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Chemically, topiramate is a sulfamate-substituted monosaccharide, related to fructose, a rather unusual chemical structure for an anticonvulsant. Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine as unchanged drug. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particularly subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically.

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BOTHELL, Wash. & INDIANAPOLIS–(BUSINESS WIRE)–Feb. 4, 2003

New therapeutic option an important development

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Lilly ICOS LLC (NYSE:LLY)(Nasdaq:ICOS) announced today that Cialis(TM) (tadalafil), an oral PDE5 inhibitor for the treatment of erectile dysfunction (ED), is available in pharmacies in Europe, as well as in Australia and New Zealand.

“The launch of Cialis in these major markets of Europe, Australia and New Zealand is an important milestone for Lilly ICOS,” said Richard Pilnik, president of European operations for Lilly.

“Cialis will be an important treatment option for many of the millions of men in these countries who suffer from ED, and we are excited about this initial launch of the product,” said Paul Clark, ICOS Chairman and chief executive officer.

Availability

Cialis is now broadly available by prescription in pharmacies in the United Kingdom, Germany, Denmark, Finland, Sweden, and Australia. Launches in additional European countries will be announced in the coming weeks. Cialis will be available in New Zealand later this month.

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WASHINGTON — The Food and Drug Administration gave its approval to AstraZeneca’s controversial cholesterol-lowering drug Crestor last month after a lengthy debate over the product’s side effects and safety. The drug, chemically known as rosuvastatin, is the sixth statin drug to be approved for managing cholesterol levels.

^ a b Core Data Sheet, Crestor Tablets (PDF). AstraZeneca PLC (June 17 2003). Retrieved on 2005-03-20. - NOTE: this is provider-oriented information and should not be used without the supervision of a physician.
^ a b c Nissen SE, Nicholls SJ, Sipahi I, et al (2006). “Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial” (PDF). JAMA 295 (13): 1556-65. doi:10.1001/jama.295.13.jpc60002. PMID 16533939. 
^ “FDA Approves New Drug for Lowering Cholesterol”, The Food and Drug Administration, August 12, 2003. Retrieved on 2005-03-20. 
^ Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW. (2003). “Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial)”. Am J Cardiol 92 (2): 152-60. PMID 12860216. 
^ Horton, Richard (October 25 2003). “The statin wars: why AstraZeneca must retreat.”. Lancet 362 (9393): 1341. PMID 14585629. Retrieved on 2005-03-20.  - No author is listed with the online abstract; full-text is not available free online.
McKillop T (November 1 2003). “The statin wars.”. Lancet 362 (9394): 1498. PMID 14602449.  - Full-text is not available free online.
^ Food and Drug Administration. “Docket No. 2004P-0113/CP1″. 
^ FDA Alert (03/2005) - Rosuvastatin Calcium (marketed as Crestor) Information. The Food and Drug Administration (March 14, 2005). Retrieved on 2005-03-20. - This page is subject to change; the date reflects the last revision date.

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Ask anyone who has had a tattoo why they did it and they will tell you two things. One, they were making a very personal statement, usually spiritually oriented, and two, after their first tattoo they were hooked.

Tattoo is not just a method of body art; it is a very spiritual custom that dates back hundreds to thousands of years in many cultures. While there are many beautiful and breathtaking designs, most people use these tattoos as a basis or template for their own personal expression.

The majority of the time, if a client does not come in with their own personal design, they will show the artist a particular design and follow up with, "but I want to make a few changes." So, when you are designing your own tattoo, such as with a Superman tattoo pic, there are a few tips to consider. Location, Location, Location!

Think about where you want to put the tattoo. For instance, you wouldn’t want to put a large, flying Superman tattoo pic on your ankle. That type of tattoo is too detailed and would be rather large so it would not be appropriate for that area.

A Superman tattoo pic like that would likely be better suited on the upper arm, hip, back or even forearm. When you think about your tattoo and what type of tattoo you want(such as a Superman tattoo pic), consider where you want it to be placed.

Size Matters

Yes, when you are looking to get a tattoo, size does matter. You really can not just choose a random design or a Superman tattoo pic with no forethought because you do need to consider the size of the tatt as well as the location. Sometimes the location will even dictate the size.

A Superman tattoo pic that is, perhaps, the big S symbol that is always shown on the front of his uniform, then you can usually size that up or down according to the location.

What are Your Colors?

Choose colors that are appropriate for the tatt, but also appropriate for you. This is generally a permanent venture, so you want something that you like and will enjoy seeing on your body for the rest of your life. A Superman tattoo pic would be blue, red and yellow.

What colors are your spirit? If you are commemorating an event, what are its colors? If you are honoring someone, what colors do you associate with them? Let your color scheme work with YOU. Or choose a standard tattoo like a Superman tattoo pic and go with it.

Choose a Design that Fits Your Spirit

Choose a design or template that fits your personal spirit. The design should speak to you. If you want a Superman tattoo pic, go for it. You may wish to combine several designs to create your own. Add elements, or if you are an artist, draw your own design.

You can find many different designs and select one that suits you. You may want to bring a friend along for input, but don’t allow them to influence you too much. After all, you will be the one walking around with the tattoo, or the Superman tattoo pic, not them.

Think Twice about Adding a Name

You may have heard this many times, but it always stands to be said again. When designing your own tattoo, you may want to think twice about putting someone’s name on it. There are a few celebrities that we can look to who can attest to this. Many people put people’s names on their tatts and wind up covering the name later.

If you want to honor the love of your life by putting their name under your Superman tattoo pic, do yourself a favor and do it some other way. A tattoo is forever unless you get it covered or lasered. Save yourself the trouble.

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Weight loss medications present in the market has side effects, to get the best out of any medication make sure to complete your weight loss program under physician. Above all also keep in mind to stop using this weight loss diet pill in the stipulated time period as it’s over usage may result in serious side effects. Every one has hidden desire to loose maximum weight as soon as possible. But finally take your time to decide about the medication you want to use for solution of obesity.

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Business Editors and Health/Medical Writers

INDIANAPOLIS–(BW HealthWire)–May 1, 2001

Man can sustain anything except for a blot on his manliness, its one thing where he can not compromise. A question raised on manliness shatters his self esteem and leaves him in an unanswerable position.

Eerectile dysfunction is one such disorder which puts a man in a vulnerable position and embarrasses him in bed. Sexual breakdown makes life worse for a man as well as his partner.

Erectile Dysfunction or impotence may be termed as the consistent inability to attain and maintain an erection sufficient for sexual intercourse. ED is a very common phenomenon, it affects an estimated 189 million men worldwide. “He to command and she to obey, he for the sword and for the needle she”

Experts believe that 80 percent to 90 percent of ED cases are related to a physical or medical condition, such as diabetes, cardiovascular diseases, and prostate cancer treatment, while 10 percent to 20 percent are due to psychological causes. In many cases, however, both psychological and physical factors contribute to the condition.

Online Cialis has proved to be a boon for the treatment of erectile dysfunction, through Online Cialis millions of people have regained their sexual life bur like its contemporaries it has its pros and cons.

Take Cialis 30 minutes to 12 hours before indulging in sex and enjoy its long lasting (36 hours) consequences. It is available in 5mg 10 mg and 20 mg packages to be taken as recommended by health care professionals.

Cialis is not recommended for people taking nitrates, it may cause precarious drop in blood pressure. The most familiar side effects of CIALIS include headache and upset stomach. Some times it may lead to back ache and muscle ache.

As with any ED tablet, in the rare event of priapism (an erection lasting more than four hours), seek immediate medical help to avoid long-term injury. In rare instances, men taking prescription ED tablets (including CIALIS) reported a sudden decrease or loss of vision.

It’s not possible to determine if these events are related directly to the ED tablets or to other factors. If you face any such problem, stop taking the drug immediately and consult your doctor.

Cialis is severely prohibited for women, children and people who are not suffering from erectile dysfunction.

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Pfizer Inc. has voluntarily recalled one lot of 100-mg capsules of Neurontin (gabapentin) because of a mechanical failure that resulted in some empty or partially filled capsules. The recall affects about 40,000 bottles of the capsules. The affected lot number is 15224V. Bottles from this lot …

Though gabapentin is not a controlled substance, it does produce psychoactive effects that could lead to abuse of the drug. However, it is widely regarded as having little or no abuse potential. Pregabalin, a gabapentinoid with higher potency marketed for neuropathic pain, is a controlled substance, under the DEA Schedule V.

^ BNF (March 2003) 45
^ Pfizer: Product Monograph Neurontin®PDF (251 KiB) Retrieved 14 August 2006
^ Mathew, NT; Rapoport A, Saper J, Magnus L, Klapper J, Ramadan N, Stacey B, Tepper S (2001). “Efficacy of gabapentin in migraine prophylaxis”. Headache 41 (2): 119–28. ISSN 0017-8748. PMID 11251695. Retrieved on 2006-08-14. 
^ Backonja, MM; Serra J (2004). “Pharmacologic management part 1: better-studied neuropathic pain diseases”. Pain Med 5 (Suppl 1): S28–47. ISSN 1526-2375. PMID 14996228. 
^ Choudhuri, I; Sarvananthan N, Gottlob I (May 26, 2006). “Survey of management of acquired nystagmus in the United Kingdom”. Eye. ISSN 0950-222X. PMID 16732211. 
^ a b c Mack, Alicia (2003). “Examination of the evidence for off-label use of gabapentin” (PDF). Journal of Managed Care Pharmacy 9 (6): 559–68. Retrieved on 2006-08-14. 
^ Pande, AC; Crockatt JG, Janney CA, Werth JL, Tsaroucha G. (2000). “Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy” (Abstract). Bipolar Disorders 2 (3 Pt 2): 249–55. PMID 11249802. Retrieved on 2006-08-14. 
^ Chouinard, G (May 2006). “The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs”. J Psychiatry Neurosci 31 (3): 168–176. ISSN 1180-4882. PMID 16699602. 
^ Frye, Mark A.; et al (2000). “A Placebo-Controlled Study of Lamotrigine and Gabapentin Monotherapy in Refractory Mood Disorders” (Abstract). Journal of Clinical Psychopharmacology 20 (6): 607–14. Retrieved on 2006-08-14. 
^ Guttuso, T Jr; Kurlan R; McDermott MP; Kieburtz K (Feb 2003). “Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial”. Obstet Gynecol 101 (2): 337–45. Retrieved on 2007-02-15. 
^ PROMETA Demonstrates Statisitcally Significant Reduction in Methamphetamine Cravings in Randomized Double-Blind Placebo Controlled Study
^ Piccirillo, JF; Finnell J, Vlahiotis A, Chole RA, Spitznagel E (2007). “Relief of idiopathic subjective tinnitus: is gabapentin effective?”. Arch Otolaryngol Head Neck Surg 133 (4): 390–7. PMID 17438255. Retrieved on 2007-07-22. 
^ “Huge penalty in drug fraud, Pfizer settles felony case in Neurontin off-label promotion.”, San Francisco Chronicle, 2004-05-14, p. C-1. 
^ Jane E. Henney, MD (2006). “Editorial: Safeguarding Patient Welfare: Who’s In Charge?”. Annals of Internal Medicine 145 (4): 305-307. Retrieved on 2006-08-14. 
^ http://www.courts.state.ny.us/reporter/3dseries/2007/2007_05813.htm Baron v. Pfizer, Inc., 2007 N.Y. Slip Op. 05813 (App. N.Y., July 5, 2007)]
^ http://dida.library.ucsf.edu
^ http://www.annals.org/cgi/content/full/145/4/284
^ FDA approved labeling for Neurontin capsules, tablets, and oral solution. (February 2005). Note that an updated labeling has been approved, but is not available online as of November 2006
^ Maria C Lasso-de-la-Vega Pharm.D (2001). “Gabapentin-associated hepatotoxicity” (Abstract). Am J Gastroenterol 96 (12): 3460–3462. Retrieved on 2007-02-14. 
^ Ayhan DOGUKAN (2006). “Gabapentin-induced coma in a patient with renal failure” (Abstract). Hemodialysis International 10 (2): 168–169. Retrieved on 2007-02-14. 
^ Bookwalter T, Gitlin M (2005). “Gabapentin-induced neurologic toxicities” (Abstract). Pharmacotherapy 25 (12): 1817–9. PMID 16305301. Retrieved on 2007-02-14. 
^ http://www.drugs.com/pro/gabapentin.html

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^ Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E (2004). “The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy”. Chest 126 (3 Suppl): 204S–233S. doi:10.1378/chest.126.3_suppl.204S. PMID 15383473. 
^ a b Whitlon DS, Sadowski JA, Suttie JW (1978). “Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition”. Biochemistry 17 (8): 1371–7. PMID 646989. 
^ Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW (2004). “Identification of the gene for vitamin K epoxide reductase”. Nature 427 (6974): 541–4. doi:10.1038/nature02254. PMID 14765195. 
^ a b Rost S, Fregin A, Ivaskevicius V, et al (2004). “Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2″. Nature 427 (6974): 537-41. doi:10.1038/nature02214. PMID 14765194. 
^ a b Hirsh J, Fuster V, Ansell J, Halperin JL (2003). “American Heart Association/American College of Cardiology Foundation guide to warfarin therapy”. J. Am. Coll. Cardiol. 41 (9): 1633–52. PMID 12742309. 
^ Delaney JA, Opatrny L, Brophy JM, Suissa S (2007). “Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding”. CMAJ 177 (4): 347-51. doi:10.1503/cmaj.070186. PMID 17698822.  Full text at PMC: 1942107
^ Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S (2007). “Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation”. Circulation 115 (21): 2689-96. doi:10.1161/CIRCULATIONAHA.106.653048. PMID 17515465. 
^ Elliott MJ, Zimmerman D, Holden RM (2007). “Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates”. Am. J. Kidney Dis. 50 (3): 433–40. doi:10.1053/j.ajkd.2007.06.017. PMID 17720522. 
^ Caraballo PJ, Heit JA, Atkinson EJ, et al (1999). “Long-term use of oral anticoagulants and the risk of fracture”. Arch. Intern. Med. 159 (15): 1750–6. PMID 10448778. 
^ Pilon D, Castilloux AM, Dorais M, LeLorier J (2004). “Oral anticoagulants and the risk of osteoporotic fractures among elderly”. Pharmacoepidemiol Drug Saf 13 (5): 289–94. doi:10.1002/pds.888. PMID 15133779. 
^ Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF (2006). “Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2″. Arch. Intern. Med. 166 (2): 241–6. doi:10.1001/archinte.166.2.241. PMID 16432096. 
^ Talmadge DB, Spyropoulos AC (2003). “Purple toes syndrome associated with warfarin therapy in a patient with antiphospholipid syndrome”. Pharmacotherapy 23 (5): 674–7. PMID 12741443. 
^ a b Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E (2004). “The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy”. Chest 126 (3 Suppl): 204S-233S. doi:10.1378/chest.126.3_suppl.204S. PMID 15383473.  (summary)
^ Crowther MA, Douketis JD, Schnurr T, et al (2002). “Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial”. Ann. Intern. Med. 137 (4): 251-4. PMID 12186515. 
^ FDA Approves Updated Warfarin (Coumadin) Prescribing Information. Retrieved on 2007-08-20.
^ a b Wadelius M, Chen LY, Downes K, et al (2005). “Common VKORC1 and GGCX polymorphisms associated with warfarin dose”. Pharmacogenomics J. 5 (4): 262-70. doi:10.1038/sj.tpj.6500313. PMID 15883587. 
^ a b Rieder MJ, Reiner AP, Gage BF, et al (2005). “Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose”. N. Engl. J. Med. 352 (22): 2285-93. doi:10.1056/NEJMoa044503. PMID 15930419. 
^ a b Sanderson S, Emery J, Higgins J (2005). “CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis”. Genet. Med. 7 (2): 97-104. PMID 15714076. 
^ Kovacs MJ, Rodger M, Anderson DR, et al (2003). “Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial”. Ann. Intern. Med. 138 (9): 714-9. PMID 12729425.  (summary of 10 mg algorithm)
^ Fennerty A, Campbell IA, Routledge PA (1988). “Anticoagulants in venous thromboembolism”. BMJ 297 (6659): 1285-8. PMID 3144365. 
^ Tait RC, Sefcick A (1998). “A warfarin induction regimen for out-patient anticoagulation in patients with atrial fibrillation”. Br. J. Haematol. 101 (3): 450-4. doi:10.1046/j.1365-2141.1998.00716.x. PMID 9633885. 
^ Millican E, Jacobsen-Lenzini PA, Milligan PE, et al (2007). “Genetic-based dosing in orthopaedic patients beginning warfarin therapy” 110 (5): 1511-5. doi:10.1182/blood-2007-01-069609. PMID 17387222.  Online tool based on the study.
^ Point-of-Care Guides - May 15, 2005 - American Family Physician. Retrieved on 2007-08-20.
^ Jack Ansell (10 March 2005). “Guidelines for implementation of patient self-testing and patient self-management of oral anticoagulation. International consensus guidelines prepared by International Self-Monitoring Association for Oral Anticoagulation”. International Journal of Cardiology. 
^ Holbrook AM, Pereira JA, Labiris R, et al (2005). “Systematic overview of warfarin and its drug and food interactions”. Arch. Intern. Med. 165 (10): 1095–106. doi:10.1001/archinte.165.10.1095. PMID 15911722. 
^ Austin, Steve and Batz, Forrest (1999). in Lininger, Schuyler W.: A-Z guide to drug-herb-vitamin interactions: how to improve your health and avoid problems when using common medications and natural supplements together. Roseville, Calif: Prima Health, 224. ISBN 0-7615-1599-2. 
^ Schofield FW (1924). “Damaged sweet clover; the cause of a new disease in cattle simulating haemorrhagic septicemia and blackleg”. J Am Vet Med Ass 64: 553-6. 
^ Roderick LM (1931). “A problem in the coagulation of the blood; “sweet clover disease of the cattle”". Am J Physiol 96: 413-6.  PDF (subscriber only).
^ Stahmann MA, Huebner CF, Link KP (1941). “Studies on the hemorrhagic sweet clover disease. V. Identification and synthesis of the hemorrhagic agent”. J Biol Chem 138: 513-27. 
^ a b Link KP (1959). “The discovery of dicumarol and its sequels”. Circulation 19 (1): 97–107. PMID 13619027. 
^ Naumov, Vladimir Pavlovich; Brent, Jonathan (2003). Stalin’s last crime: the plot against the Jewish doctors, 1948-1953. London: HarperCollins. ISBN 0-06-019524-X. 

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