Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Losartan potassium is the first of a new class of orally active antihypertensive drugs which antagonise the action of angiotensin (AT) II at the AT1 receptor subtype. Losartan potassium is converted by the liver to the active metabolite E-3174, which is a more potent antagonist at the AT1 receptor. E-3174 is responsible for most of the pharmacological effects of losartan potassium, and its long half-life contributes to the extended duration of action of the drug. Losartan potassium is effective as a once-daily antihypertensive agent. In mild to moderate hypertension, losartan potassium has similar efficacy to enalapril, atenolol and felodipine extended release. When losartan potassium is combined with hydrochlorothiazide there is a further reduction in blood pressure. Losartan potassium is well tolerated in mild, moderate and severe essential hypertension, with dizziness being reported as the only drug-related adverse effect. The overall rate of patient withdrawal from therapy due to adverse experiences with losartan potassium is lower (2.3%) than that of placebo (3.7%). First-dose hypotension is uncommon, perhaps due to the slower onset of action of the drug, and cough does not appear to be a significant problem. A number of areas concerning the safety and efficacy of losartan potassium remain to be clarified. In particular, long term tolerability studies are needed; cough only became apparent as an adverse effect of ACE inhibitors after 3 to 4 years of use. Postmarketing surveillance has shown that angioedema, a rare but life-threatening adverse effect of ACE inhibitors, also occurs with losartan potassium. Further data are needed on the use of losartan potassium in patients with renal impairment before accepting the recommendation that dosage adjustment is not necessary. The pharmacokinetics and pharmacodynamics of losartan potassium in patients with hepatic disease also require further investigation. Losartan potassium increases uric acid secretion and lowers plasma uric acid levels, which may be of benefit when losartan potassium is combined with a thiazide diuretic, but which may otherwise lead to uric acid stone formation and possibly to nephropathy. Simple control of blood pressure is no longer an adequate goal in the management of hypertension. Any new antihypertensive agent should also reduce cardiovascular events, prevent or cause regression of end-organ damage such as left ventricular hypertrophy, atherosclerosis and renal failure, and should not impair quality of life. Such data on losartan potassium are not currently available. Losartan potassium is likely to be used in patients who are intolerant of ACE inhibitors, but its future in the management of hypertension will depend on long term tolerability studies and data on its effects beyond simple blood pressure control.
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PMID:A risk-benefit assessment of losartan potassium in the treatment of hypertension. 901 Jun 43

Valsartan competitively and selectively inhibits the actions of angiotensin II at the AT1 receptor subtype which is responsible for most of the known effects of angiotensin II. In clinical trials in patients with mild to moderate essential hypertension valsartan was as effective as losartan, lisinopril, enalapril, amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure in patients who did not respond sufficiently to valsartan monotherapy. Preliminary data also suggest valsartan may be effective in patients with severe essential hypertension. The drug was as effective as lisinopril as treatment for mild to moderate essential hypertension in patients with renal insufficiency and did not worsen renal function. Headache, dizziness and fatigue were the most common adverse events in placebo-controlled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients. Compared with ACE inhibitors, valsartan was associated with a significantly lower incidence of dry cough. Thus, valsartan is an effective treatment for mild to moderate essential hypertension and may be particularly useful in patients who experience persistent cough during ACE inhibitor therapy.
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PMID:Valsartan. A review of its pharmacology and therapeutic use in essential hypertension. 925 84

Valsartan/hydrochlorothiazide (HCTZ) combines an angiotensin II AT1 receptor blocker with a thiazide diuretic to produce additive blood pressure reductions without major effects on heart rate. HCTZ did not significantly alter valsartan pharmacokinetics; during combination therapy, HCTZ pharmacokinetics differed from those seen with HCTZ monotherapy. In clinical trials in patients with essential hypertension, adding HCTZ 12.5 or 25 mg/day to valsartan 80 mg/day resulted in a greater blood pressure reduction than increasing the valsartan dosage from 80 to 160 mg/day. The valsartan/HCTZ combination was generally more effective than either drug given alone. Efficacy of the combination was maintained during up to 3 years of treatment. Valsartan/HCTZ was well tolerated in both short and long term trials. The most common adverse events were dizziness, headache and fatigue. The overall incidence of adverse events with the combination was similar to that with placebo. HCTZ-induced hypokalaemia was less common during combination therapy.
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PMID:Valsartan/hydrochlorothiazide. 1035

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

A large-scale, 8-week, open-label, clinical experience trial evaluated the efficacy of the angiotensin II receptor (AT1 subtype) blocker candesartan cilexetil (16 to 32 mg once daily) either alone or as add-on therapy in 6465 hypertensive patients. The study population was 52% female and 16% African American with a mean age of 58 years. It included 5,446 patients who had essential hypertension (HBP) and 1,014 patients who had isolated systolic hypertension (ISH). These patients had either untreated or uncontrolled hypertension (systolic blood pressure [SBP] 140 to 179 mm Hg or diastolic blood pressure [DBP] 90 to 109 mm Hg inclusive at baseline) despite a variety of antihypertensive medications including diuretics, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, and alpha- or beta-blockers, either singly or in combination. The mean baseline blood pressure for the HBP group was 156/97 mm Hg. Candesartan cilexetil as monotherapy (in 51% of HBP patients) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg. As add-on therapy (in 49% of HBP patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.8/11.3 mm Hg), calcium antagonists (16.6/11.2 mm Hg), beta-blockers (16.5/ 10.4 mm Hg), ACE inhibitors (15.3/10.0 mm Hg), alpha-blockers (16.4/10.4 mm Hg). The mean baseline blood pressure for the ISH group was 158/81 mm Hg. Candesartan cilexetil, as monotherapy (in 34% of ISH patients), reduced SBP/DBP by 17.0/4.4 mm Hg. As add-on therapy (in 66% of ISH patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.4/5.1 mm Hg), calcium antagonists (15.6/3.6 mm Hg), beta-blockers (14.0/4.8 mm Hg), ACE inhibitors (13.4/4.3 mm Hg), and alpha-blockers (11.6/4.5 mm Hg). The further blood pressure lowering effects of candesartan cilexetil as add-on therapy were seen regardless of age, sex, and race. Overall, 6.8% of the 6465 patients withdrew because of adverse events, most commonly headache (6.3%) and dizziness (5.0%). Orthostatic hypotension was infrequent; 0.2% with candesartan cilexetil alone, and 0.8% with candesartan cilexetil as add-on therapy. Thus, candesartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice settings.
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PMID:Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. 1141 37

Posttransplant erythrocytosis (PTE) is defined as a persistently elevated hematocrit to a level greater than 51% after renal transplantation. It occurs in 10% to 15% of graft recipients and usually develops 8 to 24 months after engraftment. Spontaneous remission of established PTE is observed in one fourth of the patients within 2 years from onset, whereas in the remaining three fourths it persists for several years, only to remit after loss of renal function from rejection. Predisposing factors include male gender, retention of native kidneys, smoking, transplant renal artery stenosis, adequate erythropoiesis prior to transplantation, and rejection-free course with well-functioning renal graft. Just as in other forms of erythrocytosis, a substantial number (approximately 60%) of patients with PTE experience malaise, headache, plethora, lethargy, and dizziness. Thromboembolic events occur in 10% to 30% of the cases; 1% to 2% eventually die of associated complications. Posttransplant erythrocytosis results from the combined trophic effect of multiple and interrelated erythropoietic factors. Among them, endogenous erythropoietin appears to play the central role. Persistent erythropoietin secretion from the diseased and chronically ischemic native kidneys does not conform to the normal feedback regulation, thereby establishing a form of "tertiary hypererythropoietinemia." However, erythropoietin levels in most PTE patients still remain within the "normal range," indicating that erythrocytosis finally ensues by the contributory action of additional growth factors on erythroid progenitors, such as angiotensin II, androgens, and insulin-like growth factor 1 (IGF-1). Inactivation of the renin-angiotensin system (RAS) by an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin II type 1 AT1 receptor blocker represents the most effective, safe, and well-tolerated therapeutic modality.
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PMID:Posttransplant erythrocytosis. 1263 34