Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.
 ...
PMID:Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study. 135 85

Soleus muscle in Wistar-Kyoto rats (WKY), as well as in most normotensive mammals, is highly fatigue resistant. In 6-mo-old spontaneously hypertensive rats (SHR), however, soleus muscle generates less specific force and experiences a more rapid rate of fatigue than in age-matched WKY. The present experiments tested the hypothesis that antihypertensive treatment with hydralazine or amlodipine would shift the contractile force and fatigue resistance profile of SHR soleus toward that which characterizes WKY. Hydralazine was given via the drinking water (100 mg/l) and amlodipine via the food (1 g/4 kg rat chow) to two separate groups of animals, starting at the age of 16 wk. At 24-26 wk of age soleus twitch and tetanic force generation and the rate of fatigue were evaluated during a 4-min period of repetitive stimulation. Although both hydralazine and amlodipine lowered blood pressure, they had different effects on muscle function. Hydralazine decreased force generation in both WKY and SHR at all stimulation frequencies; it did not change the fatigue properties of SHR but made WKY soleus less fatigue resistant. Amlodipine, on the other hand, increased contractile force in both WKY and SHR and increased fatigue resistance in SHR. Amlodipine is a dihydropyridine that blocks L-type channels, thereby preventing entry of Ca2+ into the muscle. We suggest that Ca2+ entry during activity stimulates Ca-activated K+ efflux in SHR and adds to the extracellular load of K+. Increased extracellular K+ can in turn depress contractile performance.
 ...
PMID:Effect of chronic blood pressure reduction on soleus muscle contractile properties in spontaneously hypertensive rats. 809 18

Preclinical studies indicate that dihydropyridine-type calcium channel antagonists modulate dopamine neurotransmitter function and can reduce cocaine-reinforced behaviors. Amlodipine, a long-acting dihydropyridine-type calcium channel antagonist related to isradipine and nifedipine, was administered in open label fashion for 12 weeks to 26 cocaine-dependent patients. In subjects expressing cocaine craving, craving significantly declined during the course of the 12 weeks. Five individuals reported flushing, headache, fatigue, nocturia, nausea, and lightheadedness. No conclusions regarding efficacy can be made due to the small number of subjects and the open-label design.
 ...
PMID:Amlodipine treatment of cocaine dependence. 1043 93

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07+/-0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29+/-0.11 mg/kg per day for those < 13 years, 0.16+/-0.11 mg/kg per day for those > or = 13 years, 0.23+/-0.14 mg/kg per day for essential, hypertension and 0.24+/-0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.
 ...
PMID:Efficacy of amlodipine in pediatric patients with hypertension. 1045 79

The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was evaluated in a "real life" setting. This open non-comparative trial included 123 men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline measurements, 2 weeks apart. Eligible patients were given AML 5 mg daily as add-on or monotherapy and were evaluated 4 weeks later. If DBP was then > 90 mmHg, the daily dose was raised to 10 mg; those with < 90 mmHg remained on 5 mg. AML was continued for 8 weeks. Other BP-lowering drugs were unchanged. Of the original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others were protocol violators, lost to follow-up or withdrew, leaving 211 available for efficacy analysis. In this major group BP was reduced from 165 +/- 15/101 +/- 4 to 139 +/- 11/83 +/- 5 after 12 weeks of AML (p < 0.05). The reduction was greater in those under 70 years, from 173 +/- 12/100 +/- 5 to 142 +/- 12/80 +/- 4 (p < 0.05). In those with BMI > 30 kg/m2, BP decreased from 165 +/- 15/101 +/- 5 to 140 +/- 12/83 +/- 5 (p < 0.05). Mean change in heart rate was -1.5 bpm (p < 0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in 3.7% it persisted during therapy. Other AE occurring in > 1% were dizziness in 1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%. We conclude that AML is an effective and well-tolerated antihypertensive suitable for most hypertensive patients.
 ...
PMID:[Multicenter community-based trial of amlodipine in hypertension in Israel]. 1095 90

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.
 ...
PMID:Treatment of hypertensive children with amlodipine. 1104 Nov 59

The authors retrospectively examined their experience with amlodipine in the treatment of hypertension in 32 pediatric-aged patients, ranging in age from 4 to 26 years, with blood pressure (BP) readings greater than the 90th percentile for age. Amlodipine was used as the sole therapy in 9 patients and with other antihypertensive therapy in 23 patients. Additional antihypertensive drugs used in combination with amlodipine included beta-adrenergic antagonists, ACE inhibitors, and diuretics. The starting dose of amlodipine was 0.13+/-0.09 mg/kg/d. The dose was increased in 20 of 32 patients to 0.23+/-0.13 mg/kg/d. Amlodipine was administered once daily to 26 patients and twice daily to 6 patients. After therapy with amlodipine was initiated, the systolic BP decreased from 141+/-15 to 132+/-9 mm Hg (P=0.01) and the diastolic BP decreased from 84+/-16 to 77+/-8 mmHg (P=0,03). There were a total of 2145 follow-up BP readings. The follow-up systolic BP was lower than the initial BP prior to starting amlodipine 59% of the time and the diastolic BP was lower than the initial BP 61% of the time. The follow-up systolic BP was lower than the 90th percentile predicted for age 33% of the time after starting amlodipine and the diastolic BF was lower than the 90th percentile for age 52% of the time. Adverse effects were noted in 4 of the 32 patients (12.5%). These included fatigue (n=2), dizziness (n=1), and ankle edema (n=1). Amlodipine therapy was discontinued in only 1 patient (the patient with ankle edema). Given its efficacy, the low incidence of adverse effects, and availability as a suspension, amlodipine is an effective agent for the treatment of hypertension in the pediatric-aged patient.
 ...
PMID:Preliminary experience with amlodipine in the pediatric population. 1677 60