Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344232 (blurred vision)
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Tricyclic antidepressants are among the commonest causes of both non-fatal and fatal drug poisoning in the world. Their toxicity is due to effects on the brain, the heart, the respiratory system and the parasympathetic nervous system. Symptoms usually appear within 4 hours of an overdose and all but the most seriously poisoned patients recover within 24 hours. The most common clinical features are dry mouth, blurred vision, dilated pupils, sinus tachycardia, pyramidal neurological signs, and drowsiness. In severe poisoning, there may be coma, convulsions, respiratory depression, hypotension and a wide range of electrocardiographic (ECG) abnormalities. The most frequent findings on the ECG are prolongation of the PR and QT intervals; the tracing may resemble bundle branch block or supraventricular or ventricular tachycardias. Treatment of poisoning due to the tricyclic antidepressants is essentially supportive, there being insufficient evidence at present to recommend the use of methods to increase elimination of the drug from the body. Gastric aspiration and lavage should be performed if more than 750 mg of drug have been taken. There must be regular monitoring for hypoxia, acidosis and hypokalaemia and these complications should be corrected enthusiastically. Convulsions should be treated with diazepam or chlormethiazole. Muscular paralysis and artificial ventilation should be employed if anticonvulsants are ineffective. Hypotension should be treated firstly by fluid replacement and then with sympathomimetic agents (dopamine or dobutamine). Antiarrhythmic drugs should only be employed if there is evidence of circulatory failure which fails to respond to correction of hypotension. Sodium bicarbonate infusions should be given to cardiotoxic patients who are acidotic and are worth trying even if the patient is not acidotic. Although physostigmine salicylate will reverse most of the features of tricyclic antidepressant poisoning, its effects are short-lived in serious toxicity and it can produce dangerous side effects; physostigmine should therefore be reserved for those patients who have complications of coma or who have resistant cardiotoxicity or convulsions. Drug screening and quantitative determination of tricyclic antidepressant serum concentrations are useful in a minority of patients who have severe, unusual or prolonged symptoms.
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PMID:Poisoning due to tricyclic antidepressant overdosage. Clinical presentation and treatment. 353 21

Hyoscine (scopolamine) is a competitive inhibitor of the muscarinic receptors of acetylcholine and it has been shown to be one of the most effective agents for preventing motion sickness. However, a relatively high incidence of side effects and a short duration of action has restricted the usefulness of this agent when administered orally or parenterally, and to counter this a novel transdermal preparation of hyoscine has been developed. Pharmacokinetic studies indicate that this new method for administering hyoscine controls the absorption process and the rate of drug entry into the systemic circulation over an extended period (72 hours), providing a means of delivery which is similar to a slow intravenous infusion. However, recent evidence suggests that the response to transdermal hyoscine treatment is variable and this may reflect pharmacokinetic differences between individuals. Controlled therapeutic trials have indicated that a single transdermal hyoscine patch is significantly superior to placebo and oral meclozine (meclizine) in preventing motion sickness. Trials comparing transdermal hyoscine with oral dimenhydrinate have failed to establish any significant differences in efficacy between the 2 drugs in small numbers of subjects, although there was always a more favourable trend towards the transdermal system. In patients with acute vertigo, transdermal hyoscine and oral meclozine were equally efficacious and both were significantly better than placebo in reducing the number of attacks of vertigo. Although transdermal hyoscine has been associated with a lower incidence of side effects than orally or parenterally administered hyoscine hydrobromide, adverse systemic effects have still been frequently reported. Most commonly cited have been dry mouth, drowsiness and impairment of ocular accommodation, including blurred vision and mydriasis (some ocular effects reported may be due to finger-to-eye contamination). Adverse central nervous system (CNS) effects, difficulty in urinating, rashes and erythema have been reported only occasionally. Thus, preliminary evidence suggests transdermal hyoscine may offer an effective and conveniently administered alternative for the prevention of motion-induced nausea and vomiting in certain situations. However, the duration of its clinical effectiveness, and its relative efficacy and tolerability compared with other agents needs to be confirmed in a few additional well-designed studies.
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PMID:Transdermal hyoscine (Scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy. 388 52

A controlled study was conducted in hypertensive patients to investigate whether captopril can be substituted for the various other antihypertensive drugs (not including diuretics) to reduce side effects and improve the quality of life. Captopril in a twice daily dose of 25-50 mg, was substituted and titrated in 54 patients. Fifty-two patients, matched by age and sex, comprised the control group, and were treated with a variety of agents. During a follow-up of 9 months, 44 of the patients receiving captopril (81%) achieved the goal of supine blood pressure less than 90 mmHg. Captopril was discontinued in two patients due to side effects. Mild proteinuria was observed in two patients. A significant reduction in scores or rates of side effects (numbness, blurred vision, insomnia, vivid dreams, cold extremities, sleepiness, sexual dysfunction and fatigue) and improvement in quality of life (general feeling, mood and concentration) was observed in the study group compared with the control group. Captopril alone in a twice daily dose of 25-50 mg, or in co-treatment with thiazide, provided sustained blood pressure control with minimal side effects and improvement in quality of life compared with the treatment of hypertension with beta-blockers, vasodilators or methyldopa.
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PMID:Captopril as a replacement for multiple therapy in hypertension: a controlled study. 391 Jul 75

A self-administered symptom questionnaire was completed by 477 patients in a hypertension clinic. The complaints of the patients were analysed according to the type of therapy being given and the dose of drug taken. Methyldopa therapy was associated with sleepiness, weakness of the limbs, sleeping longer at night, and rising more frequently at night to pass urine. Diarrhoea, impotence, failure of ejaculation, blurred vision, depression, and the symptoms of postural hypotension were not related to methyldopa therapy. Bethanidine administration was related to postural hypotension, impotence, and failure of ejaculation but not to weakness of the limbs, blurred vision, depression, or diarrhoea. Patients receiving guanethidine complained of postural hypotension, failure of ejaculation, and had their bowels open more frequently. Similarly, patients receiving propranolol had an increased frequency of defaecation but also tended to complain of weakness of the limbs.Considering each drug individually, 5% of patients failed to take the prescribed dose of diuretic whereas
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PMID:Side effects of hypotensive agents evaluated by a self-administered questionnaire. 472 58

1 Preliminary results of a double-blind placebo-controlled trial of mianserin and maprotiline carried out in 58 outpatients with primary depressive illness are reported. 2 Patients received six weeks' treatment with 30 to 90 mg mianserin, 75 to 225 mg maprotiline or one to three capsules of placebo, all medication being taken at night. 3 There were statistically significant improvements in each treatment group and a better response to mianserin than to placebo or maprotiline on the Hamilton Rating Scale for Depression, after one week's treatment. 4 Neither mianserin nor maprotiline was superior to placebo after two or four weeks' treatment and relatively few patients completed six weeks' treatment because of a generally unsatisfactory response. 5 Unwanted effects were not particularly troublesome, though mianserin and maprotiline caused more drowsiness and blurred vision than did placebo, while maptrotiline produced more constipation than either of the other two treatments. 6 The importance of placebo-controlled trials of antidepressants is emphasized and the precautions that should be taken when they are carried out in outpatients are described.
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PMID:Placebo-controlled trial of mianserin and maprotiline in primary depressive illness: a preliminary report. 633 11

Twenty cancer patients who received chemotherapy were entered into a double-blind crossover design antiemetic study comparing 1 mg levonantradol, an investigational synthetic cannabinoid, to 10 mg prochlorperazine. Sixteen patients completed the crossover. For each antiemetic course, four doses of each study medication were given intramuscularly 2 hours before chemotherapy and then 2, 6, and 10 hours after chemotherapy administration. There were no statistical differences in patients' responses to levonantradol and prochlorperazine. The frequency of side effects was greater with levonantradol than with prochlorperazine. The most common side effect of levonantradol were somnolence, dry mouth, dizziness, tachycardia, postural hypotension, and blurred vision, while those for prochlorperazine were somnolence, dry mouth, and tachycardia.
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PMID:Double-blind multiple-dose crossover study of the antiemetic effect of intramuscular levonantradol compared to prochlorperazine. 637 43

In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.
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PMID:A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder. 638 93

The pharmacology, pharmacokinetics, clinical trials, side effects, and dosage of amoxapine are reviewed. Amoxapine is a tricyclic dibenzoxazepine antidepressant that is chemically similar to the antipsychotic agent loxapine. In animal tests, amoxapine and its metabolites block reuptake of the neurotransmitter norepinephrine, with little effect on serotonin. It is rapidly and virtually completely absorbed when administered orally; peak serum concentrations occur one to two hours after ingestion. Amoxapine is widely distributed throughout body tissues and is 90% bound to serum proteins. Aromatic hydroxylation in the liver produces two major metabolites, which are excreted in the urine primarily but also in the feces. Amoxapine's elimination half-life is eight hours; one of the metabolites has a long half-life (30 hours). In clinical trials, amoxapine has been compared with amitriptyline and imipramine in several types of depressed patients. In some studies, amoxapine's therapeutic effects were measurable earlier (at one or two weeks after initiation of therapy) than those of the amitriptyline or imipramine, but generally only a portion of the depression-rating scales yielded statistically significant differences. Side effects noted during amoxapine therapy include hypotension (42%), drowsiness (14%), xerostomia (14%), constipation (12%), blurred vision (7%), fatigue (5%), and vertigo (5%). Amoxapine is approved by FDA for use in patients with neurotic or reactive depressive disorders, endogenous or psychotic depression, and depression accompanied by anxiety or agitation. The usual adult dosage is 200-300 mg daily, either in divided doses or a single bedtime dose. Amoxapine is a safe and effective antidepressant with no striking advantages over other available agents.
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PMID:Evaluation of amoxapine. 676 65

Studies were conducted to evaluate the efficacy of scopolamine, absorbed through intact skin, in preventing motion sickness at sea. Efficacy of transdermal scopolamine was compared with oral dimenhydrinate and placebo. Transdermal applications were made 4 to 16 hr before exposure to motion. Dimenhydrinate or placebo was given 1.5 hr before motion and again 2.5 hr after motion began. Comparison with placebo indicated that transdermal scopolamine provided protection against motion sickness at a significance level of p = 0.0001 and oral dimenhydrinate at a level of p = 0.05. Dry mouth, drowsiness, and blurred vision associated with transdermal scopolamine therapy were minimal.
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PMID:Transdermal scopolamine in the prevention of motion sickness at sea. 700 21

Complications from mydriatic and cycloplegic drugs are rare compared with their extensive use. Adverse effects are often related to dosage or other factors. The ocular complications include increased intraocular pressure, pigmentation of the conjunctiva and cornea, pigment in the anterior chamber, lacrimal duct blockage, macular edema, corneal endothelium damage, hyperemia, allergy, discomfort, and blurred vision. The systemic complications are those common to sympathomimetic and parasympatholytic drugs and include tachycardia, hypertension, headache, faintness. pallor, trembling, excessive sweating, palpitations, arrhythmias, confusion, hallucinations, drowsiness, ataxia, flushed skin, high fever, dysarthria, thirst, dry mouth, convulsions, disorientation, nervousness, coma, and death. An understanding of all possible side effects is of paramount importance to those using these drugs in the treatment of anticholinesterase poisoning. This review is intended as a ready reference to the adverse effects of mydriatic and cycloplegic drugs.
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PMID:Mydriatic and cycloplegic drugs: a review of ocular and systemic complications. 703 29


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