Sublingual Nitroglycerin Tablets Research Articles

Nitroglycerin improves the visibility of fibula-free flap perforators on computed tomography angiography in patients with oral or maxillofacial lesion

PurposeTo investigate the improvement of image quality and visualization of fibula-free flap (FFF) perforators on computed tomography angiography (CTA) after administration of sublingual nitroglycerin (NTG) tablets. MethodsA total of 60 patients with oral or maxillofacial lesions before CTA of the lower extremity were randomly divided into two groups (NTG group and non-NTG group). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), overall image quality and grading of vessels were evaluated and compared. The lumen diameters of the major arteries and the proximal and distal peroneal perforators were measured. The number of visible perforators in muscular clearance and muscular layer was also counted and compared between the two groups. ResultsThe CNR of posterior tibial artery and overall image quality of CTA images in the NTG group was significantly higher than that in the non-NTG group (p < 0.05), although the SNR and CNR of other arteries did not show significant differences (p > 0.05). The lumen diameters of the peroneal artery and its perforators, anterior tibial artery, and posterior tibial artery were significantly larger in the NTG group (p < 0.001), while no significant difference prevailed in the diameter of the popliteal artery between the two groups (p = 0.298). Compared with the non-NTG group, a significant increase in the number of visible perforators was noted in the NTG group (p < 0.001). ConclusionsThe administration of sublingual NTG in CTA of the lower extremity can improve the image quality and visualization of perforators, which aids to surgeons select the optimum FFF.

Medication-administration-via-enteral-feeding-tubes-a-survey-of-nurses-knowledge-and-practice

Introduction: Enteral feeding is a type of nutritional support for critically ill patients who are unable to tolerate oral feeding. It is vital to ensure that nurses practise proper administration techniques via enteral feeding tubes (EFT) to ensure that medications can be delivered safely and effectively. Objective: This study aims to assess the knowledge and practice of nurses on medication administration through EFT. The association between demographics and knowledge was also explored. Method: This study is a cross-sectional, self-administered, content-validated, pre-tested questionnaire survey involving all nurses who worked in the ward setting at Hospital Queen Elizabeth II from August to December 2020. Result: A total of 409 questionnaires were sent out with 252 responses received. The majority of respondents were female (n = 240, 95.6%) with a median working experience of 84 months (interquartile range of 44 months). Most nurses knew that the immediate-release dosage forms (n = 237, 94.4%) may be crushed and administered through EFT. Similarly, most nurses were aware that sublingual nitroglycerin (GTN) tablets should not be crushed (n = 232, 92.8%) and that nystatin suspension should not be administered via EFT (n = 212, 85.1%). However, about half of the nurses responded incorrectly when questioned about the particulars of EFT involving the administration of sustained-release medications (n = 152, 60.6%), soft gelatin capsules (n = 111, 44.4%) and hard gelatin capsules (n = 102, 40.6%). Meanwhile, in terms of practice, a majority of the nurses would correctly routinely flush the EFT before (n = 226, 90.4%) and after (n = 245, 98.8%) the administration of medications. However, only a small proportion of nurses (n = 43, 17.3%) demonstrated the appropriate practice of administering all medications separately all the time. Furthermore, it was also worth noting that for some specific knowledge-based questions, nurses from the intensive care setting had more correct responses when compared to those from the general ward setting (p < 0.05). Conclusion: The knowledge gap and inconsistencies in practices amongst nurses related to the use of EFT may lead to suboptimal delivery of medications, whilst potentially compromising patient outcomes. Hence, continuous educational programs should be carried out to ensure safe and effective drug administration through EFT.

Nitrates administered by spray versus tablet: comparison of coronary vasodilation on CT angiography

To compare the coronary vasodilation effects of spray with those induced by tablet administration in coronary CT angiography (CCTA). A total of 2024 patients who underwent CCTA were identified for this retrospective study, including 828 patients with spray (spray group) and 1169 with tablets (tablet group). Of these, 93 patients underwent CCTA at least twice using both spray and tablets. The number of measurable segments and diameters of all 18 segments was measured. The number of measurable segments was compared between groups. No statistically significant differences were evident between these two groups in terms of clinical characteristics. All coronary segments except the ramus intermedius (RI) and left posterior descending artery (L-PDA) were significantly larger in the spray group than in the tablet group (all p< 0.001). In peripheral and branch vessels, as well as in central and main coronary arteries, the diameters were significantly larger in the spray group than in the tablet group (all p< 0.001). Although not always statistically significant, all coronary segments tended to be more measurable on CCTA with spray than with tablet. In the subgroup that underwent CCTA twice using both spray and tablets, all coronary segments except the RI, obtuse marginal artery 2 (OM2), and L-PDA were significantly larger in the spray group than in the tablet group (all p< 0.05). Lingual isosorbide dinitrate (ISDN) spray was more efficacious than sublingual nitroglycerin (NTG) tablets in coronary vasodilation for CCTA. Therefore, lingual ISDN spray should be preferred over sublingual NTG tablets for CCTA. • Lingual ISDN spray was more efficacious than sublingual NTG tablet for coronary vasodilation in coronary CT angiography, even in elderly patients. • The diameters of all coronary segments except RI and L-PDA were significantly larger, and there were significantly more coronary segments greater than 1.5mm, except RI and L-PDA, in the spray group than in the tablet group in the whole study group. • Even in peripheral and branch vessels, the diameters of coronary arteries were significantly larger in the spray group than in the tablet group, and they were also larger in elderly patients.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

BackgroundOrganic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study.Methods and designThis will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies.DiscussionData from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures.Trial registrationClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

Nitrates as an integral part of optimal medical therapy and cardiac rehabilitation for stable angina: review of current concepts and therapeutics.

The goals of optimal medical therapy in patients with stable angina pectoris are to reduce the risk of cardiovascular mortality and future cardiovascular events, improve exercise capacity, and enhance quality of life. Whereas myocardial revascularization is frequently employed in the management of patients with stable angina, a variety of pharmacologic interventions are recommended as part of optimal medical management. The use of short- and rapidly-acting nitrates (eg, sublingual nitroglycerin spray and tablets) is at the core of the therapeutic armamentarium and should be integrated into optimal medical therapy for stable angina along with exercise therapy. The potential clinical implications from these observations are that prophylactic sublingual nitrates, when combined with cardiac rehabilitation, may allow the patient with angina to exercise to a greater functional capacity than without sublingual nitrates.

Very Late Stent Thrombosis After Dual Antiplatelet Therapy Discontinuation in a Patient with a History of Acute Stent Thrombosis

To describe a case of very late stent thrombosis after dual antiplatelet discontinuation in a patient with a previous history of stent thrombosis. A 62-year-old man with a history of coronary artery disease, multiple acute coronary syndromes requiring percutaneous coronary interventions with multiple stent placements, and acute stent thrombosis resulting in ST segment elevation myocardial infarction presented to the hospital with chest pain. The chest pain was not relieved by 4 sublingual nitroglycerin tablets. Five days prior to his presentation, the patient had been instructed to discontinue both aspirin and clopidogrel in preparation for a left ankle fusion procedure. He was taken to the cardiac catheterization laboratory where he was found to have thrombosis in a sirolimus-eluting stent placed more than 3 years ago. Thrombectomy and balloon angioplasty were performed, and the patient completed his hospital course without complications. Stent thrombosis associated with drug-eluting stents is a complicated pathophysiologic phenomenon with multiple patient-, procedure-, and device-related factors. Application of these risk factors to quantify the risk of stent thrombosis as they apply to a single patient is unknown. Discontinuation of recommended dual antiplatelet therapy with aspirin plus a thienopyridine has been identified as a major risk factor for stent thrombosis, but the optimal duration of dual antiplatelet therapy remains unknown. Current recommendations suggest extending dual antiplatelet therapy beyond one year in patients with low bleeding risk. Given the overall data at this time and the severity of stent thrombosis, it seems prudent to continue dual antiplatelet therapy with aspirin indefinitely plus a thienopyridine for at least one year, with continuation beyond one year on a case-by-case basis depending on the risks of in-stent thrombosis and bleeding. In patients with a low risk of bleeding, indefinite continuation of dual antiplatelet therapy may be reasonable.

Apical ballooning syndrome

After a family argument, an 83-year-old woman experienced chest pain, a "racing heart," and a choking sensation and was brought to the emergency department. The chest pain lasted 10 to 15 minutes; was sharp, substernal, and nonradiating; and was associated with dyspnea and a bout of emesis. A sublingual nitroglycerin tablet partially alleviated the pain, but the patient felt syncopal. Her symptoms persisted despite the administration of supplemental oxygen and a second sublingual nitroglycerin tablet. The patient had a history of gastroesophageal reflux disease, allergic rhinitis, and osteoarthritis. Her oral medications included esomeprazole (40 mg/d), aspirin (81 mg/d), and fluticasone nasal spray. She had discontinued valdecoxib 3 weeks earlier.

Review Article: Treatment of Unstable Angina Pectoris/Non-ST-Segment Elevation Myocardial Infarction in Elderly Patients

Elderly patients with unstable angina pectoris/non-ST-segment elevation myocardial infarction should be hospitalized. Precipitating factors should be identified and corrected. Electrocardiogram monitoring is important. Aspirin should be given as soon as possible and continued indefinitely. Clopidogrel should given for up to 9 months in patients in whom an early noninterventional approach is planned or in whom a percutaneous coronary intervention (PCI) is planned. Clopidogrel should be withheld for 5-7 days in patients in whom elective coronary artery bypass graft surgery (CABGS) is planned. A platelet glycoprotein IIb/IIIa inhibitor should also be given in addition to aspirin, clopidogrel, and heparin in patients in whom cardiac catheterization and PCI are planned. Patients whose symptoms are not fully relieved with three 0.4-mg sublingual nitroglycerin tablets or spray taken 5 minutes apart and the initiation of an intravenous beta blocker should be treated with continuous intravenous nitroglycerin. Beta blockers and angiotensin-converting enzyme (ACE) inhibitors should be given and continued indefinitely. The benefit of long-acting nondihydropyridine calcium channel blockers is limited to symptom control. Intra-aortic balloon pump counterpulsation should be used for severe ischemia that is continuing or occurs frequently despite intensive medical therapy or for hemodynamic instability. Statins should be used if the serum low-density lipoprotein (LDL) cholesterol is >or=100 mg/dl and continued indefinitely. Enoxaparin is preferable to intravenous unfractionated heparin in the absence of renal failure and unless CABGS is planned within 24 hours. Thrombolysis is not beneficial. High-risk patients should have an early invasive strategy with CABGS or PCI performed depending on the coronary artery anatomy, left ventricular function, presence or absence of diabetes, and findings on noninvasive testing. Following hospital discharge, patients should have intensive risk factor modification with cessation of smoking, maintenance of blood pressure below 135/85 mmHg, indefinite use of statins if needed to maintain the serum LDL cholesterol <100 mg/dl, intensive control of diabetes, maintenance of optimal weight, and daily exercise. Patients should be treated indefinitely with aspirin, beta blockers, and ACE inhibitors and with clopidogrel for up to 9 months. Nitrates should be given for ischemic symptoms. Hormonal therapy should not be given to postmenopausal women.

Issues in contemporary drug delivery. Part VI: Advanced cardiac drug formulations.

To identify and discuss the clinical utility of new delivery systems and formulations of cardiac drugs. Studies describing or evaluating new drug delivery systems for cardiac drugs were identified through a MEDLINE literature search. All studies describing or evaluating new delivery systems for cardiac drugs were reviewed. Data were abstracted and evaluated by each author independently. The most common oral sustained-release formulations include the wax-matrix system, the gastrointestinal therapeutic system (GITS), and the spheroidal oral drug absorption system (SODAS). The wax-matrix delivery system is limited by the occurrence of "dose-dumping." In a low-pH setting, the wax-matrix formulation may dissolve too rapidly, liberating the entire dose in a short period of time. The clinical relevance of this phenomenon is unknown. The GITS and SODAS formulations are less likely to be affected by pH and food. Nitroglycerin is available by many routes of administration. The topical patch forms are convenient to use, but are associated with the development of tolerance. A buccal formulation incorporates a relatively short onset of effect with a three- or four-times-daily dosing regimen. Although tolerance is less of a problem with buccal nitroglycerin than with topical nitrates, this formulation is less convenient to use because of buccal irritation and interference with eating and talking. A new spray formulation of nitroglycerin offers longer shelf-life storage stability and an easier mode of administration. The spray canister is stable for three years compared with 12 weeks for an opened bottle of sublingual nitroglycerin tablets. Sublingual administration of oral cardiac drugs offers the potential for a more rapid onset of effects. Although nifedipine is often given sublingually, objective data indicate that it is not absorbed buccally but rather in the stomach. It appears that the chew-and-swallow route is most appropriate for nifedipine. Captopril is absorbed sublingually but its efficacy has not been demonstrated. Transdermal clonidine improves compliance and is associated with fewer adverse effects than oral clonidine. Transdermal formulations of beta-blockers are currently being evaluated. Further advancements in the development of novel delivery systems for cardiac drugs are expected in the future.

Clinical Effects of Nitrendipine on Variant Angina Pectoris.

The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg.

Nitroglycerin‐induced hypotension, bradycardia, and asystole: Report of a case and review of the literature

A 36-year-old man presented with a prolonged history of chest pain, and was given two sublingual nitroglycerin tablets. Subsequently, the patient became hypotensive, bradycardiac, apneic, and lost consciousness. The bradycardia resolved spontaneously. No evidence for acute myocardial infarction or ischemic disease was found. Thirty-four cases reported to date are reviewed, demonstrating that this response appears to be an independent effect of nitroglycerin taken in any form, in patients with and without myocardial infarction and to be unpredictable, especially without evidence of inferior or right ventricular infarction. Careful monitoring is warranted when administering nitroglycerin.

Comparative evaluation of a new formulation of isosorbide dinitrate oral spray and sublingual nitroglycerin tablets

The magnitude and time course of the hemodynamic effect of a new formulation of an aqueous solution of isosorbide dinitrate (ISDN) spray were compared with those of sublingual nitroglycerin (NTG) tablets in 12 patients with chronic congestive heart failure. The patients received, in a random order, ISDN spray, 2.5 mg, or sublingual NTG, 0.8 mg. Hemodynamic measurements were performed before and at 1, 3, 5, 10, 20, 30 and 60 minutes after each drug. The second drug was given only after return of the hemodynamic parameters to baseline, plus a washout period of 2 hours. The hemodynamic variables measured were comparable at baseline. Both drugs produced hemodynamic improvement including a decrease in pulmonary capillary wedge pressure (PCWP), right atrial pressure and systemic and pulmonary vascular resistances. Only ISDN spray significantly increased cardiac output. The onset of action of ISDN spray was significantly more rapid than that of NTG. This was primarily evident in the decrease in PCWP. With ISDN spray the decrease started at 1 minute after administration, and at 3 minutes a decrease of 8.6 mm Hg was already found. The corresponding value for sublingual NTG was 1.6 mm Hg. The difference was highly significant (p < 0.02). The peak effect of ISDN spray on PCWP and right atrial pressure was greater than that of NTG. Thus, the onset of the hemodynamic effect of the new formulation of ISDN spray is much more rapid than that of sublingual NTG tablets. At the doses used, the magnitude of the effect of the ISDN spray on some of the hemodynamic variables is greater than that of sublingual NTG.

Efficacy and safety of amlodipine in vasospastic angina: An interim report of a multicenter, placebo-controlled trial

Amlodipine demonstrated significant antianginal and antiischemic effects and was well tolerated, with a low incidence of serious side effects. The double product remained unchanged during exercise testing, suggesting that the antiischemic effects of amlodipine occur without a decrease in myocardial oxygen consumption. There was a reduction in angina1 episodes and nitroglycerin consumption during singleblind and double-blind active treatment but not during double-blind placebo therapy. Total exercise time, time to 1 mm ST segment depression, time to onset of angina, and maximal ST segment depression were improved by active compared with placebo therapy. In conclusion, amlodipine is well-tolerated and efficacious antiischemic and antianginal therapy for patients with chronic stable angina pectoris. In once-daily doses of 10 mg, amlodipine significantly reduces the number of angina1 attacks and consumption of sublingual nitroglycerin tablets. Amlodipine also improves exercise test variables as long as 24 hours after dosage.

Intravenous epinephrine abuse

A 19-year-old man with a history of intravenous cocaine and amphetamine abuse injected 1.1 mg of epinephrine intravenously from an over-the-counter bronchodilator inhaler. Within seconds, headache, nausea, numbness of hands and feet, precordial chest discomfort, and palpitations developed. The patient was given a sublingual nitroglycerin tablet by a bystander and promptly had a syncopal episode. Hypotension was observed in the emergency department 10 minutes later. Administration of 2 L of Ringer's lactate maintained blood pressure at 80–90 mm Hg systolic. An electrocardiogram showed ischemic changes in the precordial leads. Cardiac enzymes remained normal. Mild hypokalemia and hyperglycemia were observed. This case illustrates an unusual route of abuse of an over-the-counter epinephrine bronchodilator.

New transdermal and transmucosal nitroglycerin delivery systems in patients with ischaemic heart disease

The efficacy of a transdermal (Nitroderm-TTS) and a transmucosal (Trinitrolong) nitroglycerin (NG) formulation has been compared with sublingual NG in 9 patients with ischaemic heart disease and stable angina pectoris. The duration and the degree of anti-ischaemic effect were assessed in terms of similar, individually adjusted work loads performed prior to and repeatedly after drug application in comparison with placebo. The anti-ischaemic effect of nitroderm appeared in 0.5-3 h after administration, reached a maximum in about 3.8 h and persisted for 7.9 h. The maximal nitroderm effect was significantly lower than that of sublingual NG or Trinitrolong. The effect of Trinitrolong was less variable and lasted for 4.6 h. It was evident in all patients 0.5 h after drug administration. Plasma NG levels were monitored in 9 patients after sublingual NG and trinitrolong and in 4 following Nitroderm. The relative bioavailability of Nitroderm and Trinitrolong according to the pharmacokinetic data was 29% and 256%, respectively, of sublingual NG tablets. A therapeutic NG level in blood (0.5 ng/ml) after Trinitrolong appeared much earlier (2 min) than after Nitroderm (1 h). A significant reduction in the effect of sublingual NG was observed during Nitroderm application. Thus, the transdermal NG formulation did not exhibit an antianginal effect lasting for 24 h; transmucosal NG had a relatively short, but more pronounced and stable antianginal effect.

Incomplete and delayed bioavailability of sublingual nitroglycerin

Eight healthy male volunteers received 16 doses of sublingual nitroglycerin tablets (0.4 mg). After 8 minutes, each subject rinsed out his mouth to halt the drug absorption process. The mouth rinses were assayed by high-performance liquid chromatography for residual nitroglycerin content. Each subject also received intravenous infusions of nitroglycerin so that the absolute bioavailability could be evaluated. Plasma nitroglycerin concentrations were determined using a specific and sensitive capillary gas chromatographic method capable of quantifying 25 pg/ml of nitroglycerin. The mean bioavailability (± standard deviation) of sublingual nitroglycerin, estimated from plasma concentrations, was 36.2 ± 24.9% (range 2.6 to 113%). The amount of drug not absorbed after 8 minutes, as determined from the analysis of the mouth rinses, varied from 2.7 to 65.8% (mean 31.4 ± 18.9%) of the administered sublingual dose. Mean nitroglycerin peak concentrations of 1.89 ± 1.64 ng/ml were obtained at a mean peak time of 5.3 ± 2.3 minutes. Thus, sublingual absorption is not instantaneous and can be relatively slow, with peak times of as long as 10 minutes. These data indicate that nitroglycerin pharmacokinetic values should not be estimated only from sublingual doses. Additionally, attempts to correlate pharmacodynamic measurements to sublingual doses must take into account the low and variable bioavailability and the potentially long peak times after sublingual nitroglycerin administration to patients.

Concomitant calcium antagonist plus isosorbide dinitrate therapy for markedly active variant angina

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 ± 9 [mean ± standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 ± 63 mg per day) alone, (2) verapamil (453 ± 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 ± 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 ± 37.3 chest pains per week, consumed 24.4 ± 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 ± 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 ± 3.6 chest pains per week and 3.5 ± 2.6 ST segment deviations per week, p < 0.05; nifedipine/isosorbide dinitrate, 3.1 ± 4.0 chest pains per week and 5.5 ± 6.6 ST segment deviations per week, p < 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another. Thus, in patients with very frequent episodes of variant angina, a calcium antagonist/isosorbide dinitrate combination is much more effective than isosorbide dinitrate alone in reducing the frequency of angina and ischemic ECG alterations.

Nitroglycerin Adsorption to Polyvinylchloride Seriously Interferes with Its Clinical Use

Extemporaneous preparations of intravenous nitroglycerin solutions are currently being used in a number of centers to control intraoperative hypertension (1), severe aortic regurgitation (2), and hypertension in pregnancy during cesarean section (3), and for reduction of myocardial ischemia (4). A satisfactory injectable product may be prepared by using sublingual nitroglycerin tablets (5), nitroglycerin adsorbed onto lactose (6), or directly synthesized nitroglycerin (7). The material is dissolved in normal saline and the solution is sterilized by filtration. With increasing use of intravenous nitroglycerin, a number of reports have been published describing apparent drug instability and binding to various intravenous containers and delivery sets. Several of these reports, however, provide conflicting data. Our center has used nitroglycerin intravenously for approximately 8 years and over this period it has been noted that often the response to the drug seemed to be inappropriate in relation to the dose administered. To determine the cause of this inconsistent dose response, a series of in vitro experiments has been performed in an effort to reproduce the findings of published reports and to relate these to our experiences with this drug. During the course of these investigations we were able to document a clinical case in which nitroglycerin was administered using two different delivery systems and thus compare our in vitro findings to an in vivo situation.