was assessed by an observer blinded to the treatment arm. Pain was recorded on a linear analog scale. At the completion of the trial, treatment was continued with glyceryl trinitrate until fissure healing was obtained or lateral sphincterotomy was performed if required for ongoing pain. A long-term follow-up assessment was made at a mean of 29 (range, 25-33) months. RESULTS: There was a significant reduction in anal resting pressure at Week 1 with glyceryl trinitrate (P = 0.001) but not placebo, and at Week 4 there was a significant reduction in pain score with glyceryl trinitrate (P = 0.001) and placebo (P = 0.01) and a significant reduction in fissure grade with glyceryl trinitrate (P = 0.0001) and placebo (P = 0.02). Forty-six percent of fissures healed with glyceryl trinitrate and 16 percent healed with placebo (P = 0.001). At long-term follow-up in 40 of 43 patients, 14 patients (35 percent) had undergone lateral sphincterotomy, and in the remainder who were treated with glyceryl trinitrate there was a significant reduction in pain score (P = 0.0002). Seventeen patients attended for repeat manometry and fissures were healed with glyceryl trinitrate in ten (59 percent) cases. High internal sphincter pressures persisted at long-term follow-up in patients successfully treated with glyceryl trinitrate, indicating that the sphincter is the cause rather than effect of anal fissure. CONCLUSION: Topical glyceryl trinitrate produces a successful internal sphincterotomy, which resulted in long-term healing of 59 percent of chronic anal fissures and significant improvement in pain. Internal sphincter spasm is the cause of chronic anal fissure.

Administration, Topical↗