Nifedipine

Interaction with Vascular Smooth Muscle Cells

In vascular smooth muscle cells, the influx of extracellular calcium through LTCCs is a critical step for initiating and maintaining contraction. patsnap.comconsensus.apppfizermedicalinformation.com Calcium binds to calmodulin, and this complex then activates myosin light chain kinase, leading to phosphorylation of myosin light chains and subsequent muscle contraction. By inhibiting LTCCs, this compound reduces the intracellular concentration of calcium ions in these cells. nih.govdrugbank.comconsensus.app This reduction in intracellular calcium diminishes the activation of the contractile machinery, leading to relaxation of the vascular smooth muscle. pfizermedicalinformation.comderangedphysiology.com Studies have demonstrated that the increase in active tension in vascular smooth muscle, which contributes to increased peripheral vascular resistance, reflects an increase in cytosolic free calcium. This compound, as a peripheral arterial vasodilator, acts directly on this process by inhibiting calcium influx. pfizermedicalinformation.com The binding of this compound to these channels, and potentially receptor-operated channels, in vascular smooth muscle results in the inhibition of calcium influx. pfizermedicalinformation.com

Interaction with Myocardial Cells

LTCCs are also present in cardiac muscle cells, where they play a vital role in excitation-contraction coupling. patsnap.comwikipedia.org The influx of calcium through LTCCs triggers the release of larger stores of calcium from the sarcoplasmic reticulum, a process known as calcium-induced calcium release, which is essential for myocardial contraction. wikipedia.org this compound blocks LTCCs in myocardial cells, thereby reducing the influx of calcium ions. nih.govdrugbank.com This can lead to a reduction in myocardial contractility, a negative inotropic effect. consensus.appnih.gov However, in intact organisms, this direct inhibitory effect on myocardial contractility may be masked by reflex responses to the vasodilating effects of this compound, such as an increase in heart rate. nih.gov Research using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has investigated the temporal changes in this compound's efficacy, suggesting that CCB-induced reductions in intracellular calcium might lead to an upregulation of calcium ion channels over time, potentially attenuating the drug's effect. biorxiv.org

Peripheral Arterial Vasodilation Mechanisms

This compound is a potent peripheral arterial vasodilator. patsnap.comdroracle.aipfizermedicalinformation.com By blocking calcium influx into vascular smooth muscle cells, it reduces their contractile tone, leading to relaxation and dilation of peripheral arteries. patsnap.compfizermedicalinformation.comderangedphysiology.com This vasodilation reduces systemic vascular resistance, also known as afterload, which is the pressure against which the heart must pump blood. patsnap.compfizermedicalinformation.com The reduction in peripheral resistance leads to a decrease in arterial blood pressure. nih.govdroracle.aidrugbank.com This afterload reduction is a primary mechanism by which this compound exerts its antihypertensive effects and reduces the workload on the heart. patsnap.compfizermedicalinformation.com

Coronary Artery Dilation Mechanisms

This compound also dilates coronary arteries and arterioles, including those in both normal and ischemic regions of the heart. patsnap.compfizermedicalinformation.com This dilation is a result of the same mechanism as in peripheral arteries: blockade of LTCCs in coronary vascular smooth muscle, leading to relaxation. nih.govpfizermedicalinformation.commims.com This property is particularly important in the treatment of vasospastic (Prinzmetal's or variant) angina, where coronary artery spasm reduces blood flow to the myocardium. pfizermedicalinformation.com By inhibiting spasm and dilating coronary vessels, this compound increases myocardial oxygen delivery. nih.govpfizermedicalinformation.com While its role in classical stable angina is also related to reducing myocardial oxygen demand through afterload reduction, the direct coronary dilation contributes to improved blood flow. pfizermedicalinformation.comahajournals.org

Data Table

Impact on Myocardial Oxygen Delivery

This compound's impact on myocardial oxygen delivery is primarily mediated through its vasodilatory effects on coronary arteries. By blocking L-type calcium channels in the smooth muscle of coronary arteries and arterioles, this compound causes these vessels to relax and dilate nih.govpfizermedicalinformation.comresearchgate.netmims.compatsnap.com. This dilation increases blood flow to the heart muscle, thereby enhancing the supply of oxygen nih.govpfizermedicalinformation.comresearchgate.netpatsnap.com. This increased oxygen delivery is particularly beneficial in conditions like vasospastic angina (Prinzmetal's angina), where coronary artery spasm reduces blood flow pfizermedicalinformation.com. In chronic stable angina, while the role of direct coronary dilation is less clear compared to vasospastic angina, the reduction in afterload (the resistance the heart pumps against) also contributes to a more favorable myocardial oxygen balance by decreasing the heart's workload and oxygen demand pfizermedicalinformation.compatsnap.com.

Absorption Studies

Research into this compound absorption has explored the dynamics of its uptake from the gastrointestinal tract, the impact of different formulations on its bioavailability, and the influence of first-pass metabolism.

This compound is reported to be almost completely absorbed from the gastrointestinal tract following oral administration. Studies using a remote-controlled drug delivery device in healthy volunteers found that dissolved this compound entered the systemic circulation completely along the intestine, with absorption occurring from the jejunum to the colon. Absorption was less rapid from the colon compared to the upper gut, but this did not result in a decrease in the extent of absorption or bioavailability. nih.gov Peak plasma concentrations are typically achieved relatively rapidly after administration of immediate-release formulations, often within 1-2 hours. ontosight.ai Research comparing oral and sublingual administration has suggested that absorption through the buccal mucosa is poor, if it occurs at all, and that appearance in plasma requires delivery to the stomach for active absorption. nih.gov Biting and swallowing the contents of a capsule has been shown to provide a more rapid rise in plasma concentrations and higher peak levels compared to sublingual administration. nih.gov

The formulation of this compound significantly impacts its absorption rate and bioavailability. Immediate-release formulations, such as capsules containing this compound dissolved in an organic solvent, lead to higher maximum plasma concentrations achieved more rapidly compared to slow-release tablets. nih.gov The bioavailability of immediate-release this compound is reported to be between 45% and 68%, partly due to first-pass metabolism. drugbank.comnih.gov Extended-release preparations have shown bioavailability up to 89% relative to the immediate-release formulation. nih.gov

Studies on specific controlled-release formulations, such as the gastrointestinal therapeutic system (GITS), indicate that the bioavailability relative to capsules is about 65% after a single dose, increasing to approximately 86% at steady-state due to prolonged absorption. nih.govresearchgate.net These formulations are designed to provide a more sustained release of the drug. nih.govresearchgate.net Research has also explored novel formulations like spontaneous emulsifying powders (SEP) and proliposomes to improve the dissolution and oral bioavailability of poorly water-soluble this compound. mdpi.comnih.gov For instance, this compound proliposomes significantly improved bioavailability in vivo, with the area under the concentration-time curve (AUC) being approximately 10 times higher compared to oral administration of free this compound in one study. mdpi.com

A significant factor contributing to the relatively low oral bioavailability of this compound (45-68%) is extensive presystemic metabolism, primarily in the liver. ontosight.aidrugbank.comnih.govahajournals.org This first-pass metabolism eliminates about half of the administered dose before it reaches the systemic circulation. ijclinmedcasereports.com The metabolism is largely mediated by the cytochrome P450 enzyme system, particularly CYP3A4. ontosight.aidrugbank.comijclinmedcasereports.com Research suggests that small intestinal P450 enzymes also play an important role in the first-pass clearance of oral this compound. doi.org

Impact of Formulation on Bioavailability

Distribution Characteristics

Following absorption, this compound is distributed throughout the body.

This compound is widely distributed throughout the body, which is consistent with its high lipid solubility. ontosight.ai It undergoes significant tissue distribution, indicated by its steady-state volume of distribution (Vd). The steady-state volume of distribution of this compound has been reported to range from 0.62 to 0.77 L/kg. drugbank.comnih.gov The volume of distribution of the central compartment is lower, approximately 0.25 to 0.29 L/kg. drugbank.comnih.govnih.gov This difference suggests that this compound distributes extensively into peripheral tissues beyond the central blood compartment. This compound is also highly protein bound in serum, with reported binding ranging from 92% to 98%. drugbank.com It is approximately 97% bound in a solution of pure albumin and shows varying degrees of binding to alpha-1-acid glycoprotein. drugbank.com Population pharmacokinetic modeling has estimated the apparent volume of distribution (V/F) to be around 2300.26 L, with notable interindividual variability. dovepress.com

Plasma Protein Binding Studies

This compound exhibits a high degree of plasma protein binding. Studies have indicated that this compound is 92-98% protein bound in serum. drugbank.compfizermedicalinformation.commims.com Specifically, it is reported to be 97±12% bound in a 40g/L solution of pure albumin. drugbank.com Binding studies have also shown protein binding percentages in solutions of alpha-1-acid glycoprotein: 51.4±5.9% in a 50mg/100mL solution and 75.5±3.5% in a 150mg/mL solution. drugbank.com The high protein binding suggests that only a small fraction of the total plasma concentration is unbound and thus pharmacologically active. researchgate.net Changes in protein binding, even small ones, can significantly impact this compound's pharmacokinetics. plos.org Studies in patients with renal or hepatic impairment have shown that protein binding may be greatly reduced in these populations. pfizermedicalinformation.combauschhealth.com

Here is a summary of plasma protein binding data:

Metabolism Pathways and Enzyme Systems

This compound undergoes extensive metabolism, primarily in the liver. ontosight.ai This extensive metabolism contributes to its bioavailability, which ranges from 45-68% for immediate-release formulations due to significant first-pass metabolism. drugbank.com

Hepatic Metabolism via Cytochrome P450 3A4 Pathway

The predominant metabolic pathway for this compound is oxidation catalyzed by the cytochrome P450 (CYP) enzyme system, specifically the CYP3A4 isoenzyme. drugbank.compfizermedicalinformation.commims.comontosight.aiijclinmedcasereports.comnih.govrelis.no This enzyme is highly expressed in the human liver and small intestine and plays a major role in the metabolism of many drugs. researchgate.net CYP3A5 also contributes to this compound biotransformation, although it is generally less metabolically active than CYP3A4. researchgate.net

The metabolism of this compound via CYP3A4 can be influenced by other drugs that either inhibit or induce this enzyme system. bauschhealth.comaafp.org For instance, inhibitors of CYP3A4, such as cimetidine and erythromycin, can decrease this compound metabolism, leading to increased plasma concentrations. aafp.orgfda.govmedcentral.com Grapefruit juice has also been shown to inhibit CYP3A4 in the small intestine wall, resulting in increased bioavailability and plasma levels of this compound. mims.comaafp.orgfda.govwikipedia.org

Metabolite Identification and Characterization

This compound is extensively metabolized into highly water-soluble, inactive metabolites. pfizermedicalinformation.combauschhealth.com The primary metabolic reaction is the oxidation of the dihydropyridine ring to the corresponding pyridine analog. ahajournals.org

A major metabolite identified in both dog and human urine is 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonylpyridine-3-carboxylic acid. drugbank.comjst.go.jpjst.go.jp This is often referred to as M-I. ahajournals.org This metabolite is then further metabolized to 2-hydroxymethyl-pyridine carboxylic acid (M-II). drugbank.comahajournals.org Another minor metabolite is dehydrothis compound, which is the pyridine analog of this compound. drugbank.comnih.gov

Metabolites account for the majority of the excreted dose. pfizermedicalinformation.combauschhealth.com

Influence of Hepatic Impairment on Metabolism

Since hepatic biotransformation is the primary route of this compound disposition, impaired liver function can significantly alter its pharmacokinetics. pfizermedicalinformation.combauschhealth.comontosight.aifda.govmedcentral.com In patients with hepatic impairment, such as liver cirrhosis, this compound has a longer elimination half-life and higher bioavailability compared to healthy volunteers. pfizermedicalinformation.combauschhealth.comnih.govfda.gov This is due to reduced clearance of the medication. nih.govmedcentral.com The degree of protein binding may also be greatly reduced in patients with hepatic impairment. pfizermedicalinformation.combauschhealth.com

Elimination Kinetics

This compound and its metabolites are primarily eliminated from the body through excretion. ontosight.ai

Half-Life Studies

The elimination half-life of this compound varies depending on the formulation administered. For immediate-release formulations, the terminal elimination half-life is approximately 2 hours. drugbank.compfizermedicalinformation.comijclinmedcasereports.com Some studies report a half-life of 2-5 hours. mims.comontosight.ai After intravenous administration, a biphasic elimination has been observed in healthy volunteers, with an alpha-phase half-life of about 13 minutes and a beta-phase half-life of approximately 1.26 hours. ahajournals.org After oral administration of higher doses or continuous infusion, a third phase with a half-life of about 8 hours can be seen. ahajournals.org

Extended-release tablet formulations of this compound have a longer elimination half-life, approximately 7 hours. bauschhealth.com In healthy elderly subjects, the elimination half-life of a sustained-release formulation was longer (6.7 hours) compared to younger subjects (3.8 hours) following oral administration. bauschhealth.com

The majority of the dose (60-80%) is recovered in the urine as inactive water-soluble metabolites. drugbank.compfizermedicalinformation.commims.combauschhealth.com Only trace amounts (less than 0.1% of the dose) of unchanged this compound are detected in the urine. pfizermedicalinformation.combauschhealth.com The remainder of the dose is eliminated in the feces in metabolized form, likely due to biliary excretion. drugbank.compfizermedicalinformation.com The pharmacokinetics of this compound are not significantly influenced by the degree of renal impairment, and significant alterations have not been reported in patients undergoing hemodialysis or chronic ambulatory peritoneal dialysis. pfizermedicalinformation.combauschhealth.com

Here is a summary of reported elimination half-lives:

Excretion Pathways

This compound is extensively metabolized, primarily in the liver via the CYP3A4 enzyme pathway. drugbank.commims.comontosight.aiastrazeneca.comnih.govijclinmedcasereports.com The majority of a this compound dose, approximately 60% to 80%, is recovered in the urine in the form of inactive water-soluble metabolites. drugbank.commims.comastrazeneca.compfizermedicalinformation.compfizer.com The remaining portion is eliminated in the feces as metabolites, likely due to biliary excretion. drugbank.comastrazeneca.compfizermedicalinformation.compfizer.com Only trace amounts (less than 0.1% of the dose) of unchanged this compound are detected in the urine. pfizermedicalinformation.compfizer.com The elimination half-life of this compound is approximately 2 to 5 hours. drugbank.commims.comontosight.aiwikipedia.org

Population Pharmacokinetics and Inter-Individual Variability Research

Significant inter-individual variability in the pharmacokinetics of this compound has been observed in clinical settings. soton.ac.ukresearchgate.netnih.gov This variability cannot be fully explained by pharmacogenomics alone. researchgate.netnih.govresearcher.lifemdpi.com Factors influencing this variability include genetic polymorphisms, the role of the gut microbiota, and pharmacokinetic differences in specific patient cohorts. researchgate.netnih.govresearcher.lifemdpi.comdovepress.comresearchgate.net

Role of Gut Microbiota in Pharmacokinetic Variability

Research suggests that the gut microbiota can influence the pharmacokinetics of this compound. researchgate.netnih.govresearcher.lifemdpi.comnih.govfrontiersin.org Studies in spontaneously hypertensive rats (SHRs) have shown that changes in gut microbiota are associated with differences in this compound pharmacokinetics. nih.govresearcher.lifemdpi.com For instance, the bioavailability of this compound was found to be decreased in SHRs compared to Wistar rats. nih.govresearcher.lifemdpi.com Specific gut bacteria, such as Bacteroides dorei, have shown negative correlations with pharmacokinetic parameters like AUC and Cmax. mdpi.comnih.gov

The gut microbiota can affect this compound pharmacokinetics through microbial biotransformation or by regulating the enzyme activity of CYP3A1 (the rat equivalent of human CYP3A4). nih.govresearcher.lifemdpi.comnih.gov Bile acids, altered by gut microbiota, may also play a role. nih.govmdpi.comnih.gov For example, glycoursodeoxycholic acid (GUDCA) has been negatively correlated with Cmax and can induce the expression of CYP3A1 in rat hepatocytes. nih.govmdpi.comnih.gov Antibiotic treatments in SHRs have further supported the impact of microbiota on this compound pharmacokinetics. nih.govmdpi.comnih.gov

Influence of Genetic Factors on Pharmacokinetics

Genetic factors, particularly polymorphisms in cytochrome P450 enzymes, are known to influence this compound pharmacokinetics. This compound is primarily metabolized by CYP3A4. drugbank.commims.comontosight.aiastrazeneca.comnih.govijclinmedcasereports.com Polymorphisms in the CYP3A4 and CYP3A5 genes can lead to inter-individual variability in enzyme activity and consequently affect this compound metabolism and clearance. dovepress.comresearchgate.netpeerj.comnih.gov

Studies have investigated the effect of specific genetic polymorphisms on this compound pharmacokinetics. For example, the CYP3A53 polymorphism has been associated with differences in AUC and Cmax. dovepress.comresearchgate.netnih.gov The CYP3A4 rs2242480 mutant genotype has been linked to increased Cmax/DW and reduced CL/F compared to the wild-type genotype. dovepress.comresearchgate.net Polymorphisms in POR (cytochrome P450 oxidoreductase), which affects CYP3A4 activity, have also been associated with differences in this compound disposition. dovepress.comnih.gov

Pharmacokinetic Profiles in Specific Patient Cohorts

The pharmacokinetics of this compound can be altered in specific patient populations.

Renal Impairment: The pharmacokinetics of this compound are generally not significantly influenced by the degree of renal impairment. pfizermedicalinformation.compfizer.comnih.govanmfonline.org Studies in patients with varying degrees of renal failure, including those undergoing hemodialysis or chronic ambulatory peritoneal dialysis, have not reported significant alterations in this compound pharmacokinetics. pfizermedicalinformation.compfizer.com While the elimination half-life may be prolonged in severe renal impairment, total systemic clearance may not differ significantly. nih.gov Plasma protein binding may be reduced in patients with renal impairment. pfizermedicalinformation.compfizer.comnih.gov

Hepatic Impairment: Since hepatic biotransformation is the predominant route of this compound disposition, pharmacokinetics may be altered in patients with chronic liver disease. pfizermedicalinformation.compfizer.com Patients with hepatic impairment, such as liver cirrhosis, tend to have a longer elimination half-life and higher bioavailability of this compound compared to healthy volunteers. pfizermedicalinformation.compfizer.com Protein binding may be greatly reduced in these patients. pfizermedicalinformation.compfizer.com

Elderly Patients: Age appears to have a significant effect on this compound pharmacokinetics. pfizer.comnih.govresearchgate.netmsdmanuals.com Clearance is often decreased in elderly subjects compared to younger individuals, resulting in a higher area under the curve (AUC). pfizer.comnih.govresearchgate.net The rate of absorption may also be lower, and the elimination half-life may be significantly longer in the elderly. nih.govresearchgate.net

Pregnant Women: this compound clearance has been shown to be increased during pregnancy compared to reported values in healthy volunteers. purdue.edu CYP3A5 expression in pregnant women significantly increased this compound clearance. purdue.edu

Dose-Response Relationships and Therapeutic Effects

This compound is effective in lowering blood pressure and managing angina pectoris. wikipedia.orgsoton.ac.ukbioline.org.br Studies have investigated the dose-response relationships and therapeutic effects of different this compound formulations. nih.govahajournals.org

In patients with essential hypertension, various this compound formulations and doses have demonstrated effectiveness in lowering blood pressure. nih.gov Research indicates a dose-response effect on blood pressure reduction. nih.govnih.gov For example, in one study, 5 mg capsules were less effective than 10 mg and 20 mg capsules or 20 mg tablets in lowering blood pressure. nih.gov The maximum antihypertensive effect of certain formulations may occur several hours after administration. ahajournals.org With continued treatment, a sustained antihypertensive effect is observed. ahajournals.org

Studies have also explored the relationship between plasma this compound concentrations and its effects. While establishing a clear concentration-effect relationship has sometimes yielded conflicting reports, individual subjects may show significant correlations between this compound concentrations and the fall in systolic blood pressure. ahajournals.orgnih.gov

In high-risk individuals with hypertension, such as those with renal impairment or diabetes mellitus, this compound, often in combination with other antihypertensive agents, has shown dose-response effects on blood pressure reduction, with higher doses achieving better control rates. nih.gov

This compound's pharmacodynamic effects also include influencing urine excretion and potentially affecting renal responses, as observed in animal studies where this compound increased basal urine excretion. mdpi.com

Pharmacokinetic Parameters in Healthy Volunteers (Example Data from a Study) bioline.org.br

Note: This table presents example data from a specific study in healthy Pakistani subjects and may not be representative of all populations or formulations.

Hemodynamic Effects

The hemodynamic effects of this compound are primarily mediated through its potent vasodilator action on peripheral arteries. patsnap.comahajournals.org This vasodilation leads to a reduction in systemic vascular resistance, a key factor in lowering blood pressure. drugbank.comnih.govpatsnap.com

Systemic Blood Pressure Reduction Dynamics

This compound effectively reduces systemic blood pressure. Studies have demonstrated a significant decrease in mean arterial pressure following this compound administration in patients with hypertension. ahajournals.orgahajournals.org The reduction in blood pressure is a direct consequence of the decreased total peripheral resistance. ahajournals.org For instance, in one study of patients with essential hypertension, a single dose of this compound led to a prompt and persistent fall in mean arterial pressure. ahajournals.org Another study using continuous ambulatory intraarterial recording in hypertensive patients showed that this compound tablets significantly lowered systolic and diastolic blood pressure over 24 hours with twice-daily dosing. nih.gov The blood pressure lowering effect during isometric and dynamic exercise testing was also observed. nih.gov

Interactive Table 1: Change in Mean Arterial Pressure After this compound Administration

Cardiac Output Modulation

This compound's effect on cardiac output is often characterized by an increase, particularly in response to the reduction in afterload caused by peripheral vasodilation. patsnap.comahajournals.orgoup.com This increase in cardiac output helps to maintain tissue perfusion despite the fall in blood pressure. ahajournals.org Studies have shown that this compound can lead to a significant increase in cardiac output at rest and during exercise. nih.govjacc.org For instance, in patients with stable exertional angina, this compound increased cardiac output at rest and during exercise. nih.gov Similarly, in patients with primary pulmonary hypertension, this compound led to an increase in cardiac index. nih.gov

Interactive Table 2: Change in Cardiac Output/Index After this compound Administration

Systemic Vascular Resistance Alterations

A primary hemodynamic effect of this compound is the reduction of systemic vascular resistance (SVR). drugbank.comnih.govpatsnap.com This is a direct result of its calcium channel blocking activity on the smooth muscle of peripheral arteries, leading to vasodilation. drugbank.comnih.govpatsnap.com Studies consistently show a significant decrease in SVR following this compound administration in various patient populations. ahajournals.orgbmj.comnih.govjacc.org For example, in patients with stable exertional angina, this compound significantly decreased SVR at rest and during exercise. nih.gov Similarly, patients with chronic cor pulmonale experienced a reduction in SVR at rest and during exercise after receiving this compound. bmj.com

Interactive Table 3: Change in Systemic Vascular Resistance After this compound Administration

Pulmonary Vascular Resistance Modulation

This compound also exerts effects on the pulmonary vasculature, leading to a reduction in pulmonary vascular resistance (PVR). bmj.comnih.govjacc.orgnih.govnih.gov This effect is particularly relevant in conditions like pulmonary hypertension. Studies in patients with primary pulmonary hypertension and pulmonary hypertension associated with connective tissue diseases have shown that this compound can significantly decrease PVR. nih.govnih.govjacc.org For instance, oral this compound produced a significant decrease in mean PVR in patients with pulmonary hypertension associated with diffuse systemic sclerosis, CREST syndrome, and mixed connective tissue disease, both acutely and long-term. nih.gov In patients with chronic cor pulmonale, this compound lowered resting and exercise PVR. bmj.com

Interactive Table 4: Change in Pulmonary Vascular Resistance After this compound Administration

Renal Hemodynamic and Functional Effects

This compound has been reported to influence renal hemodynamics and function. Studies suggest that calcium channel blockers, including this compound, can enhance renal hemodynamic effects. annualreviews.org this compound has been reported to increase glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). annualreviews.orgahajournals.org For example, intravenous administration of this compound to patients with essential hypertension increased both GFR (maximum 24%) and ERPF (maximum 30%). annualreviews.org In a study of essential hypertensive patients, this compound monotherapy significantly increased GFR and ERPF and markedly reduced renal vascular resistance. ahajournals.org These changes in renal function were observed independently of the systemic blood pressure effects in this study. ahajournals.org However, some studies have not consistently shown these effects. annualreviews.org In anesthetized rats, this compound increased urine output and natriuresis. mdpi.com

Interactive Table 5: Change in Renal Hemodynamics and Function After this compound Administration

Efficacy in Essential Hypertension

Studies have explored the effectiveness of this compound in reducing blood pressure in patients with essential hypertension. While historically used for rapid blood pressure reduction, more recent research with slow-release formulations has indicated its efficacy as a monotherapy for mild to moderate hypertension. nih.govoup.com A placebo-controlled study comparing slow-release this compound with cyclopenthiazide-potassium in patients with mild to moderate essential hypertension found similar blood pressure lowering efficacy between the two treatments over a study period of up to 28 weeks. nih.govoup.com

Use in Hypertensive Disorders of Pregnancy

This compound is utilized in the management of hypertensive disorders of pregnancy, including severe hypertension during pregnancy and post-partum hypertension. nih.gov Research, including a meta-analysis of randomized controlled trials, has compared the efficacy of this compound with other antihypertensive medications in this population. nih.gov This meta-analysis, comprising 22 trials with 2595 participants, found that the time and number of doses required to achieve target blood pressure were lower in the this compound group compared to other antihypertensive medications, particularly in patients with severe hypertension. nih.gov Another study investigating the use of extended-release this compound in women with severe preeclampsia during labor and delivery found that those treated with this compound were less likely to require fast-acting intravenous medications for dangerously high blood pressure. heart.org This study also observed trends toward fewer Cesarean deliveries and less neonatal intensive care admissions in the this compound group. heart.org Comparative studies with labetalol in pregnant women with chronic hypertension have shown both drugs to be effective in controlling blood pressure to target levels. ahajournals.org

Comparative Efficacy Studies with Other Antihypertensive Agents

Comparative studies have evaluated the efficacy of this compound against other classes of antihypertensive medications. Research has compared long-acting this compound formulations (such as GITS) with beta-blockers, ACE inhibitors, ARBs, and diuretics. e-century.usnih.gov

A meta-analysis indicated that this compound was more effective than other antihypertensive medications in reducing blood pressure, especially in severe hypertension in pregnant patients. nih.gov In a study comparing sustained-release this compound with sustained-release propranolol, this compound GITS was found to be more efficacious in reducing sitting and standing blood pressure. nih.gov The INSIGHT trial compared this compound GITS with co-amilozide (hydrochlorothiazide/amiloride) and found no significant difference in the primary outcome of composite cardiovascular or cerebrovascular events, suggesting similar protection against these events. nih.gov

Studies comparing this compound with other calcium channel blockers like amlodipine have also been conducted. One trial found that amlodipine provided greater protection against loss of blood pressure control following missed doses compared to this compound GITS. researchgate.net

In the context of hypertensive disorders of pregnancy, comparisons with labetalol and hydralazine have been made. While a meta-analysis suggested this compound was more effective in reducing blood pressure in severe hypertension during pregnancy nih.gov, a randomized controlled trial comparing oral labetalol and this compound for severe hypertension in pregnancy found that while both were effective, oral labetalol showed better blood pressure control with fewer doses in cases where systolic BP was < 180 mmHg and diastolic BP was < 120 mmHg. medrxiv.org Another study comparing this compound, labetalol, and hydralazine in hypertensive emergencies in severe preeclampsia found that single-dose this compound was the most effective in achieving a 20% reduction in mean arterial pressure, although hydralazine was most effective when administered up to three doses within 60 minutes. f1000research.com

Long-term Outcomes in Hypertension Management

Research has also focused on the long-term outcomes associated with this compound use in hypertension management. Large trials have investigated the effectiveness of long-acting this compound formulations in preventing hypertension-related complications. e-century.us Studies have consistently shown the safety and efficacy of these formulations over the long term. e-century.us A nationwide retrospective database analysis comparing generic and brand-name long-acting this compound for hypertension treatment over a mean follow-up of 4.1 years found comparable outcomes regarding all-cause mortality and composite cardiovascular outcomes. nih.gov The ACTION study, which included a significant proportion of patients with both stable symptomatic angina and hypertension, demonstrated that the addition of this compound GITS to the treatment regimen resulted in a significant reduction of cardiovascular morbidity in this high-risk group. medscape.com

Efficacy in Chronic Stable Angina

This compound has shown efficacy in the treatment of chronic stable angina. nih.govahajournals.org Studies have demonstrated that this compound can reduce the frequency of angina episodes and increase exercise tolerance. nih.govnih.gov A double-blind placebo-controlled crossover trial in patients with chronic stable angina pectoris showed that this compound significantly reduced the frequency of angina by 55% and increased exercise time by 34% compared to placebo. nih.gov These antianginal effects are thought to be due to a reduced myocardial oxygen demand for a specific workload and potentially an increased blood supply to ischemic myocardium. nih.gov The IMAGE trial also reported that this compound reduced the frequency of angina and increased mean exercise time in patients with chronic stable angina. nih.gov The ACTION study further supported the use of this compound GITS for the long-term treatment of patients with coronary disease and angina pectoris, showing that it not only relieved angina symptoms but also prolonged cardiovascular event-free and procedure-free survival. medscape.com this compound GITS has also been found effective in combination with beta-blockers in patients with chronic stable angina inadequately controlled on beta-blocker therapy alone, showing improvements in time to onset of ST segment depression, time to anginal pain, and time to termination of exercise. mcmaster.ca

Efficacy in Vasospastic Angina

Research indicates that this compound is effective in the management of vasospastic angina, also known as Prinzmetal's or variant angina. pfizermedicalinformation.comrxlist.compfizer.com This condition is characterized by coronary artery spasm, which reduces blood flow to the heart muscle. pfizermedicalinformation.compfizer.com Studies have shown that this compound is a potent inhibitor of coronary artery spasm, regardless of whether it occurs spontaneously or is induced by agents like ergonovine. pfizer.com

Another study involving 127 patients with Prinzmetal's angina treated with this compound capsules reported a significant reduction in the weekly occurrence of angina attacks, from 16 to 2. ahajournals.org This treatment also reduced nitroglycerin requirements and resulted in complete control of angina in 63% of patients. ahajournals.org The frequency of angina was reduced by at least 50% in 87% of cases. ahajournals.org Comparative studies, such as one involving 19 patients with coronary arterial spasm, suggested that both this compound and isosorbide dinitrate were effective in reducing the frequency of angina and nitroglycerin consumption compared to a lead-in phase. capes.gov.br In this study, the mean frequency of angina was similar between the this compound and isosorbide dinitrate phases. capes.gov.br A 50% or greater decrease in angina frequency compared to baseline was observed in 13 of 18 patients on this compound and 10 of 16 on isosorbide dinitrate. capes.gov.br

Impact on Exercise Tolerance and Angina Frequency

This compound has also been investigated for its effects on exercise tolerance and angina frequency in patients with chronic stable angina (effort-associated angina). pfizermedicalinformation.comrxlist.com In these patients, this compound works by reducing myocardial energy consumption and oxygen requirements through the dilation of peripheral arterioles, which reduces total peripheral resistance (afterload). pfizer.com

Controlled trials of up to eight weeks duration have shown that this compound is effective in reducing angina frequency and increasing exercise tolerance in patients with chronic stable angina. pfizermedicalinformation.comrxlist.compfizer.com For instance, a study administering 10 mg of sublingual this compound to ten patients with angina pectoris demonstrated increased exercise tolerance during bicycle exercise tests. nih.gov this compound led to prolonged work time and the achievement of higher work loads. nih.gov The total work performed increased by 50% in one test and 23% in another, approximately 50 minutes after drug administration. nih.gov This improved work capacity was attributed to diminished heart work due to a fall in systemic vascular resistance. nih.gov

A study using this compound-GITS (Gastrointestinal Therapeutic System) in patients with chronic stable angina showed a reduction in the weekly number of anginal episodes from 5.7 to 1.8 (P=.0001) and a decrease in ischemic events (assessed by ambulatory ECG monitoring) from 7.3 to 4 (P=.0001). ahajournals.org The drug reduced ischemia over a 48-hour period, both alone and in combination with a beta-blocker. ahajournals.org

Table 1: Summary of this compound's Impact on Angina Frequency and Exercise Tolerance

Efficacy in Primary Pulmonary Arterial Hypertension

In primary pulmonary arterial hypertension (IPAH), a subset of patients exhibits acute pulmonary vasoreactivity and may benefit from calcium channel blocker therapy, including this compound. ahajournals.orgfrontiersin.orgbjcardio.co.uk While only a minority of IPAH patients are acute responders, long-term administration of high-dose calcium channel blockers has been suggested to prolong survival in these responsive individuals. ahajournals.orgresearchgate.net

A study involving 64 patients with primary pulmonary hypertension treated with high doses of calcium channel blockers, including this compound, identified responders based on an acute reduction in pulmonary artery pressure and pulmonary vascular resistance of more than 20% after a challenge. researchgate.net Among these responders, 94% were alive after five years, compared to 55% of non-responders (P = 0.003). researchgate.net The survival rate of responders was also significantly better than that of a historical control group from the NIH registry. researchgate.net Another study found that among 70 patients displaying acute pulmonary vasoreactivity, only 38 showed long-term improvement with calcium channel blocker therapy. ahajournals.org Long-term responders had less severe disease at baseline and a more pronounced fall in mean pulmonary artery pressure during acute vasodilator testing. ahajournals.org

Hemodynamic Response in Pulmonary Circulation

This compound's impact on pulmonary circulation involves its vasodilatory properties. In patients with pulmonary hypertension secondary to chronic obstructive lung disease, a single dose of this compound led to a significant improvement in pulmonary circulation and right ventricular pump function. nih.gov An increase in tissue oxygen delivery was also observed. nih.gov These effects were sustained after 15 days of oral intake. nih.gov

Research also suggests that in experimental models of established pulmonary hypertension, this compound might exacerbate pulmonary vascular hemodynamics by increasing right ventricular systolic pressure, potentially through the activation of calcium-sensing receptors (CaSR) in pulmonary arterial smooth muscle cells. ahajournals.org In normal pulmonary arterial smooth muscle cells with low CaSR expression, this compound primarily blocks voltage-dependent calcium channels (VDCC), leading to vasodilation. ahajournals.org However, in IPAH and experimental PH where CaSR is upregulated, this compound can activate CaSR and increase intracellular calcium. ahajournals.org

Table 2: Hemodynamic Effects of this compound in Pulmonary Hypertension

Long-term Efficacy and Survival Outcomes in Pulmonary Hypertension

For the subset of IPAH patients who are acute responders to vasodilators, long-term calcium channel blocker therapy, including this compound, has been associated with sustained functional and hemodynamic improvement and prolonged survival. frontiersin.orgahajournals.orgresearchgate.net

A meta-analysis of eight trials investigating this compound therapy in pulmonary hypertensive disorders demonstrated a significant decrease in pulmonary artery pressure over weeks to months of treatment, with a mean reduction of -7 mm Hg (95% confidence interval, -3 to -11 mm Hg; P < 0.01) in homogeneous trials. nih.gov This decrease in pulmonary artery pressure was associated with an amelioration of clinical symptoms. nih.gov

In a study following six patients with primary pulmonary hypertension treated with this compound for 4 to 14 months, cardiac output increased and total pulmonary resistance decreased compared to baseline values. nih.gov Pulmonary arterial pressure remained unchanged. nih.gov This suggests potential long-term benefits in terms of cardiac function and pulmonary vascular resistance. nih.gov

For long-term responders to calcium channel blockers in IPAH, survival rates are significantly higher compared to non-responders. researchgate.net As noted earlier, a five-year survival rate of 94% was observed in responders treated with high-dose calcium channel blockers, including this compound. researchgate.net

Tocolysis in Preterm Labor

Research has explored the use of this compound as a tocolytic agent to inhibit uterine contractions and delay delivery in cases of preterm labor. A systematic review and meta-analysis of randomized controlled trials involving 2179 women found that this compound was associated with a significant reduction in the risk of delivery within 7 days of treatment initiation and before 34 weeks' gestation when compared to β2-adrenergic-receptor agonists. nih.gov This analysis also indicated a lower risk of respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, neonatal jaundice, and admission to the neonatal intensive care unit with this compound compared to β2-adrenergic-receptor agonists. nih.gov

However, some studies suggest that while this compound can inhibit uterine contractions, its effectiveness in significantly prolonging pregnancy beyond 48 hours or 7 days compared to control groups may not be statistically significant in all cases. nih.govinajog.com For instance, one randomized, double-blind, placebo-controlled trial found no significant difference in delivery before 37 weeks or delivery at least 48 hours from randomization between the this compound and placebo groups. nih.gov

Despite some variations in findings regarding the extent of pregnancy prolongation, this compound is considered an effective option for inhibiting uterine contractions in threatened preterm labor, potentially allowing time for corticosteroid administration to enhance fetal lung maturity. pjmhsonline.comdovepress.com

Here is a summary of findings from a meta-analysis comparing this compound to β2-adrenergic-receptor agonists in preterm labor:

Data source: nih.gov

Safety and Efficacy in Pregnancy

This compound is considered safe for use in pregnancy with little teratogenic or fetotoxic potential. nih.gov Studies have evaluated its efficacy and safety in managing hypertensive disorders of pregnancy, such as gestational hypertension and severe preeclampsia. medicopublication.comijrcog.orgmedicopublication.comijbcp.com

Research indicates that oral this compound can be effective in managing severe hypertension in pregnancy, with some studies suggesting it may decrease blood pressure more rapidly compared to intravenous labetalol. ijrcog.org In a prospective observational study, this compound showed significantly better clinical outcomes and a better safety profile in terms of adverse effects compared to other antihypertensives in patients with pregnancy-induced hypertension. medicopublication.commedicopublication.com Another study comparing this compound and methyldopa in moderate gestational hypertension found both to be effective in controlling blood pressure with minimal side effects, though this compound showed a significant reduction in systolic blood pressure at four weeks. ijbcp.com

For women with severe preeclampsia, research suggests that daily treatment with extended-release this compound during labor and delivery may lead to better blood pressure control and reduce the need for fast-acting intravenous medications. heart.org Studies also observed trends towards fewer Cesarean deliveries and less neonatal intensive care admissions for newborns when mothers were treated with this compound during labor induction for high blood pressure. heart.org

Potential Applications in Dysmenorrhea and Bladder Irritability

This compound has potential and theoretical indications for the treatment of dysmenorrhea and bladder irritability due to its smooth muscle relaxing properties. nih.govresearchgate.netresearchgate.net Dysmenorrhea is thought to be caused by strong uterine contractions linked to high levels of prostaglandins. ranzcogasm.com.au As a calcium channel blocker that inhibits uterine contractions, this compound could theoretically offer therapeutic benefits. ranzcogasm.com.au

However, the evidence supporting the efficacy of this compound for primary dysmenorrhea is currently limited and of very low quality. researchgate.netranzcogasm.com.au Small randomized controlled trials have suggested that this compound may be effective for pain relief compared to placebo, with some participants indicating a preference for this compound over previous analgesics. researchgate.netranzcogasm.com.au Despite these preliminary findings, larger and higher-quality trials are needed to confirm its effectiveness for this indication. researchgate.netranzcogasm.com.au

Impact on Embryo Transfer Outcomes

The potential for this compound to improve outcomes in in-vitro fertilization (IVF) by reducing uterine contractions during embryo transfer has been investigated. sid.irmivf.com.auzums.ac.ir Uterine contractions at the time of embryo transfer have been inversely related to implantation and pregnancy rates. mivf.com.au

However, research findings on the impact of this compound on embryo transfer success rates have been mixed. A double-blinded randomized clinical trial involving ninety-eight infertile women found that a single dose of 20 mg this compound administered thirty minutes before embryo transfer had no statistically significant effect on improving clinical pregnancy or live birth rates compared to a placebo group. sid.irzums.ac.ir Similarly, an interim analysis of another randomized, double-blinded, placebo-controlled trial found no statistical differences in implantation rate or clinical pregnancy rate between the this compound and placebo groups. mivf.com.au

Conversely, one interventional clinical trial in women with recurrent implantation failure reported clinical pregnancy in 15 out of 60 patients who received a 10 mg dose of this compound two hours before embryo transfer.

Impact on Glomerular Filtration Rate and Renal Plasma Flow

Studies have investigated the effects of this compound on glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in various patient populations, particularly those with hypertension.

In hypertensive patients with moderately severe renal dysfunction, this compound GITS (a sustained-release formulation) also led to increases in GFR and ERPF, by 18% and 20% respectively, after 5 weeks. nih.gov Similar to essential hypertensive patients, these changes were independent of the blood pressure response. nih.gov

Research in the context of cyclosporine-associated hypertension has shown that while this compound can reduce systemic vasoconstriction, it did not consistently translate into improved renal function or a reversal of vasoconstriction within the kidney at the doses studied. ahajournals.org However, calcium channel blockers, including dihydropyridines like this compound, have been suggested to ameliorate experimental nephrotoxicity from cyclosporine and prevent renal vasoconstriction. ahajournals.org

Studies comparing different types of calcium channel blockers have suggested that L-type calcium channel blockers like this compound may increase both renal plasma flow and GFR, potentially indicating a preferential effect on afferent arterioles. physiology.org

Here is a summary of the impact of this compound on GFR and ERPF in essential hypertensive patients:

Data source: nih.gov

Compound Names and PubChem CIDs

Renal Vascular Resistance Modulation

Research has investigated the effects of this compound on renal vascular resistance. Studies in patients with severe chronic congestive heart failure demonstrated that oral this compound was associated with a decrease in systemic vascular resistance and mean arterial blood pressure. While renal vascular resistance also decreased, no significant change was observed in renal blood flow or glomerular filtration rate in this specific population. nih.gov

Further studies, such as those conducted in spontaneously hypertensive rats (SHR), have compared the peripheral vascular effects of this compound in normotensive and hypertensive models. These studies indicated that this compound was effective in reducing resistance in various vascular beds, and notably, it reduced renal vascular resistance to a greater extent in SHR compared to normotensive rats. tandfonline.com

In studies involving the inhibition of nitric oxide synthase in humans, this compound was shown to partially restore renal vascular resistance that had increased due to sustained nitric oxide deficiency. ahajournals.org Additionally, research in animal models of cyclosporin A nephrotoxicity has explored the impact of this compound on renal hemodynamics. One study found that administering this compound simultaneously with cyclosporin A prevented the characteristic increase in renal vascular resistance and decline in renal function. However, administering this compound after a period of cyclosporin A exposure did not improve renal hemodynamics. portlandpress.com

In hypertensive patients with renal failure, plasma concentrations of this compound were found to be significantly correlated with effects on blood pressure, forearm blood flow, and peripheral resistance. These effects did not vary with the degree of renal failure. nih.gov

Effects on Urinary Albumin Excretion

The impact of this compound on urinary albumin excretion has been examined in various patient populations. In essential hypertensive patients, this compound monotherapy effectively lowered blood pressure and increased glomerular filtration rate and effective renal plasma flow. However, urinary albumin excretion remained unchanged in this study. ahajournals.org

Research in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus investigated the effects of nilvadipine, a this compound analog, on urinary albumin excretion. This study reported a significant reduction in urinary albumin excretion after 24 weeks of nilvadipine treatment, suggesting a potential role in slowing the progression of diabetic nephropathy in this specific group. nih.gov

A randomized, double-blind trial in normotensive type 1 diabetic patients with microalbuminuria investigated the long-term effects of this compound. This study found that long-term treatment with this compound reduced urinary albumin excretion and glomerular filtration rate in this population. nih.gov

Conversely, a study on the effects of low-dose this compound on urinary protein excretion rate in patients with renal disease observed that while this compound lowered mean arterial blood pressure and attenuated proximal tubular sodium reabsorption, it did not affect proximal tubular protein reabsorption or immediately reduce urinary albumin or IgG excretion rates. oup.com Continued treatment for one week did not influence 24-hour protein excretion, but an increase in proteinuria was observed during daily activities in the first four hours after drug intake compared to the supine position. oup.com

A comparison between perindopril and this compound in hypertensive and normotensive diabetic patients with microalbuminuria found that both drugs had similar effects on urinary albumin excretion, preventing increases in albuminuria in normotensive patients and decreasing it in hypertensive patients. bmj.com

Role in Renal Impairment and Chronic Kidney Disease

The role of this compound in the context of renal impairment and chronic kidney disease (CKD) has been explored, with studies yielding varying results and perspectives. In hypertensive patients with renal failure, this compound was found to be effective in lowering blood pressure and may improve renal function in some individuals. nih.gov

However, the ability of dihydropyridine calcium channel blockers, including this compound, to protect kidney function in hypertensive patients with CKD has been questioned. dovepress.com Some research suggests that classical first- and second-generation dihydropyridine calcium antagonists like this compound may increase rather than decrease intraglomerular pressure, potentially increasing glomerular filtration rate but also proteinuria unless a marked reduction in blood pressure is achieved. dovepress.com

A multicenter randomized controlled trial comparing manidipine and this compound in hypertensive patients with moderate chronic renal function impairment found that both drugs significantly reduced blood pressure. However, proteinuria increased in the this compound group, while it did not significantly change in the manidipine group. tandfonline.com

While blocking the renin-angiotensin-aldosterone system (RAAS) is considered a standard approach for hypertension and proteinuria in CKD, some indications suggest that certain calcium channel blockers may be useful in managing uncontrolled blood pressure in CKD patients. dovepress.comecrjournal.com

Investigation of Lipogenesis Modulation in Renal Tissue

Research has delved into the potential of this compound to modulate lipogenesis in renal tissue. Lipid accumulation in renal cells is implicated in the pathogenesis of obesity-related kidney disease and can serve as a marker for renal failure or fibrosis. biorxiv.orgmdpi.com

Studies utilizing renal cell models have examined the effects of this compound on lipogenesis enzymes and lipotoxicity. One study found that this compound activated several enzymes involved in the production of cholesterol, triglycerides, and phospholipids. biorxiv.org this compound exposure in these models induced a significant accumulation of cytosolic free fatty acids, stimulated reactive oxygen species production, upregulated markers of kidney injury, inhibited AMPK activity, and triggered the transcription of SREBP-1/2 and lipin-1, suggesting a potential for this compound to induce lipotoxicity and renal damage. biorxiv.orgnih.gov

This research suggests that this compound may induce lipid accumulation in the kidney, potentially via the AMPK-SREBP-1/2 pathway. biorxiv.orgmdpi.com Further in vivo studies using a doxorubicin-induced kidney injury rat model demonstrated that this compound may exacerbate renal fibrosis and lipogenesis, with higher expression of CD36/SREBP-1/2 signals observed. nih.govmdpi.com These findings highlight the importance of monitoring this compound use and lipid content in patients with CKD due to the potential for lipogenesis to impact renal function and fibrosis. nih.govmdpi.com

High Altitude Pulmonary Edema

This compound has been studied for its potential role in the prevention and treatment of high altitude pulmonary edema (HAPE). HAPE is related to increased pulmonary artery pressure secondary to hypoxic vasoconstriction. jwatch.org Studies have shown that this compound can help prevent and treat HAPE by lowering pulmonary artery pressure and reducing hypoxia. jwatch.orgmedscape.com

A randomized trial in mountaineers with a history of HAPE demonstrated that prophylactic this compound reduced the likelihood of developing pulmonary edema compared to placebo. jwatch.org this compound-treated subjects also exhibited lower pulmonary artery pressures. jwatch.orgatsjournals.org For individuals with a prior history of HAPE, this compound is suggested as prophylaxis when ascending to altitudes above 2500m, supported by randomized controlled trials showing decreased incidence of HAPE and improved oxygen saturation in susceptible patients. emdocs.net

However, a double-blind trial evaluating whether this compound can prevent acute mountain sickness (AMS) found that while this compound lowered pulmonary artery pressures, it did not affect arterial oxygen levels or the incidence of AMS. atsjournals.orgjwatch.org This suggests that lowering pulmonary artery pressure alone may not have a beneficial effect on gas exchange and AMS symptoms in individuals not susceptible to HAPE. atsjournals.org Therefore, the use of this compound in high altitude medicine is primarily recommended for the prevention and treatment of HAPE. atsjournals.org

Achalasia

Research has explored the use of this compound in the management of achalasia, a disorder characterized by impaired relaxation of the lower esophageal sphincter (LES). This compound, as a calcium channel blocker, inhibits cellular uptake of calcium, which can impede contraction and promote relaxation of smooth muscle. wjgnet.com

Studies have shown that this compound can decrease LES pressures and provide symptomatic relief in patients with achalasia, although with variable efficacy. wjgnet.comnih.gov Early investigations in the late 1970s and 1980s explored the efficacy of calcium channel blockers for achalasia. wjgnet.com

In a double-blind, placebo-controlled, crossover trial, sublingual this compound was found to reduce symptoms of achalasia, although substantial symptoms could still remain. nih.gov this compound significantly reduced LES pressure, but the effect was less pronounced than that achieved by pneumatic dilatation or myotomy. nih.gov While this compound may be considered for patients at high risk for more invasive procedures, it is not typically recommended as a standard alternative to these modalities due to its limited effect on LES pressure and unchanged esophageal emptying rates in some studies. nih.gov

Comparisons with other treatments for achalasia, such as isosorbide dinitrate, have suggested that while isosorbide dinitrate might be more effective and faster in relaxing the LES, this compound was sometimes preferred due to its effect on reducing the amplitude of esophageal pressure waves less. karger.com However, some studies indicated that isosorbide dinitrate was more effective than this compound in relieving symptoms and improving esophageal emptying. osti.gov

Despite some limitations, this compound has demonstrated the ability to improve smooth muscle function in esophageal motility disorders like achalasia in some studies. acpjournals.org

Compound Names and PubChem CIDs

Data Tables

While specific raw data tables from individual studies are not directly extractable in a universally interactive format within this text-based response, the findings presented in the sections above summarize key quantitative and qualitative results from the cited research. For instance, the reduction in renal vascular resistance in SHR compared to WKY rats tandfonline.com, the percentage reduction in LES pressure with this compound in achalasia studies nih.gov, and the changes in urinary albumin excretion reported in various patient groups ahajournals.orgnih.govnih.gov represent data points and trends discussed in the research.

For example, a summary of renal hemodynamic effects from one study nih.gov could be conceptually represented as:

Similarly, data on urinary albumin excretion nih.gov could be summarized:

These conceptual tables illustrate the type of data discussed in the research findings for each section.

Distal Ureteric Calculi

Research has explored the use of this compound as a medical expulsive therapy (MET) for distal ureteric stones. The rationale behind this application is based on this compound's ability to relax smooth muscles, potentially facilitating the passage of stones through the ureter.

Studies have compared the efficacy of this compound with other medical expulsive therapies, such as alpha-blockers like tamsulosin, and with placebo or control groups. One randomized controlled study involving patients with distal ureteric calculus less than 10 mm compared this compound (30 mg/day), alfuzosin (10 mg/day), and placebo. Stone expulsion rates were observed in 60% of patients in the this compound group, 85.7% in the alfuzosin group, and 20% in the placebo group. A statistically significant difference was noted between the this compound and placebo groups (P<0001). journalcra.com The mean pain attack episodes were also statistically significant between groups. journalcra.com

Another randomized clinical trial comparing tamsulosin and this compound for distal ureterolithiasis in patients with stones in the juxtavesical tract found a stone expulsion rate of 55% for the this compound group and 80% for the tamsulosin group (P = 0.004). nih.gov The mean expulsion time was 23 days for the this compound group and 9 days for the tamsulosin group (P < 0.001). nih.gov The mean number of analgesic injections was also higher in the this compound group. nih.gov

A meta-analysis comparing tamsulosin and this compound for distal ureteral calculi included 12 randomized controlled trials with 4961 patients. dovepress.com The analysis indicated that tamsulosin significantly increased the expulsion rate compared to this compound (risk ratio = 1.29, 95% CI [1.25, 1.33], P < 0.00001). dovepress.com Tamsulosin was also associated with a lower risk of complications. dovepress.com

A study investigating the combination of tamsulosin and this compound versus tamsulosin alone for lower ureteric stones (5-10 mm) reported an expulsion rate of 87.5% in the combination group and 65.6% in the tamsulosin alone group (p<0.05). ijbcp.com The mean expulsion time was shorter in the combination group (6.68 ± 1.89 days) compared to tamsulosin alone (8.52 ± 2.62 days) (p<0.05). ijbcp.com

These studies suggest that this compound can be effective as medical expulsive therapy for distal ureteric stones compared to placebo, but alpha-blockers like tamsulosin may demonstrate superior stone expulsion rates and shorter expulsion times in comparative studies.

Cognitive Impairment

The potential effect of this compound on cognitive impairment has been explored, particularly in the context of vascular risk factors such as hypertension and diabetes. Hypertension is recognized as a risk factor for cognitive decline and dementia. frontiersin.org, ahajournals.org

While some studies on calcium channel blockers in general, such as the SYST-EUR trial with nitrendipine (another calcium channel blocker), have shown a reduction in the incidence of dementia, research specifically on this compound's direct impact on cognitive function in humans is less extensive and conclusive. frontiersin.org

Animal studies, such as one using a type 2 diabetic mouse model (KK-Ay mice), have investigated the effect of this compound on diabetes-associated cognitive impairment. ahajournals.org Oral administration of this compound at a nonhypotensive dose improved cognitive function in these mice. ahajournals.org The study suggested that this compound might ameliorate impaired cognitive function through mechanisms including attenuation of hyperinsulinemia and superoxide production in the brain, and possible upregulation of a neural differentiation-controlling gene. ahajournals.org

The relationship between hypertension treatment and cognitive function is complex, and while controlling blood pressure is important for reducing vascular risk, the specific effects of different antihypertensive agents on cognitive outcomes require further research.

Frostbite Secondary Prevention (Topical Application)

Topical application of this compound has been explored as a potential intervention for the secondary prevention of sequelae in patients who have previously experienced frostbite. The rationale is based on this compound's vasodilatory properties, which could potentially improve blood flow to cold-exposed tissues.

A study investigated the thermal response in the digits of hands and feet of subjects who had recovered from previous frostbite. nih.gov, nih.gov, researchgate.net The study compared the effect of a topical 10% this compound preparation under different conditions, including healthy digits, frostbitten digits without amputation, and frostbitten digits with amputation. nih.gov, nih.gov, researchgate.net

Under cold conditions (after immersion in cold water), topical this compound application improved the cold response in healthy fingers, resulting in them being significantly less cold compared to when no this compound was applied. nih.gov, nih.gov, researchgate.net However, the study observed a negative effect on previously frostbitten digits that had undergone amputation, with these digits losing more temperature when treated with the this compound cream. nih.gov, nih.gov, researchgate.net Topical this compound also had detrimental effects on toes in all conditions tested. nih.gov, nih.gov, researchgate.net

Under basal conditions (without thermal stress), this compound showed a cooling effect on healthy and post-amputated tissue. nih.gov, nih.gov, researchgate.net

The findings suggest that topical this compound may be a potentially interesting tool for healthy digits exposed to cold, provided adequate thermal insulation is maintained, as it led to warmer temperatures in this context. nih.gov, nih.gov, researchgate.net However, the study highlights potentially harmful effects on previously frostbitten tissue, particularly amputated digits and toes. nih.gov, nih.gov, researchgate.net Further research is needed to clarify its usefulness in previously frostbitten tissue without amputation at mild cold temperatures. nih.gov

Vasodilation-Related Adverse Effects

This compound's inhibition of calcium influx into vascular smooth muscle cells causes relaxation and dilation of peripheral arteries and arterioles mims.comnih.gov. This widespread vasodilation can lead to several common adverse effects:

Headache: Vasodilation of cerebral blood vessels is a common cause of headache ahajournals.orgphysiology.orghealthline.com.

Flushing: Cutaneous vasodilation results in a sensation of warmth and reddening of the skin, particularly in the face and neck ahajournals.orgphysiology.orghealthline.com.

Dizziness and Lightheadedness: Reduced peripheral resistance can lead to a drop in blood pressure, causing dizziness or lightheadedness, especially upon standing (orthostatic hypotension) ahajournals.orgphysiology.orghealthline.com.

Peripheral Edema: this compound commonly causes peripheral edema, typically in the lower extremities. This is thought to be associated with arterial vasodilation rather than left ventricular dysfunction ahajournals.orghres.ca. The exact mechanism is uncertain, but it may involve increased capillary hydrostatic pressure due to preferential arteriolar dilation ahajournals.org. Peripheral edema was reported in 10.1% of patients in studies with extended-release this compound hres.ca.

Gastrointestinal System Effects

While less frequent than vasodilation-related effects, this compound can affect the gastrointestinal system.

Nausea and Constipation: These are reported adverse effects ahajournals.orghealthline.com. The mechanism may involve effects on smooth muscle in the gastrointestinal tract, although this compound has less effect on gastrointestinal smooth muscle compared to other calcium channel blockers like verapamil ahajournals.org.

Heartburn: Heartburn has been reported as a less common side effect researchgate.net.

GI Obstruction: In rare cases, symptoms of GI obstruction have occurred in patients with a history of GI strictures when using extended-release this compound tablets medcentral.com. The intact tablet shell of some extended-release formulations (like the GITS system) is excreted in feces, which is a common feature of osmotic-controlled delivery devices e-century.us.

GI Irritation and Bleeding: These have been reported rarely with extended-release formulations, although a causal relationship has not been definitively established medcentral.com.

Corrosive Effect: Case reports have described esophageal and gastric mucosal damage potentially related to this compound ingestion researchgate.net.

Gum Hyperplasia

Gingival hyperplasia, or overgrowth of gum tissue, is a recognized adverse effect associated with calcium channel blockers, including this compound mdpi.commedscape.comnih.gov. The prevalence of gingival enlargement has been reported as significantly higher in patients treated with this compound compared to control groups mdpi.com.

The exact mechanisms by which calcium antagonists induce gingival hyperplasia are still under investigation, but leading hypotheses involve the drug's interaction with gingival fibroblasts mdpi.commedscape.com. Research suggests that this compound may inhibit the influx of calcium ions necessary for the normal degradation and synthesis of collagen medscape.com. This can lead to an excessive accumulation of collagen and other extracellular matrix molecules in the gingival tissue mdpi.commedscape.comresearchgate.netresearchgate.net. Studies have shown altered gene expression profiles in human gingival fibroblasts treated with this compound, including upregulation of matrix metalloproteinase 24 and 8 (MMP24, MMP8) and increased E-cadherin levels, alongside downregulation of other matrix metalloproteinases and integrins mdpi.comresearchgate.net. These findings support the idea that this compound disrupts the normal balance of extracellular matrix turnover, leading to tissue accumulation mdpi.comresearchgate.net. Poor oral hygiene and higher drug doses have been associated with increased severity of this compound-induced gingival enlargement nih.gov.

Reflex Tachycardia and Palpitations

This compound's potent vasodilatory effect leads to a decrease in peripheral vascular resistance and blood pressure mims.comnih.govdroracle.ai. The body compensates for this rapid drop in blood pressure through the baroreceptor reflex, which activates the sympathetic nervous system researchgate.netdroracle.airesearchgate.netnih.gov. This sympathetic activation results in an increase in heart rate (reflex tachycardia) and contractility to maintain cardiac output researchgate.netdroracle.airesearchgate.net. Palpitations are a subjective awareness of this increased heart rate ahajournals.orgresearchgate.netresearchgate.net.

Reflex tachycardia is more pronounced with immediate-release formulations due to the rapid onset of vasodilation and subsequent rapid drop in blood pressure droracle.airesearchgate.netwikipedia.org. Extended-release formulations, which provide a slower and more sustained reduction in blood pressure, are associated with less reflex tachycardia researchgate.netdroracle.airesearchgate.net. Concomitant use of beta-blockers can help counteract this compound-induced reflex tachycardia nih.govdroracle.ai.

Proischemic Effects and Myocardial Ischemic Damage

Concerns have been raised regarding the potential for this compound, particularly short-acting formulations, to exacerbate myocardial ischemia or cause myocardial damage nih.govahajournals.orgneurology.orgpharmacologyeducation.org. Several mechanisms have been proposed for these proischemic effects:

Coronary Steal Phenomenon: In the presence of coronary artery stenosis, potent vasodilation by this compound in healthy coronary vessels can divert blood flow away from ischemic areas supplied by narrowed vessels, potentially worsening ischemia medcentral.comwikipedia.orgpharmacologyeducation.orgahajournals.org. While the concept of coronary steal in humans with this compound is debated, some studies suggest an increase in angina in patients with coronary collaterals may be associated with this phenomenon ahajournals.org.

Increased Myocardial Oxygen Demand: Reflex tachycardia and increased cardiac contractility, driven by sympathetic activation in response to vasodilation, increase the heart's workload and oxygen demand medcentral.compharmacologyeducation.orgnih.gov. In patients with compromised coronary blood flow, this increased demand may outstrip the available oxygen supply, leading to or worsening ischemia medcentral.compharmacologyeducation.org.

Profound Hypotension: Excessive and poorly tolerated hypotension, particularly with immediate-release formulations, can reduce coronary perfusion pressure, potentially leading to myocardial ischemia or infarction medcentral.comahajournals.orgneurology.org.

Negative Inotropic Effects: Although this compound's negative inotropic effect (reducing contractility) is usually counterbalanced by reflex sympathetic activation at therapeutic doses, it can become clinically significant, especially in patients with pre-existing left ventricular dysfunction researchgate.netmedcentral.com. This can further compromise cardiac function and potentially worsen ischemia neurology.org.

Proarrhythmic Effects: Some evidence suggests that short-acting this compound may have proarrhythmic effects, which could contribute to adverse cardiovascular events, particularly in vulnerable patients ahajournals.orgneurology.org.

Meta-analyses and case-control studies, particularly in the 1990s, raised concerns about a potential dose-dependent increase in the risk of myocardial infarction and mortality in hypertensive patients receiving short-acting calcium channel blockers, including this compound medcentral.comnih.govahajournals.orgahajournals.org. For instance, a meta-analysis indicated a dose-response relationship, with higher daily doses of short-acting this compound (e.g., 80 mg/d) associated with a significantly increased risk of mortality compared to lower doses ahajournals.org. However, the interpretation and applicability of these findings, especially to newer extended-release formulations and in different patient populations, have been debated, with some analyses highlighting limitations in the earlier studies nih.govahajournals.org. Studies with extended-release this compound formulations have generally shown a more favorable cardiovascular safety profile e-century.usahajournals.org.

Data Tables

While specific comprehensive data tables detailing the frequency and mechanisms across numerous studies are extensive and beyond the scope here, the search results provide some representative data points on adverse event frequency:

Negative Inotropic Effects

This compound, as a calcium channel blocker, can exert a negative inotropic effect, meaning it can reduce the force of myocardial contraction. This effect is related to its primary mechanism of inhibiting calcium influx into cardiac muscle cells, which is essential for excitation-contraction coupling. hres.ca While this compound has a greater direct negative inotropic action on human ventricular myocardium compared to non-dihydropyridines like verapamil and diltiazem in isolated preparations, this effect is often counterbalanced in clinical practice. hres.caahajournals.orgeur.nl Therapeutic doses of this compound typically induce peripheral vasodilation, which triggers a baroreceptor-mediated reflex tachycardia and increased cardiac contractility, potentially masking the direct negative inotropic effect. hres.caeur.nl

However, the negative inotropic effect can become clinically significant, particularly in patients with pre-existing left ventricular dysfunction or when used in conjunction with beta-blockers, which blunt the reflex sympathetic response. mims.comahajournals.orgeur.nl Studies in isolated heart preparations have demonstrated a dose-dependent decrease in left ventricular systolic pressure and the maximum rate of pressure increase (dp/dt) with this compound. hres.ca Research in immature rabbit hearts suggests that in neonatal myocytes, the negative inotropic effect of L-type Ca2+ channel blockers like this compound might be primarily due to shortening of the action potential duration, thereby decreasing calcium influx through the sodium-calcium exchanger (NCX), rather than a direct effect on L-type calcium channel-mediated calcium transient amplitude as seen in adults. researchgate.net

Proarrhythmic Effects

The potential for this compound to induce proarrhythmic effects has been a subject of investigation. While some early reports and meta-analyses suggested a possible association between short-acting this compound and increased risk of stroke, attributed in part to proarrhythmic effects, other studies have not provided convincing evidence for a direct proarrhythmic effect of this compound. ahajournals.orgneurology.orgahajournals.org Some research, in fact, has indicated potential antiarrhythmic effects with other dihydropyridines like nimodipine. ahajournals.org

However, the reflex sympathetic activation induced by the rapid vasodilation from short-acting this compound can lead to tachycardia and increased cardiac output, which theoretically could contribute to arrhythmias in susceptible individuals. ahajournals.orgneurology.org A study in rabbit Purkinje fibers suggested that a high concentration of this compound might counteract the proarrhythmic effects of ondansetron by inhibiting L-type Ca++ current, indicating a complex interplay with cardiac electrophysiology. researchgate.net Despite some concerns, large randomized controlled trials with long-acting this compound formulations have not found an increased risk of all-cause mortality, which might be expected if significant proarrhythmic effects were common. oup.com

Severe Hypotension and Associated Risks

This compound is a potent vasodilator, and its primary therapeutic effect is blood pressure reduction. mims.comresearchgate.netfda.gov However, this vasodilatory action can lead to severe hypotension, particularly with immediate-release formulations or during initial titration and dosage adjustments. fda.govnih.gov Severe hypotension can result in decreased coronary perfusion pressure and reflex cardiac acceleration, potentially increasing myocardial ischemic damage, especially in patients with coronary artery disease. ahajournals.org

The risk of severe hypotension is also increased in patients receiving concomitant beta-blockers or undergoing certain types of anesthesia. mims.comfda.gov In patients with severe aortic stenosis, the reduction in vascular resistance caused by this compound can lead to impaired blood flow to the coronary arteries and potentially ventricular collapse and dysfunction. nih.goveprajournals.com Overdose of this compound can cause systemic vasodilation, severe hypotension, and reflex tachycardia, which can progress to shock and be potentially fatal. nih.govresearchgate.net

Rebound Hypertension or Angina upon Abrupt Discontinuation

Abrupt discontinuation of this compound after prolonged use may lead to rebound hypertension or angina. researchgate.netnih.gov While the exact mechanism is not fully established, it is believed to be related to the sudden withdrawal of the vasodilatory effect. eprajournals.comnih.gov This can result in a rapid increase in blood pressure or a worsening of anginal symptoms, particularly in individuals with underlying coronary artery disease. eprajournals.comnih.gov This phenomenon is more commonly associated with the cessation of the vasodilatory effects rather than direct withdrawal symptoms akin to those seen with beta-blockers. eprajournals.com Awareness of this potential rebound effect is important, especially considering the widespread use of calcium antagonists. nih.gov

Effects on Proteinuria and Glomerular Hypertension

The effects of this compound on proteinuria and glomerular hypertension have been examined in various studies. While some calcium channel blockers, particularly non-dihydropyridines like diltiazem and verapamil, have been associated with decreases in proteinuria, dihydropyridine calcium antagonists like this compound have shown varied effects. jwatch.orgacpjournals.org

Some clinical studies have suggested that this compound may increase urinary protein excretion and potentially lead to renal dysfunction. acpjournals.orgmdpi.com This contrasts with agents that lower glomerular capillary pressure, which can decrease proteinuria. acpjournals.org However, other research, including studies in spontaneously hypertensive rats (SHR) with uninephrectomy, found that this compound reduced glomerular capillary pressure (PGC) and significantly reduced proteinuria and glomerular sclerosis, suggesting a potential to prevent progressive kidney damage, comparable to ACE inhibitors in this model. nih.gov

A study comparing sustained-release this compound (GITS) with enalapril in elderly nondiabetic hypertensive patients found that both drugs reduced proteinuria by 37%, despite having disparate effects on neurohormonal activation and ambulatory blood pressure control. karger.com This suggests that this compound GITS can be effective in reducing proteinuria in this population. karger.com Another study in essential hypertensive patients showed that this compound monotherapy did not adversely affect renal function and could improve glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the short term, although these gains were not always sustained in long-term therapy. ahajournals.orgoup.com The effect on renal function appeared to be independent of the systemic blood pressure-lowering effect. ahajournals.org

Data Table: Effects of this compound vs. Enalapril on Proteinuria and Neurohormones

*Data based on a study in elderly nondiabetic hypertensive patients. karger.com

Exacerbation of Lipogenesis in Kidney

Recent research has indicated that this compound may exacerbate lipogenesis in the kidney. Lipid accumulation in renal cells is implicated in the pathogenesis of kidney injury and can contribute to renal fibrosis. mdpi.comnih.govbiorxiv.orgdntb.gov.ua

Studies using rat renal tubular cells (NRK52E) have shown that this compound can activate enzymes involved in lipogenesis, suggesting increased production of cholesterol, triacylglycerides, and phospholipids. nih.govbiorxiv.org this compound exposure has been found to induce the accumulation of cytosolic free fatty acids, stimulate reactive oxygen species production, and upregulate proteins associated with kidney injury like CD36 and KIM-1 (kidney injury molecule-1). mdpi.comnih.govbiorxiv.org

The proposed mechanism involves this compound inhibiting the AMP-activated protein kinase (AMPK) pathway, which in turn triggers the transcription of sterol regulatory element-binding proteins (SREBP-1/2) and lipin-1, key regulators of lipogenesis. mdpi.comnih.govbiorxiv.org This suggests that this compound may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake via CD36 upregulation, potentially aggravating renal fibrosis. mdpi.com Animal model studies in doxorubicin-induced kidney injury rats have supported these in vitro findings, showing that this compound significantly induced the expression of markers related to lipogenesis and renal fibrosis. mdpi.comdntb.gov.ua

Data Table: Effects of this compound on Lipogenesis Markers in NRK52E Cells (at 30 µM for 48h)

*Data synthesized from in vitro studies in NRK52E cells. nih.govbiorxiv.org Specific percentage changes are provided where available from the sources for the 30 µM concentration at 48 hours, or indicated as increased/decreased if specific percentages were not provided or varied by dose/time.

Patients with Compromised Cardiovascular Conditions

This compound should be used with caution in patients with certain compromised cardiovascular conditions. In patients with severe heart failure, there have been isolated reports of severe hypotension and reduced cardiac output following this compound administration. hres.ca this compound should be used cautiously in these patients. hres.ca In patients with severe aortic stenosis, this compound may not produce its usual afterload-reducing effects, and there is a possibility that its negative inotropic action could lead to heart failure if end-diastolic pressure is elevated. hres.ca Immediate-release this compound is generally not recommended in patients with unstable angina or within the first 1-2 weeks after acute myocardial infarction, except with concomitant beta-blockade, due to the risk of reflex tachycardia and increased myocardial oxygen demand, potentially worsening ischemia. nih.govmedcentral.comhres.ca

Elderly Patients

The safety of this compound in elderly patients has been a focus of research, particularly concerning different formulations. While studies have demonstrated the efficacy and safety of this compound in elderly patients, immediate-release formulations are generally not recommended due to the risk of adverse effects such as myocardial ischemia and excessive hypotension. droracle.ainih.gov Short-acting this compound has been classified as a potentially inappropriate medication for the elderly according to Beers criteria due to the risk of excess hypotension. neurology.org Use of short-acting this compound in elderly hypertensive patients has been associated with an increased risk of stroke. neurology.org This increased risk may be attributed to hemodynamic fluctuations and potential prohemorrhagic, proischemic, and proarrhythmic effects. neurology.org Even low doses of sublingual this compound have been suggested to cause myocardial ischemia in some elderly patients with left ventricular hypertrophy (LVH), potentially linked to a marked reduction in coronary perfusion pressure. droracle.ainih.gov Sustained-release formulations are preferred for elderly patients due to a smoother pharmacokinetic profile and fewer side effects. droracle.ai Older subjects exposed to this compound have shown a significantly higher risk for all-cause and cardiac-related mortality compared to those using beta-blockers in some studies, with the risk increasing with higher average daily doses and recent therapy initiation, remaining significant even for prolonged-acting formulations. nih.gov

Patients with Hepatic Impairment

This compound undergoes hepatic metabolism, primarily via the CYP3A4 pathway. nih.gov Hepatic impairment can affect the pharmacokinetics of this compound, leading to increased plasma concentrations and a prolonged half-life due to reduced clearance. nih.govpediatriconcall.com Studies have shown that in patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment, the area under the plasma concentration-time curve (AUC) for this compound is significantly increased, as are maximum plasma concentrations (Cmax). hres.canih.gov For instance, in one study, AUC increased by 93% and 253% in mild and moderate hepatic impairment, respectively, while Cmax increased by 64% and 171%. nih.gov This necessitates careful monitoring and potential dose adjustment in patients with mild to moderate hepatic impairment. hres.canih.gov The pharmacokinetics of extended-release this compound have not been investigated in patients with severe hepatic impairment, and some formulations are contraindicated in patients with moderate or severe hepatic impairment. hres.ca Although a definite causal relationship has not been established in all cases, laboratory test abnormalities, including increases in alkaline phosphatase and reports of cholestasis (with or without jaundice), have been associated with this compound use in patients with hepatic impairment. medcentral.com

Compound Names and PubChem CIDs

Data Tables

Here is an interactive data table summarizing pharmacokinetic changes in patients with hepatic impairment based on search results:

Here is an interactive data table summarizing the risk of stroke with short-acting this compound in elderly hypertensive patients based on search results: