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| ===Contraindications=== | ===Contraindications=== | ||
| Donepezil should be used with caution in people with cardiac disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome. | Donepezil should be used with caution in people with cardiac disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome. | ||
| Patients with gastrointestinal disorders should use caution because nausea or vomiting may occur. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, patients who have a predisposition to seizures should be treated with caution.<ref name="ReferenceA">Aricept (donepezil hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Co., Ltd.; 2010 Nov.</ref> | Patients with gastrointestinal disorders should use caution because nausea or vomiting may occur. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, patients who have a predisposition to seizures should be treated with caution.<ref name="ReferenceA">Aricept (donepezil hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Co., Ltd.; 2010 Nov.</ref> | ||
| On average, 10% to 70% of patients show adverse drug reactions (ADRs)depending upon type and severity of the ADRs. The most frequent ADRs include body events (45%), cardiovascular problems (18%), alterations in the digestive system (34%), hematic and lymphatic alterations (5%), metabolic and nutritional changes (6%), musculoskeletal problems (17%), complications in the respiratory system (22%), skin and appendages (14%), special senses (5%), urogenital (24%), and CNS (52%) (agitation, insomnia, confusion, depression, anxiety, dizziness, vertigo, headache, restlessness, hallucinations).<ref>{{cite journal |author=Ramón Cacabelos |title= Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. |journal=Neuropsychiatric Disease and Treatment |volume=3(3) |pages=303–333|date=2007}}</ref> | |||
| == Mechanism of action == | == Mechanism of action == | ||
Revision as of 21:32, 15 January 2015
Pharmaceutical compound | |
| Clinical data | |
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| Trade names | Aricept |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a697032 |
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| Routes of administration | Oral tablet, 5,10 & 23mg |
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| Pharmacokinetic data | |
| Bioavailability | 100 (%) |
| Protein binding | 96% |
| Elimination half-life | 70 hours |
| Excretion | 0,11-0,13 (l/h/kg) |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.125.198  |
| Chemical and physical data | |
| Formula | C24H29NO3 |
| Molar mass | 379.492 g/mol g·mol |
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Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, and now sold as a generic by multiple suppliers, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of Alzheimer's disease. Common side effects include gastrointestinal upset. It has an oral bioavailability of 100% and easily crosses the blood–brain barrier. Because it has a biological half-life of about 70 hours, it can be taken once a day.
Medical uses
Alzheimer's disease
Currently, no definitive proof shows the use of donepezil or other similar agents alters the course or progression of Alzheimer's disease (AD). However, 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis of no significant improvement in functional outcome, quality of life, or behavioral symptoms. However, NICE revised its guidelines to suggest donepezil be used in moderate-stage patients for whom the evidence is strongest.
In 2006 the U.S. Food and Drug Administration also approved donepezil for treatment of severe dementia.
Adverse effects
Common side effects include bradycardia, nausea, diarrhea, anorexia, abdominal pain, and vivid dreams.
In 2006, Eisai, the manufacturer, issued a statement that a single vascular dementia study found a difference in the percentage of study participants who died in the donepezil group (1.7%) versus the placebo group (0%). This could be due to an unusually low death rate on the placebo group. An analysis of all three vascular dementia trials, according to Eisai, "shows no statistically significant differences in observed mortality rates between the donepezil and placebo groups."
Contraindications
Donepezil should be used with caution in people with cardiac disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome.
Patients with gastrointestinal disorders should use caution because nausea or vomiting may occur. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, patients who have a predisposition to seizures should be treated with caution.
On average, 10% to 70% of patients show adverse drug reactions (ADRs)depending upon type and severity of the ADRs. The most frequent ADRs include body events (45%), cardiovascular problems (18%), alterations in the digestive system (34%), hematic and lymphatic alterations (5%), metabolic and nutritional changes (6%), musculoskeletal problems (17%), complications in the respiratory system (22%), skin and appendages (14%), special senses (5%), urogenital (24%), and CNS (52%) (agitation, insomnia, confusion, depression, anxiety, dizziness, vertigo, headache, restlessness, hallucinations).
Mechanism of action
The precise mechanism of action of donepezil in patients with Alzheimer's disease is not fully understood. Certainly Alzheimer's disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimer’s disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain. It is note that the hippocampal formation play an important role in the processes of control of attention, memory and learning. Just the severity of the loss of cholinergic neurons of the central nervous system (CNS) has been found to correlate with the severity of cognitive impairment. Donepezil binds and inactivates reversibly the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This results in an increased acetylcholine concentrations at cholinergic synapses.
Research
Donepezil has been tested (off label) in other cognitive disorders, including Lewy body dementia, and vascular dementia, but it is not currently approved for these indications. Donepezil has also been found to improve sleep apnea in Alzheimer's patients.
Donepezil has also been studied in patients with mild cognitive impairment, schizophrenia, attention deficit disorder, post-Coronary artery bypass surgery cognitive impairment, cognitive impairment associated with multiple sclerosis, CADASIL syndrome, and Down syndrome. A three-year National Institutes of Health trial in patients with mild cognitive impairment reported donepezil was superior to placebo in delaying rate of progression to dementia during the initial 18 months of the study, but this was not sustained at 36 months. In a secondary analysis, a subgroup of individuals with the apolipoprotein E4 genotype showed sustained benefits with donepezil throughout the study. At this time, though, donepezil is not indicated for prevention of dementia.
A 2001 study suggested that donepezil can improve speech in autistic children. The study found the speech of autistic children that was originally mildly to moderately affected appeared to improve with the use of donepezil.
Development and marketing
Research leading to the development of donepezil began in 1983 at Eisai, and the first Phase I clinical trial took place in 1989. In 1996, Eisai received approval from the United States Food and Drug Administration (USFDA) for donepezil under the brand Aricept, which it co-marketed with Pfizer. As of 2011, Aricept was the world's best-selling Alzheimer's disease treatment. The first generic donepezil became available in November 2010 with the USFDA approval of a formulation prepared by Ranbaxy Labs. In April 2011 a second generic formulation, from Wockhardt, received tentative USFDA marketing approval.
See also
References
- Birks J, Harvey RJ (2006). Birks, Jacqueline (ed.). "Donepezil for dementia due to Alzheimer's disease". Cochrane Database Syst Rev (1): CD001190. doi:10.1002/14651858.CD001190.pub2. PMID 16437430.
- "aricept". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
- Steele LS, Glazier RH (April 1999). "Is donepezil effective for treating Alzheimer's disease?". Can Fam Physician. 45: 917–9. PMC 2328349. PMID 10216789.
- Aricept (donepezil hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Co., Ltd.; 2010 Nov.
- Ramón Cacabelos (2007). "Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics". Neuropsychiatric Disease and Treatment. 3(3): 303–333.
- Davies P, Maloney AJ (December 1976). "Selective loss of central cholinergic neurons in Alzheimer's disease". Lancet. 2 (8000): 1403. PMID 63862. Retrieved 2014-12-23.
- Kása P, Rakonczay Z, Gulya K (August 1997). "The cholinergic system in Alzheimer's disease". Prog. Neurobiol. 52 (6): 511–35. PMID 9316159. Retrieved 2014-12-23.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Rojas-Fernandez CH (February 2001). "Successful use of donepezil for the treatment of dementia with Lewy bodies". Ann Pharmacother. 35 (2): 202–5. doi:10.1345/aph.10192. PMID 11215841.
- Malouf R, Birks J (2004). Malouf, Reem (ed.). "Donepezil for vascular cognitive impairment". Cochrane Database Syst Rev (1): CD004395. doi:10.1002/14651858.CD004395.pub2. PMID 14974068.
- Moraes W, Poyares D, Sukys-Claudino L, Guilleminault C, Tufik S (March 2008). "Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study". Chest. 133 (3): 677–83. doi:10.1378/chest.07-1446. PMID 18198262.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Doraiswamy PM (2007). "Donepezil for cognitive decline following coronary artery bypass surgery: a pilot randomized controlled trial". Psychopharmacology Bulletin. 40 (2): 54–62. PMID 17514186.
- Petersen, RC (Jun 9, 2005). "Vitamin E and donepezil for the treatment of mild cognitive impairment". The New England Journal of Medicine. 352 (23): 2379–88. doi:10.1056/nejmoa050151. PMID 15829527.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - "Alzheimer's Drug Shows Promise As Treatment for Autism -- Arehart-Treichel". Psychiatric News. pn.psychiatryonline.org. 2001-11-16. Retrieved 2009-08-18.
- Donepezil hydrochloride: a double-blind study in autistic children
- Sugimoto, Hachiro; Ogura, Hiroo; Arai, Yasuo; Iimura, Youichi; Yamanishi, Yoshiharu (25 January 2002), "Research and Development of Donepezil Hydrochloride, a New Type of Acetylcholinesterase Inhibitor", The Japanese Journal of Pharmacology, vol. 89, no. 1 (published 2002), pp. 7–20, doi:10.1254/jjp.89.7, retrieved 25 April 2011
- Kanoko Matsuyama (25 April 2011). "Eisai Aricept Patch for Alzheimer's Isn't Ready for Approval". Bloomberg. Retrieved 25 April 2011.
- "Ranbaxy gets FDA nod for Alzheimer's drug". The Indian Express. New Delhi, India: Indian Express Group. 30 November 2010. IndianExpress.com. Retrieved 25 April 2011.
- Staff Writer (25 April 2011). "Wockhardt Obtains US FDA Nod For Generic Version Of Aricept Tablets". RTTNews. Retrieved 25 April 2011.
External links
- Brenner, George D.; George M., PhD. Brenner (2000). Pharmacology. Philadelphia: W. B. Saunders. ISBN 0-7216-7757-6.
{{cite book}}: CS1 maint: multiple names: authors list (link) - Acting Editor-in-Chief Louise Welbanks. (2000). Compendium of Pharmaceuticals and Specialities, 2000 (25th ed.). Canadian Pharmaceutical Assn. ISBN 0-919115-76-4.
{{cite book}}:|author=has generic name (help) - Official Aricept product site
- Aricept entry at Drugs.com
- http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=20081395
- 3D Molecular structure of Donepezil
- Acetylcholinesterase: A gorge-ous enzyme QUite Interesting PDB Structure article at PDBe
| Psychoanaleptics: Anti-dementia agents (ATC code N06D and others) | |
|---|---|
| AChE inhibitor medications | |
| Other medications | |
| Experimental BACE inhibitors | |