Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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The safety and tolerability of lisinopril were assessed in 1,476 patients [1,165 hypertensives and 311 patients with congestive heart failure (CHF)] and 211 normal volunteers. The duration of lisinopril therapy ranged from 1 day to 16 months, with a mean duration of 105 days. In the hypertensive population, the most frequent clinical adverse experiences on lisinopril alone were headache, dizziness, cough, and diarrhea. Not all of these adverse experiences were thought to be drug related. Five percent of patients were discontinued because of adverse clinical experiences; cough and dizziness were the most common reasons for discontinuation. Two of 1,165 (0.17%) hypertensive patients treated with lisinopril died, compared to 0.41% of hypertensive patients on other therapies. Neither case was considered to be drug related. In patients with CHF, the most frequent clinical adverse experiences were dizziness, diarrhea, hypotension, fatigue, headache, and rash. Not all of these adverse experiences were thought to be drug related. The percent of CHF patients discontinuing because of an adverse clinical experience was 7.4%; the most frequent causes for discontinuation were hypotension, dizziness, or renal impairment. Twelve deaths occurred in 311 CHF patients treated with lisinopril (3.9%) compared to 4/104 (3.8%) of CHF patients treated with placebo and 2/65 (3.1%) treated with captopril. Hypotension, orthostatic effects, or dizziness following the initial lisinopril dose occurred infrequently in patients treated with lisinopril. In hypertensive patients with normal renal function, including those treated previously or concomitantly with diuretic therapy, a first-dose hypotensive episode was reported in six of 955, or 0.6%. The incidence was higher (6.7%) in hypertensive patients with impaired renal function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The safety and tolerability of lisinopril in clinical trials. 244 61

To investigate the pharmacokinetics and pharmacodynamics of a new angiotensin converting enzyme (ACE) inhibitor, ramipril (HOE 498), in patients with cardiac insufficiency (NYHA III-IV), we performed an open trial with a follow-up of 10 days. Twenty-seven patients (18 females, 9 males), mean aged 62 years (46-83) with severe heart failure, were included. After a single oral dose of 5 mg ramipril, the plasma and urine levels of ramipril, ramiprilat, ACE plasma activity, standard laboratory values, blood pressure and pulse rate were evaluated. The maximal plasma level of ramipril was 57.0 +/- 26.8 ng/ml after 1.4 h; t1/2 was 2.4 +/- 1.2 h. The peak level of ramiprilat was 27.9 +/- 24 ng/ml after 4.6 h; t1/2 for the active compound was 6 +/- 4.2 h. The total recovery of ramipril and metabolites in urine was on average 39 +/- 17.5% within 96 h. Ninety-five percent inhibition of ACE activity was observed in all patients and 80% inhibition lasted 24 h. Systolic and diastolic blood pressure decreased without changes in heart rate. Five patients had mild side effects: hypotension, diarrhea, and dizziness. In conclusion, in patients with severe heart failure, plasma levels of drug and active metabolite were higher and remained measurable longer, with more sustained inhibition of ACE activity than reported in healthy volunteers. This indicates that titration should start with lower doses (1.25-2.5 mg) and that doses above 5 mg may rarely be necessary.
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PMID:Pharmacokinetic and pharmacodynamic properties of ramipril in patients with congestive heart failure (NYHA III-IV). 247 2

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.
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PMID:Clinical experience with lisinopril. Observations on safety and tolerability. 255 Jun 41

The selective serotonin-1A receptor partial agonist anxiolytics represent a new class of pharmacologic agents that have demonstrated efficacy in the treatment of generalized anxiety disorder (GAD). These compounds offer a completely different pharmacologic approach to this disorder from previous medications. The selective 5-hydroxytryptamine-1A (5-HT1A) anxiolytics buspirone, gepirone, ipsapirone, and SM-3997 have several important new and unique features that will be reviewed in this paper. These features include no cross-tolerance with alcohol or benzodiazepines, no evidence of abuse or misuse potential, and no withdrawal symptoms or rebound anxiety on cessation of therapy. The 5-HT1A anxiolytics have no muscle relaxant, sedative, or anticonvulsant properties and do not impair psychomotor functioning. They do have a slower onset of effect than standard benzodiazepines-clinical response is usually noted in 1-3 weeks. The side effect profile is quite different from that of the benzodiazepines. It includes gastrointestinal symptoms such as nausea and diarrhea, headache, dizziness, and restlessness. Some patients with GAD who have received chronic (greater than 1 month) benzodiazepine therapy may not respond as well to these compounds initially as will patients with no prior benzodiazepine treatment, especially if the benzodiazepine has been discontinued only recently. These compounds, buspirone in particular, have been shown to have excellent maintenance and prophylactic properties and to be well tolerated with long-term therapy (greater than 3 months). Because of their unique mechanism of action and side effect profile, and no evidence of misuse or abuse potential or interference with mental acuity, these compounds represent a definite advance in the pharmacologic management of GAD.
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PMID:Serotonin-1A anxiolytics: an overview. 256 39

A clinical-epidemiological study of an accidental poisoning by Robinia pseudoacacia L. (lucust tree) in six school children has been made. The case had sucked and/or chewed the bark of this plant. The clinical symptoms were abdominal pain, thirst, nausea, vomiting, dry throat, muscle weakness, mydriasis, headache, dizziness and diarrhea. The treatment was activated charcoal in 5 cases and subsequent gastric lavage in 3 cases. The results was favorable. The poisoning took place in the school yard during the mid-morning recreation period. Only girls were affected (average age 6.5 +/- 2.1 years old). The attack rate was 31.6% for the school children who tasted the bark, and chewing it constituted the highest factor of risk (p = 0.03). Recommendations have been made to prevent childhood accidents.
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PMID:[Clinico-epidemiologic study of accidental poisoning with Robinia pseudoacacia L. in school children]. 265 7

Data from 1,878 courses of intravenous ciprofloxacin therapy, administered to 1,869 patients in 59 clinical trials, were analyzed for drug safety. The 985 men and 884 women had a mean age of 50 years, and more than one third were over 60 years of age. An overwhelming majority had at least one accompanying systemic illness, and the condition of more than half the patients was only fair or poor at the onset of therapy. Ciprofloxacin was administered in a unit dose of either 200 mg (68 percent of the patients) or 300 mg (28 percent) by intravenous infusion, generally over 30 minutes every 12 hours, at a mean daily dosage of 456 mg. The duration of intravenous therapy ranged from one to 57 days, with a mean of seven days; over 1,000 patients were treated for more than five days. Adverse events considered probably or possibly related to intravenous ciprofloxacin were reported in 15.8 percent of the courses; therapy was discontinued prematurely in 3 percent. Local reactions at the site of infusion were the most common, occurring in 4.4 percent of the courses. Changes in blood chemistry values (4.1 percent) included increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Reports of adverse effects referable to the gastrointestinal tract (3.0 percent) were primarily nausea and diarrhea. Central nervous system reactions (1.8 percent) included convulsive seizures, headache, and dizziness. In comparative trials, events considered probably or possibly drug related were reported for 17.3 and 13.6 percent of the ciprofloxacin- and ceftazidime-treated patients, respectively. The incidence of adverse events other than local reactions at the infusion site was not significantly different between the ciprofloxacin- and ceftazidime-treated patients (12.7 percent versus 11.0 percent, p greater than 0.2).
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PMID:Safety of intravenous ciprofloxacin. A review. 268 31

Four multicentre clinical trials on interruption of early pregnancy (less than or equal to 49 days of amenorrhea) using RU 486 have been conducted in China, including 2321 subjects. The data from trials 1, 2 and 4 are presented here. RU 486 (600 mg as a single dose) was given to 299 women. A further 422 women were given RU 486 (600 mg) plus a vaginal suppository containing the Chinese domestic prostaglandin PGO5 (1 mg) 36-60 hours later. Complete abortion was achieved in 63.5% of patients receiving RU 486 alone and in 94.1% of patients receiving RU 486 plus PG (p less than 0.001). RU 486 given alone showed decreasing efficacy as the duration of amenorrhea increased. However, RU 486 combined with PG was equally effective at all time points studied (less than or equal to 35 days of amenorrhea: 98.1%, 36-42 days: 92%, 42-49 days: 87.4%). When compared with RU 486 alone Ru 486 + PG also produced a shorter bleeding time and a lower volume of blood loss (n = 21, 52 ml vs n = 13, 117 ml). Two patients from the RU 486+PG group and 4 given RU 486 alone suffered heavy bleeding, necessitating emergency curettage. No transfusions were required. The time elapsed between RU 486 intake and expulsion of the conceptus was significantly shorter in the RU 486+PG group (n = 97, 31 days) than that in the RU 486 alone group (n = 95, 4.4 4.4 days). Main side effects, nausea/vomiting and headache/dizziness, were mainly due to RU 486. PG increased the incidence of diarrhea and uterine cramp.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:RU 486 (mifepristone): clinical trials in China. 269 37

This report reviews the gastrointestinal and central nervous system complaints and clinical course in 10 adult patients with abdominal epilepsy. Abdominal symptoms included paroxysmal pain, nausea, bloating, and diarrhea. Nervous system manifestations included dizziness, headache, confusion, syncope and transient blindness. Each patient had specific electroencephalographic abnormalities of a temporal lobe seizure disorder. Anti-convulsant therapy has resulted in the sustained abolition of symptoms in each case.
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PMID:The spectrum of abdominal epilepsy in adults. 280 81

A 15-year-old boy with diarrhea, dizziness, dysesthesias, and depression is described. On admission, his blood pressure was 110/84 reclining but less than 40 systolic while standing. Vibratory sensation and nerve conduction velocities were decreased in his lower extremities. CSF protein concentration was normal but sural nerve biopsy demonstrated generalized demyelination. Extensive toxicologic and metabolic screening proved unremarkable. Norepinephrine concentrations in plasma and urine, and CSF concentration of 3-methoxy-4-hydroxy phenylglycol (MHPG) were markedly reduced. The patient demonstrates a combination of autonomic dysfunction, peripheral neuropathy, and affective disorder. This collection of clinical and neurochemical findings represents a previously unreported entity involving a defect of both central and peripheral noradrenergic systems.
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PMID:Autonomic dysfunction, peripheral neuropathy, and depression. 285 34

In 984 patients with generalized anxiety disorder who received buspirone in double-blind studies, the incidence of drowsiness (9 percent) did not differ significantly from that (10 percent) reported in 334 patients who received placebo. A probability value of p less than or equal to 0.10 was the criterion for significance. The incidence of drowsiness in buspirone-treated patients was significantly less than that in each of the groups receiving diazepam (32 percent), clorazepate (26 percent), lorazepam (58 percent), or alprazolam (43 percent). The side effects that did occur significantly more frequently in the buspirone group than in the placebo group were dizziness (9 percent versus 2 percent), headache (7 percent versus 2 percent), nervousness (4 percent versus 1 percent), light-headedness (4 percent versus less than 1 percent), diarrhea (3 percent versus less than 1 percent), paresthesia (2 percent versus less than 1 percent), excitation (2 percent versus less than 1 percent), and sweating/clamminess (1 percent versus 0 percent). The severities of these effects were predominantly rated as only mild or moderate. Fatigue occurred less frequently in buspirone-treated patients than in those receiving any of the benzodiazepines, and weakness occurred more frequently in diazepam-treated patients. Depression occurred less frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or lorazepam. Impotence occurred only in clorazepate- and lorazepam-treated patients. Decreased libido occurred more frequently in diazepam-treated patients, whereas increased libido was more frequent in clorazepate-treated patients. Nausea was reported more frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or alprazolam; diarrhea occurred more frequently in the buspirone group than in the diazepam group. The mean daily doses of the various treatments were buspirone, 20 mg; diazepam, 20 mg; clorazepate, 24 mg; lorazepam, 3 mg; and alprazolam, 1.5 mg. In an open-field study in West Germany involving 5,414 patients, gastrointestinal-related complaints were the most frequently reported side effects.
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PMID:Review of the side-effect profile of buspirone. 287 Jun 41


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