Udho Thadani - Academia.edu (original) (raw)
Papers by Udho Thadani
The American Journal of Cardiology, 1986
Journal of the American College of Cardiology, 1998
induced atnal Cbrtllawn (AF) a(~mdmcharge. Both groups were comparabte concemmg age. pend6f. heef... more induced atnal Cbrtllawn (AF) a(~mdmcharge. Both groups were comparabte concemmg age. pend6f. heef! dlaease. LVEF. dmwwon ol tha len amum andprevmuaeplsodesolAF. Rrlsum:aeetable CMchMn. We conclude Ihat tha m@ementatmn al an 6cw WI sub peaorslcanIn~deRbn~~vsclwda~lrfICD~10~ nm 6hOch Impefhlnce and lim arsrgv f6aulmmQntl (Qf 6mal c6rdlovenm.
Drugs for Heart Disease, 1987
Journal of the American College of Cardiology, 1998
Retrospective examination of acute gastrointestinal (GI) lethality in our rat bone marrow transpl... more Retrospective examination of acute gastrointestinal (GI) lethality in our rat bone marrow transplantation studies showed indication of a protective effect, with a dose modifying factor (DMF) of 1.06 (95% confidence interval: 0.99-1.12). A randomized study, using the same experimental design, was conducted specifically to look for GI protection. Animals were randomized into captopril or non-drug arms and irradiated in a 6-fraction total body irradiation regimen, followed by bone marrow transplantation. Rats received captopril in the drinking water at 500 mg/l (70 mg/kg/day), starting 9 days prior to irradiation and continuing throughout the experiment. The 50% lethal dose at 6 days was 20.8 (20.4-21.7) Gy in the non-drug arm and 20.6 (20.3-20.9) Gy in the captopril arm, for a DMF of 0.99 (0.94-1.04). If the randomized and historical studies are combined the DMF is 1.00 (0.93-1.05). We are unable to find any evidence that the angiotensin converting enzyme (ACE) inhibitor captopril provides protection from acute GI injury in this model. Clearly, it should not be assumed that captopril will modulate radiation reactions in all tissues.
Evidence-based Medicine, Nov 4, 2017
Commentary on: Ledwoch J, Fuernau G, Desch S, et al . Drug-eluting stents versus bare-metal sten... more Commentary on: Ledwoch J, Fuernau G, Desch S, et al . Drug-eluting stents versus bare-metal stents in acute myocardial infarction with cardiogenic shock. Heart 2017;103:1177–84. Early revascularisation improves acute and long-term outcomes of patients presenting with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). However, which type of stent to use for revascularisation remains controversial. Earlier small single-centre non-randomised study and registry data concluded that a drug-eluting stent (DES) is superior to a bare metal stent (BMS) as it improved clinical outcomes in these patients.1 2 Current European Society Guidelines recommend the use of DES, while American Society guidelines do not. This study examined the impact of BMS versus DES use on clinical outcomes in patients who had participated in the previously reported the Intra-aortic Balloon Pump (IABP) in Cardiogenic Shock II Trial (IABP-SHOCK II) which showed …
Postgraduate Medicine, Apr 1, 1992
Continuous therapy with nitrates rapidly produces tolerance along with loss or diminution of circ... more Continuous therapy with nitrates rapidly produces tolerance along with loss or diminution of circulatory, antianginal, and anti-ischemic effects. Development of tolerance can be avoided by various approaches. In patients with stable angina, intermittent use of nitrates with long nitrate-free intervals, use of transdermal nitroglycerin during the day or oral isosorbide dinitrate or isosorbide-5-mononitrate twice daily in the morning and early afternoon, and intermittent use of nitrates in combination with another class of antianginal agent are appropriate. In patients with unstable angina, continuous therapy with intravenous nitroglycerin is recommended during the acute phase of angina. Despite development of partial tolerance, oral isosorbide dinitrate, 30 to 60 mg four times a day, plus hydralazine may be useful for patients with congestive heart failure who cannot tolerate angiotensin-converting enzyme inhibitors. Concomitant use of sulfhydryl donors or angiotensin-converting enzyme inhibitors, agents that might theoretically prevent nitrate tolerance, is not recommended. Data on these agents are conflicting, and added costs and adverse effects are likely to preclude their use in the future.
Die Wirksamkeit oral verabreichter Nitrate bei der Behandlung der Angina pectoris ist angezweifel... more Die Wirksamkeit oral verabreichter Nitrate bei der Behandlung der Angina pectoris ist angezweifelt worden. Nach anfanglicher Begeisterung fur diese „Langzeit-Nitrate“ wurde im Tierversuch nachgewiesen, das Nitrate einem erheblichen First-pass-Metabolismus in der Leber unterliegen und das die systemischen Plasmakonzentrationen der Substanzen niedrig sind [9] . Dennoch hatte die Erfahrung, das orales Isosorbiddinitrat (ISDN) beim Menschen anhaltende hamodynamische Wirkungen hat [5] und die Belastungstoleranz bei Angina pectoris erhoht [6], die zunehmende Verwendung oraler Nitrate zur Folge. Es besteht jedoch noch immer eine Unsicherheit bezuglich ihrer Langzeitanwendung, da sich nachgewiesenermasen bald eine Toleranz gegenuber den Kreislaufwirkungen der Nitrate entwickelt [7, 11]. Allgemein wird angenommen, das eine solche Toleranz keine klinische Bedeutung hat, doch angesichts der Tatsache, das die gunstigen Wirkungen der Nitrate bei Angina pectoris zumindest teilweise mit ihrer systemischen Gefaswirkung zusammenhangen, konnte die Kreislauftoleranz moglicherweise mit einer Veranderung der antianginosen Wirkung einhergehen. Die vorliegende Studie wurde zwecks Prufung der Kreislauf- und klinischen Wirkungen einer akuten und einer Langzeittherapie mit oralem ISDN unternommen sowie um festzustellen, wie schnell sich eine Kreislauftoleranz gegenuber ISDN bzw. eine Kreuztoleranz gegenuber sublingualem Nitroglycerin (NTG) entwickelt. Uber Teile dieser Studie wurde einzelnen anderweitig berichtet [12–14].
PubMed, Nov 27, 2001
Nisoldipine, a dihydropyridine calcium antagonist, has greater vascular selectivity than other ca... more Nisoldipine, a dihydropyridine calcium antagonist, has greater vascular selectivity than other calcium channel antagonists and does not depress the intact myocardium in vivo. It should be taken on an empty stomach. Both rapid-release and coat-core formulations are available for clinical use, but only the coat-core formulation extends antihypertensive, antiischemic, and antianginal effects throughout the dosing interval when given once daily. The coat-core formulation in daily doses of 10 to 40 mg does not cause the proischemic effects reported with the rapid-release formulation. When given as monotherapy, the coat-core formulation is highly effective in lowering blood pressure to a similar extent as other long-acting calcium channel blockers, diuretics, beta-blockers, or angiotensin-converting enzyme (ACE) inhibitors. The antihypertensive effects are potentiated when the coat-core formulation of nisoldipine is given in combination with lisinopril. In patients with stable angina pectoris nisoldipine coat-core increases exercise duration, reduces anginal frequency and myocardial ischemia, and is effective as monotherapy or in combination with a beta-blockers. In monotherapy the drug is as effective as other long-acting calcium channel blockers or a beta-blocker. The effects of nisoldipine coat-core in patients with heart failure are unclear at present.
PubMed, Mar 1, 1994
As a result of recent advances in our understanding of the role of nitric oxide and endothelial-d... more As a result of recent advances in our understanding of the role of nitric oxide and endothelial-derived relaxing factor (EDRF) in vascular control, physicians now have the potential to overcome the loss of EDRF effect by administering nitrates. Nitrates are converted to nitric oxide, resulting in vasodilator effects that improve the myocardial oxygen supply-demand imbalance responsible for myocardial ischemia. This discovery has resulted in a renewed interest in the nitrates for the treatment of ischemic syndromes, particularly chronic stable angina pectoris. Over the past 2 years, an important new formulation of nitrate has become available--isosorbide-5-mononitrate. Three different mononitrate formulations are available in the United States: Ismo tablets in December 1992; followed over a year later by Monoket tablets, available since June 1993; and Imdur extended-release tablets, available since August 1993. Although the mononitrates share the same generic name, they are not similar in regard to their formulations, which suggests the need for future studies designed to explore any clinical differences.
![Research paper thumbnail of Oxprenolol in angina pectoris [proceedings]](https://attachments.academia-assets.com/116099563/thumbnails/1.jpg)
](PubMed, Nov 1, 1976
Relation of heart rate and systolic blood pressure to the onset of pain in angina pectoris.
PubMed, 1985
Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate and is nearly 100% bioav... more Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate and is nearly 100% bioavailable after oral administration. Following administration of single oral doses of 10 to 50 mg, isosorbide-5-mononitrate exerts beneficial hemodynamic, anti-ischemic and anti-anginal effects within 30 to 45 minutes and the effects persist for several hours. During sustained therapy with conventional formulation, persistent anti-ischemic and anti-anginal effects have been reported when the drug is given in a dose of 20 mg two or three times a day. However, tolerance to anti-anginal and anti-ischemic effects develops rapidly if used in higher doses of 50 mg three times a day. Tolerance to anti-anginal effects within 20 hours of administration of a single oral dose of 100 mg, slow release isosorbide-5-mononitrate has been reported. Further, no improvement in exercise tolerance or ST segment depression could be documented at 4, 20 or 24 hours after therapy for one week with either 50 or 100 mg slow release isosorbide-5-mononitrate once a day. From the available reports, the most effective way to prescribe isosorbide-5-mononitrate for angina pectoris appears to be the conventional formulation in a dose of 20 mg two or three times a day.
PubMed, Jul 1, 1975
1. In healthy subjects the plasma concentration of unchanged drug, heart rate response to exceris... more 1. In healthy subjects the plasma concentration of unchanged drug, heart rate response to excerise and attenuation of isoprenaline tachycardia were maximal at one hour after ingestion of a range of doses of propranolol, oxprenolol, practolol, tolamolol, atenolol and metoprolol. 2. There was a within-drug relationship between plasma concentration of unchanged drug and the attenuation of exercise and iosprenaline tachycardia. There was no similar between-drug relationship. 3. There was a similar exponential relationship between oral dose and reduction of exercise tachycardia for all six drugs. 4. The linear relationship between oral dose and antagonism of infused isoprenaline was significantly greater for oxprenolol and propranolol than for the other four drugs. 5. "Cardioselective" activity was the only ancillary pharmacological property which differentiated the activity of these drugs in normal subjects.
The efficacy of the oral nitrates in the therapy for angina pectoris has been questioned. After i... more The efficacy of the oral nitrates in the therapy for angina pectoris has been questioned. After initial enthusiasm for these “long-acting nitrates,” it was demonstrated in animals that the nitrates underwent extensive first-pass hepatic metabolism and that systemic drug levels were low [9]. However, demonstrations in man that oral isosorbide dinitrate (ISDN) prolonged hemodynamic effects [5] and improved exercise tolerance in angina pectoris [6] have been followed by increasing use of the oral nitrates. However, uncertainty persists regarding long-term use, as tolerance has been shown to develop quickly to the circulatory effects of the nitrates [7, 11]. It is generally assumed that such tolerance is not clinically relevant, but as the beneficial effects of the nitrates in angina pectoris are, at least in part, related to their systemic vascular effects, circulatory tolerance might be expected to be associated with changes in antianginal effects. This study was undertaken to study the circulatory and clinical effects of acute and sustained oral therapy with ISDN and to study the rapidity with which circulatory tolerance to ISDN and cross-tolerance to sublingual glyceryl trinitrate (GTN) develops. The details of portions of this study have been reported elsewhere [12–14].
Catheterization and Cardiovascular Diagnosis, 1978
A submltral annular left ventricular aneurysm In a Nigerian patient Is described. The features co... more A submltral annular left ventricular aneurysm In a Nigerian patient Is described. The features consisted of an abnormal bulge on the left heart border with curvilinear calcification, an echo-free space behind the posterior left ventricular wall, and unusual anglographlc appearance of the left circumflex coronary artery. The diagnosis was confirmed by pulmonary artery and left ventricular angiography. The patient underwent open heart surgery and a multlloculated submltral annular left ventricular aneurysm which was adherent to the pericardium was successfully resected.
PubMed, Sep 1, 1979
Hemodynamic profiles at rest and during bicycle exercise are described in 50 normal male subjects... more Hemodynamic profiles at rest and during bicycle exercise are described in 50 normal male subjects. In nine of these, the hemodynamics at rest and during exercise in the supine position have been compared to those in the sitting position. In the supine position, the observed and derived hemodynamic parameters at rest and during exercise (mean +/- standard deviation) were: heart rate 77 +/- 11 vs 127 +/- 17 beats . min-1, brachial arterial mean pressure, 12.4 +/- 1.2 vs 15.0 +/- 1.6 kPa (93 +/- 9 vs 113 +/- 12 mmHg), pulmonary arterial mean pressure 1.9 +/- 0.5 vs 3.2 +/- 0.8 kPa (14 +/- 4 vs 24 +/- 6 mmHg), left ventricular end-diastolic pressure 1.2 +/- 0.4 vs 1.7 +/- 0.7 kPa (9 +/- 3 vs 13 +/- 5 mmHg), cardiac output 6.3 +/- 1.5 vs 12.0 +/- 3.0 1 . min-1, stroke volume 88 +/- 22 vs 95 +/- 23 cm3, and left ventricular stroke work 0.93 +/- 0.27 vs 1.26 +/- 0.34 J . beats-1. Comparison of hemodynamic data in the supine and sitting position showed that pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, cardiac output, stroke volume, and left ventricular stroke work were lower and heart rate higher in the sitting position, while brachial arterial and pulmonary arterial mean pressures were similar in the two positions. During exercise, the absolute values of pulmonary capillary wedge pressure, left ventricular end-diastolic pressure and stroke volume were lower and heart rate higher in the sitting position, while cardiac output and left ventricular stroke work were similar in the two positions. Comparison of changes from rest to exercise in the supine and sitting postures revealed similar increases in heart rate, pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, cardiac output, and stroke volume in the two positions.
PubMed, Jun 1, 1984
Nitrates are effective in the management of exertional angina pectoris primarily due to their per... more Nitrates are effective in the management of exertional angina pectoris primarily due to their peripheral effects i.e. venodilation and arterial dilation, and thereby reduction in myocardial oxygen demand. These drugs also improve collateral blood flow in ischemic areas and in some patients may increase coronary blood flow by modifying tonus in the conductive or conduit coronary vessels. Sublingual nitroglycerin is the most effective antianginal agent but its prophylactic use is limited by its short duration of action. Until recently, the efficacy of long-acting oral nitrates was seriously questioned. However, recent data suggests that when given acutely in adequate doses, oral nitrates, transcutaneous and buccal preparations of nitroglycerin all exert prolonged hemodynamic and antianginal effects. Development of tolerance to the circulatory and antianginal effects during chronic therapy, however, remains a concern. Published literature suggests that tolerance to the circulatory effects and to headaches develops rapidly during sustained therapy with long-acting nitrates. However, reports regarding the development of tolerance to the antianginal effects and reduction of ST segment depression remain conflicting. Partial tolerance to the antianginal effects has been well-documented during chronic therapy with isosorbide dinitrate. Duration of improvement in exercise tolerance during four times daily therapy with isosorbide dinitrate has been shown to be shortened compared to prolonged effects following acute therapy. Recent data suggests that given in high doses, beneficial effects of ST segment depression during exercise may also diminish during chronic therapy with long acting nitrates. Tolerance to antianginal and circulatory effects can be reversed by withholding long-acting nitrates for 24 to 36 hours. Furthermore, initial studies suggest that tolerance to antianginal effects during sustained therapy can be avoided by giving smaller but effective doses of ISDN (20 to 40 mg) twice a day rather than prescribing larger doses more frequently.
The American Journal of Cardiology, 1986
Journal of the American College of Cardiology, 1998
induced atnal Cbrtllawn (AF) a(~mdmcharge. Both groups were comparabte concemmg age. pend6f. heef... more induced atnal Cbrtllawn (AF) a(~mdmcharge. Both groups were comparabte concemmg age. pend6f. heef! dlaease. LVEF. dmwwon ol tha len amum andprevmuaeplsodesolAF. Rrlsum:aeetable CMchMn. We conclude Ihat tha m@ementatmn al an 6cw WI sub peaorslcanIn~deRbn~~vsclwda~lrfICD~10~ nm 6hOch Impefhlnce and lim arsrgv f6aulmmQntl (Qf 6mal c6rdlovenm.
Drugs for Heart Disease, 1987
Journal of the American College of Cardiology, 1998
Retrospective examination of acute gastrointestinal (GI) lethality in our rat bone marrow transpl... more Retrospective examination of acute gastrointestinal (GI) lethality in our rat bone marrow transplantation studies showed indication of a protective effect, with a dose modifying factor (DMF) of 1.06 (95% confidence interval: 0.99-1.12). A randomized study, using the same experimental design, was conducted specifically to look for GI protection. Animals were randomized into captopril or non-drug arms and irradiated in a 6-fraction total body irradiation regimen, followed by bone marrow transplantation. Rats received captopril in the drinking water at 500 mg/l (70 mg/kg/day), starting 9 days prior to irradiation and continuing throughout the experiment. The 50% lethal dose at 6 days was 20.8 (20.4-21.7) Gy in the non-drug arm and 20.6 (20.3-20.9) Gy in the captopril arm, for a DMF of 0.99 (0.94-1.04). If the randomized and historical studies are combined the DMF is 1.00 (0.93-1.05). We are unable to find any evidence that the angiotensin converting enzyme (ACE) inhibitor captopril provides protection from acute GI injury in this model. Clearly, it should not be assumed that captopril will modulate radiation reactions in all tissues.
Evidence-based Medicine, Nov 4, 2017
Commentary on: Ledwoch J, Fuernau G, Desch S, et al . Drug-eluting stents versus bare-metal sten... more Commentary on: Ledwoch J, Fuernau G, Desch S, et al . Drug-eluting stents versus bare-metal stents in acute myocardial infarction with cardiogenic shock. Heart 2017;103:1177–84. Early revascularisation improves acute and long-term outcomes of patients presenting with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). However, which type of stent to use for revascularisation remains controversial. Earlier small single-centre non-randomised study and registry data concluded that a drug-eluting stent (DES) is superior to a bare metal stent (BMS) as it improved clinical outcomes in these patients.1 2 Current European Society Guidelines recommend the use of DES, while American Society guidelines do not. This study examined the impact of BMS versus DES use on clinical outcomes in patients who had participated in the previously reported the Intra-aortic Balloon Pump (IABP) in Cardiogenic Shock II Trial (IABP-SHOCK II) which showed …
Postgraduate Medicine, Apr 1, 1992
Continuous therapy with nitrates rapidly produces tolerance along with loss or diminution of circ... more Continuous therapy with nitrates rapidly produces tolerance along with loss or diminution of circulatory, antianginal, and anti-ischemic effects. Development of tolerance can be avoided by various approaches. In patients with stable angina, intermittent use of nitrates with long nitrate-free intervals, use of transdermal nitroglycerin during the day or oral isosorbide dinitrate or isosorbide-5-mononitrate twice daily in the morning and early afternoon, and intermittent use of nitrates in combination with another class of antianginal agent are appropriate. In patients with unstable angina, continuous therapy with intravenous nitroglycerin is recommended during the acute phase of angina. Despite development of partial tolerance, oral isosorbide dinitrate, 30 to 60 mg four times a day, plus hydralazine may be useful for patients with congestive heart failure who cannot tolerate angiotensin-converting enzyme inhibitors. Concomitant use of sulfhydryl donors or angiotensin-converting enzyme inhibitors, agents that might theoretically prevent nitrate tolerance, is not recommended. Data on these agents are conflicting, and added costs and adverse effects are likely to preclude their use in the future.
Die Wirksamkeit oral verabreichter Nitrate bei der Behandlung der Angina pectoris ist angezweifel... more Die Wirksamkeit oral verabreichter Nitrate bei der Behandlung der Angina pectoris ist angezweifelt worden. Nach anfanglicher Begeisterung fur diese „Langzeit-Nitrate“ wurde im Tierversuch nachgewiesen, das Nitrate einem erheblichen First-pass-Metabolismus in der Leber unterliegen und das die systemischen Plasmakonzentrationen der Substanzen niedrig sind [9] . Dennoch hatte die Erfahrung, das orales Isosorbiddinitrat (ISDN) beim Menschen anhaltende hamodynamische Wirkungen hat [5] und die Belastungstoleranz bei Angina pectoris erhoht [6], die zunehmende Verwendung oraler Nitrate zur Folge. Es besteht jedoch noch immer eine Unsicherheit bezuglich ihrer Langzeitanwendung, da sich nachgewiesenermasen bald eine Toleranz gegenuber den Kreislaufwirkungen der Nitrate entwickelt [7, 11]. Allgemein wird angenommen, das eine solche Toleranz keine klinische Bedeutung hat, doch angesichts der Tatsache, das die gunstigen Wirkungen der Nitrate bei Angina pectoris zumindest teilweise mit ihrer systemischen Gefaswirkung zusammenhangen, konnte die Kreislauftoleranz moglicherweise mit einer Veranderung der antianginosen Wirkung einhergehen. Die vorliegende Studie wurde zwecks Prufung der Kreislauf- und klinischen Wirkungen einer akuten und einer Langzeittherapie mit oralem ISDN unternommen sowie um festzustellen, wie schnell sich eine Kreislauftoleranz gegenuber ISDN bzw. eine Kreuztoleranz gegenuber sublingualem Nitroglycerin (NTG) entwickelt. Uber Teile dieser Studie wurde einzelnen anderweitig berichtet [12–14].
PubMed, Nov 27, 2001
Nisoldipine, a dihydropyridine calcium antagonist, has greater vascular selectivity than other ca... more Nisoldipine, a dihydropyridine calcium antagonist, has greater vascular selectivity than other calcium channel antagonists and does not depress the intact myocardium in vivo. It should be taken on an empty stomach. Both rapid-release and coat-core formulations are available for clinical use, but only the coat-core formulation extends antihypertensive, antiischemic, and antianginal effects throughout the dosing interval when given once daily. The coat-core formulation in daily doses of 10 to 40 mg does not cause the proischemic effects reported with the rapid-release formulation. When given as monotherapy, the coat-core formulation is highly effective in lowering blood pressure to a similar extent as other long-acting calcium channel blockers, diuretics, beta-blockers, or angiotensin-converting enzyme (ACE) inhibitors. The antihypertensive effects are potentiated when the coat-core formulation of nisoldipine is given in combination with lisinopril. In patients with stable angina pectoris nisoldipine coat-core increases exercise duration, reduces anginal frequency and myocardial ischemia, and is effective as monotherapy or in combination with a beta-blockers. In monotherapy the drug is as effective as other long-acting calcium channel blockers or a beta-blocker. The effects of nisoldipine coat-core in patients with heart failure are unclear at present.
PubMed, Mar 1, 1994
As a result of recent advances in our understanding of the role of nitric oxide and endothelial-d... more As a result of recent advances in our understanding of the role of nitric oxide and endothelial-derived relaxing factor (EDRF) in vascular control, physicians now have the potential to overcome the loss of EDRF effect by administering nitrates. Nitrates are converted to nitric oxide, resulting in vasodilator effects that improve the myocardial oxygen supply-demand imbalance responsible for myocardial ischemia. This discovery has resulted in a renewed interest in the nitrates for the treatment of ischemic syndromes, particularly chronic stable angina pectoris. Over the past 2 years, an important new formulation of nitrate has become available--isosorbide-5-mononitrate. Three different mononitrate formulations are available in the United States: Ismo tablets in December 1992; followed over a year later by Monoket tablets, available since June 1993; and Imdur extended-release tablets, available since August 1993. Although the mononitrates share the same generic name, they are not similar in regard to their formulations, which suggests the need for future studies designed to explore any clinical differences.
PubMed, Nov 1, 1976
Relation of heart rate and systolic blood pressure to the onset of pain in angina pectoris.
PubMed, 1985
Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate and is nearly 100% bioav... more Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate and is nearly 100% bioavailable after oral administration. Following administration of single oral doses of 10 to 50 mg, isosorbide-5-mononitrate exerts beneficial hemodynamic, anti-ischemic and anti-anginal effects within 30 to 45 minutes and the effects persist for several hours. During sustained therapy with conventional formulation, persistent anti-ischemic and anti-anginal effects have been reported when the drug is given in a dose of 20 mg two or three times a day. However, tolerance to anti-anginal and anti-ischemic effects develops rapidly if used in higher doses of 50 mg three times a day. Tolerance to anti-anginal effects within 20 hours of administration of a single oral dose of 100 mg, slow release isosorbide-5-mononitrate has been reported. Further, no improvement in exercise tolerance or ST segment depression could be documented at 4, 20 or 24 hours after therapy for one week with either 50 or 100 mg slow release isosorbide-5-mononitrate once a day. From the available reports, the most effective way to prescribe isosorbide-5-mononitrate for angina pectoris appears to be the conventional formulation in a dose of 20 mg two or three times a day.
PubMed, Jul 1, 1975
1. In healthy subjects the plasma concentration of unchanged drug, heart rate response to exceris... more 1. In healthy subjects the plasma concentration of unchanged drug, heart rate response to excerise and attenuation of isoprenaline tachycardia were maximal at one hour after ingestion of a range of doses of propranolol, oxprenolol, practolol, tolamolol, atenolol and metoprolol. 2. There was a within-drug relationship between plasma concentration of unchanged drug and the attenuation of exercise and iosprenaline tachycardia. There was no similar between-drug relationship. 3. There was a similar exponential relationship between oral dose and reduction of exercise tachycardia for all six drugs. 4. The linear relationship between oral dose and antagonism of infused isoprenaline was significantly greater for oxprenolol and propranolol than for the other four drugs. 5. "Cardioselective" activity was the only ancillary pharmacological property which differentiated the activity of these drugs in normal subjects.
The efficacy of the oral nitrates in the therapy for angina pectoris has been questioned. After i... more The efficacy of the oral nitrates in the therapy for angina pectoris has been questioned. After initial enthusiasm for these “long-acting nitrates,” it was demonstrated in animals that the nitrates underwent extensive first-pass hepatic metabolism and that systemic drug levels were low [9]. However, demonstrations in man that oral isosorbide dinitrate (ISDN) prolonged hemodynamic effects [5] and improved exercise tolerance in angina pectoris [6] have been followed by increasing use of the oral nitrates. However, uncertainty persists regarding long-term use, as tolerance has been shown to develop quickly to the circulatory effects of the nitrates [7, 11]. It is generally assumed that such tolerance is not clinically relevant, but as the beneficial effects of the nitrates in angina pectoris are, at least in part, related to their systemic vascular effects, circulatory tolerance might be expected to be associated with changes in antianginal effects. This study was undertaken to study the circulatory and clinical effects of acute and sustained oral therapy with ISDN and to study the rapidity with which circulatory tolerance to ISDN and cross-tolerance to sublingual glyceryl trinitrate (GTN) develops. The details of portions of this study have been reported elsewhere [12–14].
Catheterization and Cardiovascular Diagnosis, 1978
A submltral annular left ventricular aneurysm In a Nigerian patient Is described. The features co... more A submltral annular left ventricular aneurysm In a Nigerian patient Is described. The features consisted of an abnormal bulge on the left heart border with curvilinear calcification, an echo-free space behind the posterior left ventricular wall, and unusual anglographlc appearance of the left circumflex coronary artery. The diagnosis was confirmed by pulmonary artery and left ventricular angiography. The patient underwent open heart surgery and a multlloculated submltral annular left ventricular aneurysm which was adherent to the pericardium was successfully resected.
PubMed, Sep 1, 1979
Hemodynamic profiles at rest and during bicycle exercise are described in 50 normal male subjects... more Hemodynamic profiles at rest and during bicycle exercise are described in 50 normal male subjects. In nine of these, the hemodynamics at rest and during exercise in the supine position have been compared to those in the sitting position. In the supine position, the observed and derived hemodynamic parameters at rest and during exercise (mean +/- standard deviation) were: heart rate 77 +/- 11 vs 127 +/- 17 beats . min-1, brachial arterial mean pressure, 12.4 +/- 1.2 vs 15.0 +/- 1.6 kPa (93 +/- 9 vs 113 +/- 12 mmHg), pulmonary arterial mean pressure 1.9 +/- 0.5 vs 3.2 +/- 0.8 kPa (14 +/- 4 vs 24 +/- 6 mmHg), left ventricular end-diastolic pressure 1.2 +/- 0.4 vs 1.7 +/- 0.7 kPa (9 +/- 3 vs 13 +/- 5 mmHg), cardiac output 6.3 +/- 1.5 vs 12.0 +/- 3.0 1 . min-1, stroke volume 88 +/- 22 vs 95 +/- 23 cm3, and left ventricular stroke work 0.93 +/- 0.27 vs 1.26 +/- 0.34 J . beats-1. Comparison of hemodynamic data in the supine and sitting position showed that pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, cardiac output, stroke volume, and left ventricular stroke work were lower and heart rate higher in the sitting position, while brachial arterial and pulmonary arterial mean pressures were similar in the two positions. During exercise, the absolute values of pulmonary capillary wedge pressure, left ventricular end-diastolic pressure and stroke volume were lower and heart rate higher in the sitting position, while cardiac output and left ventricular stroke work were similar in the two positions. Comparison of changes from rest to exercise in the supine and sitting postures revealed similar increases in heart rate, pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, cardiac output, and stroke volume in the two positions.
PubMed, Jun 1, 1984
Nitrates are effective in the management of exertional angina pectoris primarily due to their per... more Nitrates are effective in the management of exertional angina pectoris primarily due to their peripheral effects i.e. venodilation and arterial dilation, and thereby reduction in myocardial oxygen demand. These drugs also improve collateral blood flow in ischemic areas and in some patients may increase coronary blood flow by modifying tonus in the conductive or conduit coronary vessels. Sublingual nitroglycerin is the most effective antianginal agent but its prophylactic use is limited by its short duration of action. Until recently, the efficacy of long-acting oral nitrates was seriously questioned. However, recent data suggests that when given acutely in adequate doses, oral nitrates, transcutaneous and buccal preparations of nitroglycerin all exert prolonged hemodynamic and antianginal effects. Development of tolerance to the circulatory and antianginal effects during chronic therapy, however, remains a concern. Published literature suggests that tolerance to the circulatory effects and to headaches develops rapidly during sustained therapy with long-acting nitrates. However, reports regarding the development of tolerance to the antianginal effects and reduction of ST segment depression remain conflicting. Partial tolerance to the antianginal effects has been well-documented during chronic therapy with isosorbide dinitrate. Duration of improvement in exercise tolerance during four times daily therapy with isosorbide dinitrate has been shown to be shortened compared to prolonged effects following acute therapy. Recent data suggests that given in high doses, beneficial effects of ST segment depression during exercise may also diminish during chronic therapy with long acting nitrates. Tolerance to antianginal and circulatory effects can be reversed by withholding long-acting nitrates for 24 to 36 hours. Furthermore, initial studies suggest that tolerance to antianginal effects during sustained therapy can be avoided by giving smaller but effective doses of ISDN (20 to 40 mg) twice a day rather than prescribing larger doses more frequently.