Pharmaceutical Sciences 藥物科學 阿茲海默症藥物治療的進展 基隆長庚紀念醫院藥劑科藥師林舒婷 陳立偉 林勇志 長庚紀念醫院藥學部藥師鄧新棠 摘要 65 2-4%65 13 NMDA Alzheimer's disease angiotensin receptor blocker acetylcholinesterase inhibitor 壹 前言 (vascular dementia) (Lewy-Body dementia) (Alzheimer's disease, AD) ( -amyloid peptide, A ) tau (tau protein) 1,2 1 2009 12 65 24510.63% 12 4.8% 3 65 2 17 3 貳 阿茲海默症流行病理學及盛行率 350 藥學雜誌第 110 冊 37
藥物科學 Pharmaceutical Sciences 2,3 65 2 1994-1996 65 13.8% 4 2009 65 15 3 (senile plaques) (neurofibrillary tangles) (nucleus basalis of Meynert) A tau (tau protein hyperphosphorylation) 參 藥物治療 ( 乙醯膽鹼酯酶抑制劑和 NMDA 受體拮抗劑 ) (acetylcholine neurosystem) NMDA (N-methyl-D-aspartate receptor antagonist) 5 肆 血管收縮素受體阻斷劑 (Angiotensin receptor blockers, ARBs) 6 ARBs (reninangiotensin system, RAS) 7 Takeda ARBs amyloid (cognitive impairment) 6 ARBs 8 1 表一阿茲海默症之症狀治療藥物特性 Donepezil Galantamine Rivastigmine Memantine AD AD AD AD CYP450 (CYP2D6 CYP3A4) (CYP2D6 CYP3A4) NMDA 5-10 mg 8-24 mg 6-12 mg 5-20 mg (bio-availability) 38 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.1
Donepezil Galantamine Rivastigmine Memantine 5 mg/day 8 mg/day 3 mg/day (1.5 mg ) 5 mg/day 5 10 mg/day 16 24 mg/day 6 12 mg/day 20 mg/day IIa IIa IIa IIa 伍 血管張力素受體阻斷劑與阿茲海默症的機轉 9 (Renin) (Angiotensinogen) 10 I (Angiotensin I) (Angiotesin converting enzyme, ACE) 8 II (Angiotensin II) Angiotensin II Ang II type 1 (AT 1 ) Ang II type 2 (AT 2 ) AT 1 AT 2 AT 2 ARBs AT 1 AT 2 10 Horiuchi AT 2 AT 2 receptor-interacting protein (ATIP) Src homology 2 domain-cantaining proteintyrosine phosphatase 1 (SHP-1) methyl methanesulphonate sensitive 2 (MMS2) inhibitor of DNA binding 1 (Id1) DNA Id ( ) 10 Horiuchi Takeda ARBs ( ) 11 9 圖一血管張力素的生合成過程 圖二 AT 2 促使 MMS2 活化而修復 DNA 10 藥學雜誌第 110 冊 39
藥物科學 Pharmaceutical Sciences 參考資料 : 圖三 ARBs 降低乙醯膽鹼 (ACh) 的釋放而 11 改善認知不良 陸 結論與討論 2010 Li (prospective cohort analysis) ARBs (ACEIs) ACEIs ARBs 8 ACEIs ARBs ARBs ACEIs ARBs ACEIs ARBs ACEIs 1. Blennow K, de Leon MJ, Zetterberg H: Alzheimer's disease. Lancet 2006; 368: 387-403. 2. Querfurth HW, LaFerla FM: Alzheimer's Disease. N Engl J Med 2010; 362: 329-44. 3. 2011 4 8 http://www.moi.gov.tw/stat/national.aspx 4. Lai CL, Liu CK, Lin RT, et al: Incidence and subtypes of dementia in Taiwan: Impact of Socio-Demographic Factors. Neurobiol Aging 1998; (Supp2): S139. 5. Press, D, Alexander M. Treatment of dementia. In: Up- ToDate, Wilterdink, JL (Ed), UpToDate, Waltham, MA, 2011. 6. Takeda S, Sato N, Takeuchi D, et al: Angiotensin Receptor Blocker Prevented -Amyloid Induced Cognitive Impairment Associated With Recovery of Neurovascular Coupling. Hypertension 2009; 54: 1345-52. 7. Park L, Anrather J, Forster C, et al.: A -induced vascular oxidative stress and attenuation of functional hyperemia in mouse somatosensory cortex. J Cereb Blood Flow Metab 2004; 24: 334-42. 8. Li NC, Lee A, Whitmer RA, et al:use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 2010; 340: b5465. 9. Gard PR: Cognitive-enhancing effects of angiotensin IV. BMC Neurosci 2008; 9: S15. 10. Horiuchi M, Mogi M, Iwai M: The angiotensin II type 2 receptor in the brain. J Renin Angiotensin Aldosterone Syst 2010; 11(1): 1-6. 11. Takeda S, Sato N, Ogihara T, et al: The renin-angiotensin system, hypertension and cognitive dysfunction in Alzheimer's disease: new therapeutic potential. Front Biosci 2008; 13: 2253-65. 40 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.1
The New Evolution of Therapeutic Drugs for Alzheimer s Disease Shu-Ting Lin 1, Li-Wei Chen 1, Yung-Chih Lin 1, Shin-Tarng Deng 2 Department of Pharmacy, Chang Gung Memorial Hospital, Keelung Branch 1 Department of Pharmacy, Chang Gung Medical Foundation, Linkou Branch 2 Abstract The elderly, is a social resource, you can learn a lot from the knowledge and history. However, the aging society also had another social problem, particularly dementia- Alzheimer's disease. Because of Taiwan's rapidly growing elderly population, the prevalence of dementia in older people also increased. Recent studies have shown that the prevalence of dementia in Taiwan, in the elderly over age 65 is about 2-4%. More than 65 years in Taiwan, the incidence of elderly people, about 13 per thousand people per year will become elderly dementia. Currently used to treat Alzheimer's disease into two main categories of drugs are acetylcholinesterase inhibitor and NMDA receptor antagonist. In addition there are other drugs under study, such as antioxidant drugs, antibodies and so on. The angiotensin receptor blockers in addition to lowering blood pressure reduced the incidence of vascular dementia, also to reduce the incidence of Alzheimer's disease and slow deterioration by some mechanisms, which will likely become a new choice as auxiliary therapy. 藥學雜誌第 110 冊 41