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Trichlormethiazide/Urapidil 1419

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Trichlormethiazide/Urapidil 1419 Trichlormethiazide/Urapidil 1419 Trimetaphan Camsilate (BAN, rINN) Trimetazidine Hydrochloride (BANM, rINNM) Profile Hidrocloruro de trimetazidina; Trimetatsidiinidihydrokloridi; Tri- Tripamide is a diuretic structurally related to indapamide. It is Cansilato de trimetafán; Méthioplégium; Trimetaphan Cam- used in the treatment of hypertension. phorsulfonate; Trimétaphan, Camsilate de; Trimetaphan Cam- metazidin Hidroklorür; Trimetazidindihidroklorid; Trimetazidin- sylate; Trimetaphani Camsilas; Trimetaphani Camsylas; Trimeth- dihydrochlorid; Trimetazidindihydroklorid; Trimétazidine, Chlo- Preparations aphan Camsylate. (+)-1,3-Dibenzylperhydro-2-oxothieno- rhydrate de; Trimétazidine, dichlorhydrate de; Trimetazidine Di- Proprietary Preparations (details are given in Part 3) [1′,2′:1,2]thieno[3,4-d]-imidazol-5-ium 2-oxobornane-10-sul- hydrochloride; Trimetazidini dihydrochloridum; Trimetazidini Hy- Thai.: Normonal. fonate; 4,6-Dibenzyl-4,6-diaza-1-thioniatricyclo[6.3.0.03.7]unde- drochloridum; Trimetazidino hidrochloridas; Trimetazine Hydro- can-5-one 2-oxobornane-10-sulfonate. chloride. 1-(2,3,4-Trimethoxybenzyl)piperazine dihydrochloride. Urapidil (BAN, rINN) Триметафана Камзилат Триметазидина Гидрохлорид C H N O ,2HCl = 339.3. B-66256M; Urapidiili; Urapidilum. 6-[3-(4-o-Methoxyphenylpip- C H N OS,C H O S = 596.8. 14 22 2 3 22 25 2 10 15 4 CAS — 5011-34-7 (trimetazidine); 13171-25-0 (tri- erazin-1-yl)propylamino]-1,3-dimethyluracil. CAS — 7187-66-8 (trimetaphan); 68-91-7 (trimetaphan metazidine hydrochloride). Урапидил camsilate). ATC — C01EB15. ATC — C02BA01. ATC Vet — QC01EB15. C20H29N5O3 = 387.5. CAS — 34661-75-1. ATC Vet — QC02BA01. ATC — C02CA06. ATC Vet — QC02CA06. OCH3 H3CO N O O O- NH N CH3 S H3C CH3 H C H3CO N N O S+ O 3 O N O (trimetazidine) N NO N H Pharmacopoeias. In Eur. (see p.vii) and Jpn. CH Ph. Eur. 6.2 (Trimetazidine Dihydrochloride; Trimetazidine Hy- 3 drochloride BP 2008). A slightly hygroscopic, white or almost white crystalline powder. Freely soluble in water; sparingly sol- Pharmacopoeias. In Jpn. Incompatibility. Trimetaphan is incompatible with thiopental uble in alcohol. Store in airtight containers. sodium, gallamine triethiodide, iodides, bromides, and strongly alkaline solutions. Profile Urapidil Hydrochloride (BANM, rINNM) Trimetazidine hydrochloride is used in angina pectoris (p.1157) Hidrocloruro de urapidil; Urapidil, Chlorhydrate d’; Urapidili Hy- Adverse Effects and Treatment and in ischaemia of neurosensorial tissues as in Ménière’s dis- drochloridum. The adverse effects of trimetaphan are mainly due to ganglionic ease (p.564); 40 to 60 mg is given daily by mouth in divided dos- Урапидила Гидрохлорид blockade. A reduction in gastrointestinal motility may cause con- es. stipation and, on prolonged use, paralytic ileus. Urinary reten- C20H29N5O3,HCl = 423.9. tion, cycloplegia, mydriasis, tachycardia, precipitation of angina, ◊ References. CAS — 64887-14-5. and gastrointestinal disturbances such as anorexia, nausea, or 1. McClellan KJ, Plosker GL. Trimetazidine: a review of its use in ATC — C02CA06. stable angina pectoris and other coronary conditions. Drugs ATC Vet — QC02CA06. vomiting, may occur. Orthostatic hypotension may be severe. 1999; 58: 143–57. Rapid intravenous infusion can result in respiratory arrest. Other 2. Ciapponi A, et al. Trimetazidine for stable angina. Available in Adverse Effects and Precautions adverse effects include raised intra-ocular pressure, dry mouth, The Cochrane Database of Systematic Reviews; Issue 4. Chich- Urapidil is reported to be well-tolerated, with adverse effects hypoglycaemia, hypokalaemia, fluid retention, weakness, urti- ester: John Wiley; 2005 (accessed 24/01/06). generally transient and most frequent at the beginning of therapy. caria, and itching. Trimetaphan crosses the placenta and can 3. Danchin N. Clinical benefits of a metabolic approach with tri- Dizziness, nausea, headache, fatigue, orthostatic hypotension, cause paralytic or meconium ileus in the neonate. metazidine in revascularized patients with angina. Am J Cardiol palpitations, nervousness, pruritus, and allergic skin reactions 2006; 98 (suppl): 8J–13J. If severe hypotension occurs, trimetaphan should be stopped and have been reported. Effects on the nervous system. Eight elderly patients aged It should be used with care in elderly patients and those with se- the patient positioned with the head lower than the feet. A vaso- 1 pressor may be given cautiously if necessary. between 72 and 94 years were reported to have developed signs vere hepatic impairment. Intravenous urapidil should not be used of parkinsonism while taking trimetazidine; the parkinsonism re- in patients with aortic stenosis. gressed completely when the drug was stopped. A retrospective Effects on the eyes. Although trimetaphan may increase intra- 1 ocular pressure, a sudden and dramatic reduction of intra-ocular study2 found that adverse effects on motor function, including Urinary incontinence. Enuresis was reported to be associat- pressure to very low levels was noted in 5 patients undergoing parkinsonism, gait disorders, and tremor, occurred in 56 of 130 ed with the use of urapidil in 2 elderly patients. surgery when the systolic blood pressure was reduced to patients taking trimetazidine and were more common in older 1. Jonville A-P, et al. Urapidil and enuresis. Lancet 1992; 339: 688. 60 mmHg with trimetaphan infusion.1 patients. Pharmacokinetics 1. Dias PLR, et al. Effect on the intraocular pressure of hypotensive 1. Marti Massó JF. Parkinsonismo por trimetazidina. Neurologia After oral doses urapidil is rapidly absorbed with a reported bio- anaesthesia with intravenous trimetaphan. Br J Ophthalmol 2004; 19: 392–5. availability of 70 to 80%. It is reported to be about 80% bound to 1982; 66: 721–4. 2. Martí Massó J-F, et al. Trimetazidine induces parkinsonism, gait plasma proteins. Urapidil is extensively metabolised in the liver, disorders and tremor. Therapie 2005; 60: 419–22. mainly by hydroxylation, and excreted mostly in urine, as metab- Precautions Preparations Trimetaphan should be avoided in patients with asphyxia or res- olites and 10 to 20% of unchanged drug. The elimination half- piratory insufficiency, uncorrected anaemia, shock or hypovol- Proprietary Preparations (details are given in Part 3) life is reported to be about 4.7 hours when given orally as cap- Arg.: Vastarel; Austria: Vastarel; Braz.: Vastarel; Chile: Vastarel; Cz.: sules and about 2.7 hours after intravenous dosage. aemia, severe arteriosclerosis, severe ischaemic heart disease, or Adexor; Preductal; Denm.: Vastarel; Fr.: Centrophene†; Vastarel; Gr.: Ata- pyloric stenosis and should only be used with extreme caution in nol; Imovexil; Intervein; Latrimet†; Liomagen; Novazidine; Trimedin; Trime- ◊ Reviews. those with hepatic or renal impairment, degenerative disease of dor; Trimevert; Vastarel; Zidin; Hong Kong: Vastarel; Hung.: Adexor; Pre- 1. Kirsten R, et al. Clinical pharmacokinetics of urapidil. Clin the CNS, Addison’s disease, prostatic hyperplasia, glaucoma, ductal; India: Flavedon; Mayozest; Metacard; Metagard; Trivedon; Indon.: Pharmacokinet 1988; 14: 129–40. cerebral or coronary vascular insufficiency, and diabetes. It Tr izedon; Irl.: Vastarel; Ital.: Vastarel; Malaysia: Metagard; Vastarel; Philipp.: Angirel; Vastarel; Pol.: Metazydyna; Preductal; Trimetaratio; Uses and Administration should be used with care in elderly or debilitated patients and Port.: Tacirel; Vastarel; Rus.: Deprenorm (Депренорм); Medarum Urapidil is an antihypertensive drug that is reported to block should be avoided in pregnancy. Owing to a histamine-liberating (Медарум); Preductal (Предуктал); Rimecor (Римекор); Trimetazide peripheral alpha adrenoceptors (see Alpha Blockers, p.1153) effect it should be used with caution in allergic subjects. (Триметазид); Singapore: Metagard; Vastarel; Spain: Idaptan; Vaso 1 Rimal†; Thai.: Matenol; Trizidine; Vastarel; Vastinol; Turk.: Vastarel; Venez.: and to have central actions. It produces a reduction in peripheral Interactions Vastarel. resistance and a fall in systolic and diastolic blood pressure, usu- Trimetaphan should be used with caution in patients being treat- ally without reflex tachycardia. ed with other antihypertensives, drugs that depress cardiac func- Urapidil is used in the management of hypertension (p.1171), in- cluding hypertensive crises. tion, or muscle relaxants, and in those taking NSAIDs or corti- Tripamide (USAN, rINN) ⊗ costeroids. The hypotensive effect is enhanced by general and Urapidil is given orally as the base and intravenously as the hy- spinal anaesthetics. Adrenaline should not be infiltrated locally at ADR-033; E-614; Tripamida; Tripamidum. 4-Chloro-N-(endo- drochloride, but doses are usually expressed in terms of the base. the site of incision when trimetaphan is being given since this hexahydro-4,7-methanoisoindolin-2-yl)-3-sulphamoylbenza- Urapidil hydrochloride 10.94 mg is equivalent to about 10 mg of may antagonise the effect of trimetaphan. mide. urapidil. Urapidil fumarate has also been given orally. Трипамид Neuromuscular blockers. For a reference to possible poten- In hypertension doses of 30 to 90 mg are given twice daily by tiation of neuromuscular blockade by trimetaphan, see Ganglion C16H20ClN3O3S = 369.9. mouth. In hypertensive crises a suggested regimen is to give an Blockers, under Interactions of Atracurium, p.1904. CAS — 73803-48-2. initial dose of 25 mg by slow intravenous injection over 20 sec- onds, repeated if necessary after 5 minutes. This may be
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