Isosorbid Dinitrate Research Articles

Gambaran Pengobatan Pasien Suspek Covid-19 Rawat Inap RS Brayat Minulya Surakarta Periode Maret - Oktober 2020

Treatment therapy for suspected COVID-19 is an important factor in the recovery of patients with suspected COVID-19. This study aims to determine the characteristics and description of the treatment of patients with suspected COVID-19. This research is a non-experimental research which was conducted retrospectively and analyzed descriptively. The sampling technique was saturated sampling on 55 patients with suspected COVID-19 in inpatient isolation at Brayat Minulya Hospital for the period March-October 2020. The results showed that most of the patients with suspected COVID-19 more dominated by female patients as many as 31 patients (56.36%), in the age group> 65 years as many as 15 patients (27.27%), with the most frequent diagnosis of moderate symptoms as many as 43 patients (78%), with comorbidities dyspepsia. as many as 5 patients (11.90%). Treatment features mostly used the 10.22% Levofloxacin antibiotic group, 6.98% vitamin C group, 1% Oseltamivir antiviral group, 2.74% multivitamin Neurobion, 0.50% zinc supplement, and the symptomatic drug Paracetamol 8.47. %, Omeprasole 6.48%, Ondancentron 4.98%, Ambroxol 4.98%, Methylprednisolone 1.50%, Trifed and Rhinos SR 0.25%, Combivent respule 0.50%, Enoxaparin 1%, Colcichin 0.25 %, Ketorolac 0.25%, comorbid drugs such as Novorapid 1.99%, Amlodipine 1.50%, Isosorbid dinitrate 0.75%, Renxamin 0.50%, Aminoral 0.50%, Haessteril 0.25%, and citicholin 0.25%.

The use of antihypertensive drugs in the treatment of essential hypertension at outpatient installations, Puskesmas Karang Rejo, Tarakan

Background: Essential hypertension is the most common type of hypertension, affecting 95% of hypertensive patients. Essential hypertension can be managed through a combination lifestyle changes and antihypertensive drugs. The aim of this study was to know the use of antihypertensive drugs in the treatment of essential hypertensive at outpatient installations, Puskesmas Karang Rejo, Tarakan.Methods: The research method is descriptive by using secondary data from complete patient medical records of the essential hypertension patients undergoing outpatient treatment at Puskesmas Karang Rejo, Tarakan in the period of January-April 2017.Results: A total of 557 medical records were selected, there were 72.53% (n = 404) female and 27.47 % (n = 153) male; age ranged from 20-80 years (mean = 50.32 years). The most common of essensial hypertension were 47.22 % (n = 263) grade II hypertension and 45.42 % (n = 253) grade I hypertension. The antihypertensive drugs were used single or in combination in the following order: Amlodipine (Calcium channel blockers), Captopril (ACE inhibitors), Hydrochlorothiazide/HCT (Diuretic), Methyldopa (alpha-2 adrenergic receptor agonist) and Isosorbid dinitrate (Vasodilator). Four hundred fifty four (81.51%) patients were treated with a single drug (monotherapy) and 103 (18.49%) patients were given combination therapy. Monotherapy and the combination of two antihypertensive drugs were used for prehypertension, grade I hypertension and grade II hypertension, with the most widely used drugs as monotherapy was amlodipine (67.86%, n =378 ) and the mostly used combination therapy of two antihypertensive drugs was Amlodipine-Hydrochlorothiazide (15.80%, n = 88). The combination of antihypertensive Amlodipin-Hydrochlorothiazide-Captopril (0.35%, n=2) was used for hypertension grade II.Conclusion: Amlodipine was the most widely used drug as monotherapy or combination drugs therapy in the treatment of essensial hypertension at outpatient installations, Puskesmas Karang Rejo.

Effects of PETN and ISDN on vascular dysfunction and oxidative stress in an experimental model of Diabetes

BackgroundVascular complications in diabetes mellitus (DM) are associated with increased reactive oxygen species (ROS) formation. Therefore we tested, if treatment with PETN, which has been shown to induce the antioxidant enzyme heme oxygenase‐1, improves ROS formation and vascular function in a diabetic rat model.Methods/ResultsDM was induced by a single i.v. injection of streptozotocin (STZ, 60mg/kg) in male Wistar rats. After 8 weeks of PETN (15mg/kg/d) vs. isosorbid dinitrate (ISDN, 10 mg/kg/d) vs. isosorbide‐5‐mononitrate (ISMN, 75mg/kg/d) treatment, rats were sacrificed. STZ‐treated rats showed an increase in vascular and cardiac ROS production, detected by HPLC. Endothelial function, measured by isometric tension studies, was impaired. PETN therapy improved almost all parameters more efficiently than ISDN, while ISMN had no protective effects. Some rats were treated with insulin (2.5U/d). Insulin normalized all parameters completely proving that STZ‐induced vascular dysfunction depends on hyperglycemia but not on unspecific toxicity of the compound.ConclusionIn diabetic rats, PETN showed more pronounced antioxidative effects than ISDN. Insulin normalized all parameters and thereby identified the underlying mechanism of cardiovascular dysfunction in STZ‐induced DM to strictly depend on insulin levels highlighting the importance of this model.

Head-up tilt table testing in syncope: Safety and efficiency of isosorbide versus isoproterenol in pediatric population

The aim of this study was to compare the diagnostic value and safety of sublingual isosorbid dinitrate (ISDN) with intravenous isoproterenol (ISOP) during head-up tilt table testing (HUTT) in pediatric patients with suspected neurocardiogenic syncope. One hundred thirty-six consecutive pediatric patients complaining of presyncope or syncope were submitted to HUTT for the first time. Those who did not develop syncope or presyncope during passive HUTT for 20 minutes underwent repeated HUTT with either 1.25 to 2.5 mg sublingual ISDN or intravenous ISOP (1-3 mug/min) for 20 minutes. There were 54 boys and 82 girls, aged 10 to 18 years with an average of 15.5 +/- 2.4 years and a median of 16 years. Among the patients with cardioinhibition or mixed responses, the severity of the bradyarrhythmia was scored 1 to 3 (restoration of effective rhythm within 10 seconds, 10-20 seconds, and >20 seconds while back to supine position, respectively). During the passive period, 24 (17.6%) of 136 patients had a positive response to HUTT. Syncope was observed in another 44 patients during either ISDN or ISOP period (14/58 [24.1%] and 30/54 [55.5%] with ISDN vs ISOP, respectively, P < .05). The time to symptoms was shorter with both ISDN and ISOP compared with passive period (6.5 +/- 2.9, 6.3 +/- 5.9, and 10.3 +/- 4.4, minutes, respectively, P < .05). The severity score for cardioinhibition response was significantly higher with ISDN compared with the passive period and ISOP (2 +/- 0.8, 1.25 +/- 0.45, and 1.26 +/- 0.45, respectively, P < .01). Sublingual ISDN is less sensitive and less safe compared to intravenous ISOP in assessing pediatric age patients with suspected neurocardiogenic syncope and with a negative result in tilt test without provocation. The simplicity of ISDN use should be weighed against the risk of longer symptoms with ISDN.

Lack of nitrate tolerance in isosorbid dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter

To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitroprusside (SNP) in internal anal sphincter (IAS) smooth muscle. Relaxation responses of ISDN, and electrical field stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. ISDN (10(-7)-10(-4) mol/L) and SNP (10(-8)-10(-4) mol/L) caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 multiply 10(-4) mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and E(max) obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.

A Comparison of Isosorbid Dinitrate and Nicorandil in Patients with Ischemic Heart Disease : It's Compliance and Effects on Major Cardiovascular Events

A Comparison of Isosorbid Dinitrate and Nicorandil in Patients with Ischemic Heart Disease : It's Compliance and Effects on Major Cardiovascular Events

RESPONSES TO CARDIOVASCULAR DRUGS DURING ALCOHOL WITHDRAWAL

To present findings on the kinetics and dynamics of cardiovascular drugs during alcohol withdrawal (AW), compared with that observed in remission. Studies were reviewed and summarized. A single-dose study in alcoholic patients with propranolol, a beta-adrenergic antagonist, showed that the negative inotropic effect was decreased and the bradycardiac effect increased during AW as compared with during early remission. The hypotensive effect of isosorbid dinitrate, commonly used as a vasodilatator, was weaker at the onset of AW, being associated with the decreased bioavailability of the drug. Verapamil, which is a L-type Ca2+ channel antagonist, produced a bradycardiac effect at the onset of AW, but no effect was observed in early remission. The effect was probably due to changes in L-type Ca2+ channels because no differences in verapamil concentrations between AW and early remission were observed. Taken together, AW modifies the dynamics and kinetics of cardiac drugs, which may have an impact on the treatment of alcoholic patients with cardiac diseases.

NITRATES IN ISCHEMIC HEART DISEASE TREATMENT, YESTERDAY AND TODAY

The problem of nitrate formulation choice in treatment of patients with ischemic heart disease is reviewed. Importance of development of shortacting nitrates in form of spray, containing nitroglycerin or isosorbid dinitrate, is highlighted. Polycomponent effects of nitrates, ensuring antianginal and antiischemic effect in patients both with stable and acute forms of ischemic heart disease are enumerated. Problem of side effects, frequency of tolerance development in long-term nitrates treatment and tolerance prevention method by interrupted nitrates prescription are analyzed. Wide opportunities of contemporary therapy with nitrates through development of new forms of special drugs, containing isosorbid – 5 – mononitrate in microspheres, are emphasized.

NH4+ conductance in Xenopus laevis oocytes.II. Effect Of hypoosmolality.

Superfusing Xenopus laevis oocytes with NH4Cl (10 mmol/l, pH 7.5) resulted in an inward current at a clamp potential of -70 mV. In paired experiments (n=22), the NH4Cl-induced peak current was -293+/-94 nA, under control conditions (osmolality: 240 mosmol/kg), and rose to -523+/-196 nA when osmolality was reduced to 144 mosmol/kg. In parallel with the rise in NH4Cl-induced inward current, membrane conductance at -70 mV doubled and the zero-current potential changed from +3.3+/-9.4 mV to -22.0+/-8.0 mV (n=22) in the presence of NH4Cl during exposure to a hypoosmolar solution. In the absence of NH4Cl, oocytes responded to hypoosmolality with a shift in zero-current potential to more negative values and an increased conductance which became partially sensitive to isosorbiddinitrate (ISDN), suggesting the activation of a volume-sensitive K+ channel. Membrane conductance in the presence of NH4Cl was decreased by ISDN to similar extents under isoosmolal and hypoosmolal conditions, indicating that NH4+ enters the oocytes through a volume-sensitive conductance separate from the ISDN-sensitive K+ channel.

NH4+ conductance in Xenopus laevis oocytes. I. Basic observations.

Current-clamp and voltage-clamp techniques were used to study the effects of NH4+ on the cell membrane conductance in Xenopus laevis oocytes. Superfusing the oocytes with NH4Cl resulted in a depolarization of the oocyte's cell membrane potential and, at a clamp potential of -70 mV, in an inward current. The magnitude of the inward current was proportional to the NH4Cl concentration in the extracellular solution and on membrane potential. The reversal potential, Erev , was -35.5 +/- 11.6 mV under control conditions and -3.1 +/- 11.0 mV (n = 19) in the presence of NH4Cl (10 mmol/l). Superfusion of the oocytes with nominally Ca2+-free solution affected the NH4Cl-evoked response only marginally. Replacement of extracellular Na+ by N-methyl-D-glucamine+ markedly reduced, but did not eliminate, the NH4Cl-sensitive current and shifted the reversal potential to more negative potentials. The NH4Cl-induced current was substantially inhibited by 0.1 mmol/l flufenamate, and was less affected by blockers of the endogenous K+ conductance, Ba2+ and isosorbiddinitrate (ISDN). The results are compatible with the activation of a conductance by NH4Cl for Na+ and NH4+. The mechanism by which NH4Cl activates the conductance remains unknown.

Effect of isosorbiddinitrate on exogenously expressed slowly activating K+ channels and endogenous K+ channels in Xenopus oocytes.

1. The effects of isosorbiddinitrate (ISDN) were tested on membrane currents and resting potential in Xenopus laevis oocytes which were either uninjected or injected with cRNA encoding for K+ channels from three distinct families (slowly activating IsK channels, delayed-rectifying Kv1.1 or inwardly rectifying IRK1 K+ channels). 2. In uninjected oocytes ISDN (1 mM) resulted in a decrease of the holding current at potentials more positive than -100 mV and in an increase at potentials below -100 mV. Increasing extracellular K+ to 100 mM shifted the reversal potential for ISDN-mediated effects to approximately -12 mV, suggesting an inhibition of a K+ conductance by ISDN. 3. In current clamp studies ISDN (1 mM) and Ba2+ (3 mM) depolarized cell membrane. ISDN and Ba2+ had no additive effects on membrane potential when applied simultaneously. In voltage clamp studies, corresponding results were observed for the effects of ISDN and Ba2+ on the holding current with an apparent K(m) of 0.21 and 0.08 mM, respectively. 4. In contrast to ISDN, the nitric oxide (NO) donors isosorbidmononitrate (ISMN) and S-nitrosocysteine (SNOC) had no effects on the holding currents in Xenopus oocytes. Moreover, the guanylate inhibitor LY 83583 did not affect ISDN-mediated holding current alterations, suggesting that ISDN acts independently of the second messenger NO. 5. ISDN inhibited exogenously expressed IsK channels with an apparent K(m) of 0.15 mM, but at 1 mM only weakly inhibited Kv1.1 and IRK1 channels. 6. It is concluded that ISDN inhibits an endogenous K+ conductance in Xenopus oocytes with a similar potency to that shown by expressed IsK channels. These effects are independent of the second messenger NO.

Prognostic significance of changes in the compliance of the pulmonary venous system after isosorbiddinitrate in patients with mitral stenosis

It is agreed that a stiff pulmonary venous bed can cause severe pulmonary hypertension. This condition can also influence the clinical and hemodynamic outcome of mitral valve replacement (MVR). This study has been aimed at assessing whether changes in the pulmonary venous compliance (PVcomp) after application of isosorbiddinitrate (ISDN) can be of prognostic value in patients 6 months after MVR. PVcomp was calculated according to the Hirakawa equation in 34 patients with isolated mitral stenosis (MS) before and after ISDN. In 19 patients (group I) there was an increase of PVcomp by more than 15% (5.3 vs. 8.1 ml/mmHg), while 15 patients (group II) showed no differences in PVcomp after ISDN, despite the significant decrease in PAP and PWP in both groups (measured with the use of Swan-Ganz thermodilution catheters). Six months after MVR a significant decrease in PAP, PWP, PVR and an increase in SVI was observed in both groups during rest. During effort (25 W), significant increases in PAP and PWP were recorded in most of patients from the group II, as opposed to group I. It is concluded that significant increase in PVcomp after ISDN in patients with MS can be a prognostic of good clinical results 6 months after MVR.

958-95 Long-term Effects of Amlodipine and Isosorbiddinitrate on Exercise-induced and Ambulatory Ischaemia in Patients with Stable Angina Pectoris

Once-daily administration of 10 mg amlodipine has been compared with two daily doses of 40 mg sustained-release isosorbiddinitrate (ISDN) in 59 patients with stable angina, using a randomized, double-blind, double-placebo, crossover study design. Nine patients dropped out due to side effects (3 during amlodipine and 6 during ISDN therapy), and one patient was excluded for technical reasons. A maximal symptom limited supine bicycle tolerance test and a 48 h ambulatory ECG monitoring were performed at the end of each 5 week period of therapy. During exercise, exercise time, time to onset of angina, and time to onset of ischaemia, i.e., 1 mm ST segment depression were measured. During ambulatory monitoring, number of anginal episodes and duration per hour of ST deviation were assessed. Amlodipine significantly prolonged time to angina (320 ± 155 vs 304 ± 126 sec; p &lt; 0.05) and time to ischaemia (292 ± 153 vs 232 ± 126 sec; p &lt; 0.001). when compared with ISDN, while exercise time was similar for both treatments. Furthermore, amlodipine reduced anginal episodes (1.2 ± 1.6 vs 2.4 ± 3.0 attacks/48 h; p &lt; 0.001), whereas, no difference was found between amlodipine and ISDN in duration of ST deviation during ambulatory monitoring. In conclusions, addressing the long-term treatment of patients with stable angina pectoris, once-daily dosing of amlodipine appears to be more effective than ISDN, as determined by its anti-anginal and anti-ischaemic effects during exercise tolerance testing and ambulatory ECG monitoring.

Altered Hemodynamic Response to Isosorbide Dinitrate in Essential Hypertension

Relaxation produced by nitrates on venous, arteriolar, and large arterial vessels is well known but has never been studied in human hypertensive aortas studied in vivo. In this investigation, the effects of acute oral administration of 20 mg of isosorbide dinitrate were evaluated in 12 patients with sustained essential hypertension and nine normotensives of the same age. Noninvasive measurements of systolic, diastolic, and mean arterial pressure, carotid-femoral pulse wave velocity and aortic-arch diastolic diameter using suprasternal echocardiography were determined before and 3 hours after drug administration. In normal subjects, isosorbid dinitrate significantly decreased systolic blood pressure and pulse pressure but did not affect diastolic and mean arterial pressure. In contrast, in hypertensives, the same dosage of isosorbid dinitrate decreased together systolic, diastolic mean, and pulse pressure. In both populations, pulse wave velocity decreased significantly whereas aortic arch diastolic diameter increased markedly. The increase was observed mainly in normal subjects. The study provided evidence that (1) both in normal subjects and hypertensives, isosorbide dinitrate caused an increase in aortic diameter together with an increase in arterial distensibility; and (2) the changes in mean arterial pressure were significant only in hypertensives, indicating that the altered vasodilator response in essential hypertension is not endothelium-mediated.

Assessment for mutagenicity of 10 pharmaceutical products following ames, micronucleus, and sperm morphology testing

AbstractTen widely used pharmaceutical agents for which mutagenicity or carcinogenicity data are still lacking were tested in parallel with three methods: Ames' bacterial mutagenicity test (TA1535, TA1537, TA98, and TA100 Salmonella strains), micronucleus (mice BDF1), and sperm morphology abnormality (mice) tests. The groups and generic names of the tested products, all produced by Pharmachim (Bulgaria), were as follows: Psychopharmaca (Loxapinsuccinate, Medazepam hydrochloride, Nomifensinmaleate, Viloxazine hydrochloride), Vasodilatators (Nitroprussid Na, Isosorbid mononitrate, Isosorbid dinitrate), Spasmolytica (Trimetoquinol), Antirheumatica (Diclofenac Na), and the antimycotic agent Lavendotricin. In all tests, negative results were obtained. To avoid false negative results, several suggestions are made.

An indirect approach for the study of the elastic modulus of the brachial artery in patients with essential hypertension

An indirect approach for the study of the changes in the incremental circumferential modulus (E) of the brachial artery after arteriolar vasodilatation was undertaken in patients with sustained essential hypertension. The product of E and the thickness (h) of the arterial wall was evaluated by means of the Moens-Korteweg equation using determinations of brachioradial pulse wave velocity and brachial artery diameter with pulsed Doppler methods. In three homogeneous groups of patients with hypertension the Eh product was studied after vasodilatation caused either by nitrendipine, a calcium entry blocking agent, or by medroxalol, an alpha and beta blocking agent, or by isosorbid dinitrate. The three drugs caused similar reductions in blood pressure and increases in arterial diameter and hence decreases in wall thickness. Variance analysis for multigroups indicated that the decrease in Eh after vasodilatation was significant for nitrendipine but not for medroxalol and isosorbid dinitrate. Covariance analysis showed that for any level in Eh product the decrease in Eh was higher for nitrendipine than for isosorbid dinitrate and medroxalol. Since the three drugs had comparable mechanical and geometrical effects, the study provided evidence that, in men with essential hypertension, the smooth muscle tone of the brachial artery was significantly more sensitive to calcium inhibition than to autonomic blockade, causing a more important decrease in elastic modulus.

Long-term treatment of the pulmonary hypertenston due to interstitial lumg fibrosis by isosorbid dinitrate: V. Ježek, A. Michaljanič, J. Fučík, J. Ježková, R. Ramaisl Institute of Physiological Regulations, Czechoslovak Academy of Sciences, and Second Clinic of Pheumology, Charles University, Prague, Czechoslovakia

Long-term treatment of the pulmonary hypertenston due to interstitial lumg fibrosis by isosorbid dinitrate: V. Ježek, A. Michaljanič, J. Fučík, J. Ježková, R. Ramaisl Institute of Physiological Regulations, Czechoslovak Academy of Sciences, and Second Clinic of Pheumology, Charles University, Prague, Czechoslovakia

Effect on nitroclycerin and other organic nitrates on the in-vitro biosynthesis of arachidonic acid-metabolits in washed human platelets

Organic nitrates exert well known vasodilating effects in coronary arteries, although the exact mechanism of action is not fully understood. In this study the influence of these drugs on the biosynthesis of eicosanoids from labelled exogenous arachidonic acid (AA) in isolated platelets was examined. Platelet malondialdehyde (MDA)-formation in the presence of the substances tested in this system was studied too. The vasodilating drugs were found to reduce the conversion rate to TxB 2, hydroxy- 5,8,10-heptadecatrienoic acid (HHT) and MDA in platelets dose-dependently. Isosorbid-5-mononitrate (ISMN), nitroglycerin (NG) and SIN 1, the active metabolite of molsidomin, showed their inhibitory effects at concentrations of about 1mM, isosorbid-dinitrate (ISDN) had a much weaker effect on platelet-biosynthesis - a concentration of about 3mM was necessary to inhibit TxB 2-formation significantly.

The effect of isosorbiddinitrate on coronary blood flow, coronary resistance and left ventricular dynamics under exercise in patients with coronary artery disease.

Myocardial blood flow (MBF) and LV dynamics were studied under exercise (bicycle ergometry) before and after sublingual administration of Isosorbiddinitrate (ISDN) in 20 patients with angiographically severe coronary disease. Before ISDN, exercise was accompanied by a 92% increase in MBF (Xenonresidue detection technique) and a 38% decrease in total coronary vascular resistance (TCVR) (p<0.01). After ISDN, MBF under equal work load (65 Watt) was 17% lower (p<0.005) whereas the exercise-induced value of TCVR remained unchanged. — In seven additional patients three exercise tests were performed, the last with a higher work load (105 Watt); in spite of ISDN, a raise of the load from 65 to 105 Watt was followed by an elevation of 27% of MBF and a significant further reduction of TCVR (−23%) (p<0.01). —After ISDN, LV and aortic pressures, stroke volume and work as well as tension time index were significantly lower under exercise of identical load, the reduction correlating significantly with the lower MBF. — It is concluded that the coronary dilatory action of nitrates does not include or affect the small, angiographically not visible resistance vessels, but rather the large capacitance arteries only.