Tricyclic Antidepressant Agent

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Michelle I. Wilde - One of the best experts on this subject based on the ideXlab platform.

  • Amitriptyline
    Drugs & Aging, 1996
    Co-Authors: Harriet M. Bryson, Michelle I. Wilde
    Abstract:

    Synopsis Amitriptyline is a Tricyclic Antidepressant Agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited. Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with Tricyclic Antidepressant Agents, may also pose a problem in the elderly. In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the Antidepressant Agents in post- herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes. Pharmacological Properties Two theories have been proposed to explain the analgesic activity of Tricyclic Antidepressant Agents: firstly, that any analgesic activity is secondary to their Antidepressant effects; and secondly, that they have an independent analgesic effect. Clinical data suggest that analgesia may be produced independently of the Antidepressant effects of these Agents; however, the precise mechanism by which this is achieved is unknown. The analgesic effects of amitriptyline have been documented in several animal models after either single or multiple doses, but the relevance of these models to chronic pain states in humans is unknown. Amitriptyline produced dose-dependent analgesia to each of 3 different noxious stimuli in 2 studies. Amitriptyline is rapidly absorbed after oral administration, but has a low oral bioavailability because of a large first-pass effect. The pharmacokinetics of amitriptyline (like those of other Tricyclic Antidepressants) are characterised by large interpatient variability. The drug is widely distributed throughout the body and is highly protein bound. Amitriptyline is extensively metabolised in the liver; the major metabolite, nortriptyline, is pharmacologically active. The terminal elimination half-life of amitriptyline ranges from 12.9 to 36.1 hours. No clear effect of older age on the pharmacokinetics of amitriptyline has been defined, although clearance may be decreased. There is no clear relationship between amitriptyline plasma concentrations and analgesic effect, although concentrations of amitriptyline plus nortriptyline needed to produce a significant analgesic effect appear to be lower than those required for an Antidepressant effect. Therapeutic Use In patients with post-herpetic neuralgia of at least 3 months’ duration, oral amitriptyline achieved a 21 to 46% reduction in pain intensity from baseline as assessed by a visual analogue scale after 3 to 6 weeks’ treatment. 47 to 67% of patients reported a good or excellent response to therapy. When subjective assessment parameters were used, amitriptyline achieved significantly better pain relief than placebo or comparator Agents (lorazepam, zimeldine and maprotiline). Up to 74% of patients with painful diabetic neuropathy reported at least good or moderate pain relief after 6 to 8 weeks’ treatment with amitriptyline. Amitriptyline achieved a significantly greater reduction in pain intensity (29 to 51%) than placebo (15%) but had a similar effect to topical capsaicin (42%) or desipramine (28%). Limited clinical data in central post-stroke pain suggest that amitriptyline may be useful in these patients. 36% of patients with fibromyalgia showed clinical improvement after 6 months’ treatment with amitriptyline compared with 19% of placebo recipients. According to 2 patient surveys, amitriptyline was as effective as other Agents and treatment modalities commonly used in this patient group. Results obtained with amitriptyline in patients with rheumatoid arthritis are conflicting. Even in a heterogeneous group of patients, namely those presenting at a pain clinic with chronic nonmalignant pain, amitriptyline demonstrated small but significant analgesic effects compared with placebo in 2 of 3 studies. These results are supported by a meta-analysis which demonstrated an overall mean analgesic effect size of 0.73 for amitriptyline. Antidepressant Agents, including amitriptyline, are widely recommended and used as adjuvant Agents in patients with cancer pain. However, few clinical trials have prospectively investigated the efficacy of amitriptyline in this patient group. Tolerability The adverse events most commonly reported with amitriptyline, even at the relatively low dosages used in pain syndromes, result from its antimuscarinic activity. 27 to 80% of patients with pain syndromes in clinical trials reported dry mouth and 17 to 62% reported tiredness/drowsiness. Since tolerance to these effects often develops, low starting doses and careful dosage titration may help to minimise toxicity. Up to 18% of patients withdrew from amitriptyline therapy as a result of adverse events. Orthostatic hypotension and tachycardia can pose a problem in elderly patients receiving Tricyclic Agents at dosages in the Antidepressant range; there is evidence that these effects may occur, albeit infrequently, at the lower dosages used in the treatment of pain. As with other Tricyclic Antidepressant Agents, raised glucose levels can occur with amitriptyline. Dosage and Administration For the treatment of chronic pain states, amitriptyline should be started at a dosage of 10 to 25 mg/day and increased by 10 to 25 mg/week to the maximum suggested or tolerated dosage. To minimise the risk of adverse events in the elderly, amitriptyline should be started at a low dosage (10 mg/day) and titrated gradually in 10mg increments. The suggested maximum dosage for the treatment of neurogenic pain is 75 mg/day. Amitriptyline, like other Tricyclic Antidepressant Agents, should be administered with caution in patients with urinary retention, prostatic hypertrophy, glaucoma, constipation, impaired liver function or cardiovascular disease. It should be avoided in those with heart block or arrhythmias or immediately after myocardial infarction and in patients with severe liver disease.

  • Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states.
    Drugs & aging, 1996
    Co-Authors: Harriet M. Bryson, Michelle I. Wilde
    Abstract:

    Amitriptyline is a Tricyclic Antidepressant Agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited. Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with Tricyclic Antidepressant Agents, may also pose a problem in the elderly. In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the Antidepressant Agents in post-herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes.

  • Paroxetine
    PharmacoEconomics, 1995
    Co-Authors: Michelle I. Wilde, Ruth Whittington
    Abstract:

    Synopsis There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to Tricyclic anti-depressants for first-line treatment of depression can be justified, considering their higher acquisition costs. The rationale for using paroxetine in the treatment of depression lies in its more favourable tolerability profile than Tricyclic anti-depressants and its lower risk of death on overdosage. Depression is one of the most common psychiatric disorders and is associated with substantial direct, indirect and intangible costs. Indirect costs account for the majority of costs associated with depression, while drug costs account for only 9 to 25% of direct costs. Therefore, increased recognition and treatment of depression has the potential to greatly reduce the overall cost of this disease. Pharmacoeconomic data on parotexine and other SSRIs in the treatment of depression are scarce. Available studies are limited to considerations of direct costs alone and are primarily based on retrospective data from clinical trials. Nevertheless, in terms of costs per succesfully-treated patient, available data suggest that the treatment costs associated with paroxetine are similar to those of amitriptyline and possibly less than those of imipramine. Paroxetine treatment costs also appear to be similar to those of amitriptyline and imipramine in terms of expected costs per patient. While one group of investigators suggested that the overall cost of administering paroxetine may also be less than that for fluoxetine and sertraline when drug costs and labour costs associated with dosage adjustment are taken into account, more data are required before conclusions on the relative pharmacoeconomic merits of SSRIs can be made. Despite the lower risk of death from overdosage with SSRIs, switching from an established Tricyclic Antidepressant to a newer Tricyclic or related Antidepressant in an attempt to avoid suicide appears to be more cost effective than switching to an SSRI. Thus, evidence available to date indicate that despite higher acquisition costs paroxetine and other SSRIs are no more costly than Tricyclic Antidepressants when total costs per succesfully treated patient or expected costs per patient are considered. With its favourable tolerability profile and low risk of death on overdosage, paroxetine should therefore be considered as an effective alternative to Tricyclic Antidepressant Agents as a first-line treatment of depression. While preliminary evidence suggests that paroxetine may have some cost savings compared with fluoxetine and sertraline when drug costs and labour costs for dosage adjustment are considered, further economic evaluarions are essential to fully define any relative pharmacoeconomic merits of paroxetine versus other SSRIs and some of the newer Tricyclic products reaching the marketplace. Disease and Cost Considerations Depression is one of the most common psychiatric disorders with a lifetime prevalence rate of up to 18%, Prevalence rates for major depression are higher in females than in males and the highest rates for major depression or dysthymia occur in patients aged ≤45 years. While the majority of patients respond to Antidepressant therapy, major depression is unrecognised or misdiagnosed in approximately 50 to 75% of affected individuals, about 30% of patients are poorly compliant with treatment and about 20% do not get their prescriptions filled. Depression recurs in 80% of patients, and chronic depression occurs in 15 to 20% of patients, Up to 15% of patients with depression die from depression-related suicide. The risk of suicide is 4 times greater in males than in females. Depression results in substantial direct, indirect and intangible costs to patients, their families and society, In fact, the costs associated with depression are comparable to those of coronary heart disease, cancer and AIDS, and are mostly related to resultant morbidity rather than to disease-related mortality. The contribution of indirect costs of depression to total costs is greater than that of direct costs (72 to 88% vs 12 to 28%). Lost productivity, absenteeism and unemployment account for the majority of indirect costs associated with depression. Drug therapy is responsible for only 9 to 25% of the total direct costs while hospitalisation accounts for most direct costs. Morbidity costs of depression appear to be greater than mortality costs. Because depression is highly treatable, associated costs (particularly indirect costs) may potentially be reduced by increased recognition and effective treatment of this illness. Rationale for Use of Paroxetine in Depression The main clinical advantages of paroxetine and other selective serotonin reuptake inhibitors (SSRIs) over Tricyclic Antidepressants are their improved tolerability profiles and reduced risk of death following overdosage; these features may translate into cost savings. The incidences of anticholinergic adverse events. cardiotoxicity, sedation, changes in bodyweight and treatment discontinuations because of adverse events are lower with paroxetine than with Tricyclic Agents. The most common adverse events with paroxetine are related to the gastrointestinal system (e.g. nausea and constipation) and central nervous system (e.g. headache, somnolence, insomnia, dizziness and tremor). The overall tolerability profile of paroxetine is similar to that of the other SSRIs. The clinical efficacy of short term paroxetine therapy is similar to that of Tricyclic Antidepressants and other SSRIs in patients with major depression. Paroxetine is also effective in patients with coexisting anxiety and as maintenance therapy for preventing relapses or recurrences of depression. Pharmacoeconomic Analyses of Paroxetine and Other SSRIs The acquisition cost of paroxetine and other SSRIs is greater than that of Tricyclic Antidepressants. Nevertheless, available data suggest that, in terms of costs per successfully-treated patient, the treatment cost of paroxetine is similar to that of amitriptyline and possibly lower than that of imipramine. In terms of expected costs per patient, the treatment cost of paroxetine appears to be similar to that of amitriptyline and imipramine. These conclusions are based on simulation models using retrospective clinical trial data: prospective data are required to consolidate these findings. Although the results of one unpublished study suggest that paroxetine may be less costly than sertraline or fluoxetine when labour costs associated with dosage adjustment and drug costs are taken into account, further data are required to determine the relative pharmacoeconomics of the SSRIs. In terms of costs associated with short term and maintenance treatment, hospitalisation, outpatient and physician visits, poor compliance, and discontinuations because of adverse events and consequent readmission rates, the cost of SSRIs is similar to or less than that of Tricyclic Antidepressants. Although SSRIs are less harmful in overdosage than Tricyclic Antidepressants, the cost of switching from an established Tricyclic Agent to an SSRI in an attempt to avoid suicide is high, and evidence suggests that switching from an older Tricyclic Antidepressant Agent to a newer Tricyclic or related Antidepressant would be more cost effective than switching to a SSRI. The cost implications of the lower risk of death by overdosage with paroxetine compared with Tricyclic Agents remain to be determined.

Harriet M. Bryson - One of the best experts on this subject based on the ideXlab platform.

  • Amitriptyline
    Drugs & Aging, 1996
    Co-Authors: Harriet M. Bryson, Michelle I. Wilde
    Abstract:

    Synopsis Amitriptyline is a Tricyclic Antidepressant Agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited. Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with Tricyclic Antidepressant Agents, may also pose a problem in the elderly. In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the Antidepressant Agents in post- herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes. Pharmacological Properties Two theories have been proposed to explain the analgesic activity of Tricyclic Antidepressant Agents: firstly, that any analgesic activity is secondary to their Antidepressant effects; and secondly, that they have an independent analgesic effect. Clinical data suggest that analgesia may be produced independently of the Antidepressant effects of these Agents; however, the precise mechanism by which this is achieved is unknown. The analgesic effects of amitriptyline have been documented in several animal models after either single or multiple doses, but the relevance of these models to chronic pain states in humans is unknown. Amitriptyline produced dose-dependent analgesia to each of 3 different noxious stimuli in 2 studies. Amitriptyline is rapidly absorbed after oral administration, but has a low oral bioavailability because of a large first-pass effect. The pharmacokinetics of amitriptyline (like those of other Tricyclic Antidepressants) are characterised by large interpatient variability. The drug is widely distributed throughout the body and is highly protein bound. Amitriptyline is extensively metabolised in the liver; the major metabolite, nortriptyline, is pharmacologically active. The terminal elimination half-life of amitriptyline ranges from 12.9 to 36.1 hours. No clear effect of older age on the pharmacokinetics of amitriptyline has been defined, although clearance may be decreased. There is no clear relationship between amitriptyline plasma concentrations and analgesic effect, although concentrations of amitriptyline plus nortriptyline needed to produce a significant analgesic effect appear to be lower than those required for an Antidepressant effect. Therapeutic Use In patients with post-herpetic neuralgia of at least 3 months’ duration, oral amitriptyline achieved a 21 to 46% reduction in pain intensity from baseline as assessed by a visual analogue scale after 3 to 6 weeks’ treatment. 47 to 67% of patients reported a good or excellent response to therapy. When subjective assessment parameters were used, amitriptyline achieved significantly better pain relief than placebo or comparator Agents (lorazepam, zimeldine and maprotiline). Up to 74% of patients with painful diabetic neuropathy reported at least good or moderate pain relief after 6 to 8 weeks’ treatment with amitriptyline. Amitriptyline achieved a significantly greater reduction in pain intensity (29 to 51%) than placebo (15%) but had a similar effect to topical capsaicin (42%) or desipramine (28%). Limited clinical data in central post-stroke pain suggest that amitriptyline may be useful in these patients. 36% of patients with fibromyalgia showed clinical improvement after 6 months’ treatment with amitriptyline compared with 19% of placebo recipients. According to 2 patient surveys, amitriptyline was as effective as other Agents and treatment modalities commonly used in this patient group. Results obtained with amitriptyline in patients with rheumatoid arthritis are conflicting. Even in a heterogeneous group of patients, namely those presenting at a pain clinic with chronic nonmalignant pain, amitriptyline demonstrated small but significant analgesic effects compared with placebo in 2 of 3 studies. These results are supported by a meta-analysis which demonstrated an overall mean analgesic effect size of 0.73 for amitriptyline. Antidepressant Agents, including amitriptyline, are widely recommended and used as adjuvant Agents in patients with cancer pain. However, few clinical trials have prospectively investigated the efficacy of amitriptyline in this patient group. Tolerability The adverse events most commonly reported with amitriptyline, even at the relatively low dosages used in pain syndromes, result from its antimuscarinic activity. 27 to 80% of patients with pain syndromes in clinical trials reported dry mouth and 17 to 62% reported tiredness/drowsiness. Since tolerance to these effects often develops, low starting doses and careful dosage titration may help to minimise toxicity. Up to 18% of patients withdrew from amitriptyline therapy as a result of adverse events. Orthostatic hypotension and tachycardia can pose a problem in elderly patients receiving Tricyclic Agents at dosages in the Antidepressant range; there is evidence that these effects may occur, albeit infrequently, at the lower dosages used in the treatment of pain. As with other Tricyclic Antidepressant Agents, raised glucose levels can occur with amitriptyline. Dosage and Administration For the treatment of chronic pain states, amitriptyline should be started at a dosage of 10 to 25 mg/day and increased by 10 to 25 mg/week to the maximum suggested or tolerated dosage. To minimise the risk of adverse events in the elderly, amitriptyline should be started at a low dosage (10 mg/day) and titrated gradually in 10mg increments. The suggested maximum dosage for the treatment of neurogenic pain is 75 mg/day. Amitriptyline, like other Tricyclic Antidepressant Agents, should be administered with caution in patients with urinary retention, prostatic hypertrophy, glaucoma, constipation, impaired liver function or cardiovascular disease. It should be avoided in those with heart block or arrhythmias or immediately after myocardial infarction and in patients with severe liver disease.

  • Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states.
    Drugs & aging, 1996
    Co-Authors: Harriet M. Bryson, Michelle I. Wilde
    Abstract:

    Amitriptyline is a Tricyclic Antidepressant Agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited. Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with Tricyclic Antidepressant Agents, may also pose a problem in the elderly. In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the Antidepressant Agents in post-herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes.

Mitchell Nides - One of the best experts on this subject based on the ideXlab platform.

  • Update on pharmacologic options for smoking cessation treatment.
    The American journal of medicine, 2008
    Co-Authors: Mitchell Nides
    Abstract:

    Although the proportion of the adult population in the United States that smokes has decreased steadily, the rate of successful quit attempts is still low. Smokers develop nicotine dependence that resembles other addictions, and may require multiple attempts and long-term treatment to sustain abstinence. Currently available first-line Agents for smoking cessation therapy include nicotine replacement therapy, which is available in several formulations, including transdermal patch, gum, nasal spray, inhaler, and lozenge; bupropion, an atypical Antidepressant; and varenicline, a partial agonist of the alpha(4)beta(2) nicotinic acetylcholine receptor that was recently developed and approved specifically for smoking cessation therapy. Second-line Agents are nortriptyline, a Tricyclic Antidepressant Agent, and clonidine, an antihypertensive drug. With the exception of varenicline, which has been shown to offer significant improvement in abstinence rates over bupropion, all of the available treatments appear similarly effective. However, the adverse event profiles of nortriptyline and clonidine make them more appropriate for second-line therapy, when first-line treatments have failed or are not tolerated. Rimonabant, a cannabinoid-1 receptor antagonist that was being developed for smoking cessation, received a nonapprovable letter from the FDA in 2006 and there is no further information as to whether development for this indication is continuing for this Agent. Nicotine vaccines are under investigation and offer promise, especially for relapse prevention. Ultimately, selection of pharmacologic Agent should be based on the patient's comorbidities and preferences, as well as on the Agent's adverse event profile.

  • Update on pharmacologic options for smoking cessation treatment.
    The American Journal of Medicine, 2008
    Co-Authors: Mitchell Nides
    Abstract:

    Abstract Although the proportion of the adult population in the United States that smokes has decreased steadily, the rate of successful quit attempts is still low. Smokers develop nicotine dependence that resembles other addictions, and may require multiple attempts and long-term treatment to sustain abstinence. Currently available first-line Agents for smoking cessation therapy include nicotine replacement therapy, which is available in several formulations, including transdermal patch, gum, nasal spray, inhaler, and lozenge; bupropion, an atypical Antidepressant; and varenicline, a partial agonist of the α 4 β 2 nicotinic acetylcholine receptor that was recently developed and approved specifically for smoking cessation therapy. Second-line Agents are nortriptyline, a Tricyclic Antidepressant Agent, and clonidine, an antihypertensive drug. With the exception of varenicline, which has been shown to offer significant improvement in abstinence rates over bupropion, all of the available treatments appear similarly effective. However, the adverse event profiles of nortriptyline and clonidine make them more appropriate for second-line therapy, when first-line treatments have failed or are not tolerated. Rimonabant, a cannabinoid-1 receptor antagonist that was being developed for smoking cessation, received a nonapprovable letter from the FDA in 2006 and there is no further information as to whether development for this indication is continuing for this Agent. Nicotine vaccines are under investigation and offer promise, especially for relapse prevention. Ultimately, selection of pharmacologic Agent should be based on the patient's comorbidities and preferences, as well as on the Agent's adverse event profile.

Salih Cengiz - One of the best experts on this subject based on the ideXlab platform.

  • Development and Validation of a Densitometric-High-Performance Thin-Layer Chromatographic Method for Quantitative Analysis of Amitriptyline in Gastric Lavage
    JPC – Journal of Planar Chromatography – Modern TLC, 2013
    Co-Authors: Zeynep Türkmen, Selda Mercan, Isil Bavunoglu, Salih Cengiz
    Abstract:

    Drug overdose is the most common method in suicide attempts. Amitriptyline (AMT), a Tricyclic Antidepressant Agent, known for potentially lethal cardiovascular and neurological effects, is used especially by intoxicated patients. The aim of this study was to validate a method for the determination of AMT in gastric lavage samples by high-performance thin-layer chromatography (HPTLC). Artificial gastric lavage was used to obtain a better extraction procedure for AMT. The method was also applied to patients who attempted suicide with AMT. A validated, accurate, and rapid HPTLC-based method was developed for quantitation of AMT in gastric content of intoxicated patients. Extraction was done from 3 mL gastric lavage sample by liquid-liquid extraction procedure with ethyl acetate- n -heptane (1:1, w / w ) in alkaline pH with 10.8. The mobile phase was an isocratic solvent system consisting of methanol-ammonia (25%) (98.5:1.5, v / v ). 3,4-Methylenedioxy-Nmethamphetamine (MDMA) was used as internal standard (IS). Analytes were quantified by TLC Scanner operating under 209 nm. The retardation factors of AMT and MDMA were determined as 0.49 and 0.25, respectively. The analytical range was set as 10–250 ng spot^−1 for AMT. Calibration was linear within the selected range in gastric lavage ( r > 0.9995). Limit of detection and limit of quantification of AMT were found to be 5.1 and 17.3 ng spot^−1, respectively. Recoveries of 25 ng spot^−1 and 100 ng spot^−1 concentrations were found 83.12% and 91.89%; bias% values were 10.91 and 3.19, respectively. The validated method was also applied on samples of five patients who attempted suicide by AMT, and concentrations in gastric lavage samples of 5 patients were found 7.1, 8.3, 9.9, 14.6, and 36.6 ng mL^−1. This successfully validated method was applied to suicide cases, and it can be conveniently employed on both antemortem and postmortem cases suspected by amitriptyline.

  • Development and validation of a densitometric-high-performance thin-layer chromatographic method for quantitative analysis of amitriptyline in gastric lavage
    Journal of Planar Chromatography – Modern TLC, 2013
    Co-Authors: Zeynep Türkmen, Selda Mercan, Isil Bavunoglu, Salih Cengiz
    Abstract:

    Drug overdose is the most common method in suicide attempts. Amitriptyline (AMT), a Tricyclic Antidepressant Agent, known for potentially lethal cardiovascular and neurological effects, is used especially by intoxicated patients. The aim of this study was to validate a method for the determination of AMT in gastric lavage samples by high-performance thin-layer chromatography (HPTLC). Artificial gastric lavage was used to obtain a better extraction procedure for AMT. The method was also applied to patients who attempted suicide with AMT. A validated, accurate, and rapid HPTLC-based method was developed for quantitation of AMT in gastric content of intoxicated patients. Extraction was done from 3 mL gastric lavage sample by liquid-liquid extraction procedure with ethyl acetate-n-heptane (1:1, w/w) in alkaline pH with 10.8. The mobile phase was an isocratic solvent system consisting of methanol-ammonia (25%) (98.5:1.5, v/v). 3,4-Methylenedioxy-Nmethamphetamine (MDMA) was used as internal standard (IS). Analy...

Zeynep Türkmen - One of the best experts on this subject based on the ideXlab platform.

  • Development and Validation of a Densitometric-High-Performance Thin-Layer Chromatographic Method for Quantitative Analysis of Amitriptyline in Gastric Lavage
    JPC – Journal of Planar Chromatography – Modern TLC, 2013
    Co-Authors: Zeynep Türkmen, Selda Mercan, Isil Bavunoglu, Salih Cengiz
    Abstract:

    Drug overdose is the most common method in suicide attempts. Amitriptyline (AMT), a Tricyclic Antidepressant Agent, known for potentially lethal cardiovascular and neurological effects, is used especially by intoxicated patients. The aim of this study was to validate a method for the determination of AMT in gastric lavage samples by high-performance thin-layer chromatography (HPTLC). Artificial gastric lavage was used to obtain a better extraction procedure for AMT. The method was also applied to patients who attempted suicide with AMT. A validated, accurate, and rapid HPTLC-based method was developed for quantitation of AMT in gastric content of intoxicated patients. Extraction was done from 3 mL gastric lavage sample by liquid-liquid extraction procedure with ethyl acetate- n -heptane (1:1, w / w ) in alkaline pH with 10.8. The mobile phase was an isocratic solvent system consisting of methanol-ammonia (25%) (98.5:1.5, v / v ). 3,4-Methylenedioxy-Nmethamphetamine (MDMA) was used as internal standard (IS). Analytes were quantified by TLC Scanner operating under 209 nm. The retardation factors of AMT and MDMA were determined as 0.49 and 0.25, respectively. The analytical range was set as 10–250 ng spot^−1 for AMT. Calibration was linear within the selected range in gastric lavage ( r > 0.9995). Limit of detection and limit of quantification of AMT were found to be 5.1 and 17.3 ng spot^−1, respectively. Recoveries of 25 ng spot^−1 and 100 ng spot^−1 concentrations were found 83.12% and 91.89%; bias% values were 10.91 and 3.19, respectively. The validated method was also applied on samples of five patients who attempted suicide by AMT, and concentrations in gastric lavage samples of 5 patients were found 7.1, 8.3, 9.9, 14.6, and 36.6 ng mL^−1. This successfully validated method was applied to suicide cases, and it can be conveniently employed on both antemortem and postmortem cases suspected by amitriptyline.

  • Development and validation of a densitometric-high-performance thin-layer chromatographic method for quantitative analysis of amitriptyline in gastric lavage
    Journal of Planar Chromatography – Modern TLC, 2013
    Co-Authors: Zeynep Türkmen, Selda Mercan, Isil Bavunoglu, Salih Cengiz
    Abstract:

    Drug overdose is the most common method in suicide attempts. Amitriptyline (AMT), a Tricyclic Antidepressant Agent, known for potentially lethal cardiovascular and neurological effects, is used especially by intoxicated patients. The aim of this study was to validate a method for the determination of AMT in gastric lavage samples by high-performance thin-layer chromatography (HPTLC). Artificial gastric lavage was used to obtain a better extraction procedure for AMT. The method was also applied to patients who attempted suicide with AMT. A validated, accurate, and rapid HPTLC-based method was developed for quantitation of AMT in gastric content of intoxicated patients. Extraction was done from 3 mL gastric lavage sample by liquid-liquid extraction procedure with ethyl acetate-n-heptane (1:1, w/w) in alkaline pH with 10.8. The mobile phase was an isocratic solvent system consisting of methanol-ammonia (25%) (98.5:1.5, v/v). 3,4-Methylenedioxy-Nmethamphetamine (MDMA) was used as internal standard (IS). Analy...