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)

Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00 +/- 38.43 (n = 12), 17.48 +/- 3.09 (n = 12), 63.43 +/- 14.84 (n = 8) and 13.52 +/- 1.42 (n = 7) pmol/24 hr, respectively (mean +/- s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions.
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PMID:Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions. 142 42

The effect of the converting enzyme inhibitor captopril as long term treatment was investigated in 14 patients with severe congestive heart failure in a double blind trial. Captopril reduced plasma concentrations of angiotensin II and noradrenaline, with a converse increase in active renin concentration. Effective renal plasma flow increased and renal vascular resistance fell; glomerular filtration rate did not change. Serum urea and creatinine concentrations rose. Both serum and total body potassium contents increased; there were no long term changes in serum concentration or total body content of sodium. Exercise tolerance was appreciably improved, and dyspnoea and fatigue lessened. Left ventricular end systolic and end diastolic dimensions were reduced. There was an appreciable reduction in complex ventricular ectopic rhythms. Adverse effects were few: weight gain and fluid retention were evident in five patients when captopril was introduced and two patients initially experienced mild postural dizziness; rashes in two patients did not recur when the drug was reintroduced at a lower dose; there was a significant reduction in white cell count overall, but the lowest individual white cell count was 4000 X 10(6)/l. Captopril thus seemed to be of considerable value in the long term treatment of severe cardiac failure.
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PMID:Captopril in heart failure. A double blind controlled trial. 638 12

The blood pressure response to the first dose of captopril (6.25 mg, 12.5 mg, or 25 mg) was measured in 65 treated, severely hypertensive patients. Mean supine blood pressure was 187/108 mm Hg immediately before captopril was given. Twenty one patients experienced a fall in supine systolic pressure greater than 50 mm Hg, including five whose pressure fell more than 100 mm Hg and two whose pressure fell more than 150 mm Hg. Six patients developed symptoms of acute hypotension, including dizziness, stupor, dysphasia, and hemiparesis. Percentage reductions in blood pressure were greatest in those with secondary hypertension (p less than 0.05), high pretreatment blood pressure (p less than 0.05), and high concentrations of plasma renin and angiotensin II (p less than 0.01). No significant correlation was found between fall in blood pressure and serum sodium concentration, age, renal function, and the dose of captopril given. A severe first dose effect cannot be consistently predicted in individual patients who have received other antihypertensive drugs for severe hypertension. Such patients should have close medical supervision for at least three hours after the first dose of captopril.
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PMID:Factors related to first dose hypotensive effect of captopril: prediction and treatment. 640 3

We compared the response of the oral angiotensin II (Ang II) receptor antagonist (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril 20 mg or placebo, during salt depletion in normal men. We also evaluated safety and tolerability. Sixteen healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Seven different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered double blind in a four-panel dose escalation, with enalapril and placebo randomised within each panel. Supine and erect blood pressure (BP) and heart rate (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and Ang II were measured at intervals. Urinary electrolytes and aldosterone were measured for the 24 h before dosing and for 24 h after dosing. Dizziness and light-headedness on standing were reported after UP 269-6 at higher doses. Enalapril caused one episode of symptomatic postural hypotension. No other drug-related adverse events (AE) were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40 mg, with no change in HR. Based on the maximal decrease in mean arterial pressure (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril 20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary aldosterone suppression was greater with enalapril than with any dose of UP 269-6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man. 756 47

This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.
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PMID:Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. 771 81

Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor antagonist. It is the first of a new class of drugs to be introduced for clinical use in hypertension. This novel agent binds competitively and selectively to the AII subtype 1 (AT(1)) receptor, thereby blocking AII-induced physiological effects. An active metabolite, E3174, contributes substantially to its antihypertensive effect, which persists throughout 24 hours after once-daily administration. In patients with mild to moderate hypertension, losartan potassium 50 to 100mg once daily as monotherapy lowers blood pressure to a similar degree to enalapril, atenolol and felodipine extended release (ER). Losartan potassium combined with hydrochlorothiazide reduces blood pressure further than either drug given separately. About one-third of patients with severe hypertension have responded to the combination product. Losartan potassium appears to be effective in elderly patients. Losartan potassium is very well tolerated. In clinical trials, dizziness was the only drug-related event reported more frequently with losartan potassium monotherapy than with placebo. First-dose hypotension is uncommon. An aspect of the drug's tolerability profile which may prove to be particularly advantageous is that it is associated with a similar incidence of cough to placebo in patients with a history of ACE inhibitor-related cough. Additionally, clinically relevant adverse metabolic effects or laboratory abnormalities have not been documented during losartan potassium therapy and renal function is preserved in patients with or without renal insufficiency. The adverse effect profile of the losartan potassium-hydrochlorothiazide combination resembles those for losartan potassium monotherapy and placebo. Long term tolerability data are limited (<2 years) but support the very good tolerability profile in shorter studies. Elements of the drug's profile yet to be assessed or reported fully in the literature include long term efficacy; potential to favourably influence cardiovascular and renovascular systems (and ultimately mortality) in patients with hypertension and, lastly, cost effectiveness and influence on quality of life. In summary, losartan potassium is the first AT(1)+ receptor antagonist to become available for the management of hypertension and, as such, it is an important new antihypertensive agent. Pending long term data as outlined above, it is likely to find initial use in patients with mild to severe hypertension who are unresponsive to, or intolerant of their current therapy. However, with its novel mechanism of action, good efficacy and favourable tolerability profile, losartan potassium is well placed to claim a prominent position in the management of patients with essential hypertension in the future.
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PMID:Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. 886 49

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

Losartan is a novel orally active nonpeptidal antihypertensive agent that specifically blocks the angiotensin II type 1 receptor. This paper compares the short- and long-term safety and tolerability of losartan with those of placebo. Approximately 3800 patients with mild-to-severe essential hypertension were enrolled in 16 double-masked and 4 open clinical trials worldwide. Of these, approximately 2900 were treated with losartan either alone or in combination with other antihypertensive drugs. These trials included patients with diabetes mellitus (n = 133). An additional 5 trials enrolled hypertensive patients with compromised renal function (n = 115) or heart failure (n = 220). Losartan dosages primarily ranged from 10 to 150 mg once daily, with most patients receiving 50 to 100 mg per day. Hypertension trials generally lasted 12 weeks. The most frequently reported adverse events were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups. Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo. The overall incidence of clinical and laboratory adverse events in the losartan- and placebo-treated groups was similar among patients with hypertension and either diabetes mellitus, renal impairment, or heart failure. The data suggest that losartan can be safely administered in hypertensive patients with concomitant illnesses. It can be considered for first-line therapy and is suitable as an alternative therapy in patients already experiencing side effects with other agents.
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PMID:Clinical safety and tolerability of losartan. 937 6

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

The mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and adverse effects of candesartan cilexetil are reviewed. Candesartan is an angiotensin II-receptor blocker (ARB). It is administered as a pro-drug that undergoes activation during gastrointestinal absorption. The agent is excreted mostly unchanged and has a terminal half-life of about nine hours (slightly longer in the elderly). Candesartan differs from other agents in its class in that it is tightly bound to angiotensin II type 1 receptors, allowing prolonged activity. In clinical trials, candesartan cilexetil has produced a dose-dependent effect when given in dosages of 2-32 mg/day. Observed trough-to-peak blood pressure ratios support a once-daily dosage regimen. The antihypertensive effect of candesartan cilexetil 4-16 mg/day was as great as that of enalapril 10-20 mg/day and amlodipine 5 mg/day and larger than that of losartan potassium 50 mg/day. Adding candesartan cilexetil to hydrochlorothiazide 12.5-25 mg/day and amlodipine 5 mg/day led to enhanced blood-pressure reductions and was well tolerated. It appears that candesartan can decrease renal perfusion without adversely affecting renal blood flow and may mediate a decrease in albuminuria in hypertensive patients with type 2 diabetes. No clinically important drug interactions have been reported. Adverse effects include headache, dizziness, nausea, diarrhea, and transient elevations in liver transaminases. The frequency of cough is similar to that seen with placebo. Candesartan cilexetil is an effective antihypertensive agent that can be used alone or in combination with other antihypertensive drugs. It is generally well tolerated and may be an option for patients who cannot tolerate angiotensin-converting-enzyme inhibitors because of cough.
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PMID:Candesartan cilexetil: an angiotensin II-receptor blocker. 1078 59


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