Tiratricol(TRIAC) - mokamelshenasi.ir of PDR/Tiratricol... · SUPPLEMENT MONOGRAPHS TOCOTR IENOLS...
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616/TIN Pekelharing HL, Lemmens AG, Beynan AC. Iron, copper and zinc status in rats fed on diets containing various concentrations of tin. Br J Nutr. 1994; 71: 103-109. Yokoi K, Kimura M, Itokawa Y. Effect of dietary tin deficiency on growth and mineral status in rats. Bioi Trace Elem Res. 1990; 223-231. Tiratricol (TRIAC) FDA warns against consuming dietary supplements containing Tiratricol. DESCRIPTION Tiratricol is an orphan drug for use in combination with levothyroxine to suppress thyroid stimulflting hormone (TSH) in patients with well-differentiated thyroid cancer who are intolerant to adequate doses of levothyroxine alone. Tiratricol is a metabolite of the thyroid hormone triiodothy- ronine (T3) and has thyroid hormone activity. Tiratricol is also marketed as a dietary supplement for weight-loss purposes. In November 2000, the Food and Drug Administration (FDA) warned against consuming dietary supplements containing tiratricol. This was based on reports of individuals using tiratricol developing side effects, such as fatigue, lethargy, profound weight loss and severe diarrhea. They were also found to have abnormal thyroid function tests. Further action by the FDA is being considered. Tiratricol is also known as triiodothyroacetic acid, TRIAC, 3,5,3' -triiodothyroacetic acid and [4-(4-hydroxy-3-iodophe- noxy)-3,5-di-iodophenyl]acetic acid. Its molecular formula is C14H91304, and its molecular weight is 621.9 daltons. ACTIONS AND PHARMACOLOGY ACTIONS Tiratricol has thyroid hormone activIty, including various metabolic effects. It also inhibits the secretion of thyroid- stimulating hormone (TSH) by the pituitary gland. Tiratricol is a product of triiodothyronine or T3 metabolism, derived by deamination and oxidative decarboxylation of the alanine chain. In humans, tiratricol production by the liver and other tissues accounts for about 14% of T3 metabolism and is increased under certain physiological conditions, such as fasting. Tiratricol may play a role in regulat.ing energy balance. MECHANISM OF ACTION The mechanism by which thyroid hormones exert their various actions has not been completely elucidated. Tiratri- col is known to act as a feedback inhibitor of TSH secretion by the pituitary gland. PDR FOR NUTRITIONAL SUPPLEMENTS PHARMACOKINETICS Much is unknown about the pharmacokinetics of tiratricol in humans. The pharmacokinetics of tiratricol appears to be similar to those of thyroxine and triiodothyronine. Tiratricol is absorbed from the small intestine following ingestion. Distribution of tiratricol in the body has not been fully elucidated. Most of this substance appears to be bound to serum proteins, including thyroxine-binding protein and albumin. It appears to be less firmly bound to serum proteins than are T4 and T3' The liver appears to be the major site of degradation of tiratricol. Tiratricol appears to be conjugated with glucuronic acid and sulfuric acid and excreted in the bile. Mainly because it is less tightly bound to serum proteins, tiratricol has a shorter half-life than T4 or T3, INDICATIONS AND USAGE The FDA has warned consumers not to purchase tiratricol- containing dietary supplements due to risk of serious health consequences, including heart attacks and strokes. Tiratricol should be used only under a 'physician's supervision. Tiratricol is currently used by some as a supplement to burn fat. The doses required to achieve this effect pose significant health risks. RESEARCH SUMMARY Tiratricol is an orphan drug. The FDA has determined that it should not be used as a dietary supplement due to serious potential health risks including heart attack and stroke. CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS , CONTRA INDICA TIONS Tiratricol is contraindicated in those with untreated thyrotox- icosis of any etiology and in those with uncorrected adrenal insufficiency. Thyroid hormones increase tissue demands for adrenocortical hormones and may thereby precipitate acute adrenal crisis. Tiratricol is also contraindicated in those who are hypersensitive to any component of a tiratricol-contain- ing product. FDA warns against consuming dietary supple- ments containing tiratricol. PRECAUTIONS Tiratricol should only be used for specific approved indica- tions and only under strict medical supervis~on. Tiratricol should not be used as a treatment for obesity. Tiratricol should be used with extreme caution in those with cardiovas- , cular disorders (including flngina, coronary artery disease and hypertension) and in the elderly who have a greater likelihood of occult cardiac disease. Concomitant use of tiratricol and sympathomimetic agents in those with coronary artery disease may increase the risk of coronary insufficien- cy. Use of tiratricol in those with concomitant diabetes mellitus, diabetes insipidus or adrenal cortical insufficiency may aggravate the intensity of their symptoms.
Transcript of Tiratricol(TRIAC) - mokamelshenasi.ir of PDR/Tiratricol... · SUPPLEMENT MONOGRAPHS TOCOTR IENOLS...
616/TIN
Pekelharing HL, Lemmens AG, Beynan AC. Iron, copper andzinc status in rats fed on diets containing various concentrationsof tin. Br J Nutr. 1994; 71: 103-109.
Yokoi K, Kimura M, Itokawa Y. Effect of dietary tindeficiency on growth and mineral status in rats. Bioi TraceElem Res. 1990; 223-231.
Tiratricol (TRIAC)
FDA warns against consuming dietary supplementscontaining Tiratricol.
DESCRIPTION
Tiratricol is an orphan drug for use in combination withlevothyroxine to suppress thyroid stimulflting hormone(TSH) in patients with well-differentiated thyroid cancerwho are intolerant to adequate doses of levothyroxine alone.Tiratricol is a metabolite of the thyroid hormone triiodothy-ronine (T3) and has thyroid hormone activity.
Tiratricol is also marketed as a dietary supplement forweight-loss purposes. In November 2000, the Food and DrugAdministration (FDA) warned against consuming dietarysupplements containing tiratricol. This was based on reportsof individuals using tiratricol developing side effects, such asfatigue, lethargy, profound weight loss and severe diarrhea.They were also found to have abnormal thyroid functiontests. Further action by the FDA is being considered.
Tiratricol is also known as triiodothyroacetic acid, TRIAC,3,5,3' -triiodothyroacetic acid and [4-(4-hydroxy-3-iodophe-noxy)-3,5-di-iodophenyl]acetic acid. Its molecular formula isC14H91304,and its molecular weight is 621.9 daltons.
ACTIONS AND PHARMACOLOGY
ACTIONS
Tiratricol has thyroid hormone activIty, including variousmetabolic effects. It also inhibits the secretion of thyroid-stimulating hormone (TSH) by the pituitary gland. Tiratricolis a product of triiodothyronine or T3 metabolism, derived bydeamination and oxidative decarboxylation of the alaninechain. In humans, tiratricol production by the liver and othertissues accounts for about 14% of T3 metabolism and isincreased under certain physiological conditions, such asfasting. Tiratricol may play a role in regulat.ing energybalance.
MECHANISM OF ACTION
The mechanism by which thyroid hormones exert theirvarious actions has not been completely elucidated. Tiratri-col is known to act as a feedback inhibitor of TSH secretionby the pituitary gland.
PDR FOR NUTRITIONAL SUPPLEMENTS
PHARMACOKINETICS
Much is unknown about the pharmacokinetics of tiratricol inhumans. The pharmacokinetics of tiratricol appears to besimilar to those of thyroxine and triiodothyronine. Tiratricolis absorbed from the small intestine following ingestion.Distribution of tiratricol in the body has not been fullyelucidated. Most of this substance appears to be bound toserum proteins, including thyroxine-binding protein andalbumin. It appears to be less firmly bound to serum proteinsthan are T4 and T3' The liver appears to be the major site ofdegradation of tiratricol. Tiratricol appears to be conjugatedwith glucuronic acid and sulfuric acid and excreted in thebile. Mainly because it is less tightly bound to serumproteins, tiratricol has a shorter half-life than T4 or T3,
INDICATIONS AND USAGE
The FDA has warned consumers not to purchase tiratricol-containing dietary supplements due to risk of serious healthconsequences, including heart attacks and strokes. Tiratricolshould be used only under a 'physician's supervision.Tiratricol is currently used by some as a supplement to burnfat. The doses required to achieve this effect pose significanthealth risks.
RESEARCH SUMMARY
Tiratricol is an orphan drug. The FDA has determined that itshould not be used as a dietary supplement due to seriouspotential health risks including heart attack and stroke.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS,CONTRA INDICA TIONS
Tiratricol is contraindicated in those with untreated thyrotox-icosis of any etiology and in those with uncorrected adrenalinsufficiency. Thyroid hormones increase tissue demands foradrenocortical hormones and may thereby precipitate acuteadrenal crisis. Tiratricol is also contraindicated in those whoare hypersensitive to any component of a tiratricol-contain-ing product. FDA warns against consuming dietary supple-ments containing tiratricol.
PRECAUTIONS
Tiratricol should only be used for specific approved indica-tions and only under strict medical supervis~on. Tiratricolshould not be used as a treatment for obesity. Tiratricolshould be used with extreme caution in those with cardiovas-,cular disorders (including flngina, coronary artery diseaseand hypertension) and in the elderly who have a greaterlikelihood of occult cardiac disease. Concomitant use oftiratricol and sympathomimetic agents in those with coronaryartery disease may increase the risk of coronary insufficien-cy. Use of tiratricol in those with concomitant diabetesmellitus, diabetes insipidus or adrenal cortical insufficiencymay aggravate the intensity of their symptoms.
SUPPLEMENT MONOGRAPHS TOCOTR IENOLS /617
FDA warns against consuming dietary supplements contain-ing tiratricoI.
ADVERSE REACTIONS
Reported adverse reactions include fatigue, lethargy, pro-
found weight loss and severe diarrhea. Tir~tricol has also
been reported to cause abnormal thyroid function tests.
INTERACTIONS
DRUGSAnticoagulants (oral). The hypoprothrombinemic effect ofanticoagulants, such as warfarin, may be potentiated.
Sympathomimetic agents. There is a possible increased riskof coronary insufficiency in those with coronary arterydisease.
Thyroid drugs (levothyroxine, tr,iiodothyronine, thyroid).Concomitant use of tiratricol with the~e thyroid drugs islikely to produce additive effects.
LABORATORY TESTS
Tiratricol is likely to alter thyroid function tests, includingTSH, 'f,4 and T3'
OVERDOSAGE
There have been no reports of overdosage with tiratricoI.Excessive doses of tiratricol theoretically may result in ahyperrnetabolic state indistinguishable from thyrotoxicosis.
DOSAGE AND ADMINISTRATION
Tiratricol is not recommended for use as a dietarysupplement.
LITERATURE
Anon. FDA warns against consuming dietary supplementscontaining tiratricol. FDA Talk Paper. Nov. 21, 2000.
Bracco D, Morin 0, Schutz Y, et al. Comparison of themetabolic effects of 3,5,3' -triiodothyroacetic acid and thyroxine.J Clin Endocrin Met. 1993;77:221-228.
Darendeliler F, Ba F. Successful therapy with 3,5,3'-triiodothyroacetic acid (TRIAC) in pituitary resistance to thyroidhormone. J Pediatr Endocrinol Metab. 1997;10(5):535-538.
Iglesias P, Dfez 11. [Therapeutic possibilities in patients withselective pituitary resistance to thyroid hormones.] [In Spanish.]Med Clin (Barc). 2008;130(9):345-350.
Medina-Gomez G, Calvo RM, Obregon MJ. Thermogenic eff~ctof triiodothyroacetic acid at low doses in rat adipose tissuewithout adverse side effects in the thyroid axis. Am J PhysiolEndocrinol Metab. 2008;294(4):E688-697.
Pisarev MA, Brenta G, Schnitman M, et al. [Triiodothyroaceticacid in euthyroid goiter. New data on its mechanisms of action.Comparison with L-thyroxin.] [In French.] Bull Acad Natl Med.2007;191(8):1705-1715; discussion 1715.
Radetti G, Persani L, Molinaro G, et al. Clinical and hormonaloutcome after two years of triiodothyroacetic acid treatment in
a child with thyroid hormone resistance. Thyroid. 1997;7:775-778.
Takeda T, Suzuki S, Uu RT, et al. Triiodothyroacetic acid hasunique potential for therapy of resistance to thyroid hormone. JClin Endocrinol Metab. 1995;80:2033-2040.
TocotrienolsDESCRIPTION
Tocotrienols comprise one of the two groups of moleculesbelonging to the vitamin E family, the other group being thetocopherols. Tocotrienols and tocopherols are sometimescollectively called tocols. Just as there are four naturaltocopherols, alpha-, beta-, gamma- and delta-tocopherol,there are also four natural tocotrienols, alpha-, beta-, gamma-and delta-tocotrienoI. The tocotrienols differ from thetocopherols in the chemical nature of the side chain or tail.Tocopherols have a saturated phytyl side chain, whereastocotrienols have an unsaturated isoprenoid or farnesyl sidechain ,possessing three double bonds.
The major source of tocotrienols are plant oils, and therichest sources are palm oil, rice bran oil, palm kernel oil andcoconut oil. Tocotrienols are also found in such cereal grainsas oat, barley and rye. Vegetable oils, such as those fromcanola, cottonseed, olive, peanut, safflower, soybean andsunflower, contain little to no tocotrienols. However, thoseoils do contain tocopherols. Corn oil has small amounts oftocotrienols.
All of the natural tocotrienols are fat-soluble, water-insolubleoils. The tocotrienols, as well as the tocopherols, possesschain-breaking, peroxyl radical scavenging activities. Incontrast to tocopherols, tocotrienols inhibit the rate-limiting enzyme of the cholesterol biosynthetic pathwaybeta-hydroxy-beta-methylglutaryl-coenzyme A (HMG-CoA)reductase.
The four natural tocotrienols are characterized by the numberof methyl groups and their position in the chromanol ring.Alpha-tocotrienol has three methyl groups located on posi-tions 5, 7 and 8 of the chromanol ring; beta-tocotrienol hastwo methyl groups located on positions 5 and 8 of the ring;gamma-tocotrienol has two methyl groups located on posi-tions 7 and 8 of the ring and delta-tocotrienol has one methylgroup located on position 8 of the ring.
While tocopherols have three chiral centers, tocotrienolshave only one chiral center. Therefore, each tocotrienol hastwo stereoisomeric possibilities in comparison with eightsuch possibilities for each of the tocopherols. The naturaltocotrienols exist as d-stereoisomers: d-alpha-tocotrienol, d-beta-tocotrienol, d-gamma-tocotrienol and d-delta-tocotrien-
