Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this 16-week trial was to determine the safety and efficacy of a step-care regimen of ramipril, an angiotensin converting enzyme inhibitor, from the minimal active dose (2.5 mg) in patients treated for mild to moderate hypertension. The trial was conducted by 102 general practitioners in 770 patients with mild to moderate hypertension. After a response rate to a 4-week placebo therapy of 9.1%, 57.0% of patients given active treatment with ramipril responded to daily doses of 2.5 mg. Ramipril 5 mg daily was effective in 55.6% of the remaining patients. There was no apparent statistically significant difference between the treatments with ramipril 10 mg or a combination of ramipril 5 mg + Lasix 20 mg daily (44.7% and 47.4% response respectively) in a 6-week double-blind arm of the study. In total, more than 90% of patients responded to treatment with ramipril by the end of the study. The incidence of adverse events was generally low, such as headache, cough, dizziness, asthenia, cramps and nausea. The incidence of cough appeared to be related both to the dosage of ramipril given and to outbreaks of influenza syndrome. Thirty-eight patients discontinued active treatment as a result of minor events such as cough, dizziness or diarrhoea, and one case each of myalgia and papular rash. There were no significant variations in laboratory parameters during the study, especially fasting blood glucose and apolipoprotein A1 and B. The results of this study provide evidence of the safety and efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The French multicentre study of ramipril in ambulatory patients with mild-to-moderate hypertension. 130 60

This 6-week, double-blind, parallel-group study compared the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitors quinapril and captopril as initial monotherapies in patients with severe hypertension (diastolic blood pressure [DBP] greater than or equal to 115 and less than or equal to 130 mm Hg). A total of 97 patients, aged between 18 and 70 years, were randomized to 5 mg oral quinapril twice daily or 25 mg captopril twice daily with maximum titration to 20 mg quinapril twice daily or 100 mg captopril twice daily. With the morning dose 25 mg hydrochlorothiazide (HCTZ) could be added at week 4 of the double-blind phase or earlier if required for safety considerations. For the monotherapy phase, mean reductions in DBP of 12.1 mm Hg were achieved with both treatments. Clinical response rates (reduction in DBP greater than or equal to 10 mm Hg) were 58% for quinapril and 44% for captopril. At the end of therapy, with optional HCTZ, mean reductions in DBP were 19.0 mm Hg for the quinapril-treated group and 16.2 mm Hg for the captopril-treated group. None of the differences achieved statistical significance. Headache was the most frequently reported adverse event in both treatment groups with 8 reports each. No clinically significant changes in laboratory data were observed in any parameter for either treatment group. Quinapril and captopril provide comparable efficacy and safety in treatment of severe hypertension when used as initial monotherapy and with the addition of optional HCTZ.
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PMID:Angiotensin converting enzyme inhibitors as initial monotherapy in severe hypertension. Quinapril and captopril. 174 16

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.
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PMID:Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 208 13

In a multicenter study in general practice, the tolerability and safety of ramipril alone and in combination with a low dose of furosemide were assessed in moderate hypertension. After a placebo run-in period involving 770 patients, 661 were included in the active treatment period and received ramipril alone (2.5-5 mg/day). After 6 weeks, the nonresponders entered in a double-blind period and they received daily ramipril 10 mg or ramipril 5 mg in combination with furosemide 20 mg. In this hypertensive population, the adverse events more commonly reported were headache, cough, dizziness, asthenia, cramps diarrhea and nausea, but not all these events were related to ramipril. There was seemingly a relation between cough prevalence and rampiril dosage; an increased incidence was also observed during the outbreaks of flu-syndrome in our country. 38 patients discontinued the active treatment due to non-serious adverse events, mainly cough, dizziness or diarrhea. No serious adverse drug reaction was observed. Laboratory data (blood cells count, electrolytes, serum creatinine, fasting blood glucose, apolipoproteins AI and B) remained most commonly unaffected. In moderate hypertension in general practice, this study confirms that ramipril is well tolerated, especially with regard to the class effects of the angiotensin converting enzyme inhibitors.
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PMID:[Tolerance to Triatec in monotherapy and in combination with Lasilix in a French multicenter study]. 214 97

Dilevalol, the RR-stereoisomer of labetalol, is a non-cardioselective beta-adrenoceptor antagonist with substantial partial beta 2-agonist and negligible alpha 1-blocking activity. Reduction in blood pressure during dilevalol administration is associated with peripheral vasodilatation, and heart rate remains essentially unchanged. Following oral administration, dilevalol is completely absorbed. Once-daily administration is possible, due to a long elimination half-life. Large well-controlled trials reveal that dilevalol is equivalent in antihypertensive efficacy to metoprolol, the ACE inhibitors captopril and enalapril, and the calcium antagonist nifedipine. Smaller noncomparative and comparative trials demonstrate the blood pressure-lowering effects of dilevalol and suggest an efficacy at least equivalent to that of the 'pure' beta-blockers atenolol and propranolol and the alpha 1-blockers urapidil and doxazosin. Dilevalol appears to be well tolerated, the most frequent adverse effects being dizziness, headache and diarrhoea in only about 7% of patients each. Unlike alpha 1-blockers and labetalol, dilevalol is not commonly associated with orthostatic hypotension. Thus, data suggest that dilevalol, with its distinctive pharmacological profile, is likely to be a useful addition to the options currently available for treating patients with mild to moderate essential hypertension.
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PMID:Dilevalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension. 218 2

Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs.
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PMID:Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 219 68

Various antihypertensive drugs reduce blood pressure by different mechanisms. In some instances, adverse reactions occur because of specific hemodynamic effects. Examples include syncope with alpha-blockade or vasodilator therapy; fatigue or exercise intolerance with the reduction in cardiac output following the use of beta-adrenergic inhibitors; edema, headaches, or dizziness with the use of vasodilators such as calcium entry blockers; renal failure in patients with renal artery stenosis or renal insufficiency following the use of ACE inhibitors; and marked hyponatremia with volume depletion following the use of diuretics, especially in elderly patients. In the majority of patients, however, blood pressure lowering can be achieved without significant adverse effects. Combining small doses of different agents with different hemodynamic actions often results in good blood pressure control and minimal reactions. Examples of these include diuretics and beta-adrenergic inhibitors, diuretics and ACE inhibitors, and beta-blockers and vasodilators.
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PMID:Do different hemodynamic effects of antihypertensive drugs translate into different safety profiles? 220 Jun 92

Recently there has been extensive development of orally active angiotensin converting enzyme (ACE) inhibitors in addition to those already marketed, for example, captopril, enalapril, lisinopril and ramipril. It was initially thought that ACE inhibitors were likely to be most useful as antihypertensive agents in conditions in which circulating renin and angiotensin II were elevated. However, it is now clear that they can also lower arterial pressure when plasma renin is not high. In addition, they have beneficial effects in cardiac failure. Thus, captopril, enalapril, lisinopril and ramipril can be used in the treatment of mild to moderate hypertension either alone or in conjunction with diuretics or calcium antagonists. Broadly speaking, efficacy appears to be similar to that of beta-blockers or diuretics. Unfortunately, however, there are no long term studies comparing one ACE inhibitor with another or with other classes of antihypertensive agents. Furthermore, there are no prognostic studies which show that use of ACE inhibitors reduces morbidity or mortality in hypertension. Many new ACE inhibitors are undergoing clinical assessment, including alacepril, cilazapril, fosenopril, perindopril, quinapril and ramipril. The drugs vary, in that some exist in the active form whereas others are prodrugs which are converted to the active agent following absorption. In addition they each possess one of several ligands, for example, carboxyl, phosphinyl or sulfhydryl groups, and so vary in their affinity for ACE. Although many of these agents are renally excreted, a small number are metabolised via the liver (e.g. quinapril and spirapril) and this may prove advantageous in the presence of renal impairment. In common with captopril and enalapril, the new ACE inhibitors inhibit the renin-angiotensin system and initial results suggest that they are effective in lowering blood pressure in essential hypertension. Furthermore, they reduce systemic vascular resistance in the absence of a reflex tachycardia. There are a number of adverse effects which are attributable to the pharmacological mechanism of the ACE inhibitors as a group; these include hypotension, particularly in patients with high renin levels, prior diuretic use, renal impairment or in the elderly. Additional adverse effects may relate to chemical structure. The high incidence of adverse effects noted in early studies related to excess dosage and to the presence of a sulfhydryl group, which the more recently developed ACE inhibitors lack. The adverse effects most commonly reported with established and new ACE inhibitors include headache and fatigue, cough, skin rashes, hypotension and diarrhoea. As a group, ACE inhibitors have an acceptable but not negligible adverse effect burden.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin converting enzyme inhibitors and moderate hypertension. 222 19

Quinapril hydrochloride is a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor that has been extensively tested and found effective when administered once-a-day to hypertensive patients of both sexes and all degrees of hypertension and cardiac compromise, including those with left ventricular hypertrophy, with and without congestive heart failure. Observations with earlier ACE inhibitors led to reports that this class of drugs was relatively ineffective in older hypertensive patients. To ascertain the role of quinapril (greater than or equal to 10 mg/day) in older patients, its blood pressure-lowering effects in 1,175 hypertensive patients less than or equal to 65 years of age were compared with those in 304 patients greater than 65 years of age. An excellent response was observed in patients greater than 65 years of age with mild to moderate hypertension (diastolic BP, 95 to 105 mm Hg) and moderate to severe hypertension (diastolic BP, 106 to 115 mm Hg). The reductions in blood pressure achieved with quinapril were at least comparable to those obtained in the younger hypertensives, and were numerically (but not statistically) greater in the mild to moderate group (-14 mm Hg v-12 mm Hg). In addition, the percentage of patients who experienced adverse experiences was lower in the greater than 65 group than in the less than or equal to 65 group (15% v 19%). The main adverse experiences reported included dizziness, headache, cough, fatigue, and hypotension. These findings indicate that quinapril is at least as safe and effective in older hypertensives as in younger patients.
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PMID:Use of quinapril in the elderly patient. 226 Nov 46


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