Gene/Protein Disease Symptom Drug Enzyme Compound
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Clinical, biochemical, haematological and erythrokinetic studies were performed on 63 adult males with prolonged lead exposure. Their most common symptoms and findings were abdominal pain (62%), gingival lead lines (48%), headache and/or dizziness (33%), muscle cramps (32%), anaemia (19%), and fatigue (18%). Colicky abdominal pain (27%) and gingival lead lines correlated with urinary lead excretion. Anaemia was mild, but more frequent in the subjects with the greatest urinary lead excretion. Other associated findings were: higher reticulocyte counts and more basophilic stippling of the RBCs, more sideroblasts and greater erythroid hyperplasia of the bone marrow, more reduction in 51Cr-tagged RBC survival time, smaller RBC mass, a more rapid plasma iron clearance, a greater plasma iron turnover and greater utilization of 59Fe in subjects with urinary lead excretion of greater than 100 microng/day in comparison with the remainder and normal controls. These findings suggest that minimal chronic exposure to lead causes an increased haemolysis with resulting increased production of erythrocytes.
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PMID:Chronic industrial exposure to lead in 63 subjects. I. Clinical and erythrokinetic findings. 103 Aug 53

To identify and measure the incidence of adverse effects of the angiotensin converting enzyme inhibitor enalapril 13,713 patients were studied for one year by prescription-event monitoring. Precise information about the duration of treatment was available for 12,543 patients. The frequency of many events was calculated, including dizziness (483 patients; 3.9%), persistent dry cough (360; 2.9%), headache (310; 2.5%) hypotension (218; 1.7%), and syncope (155; 1.2%). Less common reactions included angioedema, urticaria, and muscle cramps. Altogether 1098 (8%) patients died and the notes of 913 of them (83%) were obtained for detailed scrutiny. With the exception of a few patients with renal failure who deteriorated during treatment (reported on separately), no death was attributed to enalapril. Enalapril was considered to be effective, even in patients with advanced cardiac failure. These results for enalapril are reassuring and provide further evidence of the value of prescription-event monitoring.
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PMID:Postmarketing surveillance of enalapril. I: Results of prescription-event monitoring. 284 1

More than 1200 patients who received pindolol for the treatment of hypertension, angina pectoris, and various arrhythmias in studies conducted in the United States were included in the New Drug Application submitted to the FDA. Nearly 1000 of these patients received pindolol as monotherapy. The side effects reported were generally transient and of mild or moderate severity. The most frequently reported side effects seen after pindolol administration, compared to those seen after placebo, were in decreasing order of incidence: headache, dizziness, insomnia, muscle pain, fatigue, weakness, nervousness, joint pain, edema, nausea, and muscle cramps. Other side effects that occurred more frequently with pindolol than with placebo but at a rather low incidence induced weight gain, bizarre dreams, visual disturbances, lethargy, and diarrhea. Nasal congestion, throat discomfort, nocturia, impotence, pruritus, anxiety, hypotension, bradycardia, and heart failure occurred only rarely. Of the 323 patients who received pindolol alone for the treatment of mild to moderate hypertension, only 20 (6.2%) were withdrawn from the study because of side effects. Overall, 3.4% of the patients treated with pindolol were withdrawn because of side effects, most of which involved the central nervous system, that is, insomnia, anxiety, dizziness, and headache. However, a few patients manifested some edema and weight gain while receiving pindolol alone. Review of the side effects data did not reveal a tendency for the incidence of side effects to be dose related. One placebo-controlled, double-blind study designed to evaluate the fixed dosages of 15, 30, and 60 mg in the treatment of mild to moderate hypertension suggested that only the incidences of insomnia and nervousness increased with increasing doses. However, these side effects were generally transient and of mild or moderate severity. The evidence indicates that pindolol has an acceptable safety profile and that any side effects that appear are generally well tolerated and disappear with continued treatment.
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PMID:Adverse reactions to pindolol administration. 704 82

The efficacy and safety of oral Tolperisone HCL was evaluated in double blind, placebo-controlled, randomized trial in 72 patients with neurolathyrism in stages I, II, and III of the disease at Kolla Duba Health Centre of Dembia District of North Gondar between January and April 1995. Taken orally daily for 12 weeks, tolperisone HCL (Mydocalm) in a dose of 150 milligrams (mgs) twice daily significantly improved subjective complaints such as muscle cramps, heaviness of the legs, startle attacks, flexor spasms and repeated falls. An overall subjective improvement was observed in 75% of the patients on tolperisone HCL and 39% of the placebo group (P = 0.002). When objectively assessed spastic muscle tone in the abductors, stiffness of Achilles and spontaneous ankle clonus were significantly reduced in tolperisone HCL group (P values = 0.001, 0.04, and 0.0001, respectively). Walking ability and speed of walking was also significantly improved. The drug is most effective in relieving symptoms of stage I and stage II disease. Some adverse effects like muscle pain, generalized body weakness and dizziness were recorded in patients taking the drug but all were minor and self limited, none requiring discontinuation of treatment. It is concluded that tolperisone is a well tolerated and efficacious drug for symptomatic treatment of neurolathyrism.
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PMID:Symptomatic treatment of neurolathyrism with tolperisone HCL (Mydocalm): a randomized double blind and placebo controlled drug trial. 957 9

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

A case of intoxication in Southern Bulgaria after a bite from the venomous spider Latrodectus tredecimguttatus is reported. The development of both local (acute pain, itching erythema, paraesthesiae in the area of the bite) and general (weakness, headache, dizziness, fever, vomiting, myalgia, muscle cramps) symptoms, which passed relatively easily, is described. The clinical picture and treatment are briefly commented on.
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PMID:A case of intoxication after a bite by Latrodectus tredecimguttatus. 1134 25

Cholinesterase inhibitors can be used as one element of a comprehensive approach to management of mild-to-moderate AD. Benefits include modest cognitive improvement, increased activation, and improved mood and behavior. Patients with other disorders, such as Lewy-body dementia, may also improve. The most common side effects include GI disturbances, insomnia, dizziness, fatigue, and muscle cramps. Adverse effects can be significantly reduced by waiting 4 to 6 weeks before increasing doses. Insomnia may be alleviated by having the patient take the medication early in the day.
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PMID:Cholinesterase inhibitors. Comparing the options for mild-to-moderate dementia. 1158 75

A prospective study on the effect of profiled hemodialysis on intradialytic symptoms was undertaken among patients recruited between September 2002 and December 2002. Evaluated intradialytic symptoms included hypotension, muscle cramps, dizziness, headache, nausea, discomfort, thirst, and shortness of breath. Symptomatic patients were allocated to one mode of combined sodium and ultrafiltration profile during hemodialysis. The programs were readily available on Fresenius MC 4008 H&E hemodialysis machines. Evaluation was performed before profiling and at 2, 4, and 6 weeks into the profiled hemodialysis. On standard hemodialysis 40 (36.4%) patients were symptomatic. Hypotension was reported in 29 (72.5%) of patients receiving standard treatment. Dizziness, headache, and muscle cramps were reported in 22 (55%), 15 (37.5%), and 9 (22.5%) patients, respectively. These symptoms were significantly (P <.05) improved at 2, 4, and 6 weeks of profiling. Other symptoms, such as discomfort, nausea, vomiting, and thirst, were infrequently reported among patients without or with profiling. There was no significant difference between the applied profiles when compared with each other. In conclusion, sodium and ultrafiltration profiling are effective techniques to reduce acute adverse side effects of hemodialysis. They improve patient well-being and dialysis tolerance, minimize interventions during dialysis.
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PMID:Profiled hemodialysis reduces intradialytic symptoms. 1535 Apr 88

Mass psychogenic illness (epidemic sociogenic attacks/mass hysteria) refers to a rapid spread of well-described signs and symptoms affecting members of a group. It might be difficult to differentiate at first from illnesses due to infections, intoxications or "bio-terrorism." We investigated such an occurrence in a small village in Lebanon chronically under threat of war. A 16-year-old single female, school student, was referred to Saint George Hospital University Medical Center, Beirut, for attacks of shortness of breath, muscle cramps, tremors and dizziness, for several days. She was referred because she was the first of eight cases from the same village to have similar symptoms. In parallel to an inpatient multidisciplinary evaluation and treatment, meetings were held with the crisis group comprising members of the hospital Psychiatry and Psychology Department, a public health representative of the Ministry of Health of Lebanon, physicians who were taking care of the other cases and a psychologist working in the area where these cases were declared. The diagnosis of mass psychogenic illness (epidemic sociogenic attacks) was reached. A common strategy was adopted in an effort to control the epidemic. Several explanations had been put forward initially by the community : bioterrorism, noxious fumes and "bad spirits." At the time of writing this report--nine months later--, the epidemic, which had abated within six weeks, was still inactive.
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PMID:Mass psychogenic illness (epidemic sociogenic attacks) in a village in Lebanon. 1768 27

Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire from 375 caregivers in Montreal. Sixty-four per cent of caregivers responded ( n = 201), and most (> or =59%) were willing to continue treatment if persons with Alzheimer's disease suffered from weight loss or loss of appetite. However, most (> or =53%) were not willing to continue treatment in the event of headache, dizziness, nausea, diarrhea, vomiting, drop in blood pressure, insomnia, muscle cramps, or stomach bleeding. The use of cholinesterase inhibitors by persons with Alzheimer's disease was positively associated with caregivers' willingness to accept greater numbers of adverse effects (adjusted relative risk = 1.97; 95% CI = 1.11 to 3.61). Caregivers appear to make a risk-benefit assessment when they decide whether or not care-recipients should continue pharmacotherapy in the event of adverse effects.
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PMID:Caregiver acceptance of adverse effects and use of cholinesterase inhibitors in Alzheimer's disease. 1823 27


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