Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMITRIPTYLINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMed1985

Evaluation of amitriptyline pharmacokinetics during peritoneal dialysis.

The pharmacokinetics of a single oral dose of amitriptyline were examined in five functionally anephric patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The concentration of the parent drug and its major metabolite nortriptyline in plasma were measured by high performance liquid chromatography. Patients on CAPD did not have a significantly extended elimination half-life (t 1/2) as compared to literature controls. However, the variation in t 1/2 was extremely large in both the CAPD and normal renal function groups (range 15-34 h and 24-70 h, respectively). No statistically significant change was observed (p less than 0.05). Although a major route of elimination was removed and there was no change in t 1/2, the drug levels in these patients should be closely monitored because of the large variability in patient metabolism.

Adult↗
PubMed1987

Steady-state concentrations of amitriptyline and its metabolite nortriptyline in Saudi patients.

The serum concentrations of amitriptyline (AMI) and its metabolite nortriptyline (NT) were determined in 54 Saudi patients treated for long durations with a daily oral dose (0.111 to 4.167 mg/kg) of AMI. Ten of these patients were concomitantly treated with neuroleptic drugs. The mean (SEM) of the dose-normalized steady-state serum concentration (Css) of AMI in patients who received AMI alone (Group I) was [46.1 (6.5) ng X ml-1/mg X kg-1], with mean NT/AMI Css ratio of 0.962 (0.122). A significantly higher mean of Css of AMI [82.3 (18.8 ng X ml-1/mg X kg-1] was acquired for patients who concomitantly received AMI and neuroleptic drugs (Group II). However, the difference in the mean NT/AMI Css ratio between Group I and Group II [0.929 (0.197)] was not significant. Also, the results of this study indicate that Css of AMI and the NT/AMI Css ratio in Saudi patients treated for depression with AMI alone are not significantly different from those reported for subjects from Western populations.

Amitriptyline↗
PubMed1991

Extremely long plasma half-life of amitriptyline in a woman with the cytochrome P450IID6 29/29-kilobase wild-type allele--a slowly reversible interaction with fluoxetine.

A 61-year-old woman, a nonsmoker, was admitted to the hospital because of endogenous depression. No concomitant disease, especially kidney or liver dysfunction, was diagnosed. After 9 days of treatment with 125 mg of amitriptyline (AMI) daily, she developed signs of a severe anticholinergic syndrome. Plasma concentrations of AMI (510 ng/ml) and nortriptyline (NOR; 320 ng/ml) were very high and the half-life of AMI was about 120 h. The debrisoquine metabolic ratio was 0.55 and 0.79 on two occasions, which shows that she had no deficiency of cytochrome P450IID6. This result was confirmed with a dextromethorphan test, analysis of restriction fragment length polymorphisms (29/29-kb fragments), and genotyping with allele-specific polymerase chain reaction (homozygous 29 kb wild-type alleles). Patients with high plasma levels of tricyclic antidepressants are usually poor metabolizers of debrisoquine. Before the administration of AMI, our patient was pretreated with fluoxetine. A slowly reversible interaction with fluoxetine or an extremely long-lasting metabolite may be responsible for the long plasma half-life of AMI.

Alleles↗
PubMed1993

Concurrent liquid chromatographic measurement of fluoxetine, amitriptyline, imipramine, and their active metabolites norfluoxetine, nortriptyline, and desipramine in plasma.

An expedient and specific liquid chromatographic method for a concurrent measurement of fluoxetine (FLU), norfluoxetine (NFLU), amitriptyline (AMI), nortriptyline (NTRIP), imipramine (IMI), and desipramine (DES) is described. Using a mixture of acetonitrile:methanol:0.056 M ammonium acetate:1 M ammonium hydroxide (100:10:4.5:2.6, by volume) as mobile phase, the compounds along with doxepin (DOX) (internal standard) were separated on a 10 mu, 8 mm x 10 cm C18 Resolve cartridge in conjunction with radial compression liquid chromatographic module, and were detected in the effluent spectrophotometrically at 220 nm. A hexane:isoamyl alcohol (98:2, by volume) solution was used for extraction of plasma and the drugs were removed from the organic phase with 0.03% phosphoric acid prior to injection. Under these conditions, no interference in the assay was observed, and the retention times of NFLU, DOX, FLU, AMI, IMI, NTRIP, and DES were 7.8, 11.6, 16, 17.8, 20.9, 31, and 35 min, respectively. The assay was highly linear (r > 0.994), and the within- and between-day coefficient of variance was consistently < or = 9.8%. This assay is currently being used to simultaneously measure these drugs in patients and to investigate their steady-state pharmacokinetics when used in combination.

Amitriptyline↗
PubMed1994

The use of therapeutic drug monitoring data to document kinetic drug interactions: an example with amitriptyline and nortriptyline.

Therapeutic drug monitoring data for amitriptyline (AT) and nortriptyline (NT) collected during 10 years (total of 4,278 analyses in 2,937 patients) were evaluated to study how other drugs affect the kinetics at steady state. The distribution of the ratio concentration/daily dose (C/D) in patients treated with the antidepressant only was compared with that in patients on different concomitant drugs. Patients on phenothiazines or dextropropoxyphene had a significantly higher mean C/D of NT than controls, both when AT and when NT had been given. The highest values were seen with levomepromazine and thioridazine. On the contrary, the mean C/D of both AT and NT in patients on carbamazepine was about 50% lower than in those treated with the antidepressant only. Benzodiazepines did not affect the steady-state kinetics of AT or NT. Intraindividual comparisons of the ratio C/D in subjects with analyses performed when off and on concomitant drugs corroborate previous results showing that drugs metabolized by the debrisoquine hydroxylase (CYP2D6) inhibit the metabolism of NT and that carbamazepine induces the metabolism of both AT and NT. Modeling of the dose dependency of the NT interactions with levomepromazine, perphenazine, and thioridazine revealed that the ratio C/D was most affected at low doses of the antidepressant and at high doses of the phenothiazine. The distribution of the doses given was the same in patients on monotherapy as in patients with interacting drugs, which means that many patients treated with phenothiazines had concentrations above the therapeutic range and that most patients treated with carbamazepine had subtherapeutic levels. The present study shows that therapeutic drug monitoring may serve as a valuable tool to discover and quantify drug interactions.

Adolescent↗
PubMed2003

Toxicokinetics of nortriptyline and amitriptyline: two case reports.

Two cases are presented of intentional intoxications with the tricyclic antidepressants (TCAs) nortriptyline (NT) and amitriptyline (AT). The peak plasma concentrations were 2290 microg/L and 2900 microg/L, respectively. The active metabolites E-10-hydroxynortriptyline (EHNT) and Z-10-hydroxynortriptyline (ZHNT) profiles were quite different as monitored for 5 to 10 days after presumed drug intake. In conclusion, these cases illustrate that (1) metabolite formation and elimination after intake of an overdose dose of NT and AT are stereoselective, and (2) NT and EHNT toxicokinetics and toxicodynamics are quite different. It also shows that a patient with a severe TCA overdose can still survive if he or she receives appropriate and quick supportive care, even if the prognostic markers QRS time, coma grade, and serum TCA levels predict poor outcome.

Adult↗
PubMed1977

Respiratory distress syndrome and thrombotic, non-bacterial endocarditis after amitriptyline overdose.

Three patients with documented or suspected amitriptyline poisoning developed a uniform clinical picture with progressive respiratory insufficiency, thrombocytopenia and evidence of embolization. Post-mortem examination revealed equally uniform changes: thrombotic, non-bacterial endocarditis (TNBE) with multiple embolization and marked pulmonary stiffness with extensive invasion of alveoli with connective tissue. The lung pathology and clinical picture of progressive respiratory insufficiency are in agreement with the respiratory distress syndrome (RDS) in the adult. The simultaneous occurrence of RDS and TNBE suggests a similar pathogenesis. Prophylactic measures are described.

Adolescent↗
PubMed1981

Amitriptyline and perphenazine (Triptafen DA) in chronic pain.

One-hundred and twenty patients with chronic pain, who had all failed to obtain relief with traditional medical treatment, were given a standard psychotropic drug mixture consisting of amitriptyline 25 mg and perphenazine 2 mg. Of those who completed 2 months of treatment, 33.68% were pain free, while 8.3% had unacceptable side-effects. The best results were obtained in patients with postherpetic neuralgia and postoperative scar pain.

Amitriptyline↗
PubMedDate not supplied

Cardiovascular effects of amitriptyline in anaesthetized dogs.

1. The effect of amitriptyline on cardiovascular variables has been studied in anaesthetized dogs. 2. In small doses (0.25 mg/dg) amitryptyline caused small increases in heart rates, contractility, blood pressure, coronary blood flow and aortic flow. 3. Large doses produced initial depressant effects on myocardial reflex rises in these and rate and blood pressure, which were followed by secondary reflex rises in these measurements. 4. The depressant effects were dose-related and were accompanied by marked increases in coronary flow and smaller increases in ortic flow. 5. The secondary reflex rises in cardiac parameters were abolished by propranolol and that of the blood pressure was much reduced.

Amitriptyline↗
PubMedDate not supplied

Amitriptyline action on sympathetic neuronal function in depressed women.

1. Noradrenaline plasma levels and cardiovascular function modifications with orthostatic challenge during therapy were studied in 59 female depressed inpatients treated with 100 mg amitriptyline daily by intramuscular route for 4 weeks. 2. Therapy induced an increase in pulse rate in supine and upright positions, a decrease of noradrenaline levels and modified standing systolic and (partially) diastolic blood pressure, particularly in elderly subjects. 3. No correlation between neurotransmitter or functional changes and drug plasma levels was noted. 4. The supposed lower noradrenergic output together with blood pressure drop in both positions suggests a reduced sympathetic tone.

Adult↗
PubMed2006

Amitriptyline poisoning in a 2-year old.

We describe a case of a 2-year-old boy who ingested 35 mg.kg(-1) of amitriptyline. He developed central nervous system toxicity, as demonstrated by coma and seizures and cardiac toxicity (cardiac arrest) within 1 h of ingestion. The cardiac toxicity was refractory to standard therapy. His cardiac rhythm alternated between ventricular tachycardia and pulseless ventricular tachycardia/ventricular fibrillation for a period of 17 h. Following prolonged cardiopulmonary resuscitation and aggressive supportive management, the patient recovered both cardiovascularly and neurologically. An echocardiogram and MRI brain were subsequently performed and were normal. The patient was discharged 2 weeks later with normal cognitive, behavioral and motor function. We discuss the benefit of prolonged and effective cardiopulmonary resuscitation in the management of this potentially fatal poisoning.

Adrenergic beta-Agonists↗
PubMed2005

Comparison of the effects of amitriptyline and flunarizine on weight gain and serum leptin, C peptide and insulin levels when used as migraine preventive treatment.

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Adult↗
PubMed1993

Forskolin and phorbol myristate acetate inhibit intracellular Ca2+ mobilization induced by amitriptyline and bradykinin in rat frontocortical neurons.

Regulations of the increase in intracellular Ca2+ concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) production by increasing intracellular cyclic AMP (cAMP) levels or activating protein kinase C (PKC) were studied in rat frontocortical cultured neurons. Amitriptyline (AMI; 1 mM), a tricyclic antidepressant, and bradykinin (BK; 1 microM) stimulated IP3 production and caused transient [Ca2+]i increases. Pretreatment with forskolin (100 microM, 15 min) decreased the AMI- and BK-induced [Ca2+]i increases by 33 and 48%, respectively. However, this treatment had no effect on the AMI- and BK-induced IP3 productions. Dibutyryl-cAMP (2 mM, 15 min) also decreased the AMI- and BK-induced [Ca2+]i increases by 23 and 47%, respectively. H-8 (30 microM), an inhibitor of protein kinase A (PKA), attenuated the ability of forskolin to inhibit the AMI- and BK-induced [Ca2+]i increases, suggesting that the activation of cAMP/PKA was involved in these inhibitory effects of forskolin. On the other hand, forskolin treatment had no effect on 20 mM caffeine-, 10 microM glutamate-, or 50 mM K(+)-induced [Ca2+]i increases. Pretreatment with phorbol 12-myristate 13-acetate (PMA; 100 nM, 90 min) decreased both the AMI-induced [Ca2+]i increases and the IP3 production by 31 and 25%, respectively. H-7 (200 microM), an inhibitor of PKC, inhibited the ability of PMA to attenuate the [Ca2+]i increases. PMA also inhibited the BK-induced IP3 production and the [Ca2+]i increases.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Food intake and the presystemic metabolism of single doses of amitriptyline and nortriptyline.

The influence of food on presystemic metabolism of single doses of amitriptyline (AMI) and nortriptyline (NT) was examined. In randomised order 25 mg tablets of each drug was given to 9 healthy, female volunteers both in the fasting state and together with a standardised breakfast. Concentrations of the drugs and of their dealkylated, hydroxylated and conjugated metabolites were measured by gas chromatography--mass spectrometry (AMI experiment) or high-pressure liquid chromatography (NT experiment). Standard pharmacokinetic parameters were calculated. Food intake did not consistently or significantly influence the bioavailability of either AMI or NT, nor the demethylation of AMI, nor the hydroxylation or the primary or secondary conjugation of NT. There were large interindividual changes in AUC of AMI after food (+94% to -44%). A significant negative correlation between AUC of AMI but not of NT during fasting conditions and per cent change in AUC after food was found (r = -0.72, P = 0.029). The implication of this (negative) correlation for an individual patient might be to keep the intake of the drug in standardised relation to food to avoid undue heavy changes in drug concentration, which might just occur with a change in time relation between intake of drug and food. From a mechanistic view the results argue against a direct and selective influence of food on the presystemic oxidation and conjugation of weakly basic drugs but does not exclude that food may reduce the presystemic metabolism of some such drugs indirectly, by enhancing their rate of hepatic delivery. Presentation of data from food interaction studies should not be restricted to general descriptions. It seems equally important to present the variability of individual data to allow inspection of the extent and direction of effects. This should be of interest for patient, prescriber as well as the regulatory agency.

Adult↗
PubMed1996

Treatment of progressive supranuclear palsy with amitriptyline: therapeutic and toxic effects.

BACKGROUND: Progressive supranuclear palsy (PSP) is a parkinsonian-like disorder characterized by postural instability, rigidity, bradykinesia, supranuclear ocular palsy, dysarthria, dysphagia, and dementia. There is no satisfactory treatment. Two patients with advanced (PSP) reported here had clinically meaningful improvement in motor function on low dose amitriptyline (AMI) but developed cognitive and behavioral disturbances at higher doses. CASE REPORTS: During 11 weeks of upward dose titration, a 65-year-old man was partially relieved of severe bradykinesia, dysarthria, and dysphagia at an optimal dose of 40 mg bid (plasma AMI 39 ng/mL) such that he could feed himself, swallow easily, and transfer from wheelchair to toilet. Nocturnal confusion and urinary incontinence appeared at 70 mg bid, then resolved at 40 mg bid. Benefits were sustained during the next 14 months. A 77-year-old man had substantial relief of severe rigidity, bradykinesia, poor balance, and blepharospasm at 10 mg bid, such that he could feed himself and walk independently. At 40 mg bid (plasma AMI 62 ng/mL) 3 weeks later, he became aggressive, irritable, and increasingly confused. He reverted to his untreated state with drug withdrawal, then improved when AMI was reintroduced at 10 mg bid (plasma AMI 17 ng/mL). CONCLUSION: Low dose AMI may improve severe motor dysfunction in PSP significantly. Dosing must be individualized for optimal response and minimal toxicity.

Activities of Daily Living↗
PubMed1999

Amitriptyline absorption in a patient with short bowel syndrome.

Oral drug therapy in patients with short bowel syndrome can be quite challenging. We report the case of a 40-yr-old woman with short bowel syndrome and depression requiring antidepressant drug therapy. After buccal administration of amitriptyline, therapeutic serum antidepressant concentrations were attained despite the patient having only 18 inches of proximal small bowel. Clinical improvement in mood was seen, with the only drug side effects being dry mouth and bitter drug taste. Buccal absorption likely is playing a major role in attaining therapeutic serum tricyclic antidepressants drug concentrations.

Administration, Oral↗