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Amitriptyline(BAN, Rinn) 376 Antidepressants Amitriptyline (BAN, rINN) leading to paralytic ileus, urinary retention, blurred vi- • imipramine sion and disturbances in accommodation, increased in- • clomipramine Amitriptilina; Amitriptyliini; Amitriptylin; Amitriptylinum. 3- • protriptyline (10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyld- tra-ocular pressure, and hyperthermia. Tolerance is of- • trazodone imethylamine; 10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cy- ten achieved if treatment is continued and adverse • desipramine cloheptene-Δ5, -propylamine. effects may be less troublesome if treatment is begun 1. Richelson E. Antimuscarinic and other receptor-blocking prop- Амитриптилин with small doses and then increased gradually, al- erties of antidepressants. Mayo Clin Proc 1983; 58: 40–6. C H N = 277.4. though this may delay the clinical response. 20 23 Effects on the blood. After a case report of agranulocytosis CAS — 50-48-6. Drowsiness may also be common, although a few linked with imipramine, review of the literature suggested that ATC — N06AA09. tricyclic antidepressants possess little or no sedative agranulocytosis associated with tricyclic antidepressant use was ATC Vet — QN06AA09. potential and may produce nervousness and insomnia. a rare idiosyncratic condition, resulting from a direct toxic effect rather than an allergic mechanism, and particularly affected the Other neurological adverse effects include headache, elderly from 4 to 8 weeks after beginning treatment.1 peripheral neuropathy, tremor, ataxia, epileptiform sei- Between 1963 and 1993 the UK CSM received 912 reports of zures, tinnitus, and occasional extrapyramidal symp- drug-induced agranulocytosis of which 38 were due to tricyclic toms including speech difficulties (dysarthria). Confu- antidepressants (12 fatal) and 1499 cases of neutropenia of which sion, hallucinations, or delirium may occur, 46 were due to tricyclics (none fatal).2 In a report3 on a patient particularly in the elderly, and mania or hypomania, who developed aplastic anaemia associated with use of remox- CH3 ipride and dosulepin it was noted that up to May 1993 the CSM N and behavioural disturbances (particularly in children) had also received 11 reports of aplastic anaemia secondary to use have been reported. of dosulepin. 4 CH3 Gastrointestinal complaints include sour or metallic Neutropenia reported in a patient after separate exposure to im- ipramine and nortriptyline, indicated that there might be cross- taste, stomatitis, and gastric irritation with nausea and intolerance between the tricyclic antidepressants and if neutrope- Amitriptyline Embonate (BANM, rINNM) vomiting. nia developed with one member of the group the use of others on Amitriptyline, Embonate d’; Amitriptylini Embonas; Embonato de Effects on the cardiovascular system are discussed in future occasions should be avoided. amitriptilina. 1. Albertini RS, Penders TM. Agranulocytosis associated with tri- more detail below. Orthostatic hypotension and tachy- cyclics. J Clin Psychiatry 1978; 39: 483–5. Амитриптилина Эмбонат cardia can occur in patients without a history of cardi- 2. CSM/MCA. Drug-induced neutropenia and agranulocytosis. Current Problems 1993; 19: 10–11. Available at: http:// (C20H23N)2,C23H16O6 = 943.2. ovascular disease, and may be particularly trouble- CAS — 17086-03-2. www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE& some in the elderly. dDocName=CON2024456&RevisionSelectionMethod= Pharmacopoeias. In Br. LatestReleased (accessed 14/08/08) BP 2008 (Amitriptyline Embonate). A pale yellow to brownish- Hypersensitivity reactions, such as urticaria and an- 3. Philpott NJ, et al. Aplastic anaemia and remoxipride. Lancet yellow, odourless or almost odourless powder. Practically insol- gioedema, and photosensitisation have been reported 1993; 342: 1244–5. uble in water; slightly soluble in alcohol; freely soluble in chlo- and, rarely, cholestatic jaundice and blood disorders, 4. Draper BM, Manoharan A. Neutropenia with cross-intolerance roform. Protect from light. between two tricyclic antidepressant agents. Med J Aust 1987; including eosinophilia, bone-marrow depression, 146: 452–3. thrombocytopenia, leucopenia, and agranulocytosis. Amitriptyline Hydrochloride (BANM, rINNM) Effects on the cardiovascular system. The cardiotoxic po- Endocrine effects include testicular enlargement, gy- tential of tricyclic antidepressants after overdosage is widely ac- Amitriptilin Hidroklorür; Amitriptilin-hidroklorid; Amitriptilino knowledged; symptoms include arrhythmias, conduction de- hidrochloridas; Amitriptyliinihydrokloridi; Amitriptyline, chlorhy- naecomastia and breast enlargement, and galactor- fects, and hypotension. This factor was, in part, responsible for drate d’; Amitriptylin-hydrochlorid; Amitriptylinhydroklorid; Am- rhoea. Sexual dysfunction may also occur. Changes in the development of antidepressants with different chemical itriptylini hydrochloridum; Amitryptyliny chlorowodorek; Hidro- blood sugar concentrations may also occur, and, very structures and pharmacological properties that are less cardiotox- cloruro de amitriptilina. occasionally, hyponatraemia associated with inappro- ic. It also led to some concern over whether tricyclic antidepres- Амитриптилина Гидрохлорид priate secretion of antidiuretic hormone. sants had adverse effects on the heart or cardiovascular system when used in usual therapeutic doses. C20H23N,HCl = 313.9. CAS — 549-18-8. Other adverse effects that have been reported are in- Since the introduction of the tricyclic antidepressants, reports, of- Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, and US. creased appetite with weight gain (or occasionally an- ten anecdotal, have been published of adverse cardiovascular ef- fects at therapeutic doses and have included malignant hyper- Ph. Eur. 6.2 (Amitriptyline Hydrochloride). A white or almost orexia with weight loss). Sweating may be a problem. 1 white powder or colourless crystals. Freely soluble in water, in tension with amitriptyline, and cardiomyopathy in a patient who Symptoms of overdosage may include excitement and 2 alcohol, and in dichloromethane. Protect from light. had received amitriptyline and imipramine. QT prolongation, restlessness with marked antimuscarinic effects, in- which in some cases progressed to torsade de pointes, has also USP 31 (Amitriptyline Hydrochloride). A white or practically 3,4 white, odourless or practically odourless, crystalline powder or cluding dryness of the mouth, hot dry skin, dilated pu- been associated with the use of some tricyclics. Sudden cardiac death in patients with pre-existing cardiac disease has been small crystals. Freely soluble in water, in alcohol, in chloroform, pils, tachycardia, urinary retention, and intestinal sta- 5-7 6 and in methyl alcohol; insoluble in ether. pH of a 1% solution in linked with amitriptyline or imipramine, although the Boston sis. Severe symptoms include unconsciousness, Collaborative Drug Surveillance Program failed to substantiate water is between 5.0 and 6.0. convulsions and myoclonus, hyperreflexia, hypother- these findings.8 In a more recent analysis, it has been suggested Stability. Decomposition occurred when solutions of am- mia, hypotension, metabolic acidosis, and respiratory that the risk of sudden cardiac death may increase with high dos- itriptyline hydrochloride in water or phosphate buffers were and cardiac depression, with life-threatening cardiac es of tricyclic antidepressants.9 Using patient medication autoclaved at 115° to 116° for 30 minutes in the presence of ex- records, it was found that the rate of sudden cardiac death in pa- cess oxygen.1 arrhythmias that may recur some days after apparent tients taking less than 100 mg of amitriptyline or its equivalent, The decomposition of amitriptyline as the hydrochloride in buff- recovery. Delirium, with confusion, agitation and hal- [presumably as a daily dose although this is not specified], did ered aqueous solution stored at 80° in the dark was accelerated lucinations, is common during recovery. not differ from that among non-users of antidepressants even in by metal ions.2 Disodium edetate 0.1% significantly reduced the those with cardiovascular disease or other conditions considered Antimuscarinic and antihistaminic properties. Studies in decomposition rate of these amitriptyline solutions but propyl 1 to increase the risk of sudden death; however, the risk was signif- gallate and hydroquinone were less effective. Sodium metabi- vitro showed antidepressant affinities for human muscarinic icantly increased in those patients on doses of 100 mg or greater sulfite produced an initial lowering of amitriptyline concentra- acetylcholine receptors and therefore the likelihood of antimus- when compared to non-users, regardless of any predisposing tion and subsequently an acceleration of decomposition. The rate carinic effects to be, in descending order: conditions. of decomposition was also much greater in amber glass am- • amitriptyline There have also been reports of sudden death in children given poules than in clear glass ones (the metal ion content of amber • protriptyline desipramine10-12 or imipramine;12-14 in at least some of these cas- glass is higher than that of clear glass). However, there were con- es plasma concentrations were not elevated and the children had • clomipramine siderable variations between different batches of amber glass no cardiac abnormality. Again, however, evaluation of much of and, since amitriptyline is photolabile, its solutions are likely to • trimipramine
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