Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
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PMID:Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. 921 Oct 87

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

A cross-sectional study involving 60 women from Sydney, Australia, and 99 women from Los Angeles, California (US), evaluated the impact of three different insertion regimens on the transient nausea associated with the contraceptive vaginal ring. The ring released 20 mcg of ethinyl estradiol and 1 mg of norethindrone acetate per day. 128 women completed the 6-month study, providing 831 woman-months of exposure. The one pregnancy recorded during the 6-month study occurred during the 7-day break between cycles 5 and 6. 53% of women experienced nausea in at least one cycle. No significant differences in side effects were noted based on insertion group: 1) early evening (5-7 p.m.); 2) late night (10 p.m. to midnight); and 3) early evening insertion, removal at bedtime, and reinsertion the next morning. In each insertion group, the incidence of nausea was greatly reduced (to 6-9%) in the second cycle of use. 9% of women experienced transient vomiting in the 24 hours after first insertion of a new ring. The remaining side effects--headache, dizziness, uterine cramps, breakthrough bleeding, weight gain, and expulsion--were rare and occurred with equal frequency in all three insertion groups. Women at both study sites expressed a high degree of satisfaction with the vaginal ring, primarily because of its convenience and effectiveness. Overnight soaking of the ring before first use has the potential to reduce the side effect of transient nausea, presumed attributable to the accumulation of ethinyl estradiol on the ring surface during storage.
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PMID:Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring. 940 4

In 25 patients with chronic renal failure treated by haemodialysis with acetate-37 mEq/l containing fluid, plasma free, total carnitine and acetate concentration before and after HD were assessed. The concentration of acetate was high-12 mmol/l in 4 patients in which carnitine concentration was low. In these patients the incidence of the so-called "dialysis intolerance" or "acetate intolerance" such as acute hypotension, nausea, vomiting and headache were increased. The correlation between the serum acetate level and carnitine level and the symptoms suggest that the acetate overload during acetate dialysis affects acetate metabolism and administration of L-carnitine decreases the amount of accumulated acyl-CoA in the cytosol, and consequently--the citrate cycle function increases and diminish the intolerance symptoms.
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PMID:[Protective role of carnitine in acetate metabolism of patients with uremia treated by hemodialysis]. 944 Dec 89

To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.
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PMID:Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension. 949 99

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.
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PMID:Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer. 952 27

The contraceptive safety and efficacy of long-term use of the oral contraceptive Belara (30 mcg ethinyl estradiol and 2 mg chlormadinone acetate) were assessed in an open, noncontrolled phase III study. Of particular interest was the effect of the anti-androgenic activity of this formulation on clinical signs of androgenization. Belara was taken by 1655 German women (mean age, 25.9 years), for a total of 22,337 cycles. A total of 12 pregnancies occurred, yielding a theoretical Pearl index of 0.269 (95% confidence interval, 0.109-0.600). No withdrawal bleeding occurred in 1655 cycles (7.4%), while spotting was documented in 2565 (11.5%) and breakthrough bleeding in 786 (3.5%). After 12 cycles of use, acne on the face/neck improved in 64.1% of affected women and completely disappeared in 53.4%. Seborrhea improved after 12 cycles in 67.9% of affected women and was cured in 58.0%. Side effects included headache (37.4%), nausea (23.1%), breast tenderness (21.7%), and vaginal discharge (19.4%). Of the 62 serious adverse events reported by 59 women, only the 2 cases of deep venous thrombosis could be linked to Belara use. Overall, these findings suggest that Belara is a well-tolerated oral contraceptive with minor side effects comparable to those associated with use of other low-dose pills.
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PMID:Efficacy and safety of the new antiandrogenic oral contraceptive Belara. 958 37

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.
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PMID:Steroidal 'add-back' therapy in patients treated with GnRH agonists. 962 21

The 3 methods of long-term contraception (LTC) approved for use in the US are intrauterine devices (IUDs), levonorgestrel subdermal implants, and sustained-release medroxyprogesterone acetate injections. Women who use reversible LTC are likely to receive care from clinicians who did not prescribe the method of contraception originally. Fortunately, most concerns arising from the use of reversible LTC can be managed by clinicians regardless of their specialty. Problems associated with an IUD can include a missing string, partial expulsion of the device, change in menstrual pattern, vaginal discharge, or infection. Headaches, weight gain, dermatologic problems, changes in hair growth, and irregularities in menses are among the problems that clinicians may confront while caring for a woman who has had subdermal hormone implants or has been taking depot injections. Besides the problems caused by or complicating specific methods of LTC, a woman may seek clinical care for a variety of general concerns. These include a desire to terminate LTC in order to become pregnant, and physical changes that are suspected to indicate pregnancy or contraceptive failure. In addition, general health conditions such as concurrent medications, hypertension, and endocrine disorders may need special consideration in a woman using LTC. There are few medical indications for discontinuing or changing LTC, even when intercurrent illnesses arise.
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PMID:Managing clinical complexities of long-term contraception. 973 86

Pharmacologic intervention is now the most effective therapy available for treating premenstrual syndrome (PMS). Although there are still no Food and Drug Administration-approved medications for this indication, several well-designed studies have been conducted, the results of which may guide the clinician's treatment of women with this disorder. Consequently, less-proven nonpharmacologic modalities, such as dietary modification, exercise regimens, and psychotherapy, are more readily supplanted by the use of medication. Three classes of agents have been shown to have varying degrees of effectiveness in relieving PMS symptoms and are increasingly being used to treat the disorder: gonadotropin-releasing hormone (GnRH) agonists, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs). While the GnRH agonists like leuprolide acetate, nafarelin acetate, or goserelin acetate have been shown to be highly effective in select cases, their side effects relegate them to use in patients who are unresponsive to other agents. More recently, the benefits of alprazolam (a benzodiazepine) and the SSRIs (especially fluoxetine) have been definitively established. In addition to these medications used to treat premenstrual syndrome in general, other drugs that are used to treat specific aspects of the disorder include danazol for headaches and spironolactone for fluid retention.
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PMID:From GnRH to SSRIs and Beyond: Weighing the Options for Drug Therapy in Premenstrual Syndrome. 974 8


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