Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a brief synopsis of the classical antihypertensive drugs a survey is given of the newer therapeutics, such as calcium antagonists, ACE-inhibitors and alpha 1-adrenoceptor antagonists. Experimental drugs, such as imidazoline receptor agonists, renin inhibitors, angiotensin II receptor antagonists, alpha 2-adrenoceptor antagonists, potassium channel openers, ketanserin, endopeptidase inhibitors, and hybrid (multifactorial) drugs are discussed, with special attention for their modes of action. In spite of the ever increasing number of antihypertensive drugs and principles, the large scale of clinical evidence for a beneficial effect of long-term treatment (in particular with respect to protection against stroke) remains limited to diuretics and beta-blockers. In spite of this limitation it seems worthwhile to consider the newer antihypertensive drugs as well, especially for optimal treatment of the individual patient. The newer drugs may in particular offer special advantages in the presence of concomitant diseases, such as diabetes mellitus, hyperlipidaemia, angina pectoris or congestive heart failure.
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PMID:New avenues in antihypertensive drug treatment. 826 86

High blood pressure (BP) in the elderly must not be ignored as a normal consequence of aging. The criteria for the diagnosis of hypertension and the necessity to treat it are the same in elderly and younger patients. The aim of treatment of elderly hypertensive patients is to decrease BP safely and to reduce risk factors associated with cerebrovascular, cardiovascular and renal morbidity and mortality. The treatment of elderly hypertensive patients should be adjusted according to the needs of the individual, based upon age, race, severity of hypertension, co-existing medical problems, other cardiovascular risk factors, target-organ damage, risk-benefit considerations and costs. In addition to the elevated BP, other cardiovascular risk factors include smoking, glucose intolerance, hyperinsulinaemia, dyslipidaemia, hypercreatininaemia, peripheral vascular disease, left ventricular hypertrophy, and microalbuminuria (or albuminuria). Thus, the choice of initial antihypertensive therapy in elderly hypertensive patients should be based not only on the expected response, but also on the effects of therapy on lipid, potassium, glucose and uric acid levels, and left ventricular anatomy and function. Co-existing medical conditions (such as asthma, diabetes mellitus, heart failure, renal failure, gout, coronary artery disease, hyperlipidaemia and peripheral vascular disease) are major determinants for the selection of antihypertensive medications. With previous therapies (diuretics, beta-blockers, etc.), good BP control in the elderly was associated with clear and statistically significant reductions in stroke-related morbidity and mortality, but the overall effects on cardiovascular and renal complications of hypertension was either more variable or less obvious. Angiotensin converting enzyme (ACE) inhibitors are not only efficacious antihypertensive agents in the elderly, but also appear promising in counteracting some of the cardiovascular and renal consequences of hypertension. They are well tolerated and have a relatively low incidence of adverse effects. ACE inhibitors possess ancillary characteristics that are potentially beneficial for many elderly patients, including reduction of left ventricular mass, lack of metabolic and lipid disturbances, no adverse CNS effects, no risk of induction of heart failure, and a low risk of orthostatic hypotension. Since ACE inhibitors may improve perfusion to the heart, kidney and brain, they are well worth considering for the treatment of elderly patients with hypertensive target organ damage, especially in patients with heart failure, and diabetic patients with early nephropathy.
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PMID:ACE inhibitors. Differential use in elderly patients with hypertension. 857 91

Creatinine clearance decreases with age by 1 ml/min/year after 40 years of age, although serum creatinine remains constant because of reduction of muscle mass. Reduction of water intake may occur in the elderly because of a reduced sensation of thirst; this is associated with a tendency to lose water with urine. The capacity to respond to sodium load is impaired in aged kidneys, thereby leading to ECV expansion and hypertension. But there is also, in the elderly, a reduced capacity for retaining sodium (FENa is higher than in young subjects), making old subjects sensitive to salt depletion and ECV contraction. Hypernatraemia (Nas > 150 mmol/l) is not infrequent in the elderly (1%) and is usually due to water deficiency (old subjects should be forced to drink), and rarely to iatrogenic excess of sodium. It is the abrupt occurrence of severe hypernatraemia that causes neurological symptoms due to dehydration and brain shrinking, which may lead to cerebral haemorrhage and death. Hyponatraemia (Nas < 130 mmol/l) is frequent among the elderly (7-11%) and is mainly due to water overload, which is usually iatrogenic. Hypovolaemic hyponatraemia occurs when salt depletion causes ECV contraction > 10%, and is due to water retention in an attempt to normalize ECV. Hypervolaemic hyponatraemia is due to ADH hypersecretion because of a decrease in 'effective' circulating blood volume. 'Pseudohyponatraemia' may occur because of hyperlipidaemia or hyperproteinaemia. It is the abrupt occurrence of severe hyponatraemia that causes neurological symptoms (water intoxication), secondary to the oedomatous swelling of the brain within the skull. While rapidly occurring hyponatraemia may be lethal, slowly occurring hyponatraemia is usually asymptomatic. Rapid correction of hyponatraemia may cause cerebral dehydration and 'osmotic demyelination syndrome' ('central pontine myelinosis'). Decrease (e.g. by diuretics) or increase (e.g. by ACE-inhibitors, non-steroidal anti-inflammatory drugs, beta-blockers) or serum potassium may occur in the elderly. Diuretics should be used with caution in elderly subjects to avoid salt depletion, hypotension and renal function impairment.
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PMID:Some sodium, potassium and water changes in the elderly and their treatment. 905 29

Diabetic ketoacidosis results from insulin deficiency and insulin resistance and is marked by hyperglycaemia, ketoacidosis, dehydration and electrolyte losses. Management includes correction of shock, dehydration, electrolyte deficits, hyperglycaemia, acidosis and sepsis (if present). Warning signs include severe dehydration, shock, pH < 7.0, hypokalaemia, hypernatraemia, hyperosmolality, hyperlipidaemia, deterioration in consciousness and diabetic ketoacidosis in very young patients. The principles of treatment include (i) admission to a unit with paediatric experience, (ii) treatment of shock, (iii) rehydration over 24-36 h, or longer if the osmolality is >360 mmoll(-1), (iv) normal saline for rehydration unless the patient is hypernatraemic, (v) avoidance of bicarbonate unless acidosis is interfering with myocardial contractility, (vi) insulin infusion to achieve a fall in blood glucose levels of 5 mmol h(-1), (vi) potassium, (vii) use of 5% glucose when the blood glucose level falls <12mmoll(-1), (ix) treatment of any complications and (x) change to subcutaneous insulin when diabetic ketoacidosis is controlled.
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PMID:Practical management of diabetic ketoacidosis in childhood and adolescence. 982 96

Nine patients (aged 18+/-1 years) on maintenance hemodialysis with metabolic acidosis and hyperlipidemia were studied before and after 2 weeks of oral sodium bicarbonate (NaHCO(3)) treatment to correct the acidosis. To control for the effect of additional sodium, they were also studied after 2 weeks of an equivalent amount of oral sodium chloride (NaCl). Oral NaHCO(3 )treatment led to significant increases in venous pH, serum bicarbonate, and serum 1, 25-dihydroxyvitamin D(3) concentrations, but no significant change in total and ionized calcium, phosphate, sodium, potassium, creatinine, blood urea nitrogen, and intact parathyroid hormone concentrations. Oral NaCl did not change any of the biochemical parameters. Before treatment of acidosis, these uremic patients had high serum triglycerides, low serum high-density lipoprotein (HDL) cholesterol, but normal total cholesterol compared with controls. Following 2 weeks of NaHCO(3) treatment, there was a significant decrease in the serum concentrations of triglycerides (P<0.01). HDL and total cholesterol did not change. There were no changes in triglycerides, HDL or total cholesterol from baseline values following 2 weeks of NaCl. Thus treatment of metabolic acidosis ameliorated hypertriglyceridemia but had no effect on HDL and total cholesterol in patients with uremia on hemodialysis. The underlying mechanism may involve 1,25-dihydroxyvitamin D3.
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PMID:Effect of metabolic acidosis on hyperlipidemia in uremia. 1060 43

IP6, a major dietary source of inositol phosphates, is a physiological antioxidant with potential to form complexes with cations linked to cell proliferation and hypercholesterolemia. Accordingly, we have examined the action of IP6 on dietary modulation of neoplasia and hyperlipidemia in a Fischer rat model (1, 2). Two studies were conducted on the effects of naturally-derived IP6, administered as purified phytate, a salt form of phytic acid (inositol hexaphosphoric acid). One study examined the effect on the growth of tumors promoted in syngeneic rats transplanted with a viral oncogene-transformed cell line. Increases in tumor incidence and growth rate of fibrosarcomas seen following administration of a special diet (containing 5% saturated fatty acids and 1.2% magnesium oxide) were completely mitigated by supplementation of the same diet with purified potassium-magnesium phytate (8.9% phytic acid by weight). The other study examined the IP6 effect on serum lipid and mineral levels in animals fed a cholesterol-enriched or standard diet. Elevated levels of serum total cholesterol, triglycerides and zinc/copper ratio associated with administration of the cholesterol-enriched diet were significantly lowered by supplementation of this diet with monopotassium phytate. Addition of monopotassium phytate to the standard diet also reduced serum lipid levels but did not significantly affect the zinc/copper ratio. These studies support a role for IP6 as a potential therapeutic agent in the treatment of cancer and hyperlipidemia.
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PMID:Inositol hexaphosphate (IP6) as an anti-neoplastic and lipid-lowering agent. 1062 43

Herein are described the development and certain properties of a new drug, pyrazinoylguanidine (PZG), intended for use as an adjunct in the treatment of hypertensive patients with type 2 diabetes, formerly called noninsulin dependent diabetes mellitus. PZG is an analog of the potassium sparing diuretic, amiloride. However, in diabetic patients, amiloride exacerbates hyperglycemia and hyperlipidemia, whereas PZG reduces them. In several studies, PZG not only reduced elevated blood pressure in subjects with essential hypertension, but also downregulated the glucose fatty acid cycle in hypertensive patients with type 2 diabetes. PZG was well tolerated in all patients, as well as in normal subjects whose blood pressures and glucose metabolism were unaffected by PZG. However, in normal subjects made hyperglycemic by giving them hydrochlorothiazide, coadministration of PZG returned blood glucose concentrations to normal. Mechanisms for these effects of PZG in human subjects were investigated in both normal Sprague-Dawley rats and rats made diabetic with streptozotocin (STZ). In isolated rat adipocytes stimulated with theophylline, PZG downregulated both lipolysis and cyclic AMP concentrations. PZG, as well as insulin, increased adipose cyclic nucleotide phosphodiesterase activity, whereas theophylline reduced it. In perfused rat liver, PZG decreased gluconeogenesis and cyclic AMP concentrations. Collectively, these studies illustrate how the side effects (toxicity) of certain drugs, such as the tendency of thiazide diuretics to cause hyperglycemia and hyperlipidemia, can be modulated and even reversed by slight changes in the chemical structure of the molecule, specifically by removal of the 3,5-diamino and 6-chloro substituents on the benzene ring of amiloride to produce PZG.
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PMID:Studies on pyrazinoylguanidine: a novel antihypertensive, hypoglycemic and lipolytic drug intended for adjunctive use in hypertensive patients with type 2 diabetes mellitus. 1078 66

This article reviews the pharmacological and clinical aspects of glimepiride, the latest second-generation sulfonylurea for treatment of Type 2 diabetes mellitus (DM). Glimepiride therapy ameliorates the relative insulin secretory deficit found in most patients with Type 2 DM. It is a direct insulin secretagogue; indirectly, it also increases insulin secretion in response to fuels such as glucose. Its action to augment insulin secretion requires binding to a high affinity sulfonylurea receptor, which results in closure of ATP-sensitive potassium channels in the beta-cells of the pancreas. The question has been raised whether insulin secretagogues by acting on vascular or myocardial potassium channels may prevent ischaemic preconditioning, a physiological adaptation that could affect the outcome of coronary heart disease, but there is evidence against this concern being applicable to glimepiride. Glimepiride's antihyperglycaemic efficacy is equal to other secretagogues. It has pharmacokinetic properties that make it less prone to cause hypoglycaemia in renal dysfunction than some other insulin secretagogues, particularly glyburide (also known as glibenclamide in Europe). Its convenient once daily dosing may enhance compliance for diabetic patients who often also require medications for other co-morbid conditions, such as hypertension, hyperlipidaemia and cardiac disease. Glimepiride is approved for monotherapy, for combination with metformin and with insulin. Clinically, its reduced risk of hypoglycaemia makes it preferable to some other insulin secretagogues when attempting to achieve recommended glycaemic control (haemoglobin A(1c) (HgbA(1c)) 7%). Using suppertime neutral protamine Hagedorn (NPH) and regular insulin with morning glimepiride in overweight diabetic patients achieves glycaemic goals more quickly than insulin alone and with lower insulin doses.
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PMID:Clinical review of glimepiride. 1133 17

We succeeded in developing a novel rabbit model of nonsteroid and nontraumatic osteonecrosis (ON) by use of a single- and low-dose lipopolysaccharide (LPS) injection. This model is simple and highly reproducible for the frequent development of multifocal and widespread ON lesions. Male adult Japanese white rabbits intravenously injected with a single injection of 10 microg/kg body weight of LPS were histopathologically examined in the early phase (3 [n = 3], 5 [n = 3], and 24 h [n = 3]) and at 4 weeks (n = 22). Seventy-seven percent of the rabbits developed multifocal ON 4 weeks after LPS injection. ON was also observed in the femoral and humeral condyle. The average percentage of necrotic area/total area examined was 86.7 +/- 29.1% and 78.8 +/- 16.7% in the proximal one third of both the femoral and humeral bones, respectively. Organized thrombi in the intraosseous small-sized arteries and arterioles were frequently seen in and around the necrotic tissues. In the early phase, LPS treatment prominently induced thrombocytopenia, hyperlipidemia, and increased plasma levels of plasminogen activator inhibitor-1 (PAI-1). The plasma level of PAI-1 was significantly higher in the rabbits with ON than in those without ON (p < 0.01). The immunohistochemical expression of tissue factor was exaggerated in monocytes/macrophages and adipocytes in both the femoral and humeral bones of the LPS-treated rabbits. Histologically, marrow necrosis and fibrin thrombi could be observed at 24 h. In addition, pretreatment with an anticoagulant, warfarin potassium, significantly decreased the incidence of LPS-induced ON (33%, n = 9, p < 0.05) associated with elongation of prothrombin time. The results of our study show that a single administration of low-dose lipopolysaccharide induces multifocal and widespread ON characterized by the pathophysiological participation of hypercoagulability in ON development. Therefore, this model would be useful for elucidating the pathogenesis of nonsteroid ON in humans especially inflammatory hypercoagulability-induced as well as for developing preventive and therapeutic strategies.
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PMID:Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits. 1142 53

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.
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PMID:Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats. 1196 Sep 55


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