الفرق بين المراجعتين لصفحة: «حمض تينيليك»
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سلام المجذوب (نقاش | مساهمات) (أنشأ الصفحة ب''''حمض تينيليك Tienilic acid''' هو مدر عروة وله تأثير خافض لحمض البول. لكنه يستخدم رسميا لعلاج [[ارتفاع...') |
(قالب معلومات الدواء، صندوق احمر لخبر سحب الدواء، تضمين نص إنكليزي في خلفية المقالة للمتابعة لاحقاً) |
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'''حمض تينيليك Tienilic acid''' هو مدر عروة وله تأثير خافض لحمض البول. لكنه يستخدم رسميا لعلاج [[ارتفاع ضغط الدم]].تم سحبه من الأسواق بعد أشهر من طرحه بسبب عدة تقارير أظهرت أنه يحدث إصابة كبدية محدثة بالدواء وقد اشتملت بعضها على حالات قاتلة. كما مركبات ال[[ثيوفين]] الأخرى يتم استحالته إلى مستقلب S أوكسيدي والذي يتفاعل تساهميا مع البروتينات الخلوية. | {{Drugbox | ||
| English = Tienilic acid | |||
| IUPAC_name = [2,3-dichloro-4-(2-thienylcarbonyl)phenoxy]acetic acid | |||
| image = Tienilic_acid.svg | |||
<!--Clinical data--> | |||
| tradename = | |||
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | |||
| pregnancy_US = <!-- A / B / C / D / X --> | |||
| pregnancy_category = | |||
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | |||
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | |||
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> | |||
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | |||
| legal_status = '''Withdrawn''' | |||
| routes_of_administration = Oral | |||
<!--Pharmacokinetic data--> | |||
| bioavailability = | |||
| protein_bound = 95% | |||
| metabolism = [[Liver|Hepatic]] | |||
| elimination_half-life = 6 hours | |||
| excretion = [[Kidney|Renal]] and biliary | |||
<!--Identifiers--> | |||
| CAS_number = 40180-04-9 | |||
| ATC_prefix = C03 | |||
| ATC_suffix = CC02 | |||
| PubChem = 38409 | |||
| DrugBank = | |||
| UNII_Ref = {{fdacite|correct|FDA}} | |||
| UNII = HC95205SY4 | |||
| KEGG = D02386 | |||
| ChEMBL = 267744 | |||
<!--Chemical data--> | |||
| C=13 | H=8 | Cl=2 | O=4 | S=1 | |||
| molecular_weight = 331.17 g/mol | |||
| smiles = C1=CSC(=C1)C(=O)C2=C(C(=C(C=C2)OCC(=O)O)Cl)Cl | |||
}} | |||
'''حمض تينيليك Tienilic acid''' هو مدر عروة وله تأثير خافض لحمض البول. لكنه يستخدم رسميا لعلاج [[ارتفاع ضغط الدم]].<ref>{{cite pmid|6844125}}</ref> | |||
{{صندوق|أحمر|تم سحبه|تم سحبه من الأسواق بعد أشهر من طرحه بسبب عدة تقارير أظهرت أنه يحدث إصابة كبدية محدثة بالدواء وقد اشتملت بعضها على حالات قاتلة.}} | |||
كما مركبات ال[[ثيوفين]] الأخرى يتم استحالته إلى مستقلب S أوكسيدي والذي يتفاعل تساهميا مع البروتينات الخلوية. | |||
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'''Tienilic acid''' ([[International Nonproprietary Name|INN]] and [[British Approved Name|BAN]]) or '''ticrynafen''' ([[United States Adopted Name|USAN]]) is a [[loop diuretic]] drug with [[uric acid]]-lowering (uricosuric) action,<ref>{{cite pmid|6844125}}</ref><ref>{{cite pmid|471151}}</ref> formerly marketed for the treatment of [[hypertension]]. It was approved by FDA on May 2, 1979, and withdrawn in 1982, after case reports in the [[United States]] indicated a link between the use of ticrynafen and [[hepatitis]].<ref>{{cite pmid|7091125}}</ref> | |||
Criminal charges were brought against [[Smith, Kline & French|SmithKline]] executives with regard to hiding data related to toxicity while gaining FDA approval. The company pleaded guilty to 14 counts of failure to report adverse reactions and 20 counts of selling a [[misbranded drug]].<ref>United States v. SmithKline Beckman et al {BLR 286} Biotechnology Law Report. September–October 1984, 3(9-10): 206-214.</ref> | |||
Tienilic acid was found to act as a suicide substrate at the [[cytochrome P450]] enzymes involved in drug metabolism. Unfortunately, the metabolic reaction carried out by these enzymes converted tienilic acid to a [[thiophene]] [[sulfoxide]] which proved highly [[electrophilic]]. This encouraged a [[Michael reaction]] leading to alkylation of a [[thiol]] group in the enzyme's active site. Loss of water from the thiophene sulfoxide restored the thiophene ring and resulted in tienilic acid being covalently linked to the enzyme, thus inhibiting the enzyme irreversibly. | |||
The above explanation is a hypothesis. It is still not known (after 15 years) if the reactive intermediate which inactivates the CYP2C9 is the thiophene sulfoxide or the thiophene epoxide. The target on the protein is also not known (could be multiple). However tienilic acid is a good mechanism based inhibitor of CYP2C9 and seems to inactivate it stoichiometrically. Progress in proteomics may one day give the answer. | |||
Recent studies indicate that in fact the primary metabolite of tienilic acid (5-OH tienilic acid) cannot be derived from a thiophene-S-oxide intermediate as was previously hypothesized. It was determined to be derived from a thiophene epoxide intermediate and this reactive intermediate is then likely a cause for the covalent binding to as well as mechanism-based inactivation of CYP2C9.<ref>{{cite PMID|22329513}}</ref> | |||
--> | |||
==مصادر== | |||
{{Reflist|2}} | |||
المراجعة الحالية بتاريخ 08:28، 19 أبريل 2013
| |
|---|---|
| Systematic (IUPAC) name | |
| [2,3-dichloro-4-(2-thienylcarbonyl)phenoxy]acetic acid | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | Withdrawn |
| Routes | Oral |
| Pharmacokinetic data | |
| Protein binding | 95% |
| Metabolism | Hepatic |
| Half-life | 6 hours |
| Excretion | Renal and biliary |
| Identifiers | |
| CAS number | 40180-04-9 |
| ATC code | C03CC02 |
| PubChem | CID 38409 |
| UNII | HC95205SY4 
|
| KEGG | D02386 |
| ChEMBL | CHEMBL267744 |
| Chemical data | |
| Formula | C13H8Cl2O4S |
| Mol. mass | 331.17 g/mol |
| |
حمض تينيليك Tienilic acid هو مدر عروة وله تأثير خافض لحمض البول. لكنه يستخدم رسميا لعلاج ارتفاع ضغط الدم.[1]
كما مركبات الثيوفين الأخرى يتم استحالته إلى مستقلب S أوكسيدي والذي يتفاعل تساهميا مع البروتينات الخلوية.
مصادر
- ↑ PMID 6844125 (PubMed)
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