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Research paper thumbnail of Niacin and laropiprant

Drugs of Today, 2010

Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to mod... more Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to modestly lowering low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a), niacin is currently the most effective available agent for raising high-density lipoprotein cholesterol (HDL-C). Despite its well-documented beneficial effects on lipids, the clinical use of niacin has been limited by its side effect profile, notably flushing. This sensation of cutaneous vasodilatation and burning has limited patient compliance and is a frequent cause of discontinuation of the drug. While pretreatment with nonsteroidal anti-inflammatory agents, such as aspirin, may reduce the incidence of flushing, present-day niacin still results in flushing in many patients. Recent studies have elucidated what we currently understand as the molecular mechanism that mediates niacin-induced flushing, specifically that niacin acting through its receptor stimulates the production of several prostaglandins, including prostaglandin (PG) I(2), PGE(2) and PGD(2). Laropiprant is a potent, highly selective prostaoid DP(1) receptor antagonist that decreases the incidence and intensity of niacin-induced flushing without affecting its beneficial lipid effects. Thus, laropiprant, when used in conjunction with niacin, can improve the tolerability of niacin and aid in medication compliance. This paper reviews the data suggesting the importance of raising HDL with niacin, describes the pharmacology of the drug, and examines the potential beneficial effects of combining niacin with laropiprant.

Research paper thumbnail of Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope

Cardiology in review

Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in ac... more Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in acute care settings. Moreover, OH may be more prevalent in the elderly due to the increased use of vasoactive medications and the concomitant decrease in physiologic function, such as baroreceptor sensitivity. OH may result in the genesis of a presyncopal state or result in syncope. OH is defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review of symptoms, and measurement of supine and standing BP with appropriate clinical tests should narrow the differential diagnosis and the cause of OH. The fall in BP seen in OH results from the inability of the autonomic nervous system (ANS) to achieve adequate venous return and appropriate vasoconstriction sufficient to maintain BP. An evaluation of patients with OH should consider hypovolemia, removal of offending medications, primary au...

Research paper thumbnail of Present-day uses of niacin: effects on lipid and non-lipid parameters

Expert Opinion on Pharmacotherapy, 2007

Existing guidelines for the prevention and treatment of coronary artery disease focus on lowering... more Existing guidelines for the prevention and treatment of coronary artery disease focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary lipid target. However, there has been increasing interest in raising high-density lipoprotein cholesterol (HDL-C) due to strong evidence linking low HDL-C levels with an increased risk of atherosclerosis. Raising HDL-C levels with lifestyle changes and pharmacologic interventions appear to reduce the risk of coronary artery disease beyond that of lowering LDL-C alone. Niacin has a substantial HDL-C raising effect, and also may beneficially alter total cholesterol, LDL-C and triglyceride levels. Niacin also exhibits antioxidant, anti-inflammatory and other beneficial effects on atherosclerosis. Niacin is safe and effective to use in women, in patients with diabetes mellitus and/or metabolic syndrome, and when used in combination with statins. Niacin has the promise of being a powerful pharmacologic agent in the fight against atherosclerotic disease, although additional clinical studies are required to examine this further.

Research paper thumbnail of Relation of Postural Vasovagal Syncope to Splanchnic Hypervolemia in Adolescents

Circulation, 2004

Background-The mechanisms of simple faint remain elusive. We propose that postural fainting is re... more Background-The mechanisms of simple faint remain elusive. We propose that postural fainting is related to excessive thoracic hypovolemia and splanchnic hypervolemia during orthostasis compared with healthy subjects. Methods and Results-We studied 34 patients 12 to 22 years old referred for multiple episodes of postural faint and 11 healthy subjects. Subjects were studied in the supine position and during upright tilt to 70°for 30 minutes and subgrouped into Sϩ, historical fainters who fainted during testing (nϭ24); SϪ, historical fainters who did not faint during testing (nϭ10); and control subjects. Supine venous occlusion plethysmography showed no differences between blood flows of the forearm and calf in Sϩ, SϪ, or control. Cardiac index, total peripheral resistance, and blood volume were not different. Using impedance plethysmography, we assessed blood redistribution during upright tilt. This demonstrated decreased thoracic blood volume and increased splanchnic, pelvic, and leg blood volumes for all subjects. However, thoracic blood volume was decreased in Sϩ compared with control volume, correlating well with the maximum upright heart rate. Splanchnic volume was decreased in the Sϩ and SϪ groups, correlating with the change in thoracic blood volume. Pelvic and leg volume changes were similar for all groups and uncorrelated to thoracic blood volume.

Research paper thumbnail of Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope

Cardiology in review

Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in ac... more Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in acute care settings. Moreover, OH may be more prevalent in the elderly due to the increased use of vasoactive medications and the concomitant decrease in physiologic function, such as baroreceptor sensitivity. OH may result in the genesis of a presyncopal state or result in syncope. OH is defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review of symptoms, and measurement of supine and standing BP with appropriate clinical tests should narrow the differential diagnosis and the cause of OH. The fall in BP seen in OH results from the inability of the autonomic nervous system (ANS) to achieve adequate venous return and appropriate vasoconstriction sufficient to maintain BP. An evaluation of patients with OH should consider hypovolemia, removal of offending medications, primary au...

Research paper thumbnail of Niacin and laropiprant

Drugs of Today, 2010

Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to mod... more Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to modestly lowering low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a), niacin is currently the most effective available agent for raising high-density lipoprotein cholesterol (HDL-C). Despite its well-documented beneficial effects on lipids, the clinical use of niacin has been limited by its side effect profile, notably flushing. This sensation of cutaneous vasodilatation and burning has limited patient compliance and is a frequent cause of discontinuation of the drug. While pretreatment with nonsteroidal anti-inflammatory agents, such as aspirin, may reduce the incidence of flushing, present-day niacin still results in flushing in many patients. Recent studies have elucidated what we currently understand as the molecular mechanism that mediates niacin-induced flushing, specifically that niacin acting through its receptor stimulates the production of several prostaglandins, including prostaglandin (PG) I(2), PGE(2) and PGD(2). Laropiprant is a potent, highly selective prostaoid DP(1) receptor antagonist that decreases the incidence and intensity of niacin-induced flushing without affecting its beneficial lipid effects. Thus, laropiprant, when used in conjunction with niacin, can improve the tolerability of niacin and aid in medication compliance. This paper reviews the data suggesting the importance of raising HDL with niacin, describes the pharmacology of the drug, and examines the potential beneficial effects of combining niacin with laropiprant.

Research paper thumbnail of Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope

Cardiology in review

Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in ac... more Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in acute care settings. Moreover, OH may be more prevalent in the elderly due to the increased use of vasoactive medications and the concomitant decrease in physiologic function, such as baroreceptor sensitivity. OH may result in the genesis of a presyncopal state or result in syncope. OH is defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review of symptoms, and measurement of supine and standing BP with appropriate clinical tests should narrow the differential diagnosis and the cause of OH. The fall in BP seen in OH results from the inability of the autonomic nervous system (ANS) to achieve adequate venous return and appropriate vasoconstriction sufficient to maintain BP. An evaluation of patients with OH should consider hypovolemia, removal of offending medications, primary au...

Research paper thumbnail of Present-day uses of niacin: effects on lipid and non-lipid parameters

Expert Opinion on Pharmacotherapy, 2007

Existing guidelines for the prevention and treatment of coronary artery disease focus on lowering... more Existing guidelines for the prevention and treatment of coronary artery disease focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary lipid target. However, there has been increasing interest in raising high-density lipoprotein cholesterol (HDL-C) due to strong evidence linking low HDL-C levels with an increased risk of atherosclerosis. Raising HDL-C levels with lifestyle changes and pharmacologic interventions appear to reduce the risk of coronary artery disease beyond that of lowering LDL-C alone. Niacin has a substantial HDL-C raising effect, and also may beneficially alter total cholesterol, LDL-C and triglyceride levels. Niacin also exhibits antioxidant, anti-inflammatory and other beneficial effects on atherosclerosis. Niacin is safe and effective to use in women, in patients with diabetes mellitus and/or metabolic syndrome, and when used in combination with statins. Niacin has the promise of being a powerful pharmacologic agent in the fight against atherosclerotic disease, although additional clinical studies are required to examine this further.

Research paper thumbnail of Relation of Postural Vasovagal Syncope to Splanchnic Hypervolemia in Adolescents

Circulation, 2004

Background-The mechanisms of simple faint remain elusive. We propose that postural fainting is re... more Background-The mechanisms of simple faint remain elusive. We propose that postural fainting is related to excessive thoracic hypovolemia and splanchnic hypervolemia during orthostasis compared with healthy subjects. Methods and Results-We studied 34 patients 12 to 22 years old referred for multiple episodes of postural faint and 11 healthy subjects. Subjects were studied in the supine position and during upright tilt to 70°for 30 minutes and subgrouped into Sϩ, historical fainters who fainted during testing (nϭ24); SϪ, historical fainters who did not faint during testing (nϭ10); and control subjects. Supine venous occlusion plethysmography showed no differences between blood flows of the forearm and calf in Sϩ, SϪ, or control. Cardiac index, total peripheral resistance, and blood volume were not different. Using impedance plethysmography, we assessed blood redistribution during upright tilt. This demonstrated decreased thoracic blood volume and increased splanchnic, pelvic, and leg blood volumes for all subjects. However, thoracic blood volume was decreased in Sϩ compared with control volume, correlating well with the maximum upright heart rate. Splanchnic volume was decreased in the Sϩ and SϪ groups, correlating with the change in thoracic blood volume. Pelvic and leg volume changes were similar for all groups and uncorrelated to thoracic blood volume.

Research paper thumbnail of Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope

Cardiology in review

Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in ac... more Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in acute care settings. Moreover, OH may be more prevalent in the elderly due to the increased use of vasoactive medications and the concomitant decrease in physiologic function, such as baroreceptor sensitivity. OH may result in the genesis of a presyncopal state or result in syncope. OH is defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review of symptoms, and measurement of supine and standing BP with appropriate clinical tests should narrow the differential diagnosis and the cause of OH. The fall in BP seen in OH results from the inability of the autonomic nervous system (ANS) to achieve adequate venous return and appropriate vasoconstriction sufficient to maintain BP. An evaluation of patients with OH should consider hypovolemia, removal of offending medications, primary au...