Razi Journal of Medical Sciences

fa تداخلات دارویی در کلینیک درمانی مبتلایان آلزایمری Drug Interactions in the Clinical Treatment of Alzheimer Patients فارماکولوژی Pharmacology مروري review article <div style="text-align: justify;">بیماری آلزایمر (AD) یک اختلال عصبی پیش‌رونده است که به تدریج منجر به کاهش حافظه و سایر عملکردهای فکری، تغییر در شخصیت و اختلالات رفتاری می‌شود. با افزایش سریع جمعیت در جهان توسعه یافته، زوال عقل ناشی از بیماری آلزایمر در حال تبدیل شدن به یک مشکل اجتماعی و اقتصادی رو به رشد است. در اروپا، تعداد تخمین زده شده بیماران مبتلا به زوال عقل بیش از شش میلیون نفر است و بیش از نیمی از این بیماران به بیماری آلزایمر مبتلا هستند. علی‌رغم پیشرفت‌های عمده در درک ما از پاتوژنز اساسی، اساس بیولوژیکی AD هنوز به‌طور کامل شناخته نشده است. از آنجایی که شکست ترکیباتی که آمیلوئید بتا را در کارآزمایی‌های بالینی هدف قرار می‌دهند به‌طور مکرر گزارش می‌شود، فرضیه آبشار آمیلوئید غالب از نظر علیت آن مورد تردید قرار گرفته است. سایر علل احتمالی نیز در حال ظهور هستند، در حالی که داروهای جدید در حال حاضر به فوریت مورد نیاز است. مواد دارویی ثبت شده برای درمان بیماری آلزایمر بررسی می‌شود. آن‌ها به گروهی از مهارکننده‌های کولین استراز (دونپزیل، ریواستیگمین، گالانتامین، تاکرین) یا آنتاگونیست‌های گیرنده‌های NMDA (ممانتین) تعلق دارند. برخی از محبوب‌ترین مکمل‌های غذایی، مشتق شده از گیاهان یا حیوانات نیز ارائه شده است. علاوه‌بر این، امیدوارکننده‌ترین مواد دارویی مصنوعی و بیولوژیکی در حال توسعه را ارائه می‌کنیم که تحت فاز II یا فاز III آزمایش‌های بالینی قرار می‌گیرند. تداخلات احتمالی این داروها با سایر داروها و مکمل‌های در کلینیک و بالین مورد بررسی قرار گرفت، به‌طوری که عوارض ناخواسته‌ای ناشی از آن‌ها در سیر درمان بیمار تأثیر معناداری به همراه دارد.</div> <div style="text-align: justify;">Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that gradually leads to decline in memory and other intellectual functions, changes in personality and behavioral disturbances. Alois Alzheimer, for the first time, recognized that the double layer of Neurofibrillary tangles and senile plaques are key Neuropathological signs of Alzheimer's disease (5). These two degenerative layers are outside the nerve cells and around the cerebral vessels, which have Amyloid deposits in the center and dystrophic neurites and dendrites in the periphery, and their astrocytes and microglia are also activated (6). Their Amyloid core is mainly beta Amyloid peptide (Aβ), in transgenic animal models of Alzheimer's disease, it has been shown that intracellular Aβ affects synapse function and consequently learning and memory (7). Despite major progress made in our understanding of the underlying pathogenesis, the biological basis of AD is still not fully understood. As failures of compounds targeting Amyloid beta in clinical trials are repeatedly reported, the prevailing Amyloid cascade hypothesis is being questioned in terms of its causality. Other probable etiologies are also emerging, while new drugs are already urgently needed. Registered drug substances for treatment of Alzheimer’s disease are reviewed. They belong to the group of cholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine, Tacrine or NMDA receptor antagonists (Memantine). They have also produced Nitromantannin, a molecule of Memantannin supplemented with a Nitro group. MW108 is a recently synthesized compound that acts as a p38 α MAP kinase inhibitor. And they can restore the basic function of the synapse and thus reduce the progression of cognitive dysfunction in Alzheimer's disease (34). In the last decade, two types of recombinant biological substances active in the production cycle of drugs for Alzheimer's patients have produced Monoclonal Antibodies that are produced against different parts of Amyloid beta, which prevent the formation or formation of Amyloid protein or tau. In addition, the most promising synthetic and biological drugs in development that are undergoing phase II or phase III clinical trials are presented. Some of the most popular dietary supplements derived from plants or animals include: Vitamin E in preventing the progression of Alzheimer's disease, the opinion of experts is controversial. (25).  Ginkgo biloba leaf extract has been used for decades to improve memory and learning ability, and possibly to improve circulation. Despite the recognition of various mechanisms such as: release of nitric oxide (NO), endothelium relaxing factor (EDRF), prostaglandins (PGI2), antioxidant activity, in clinical studies there are still questions about the positive therapeutic effects of ginkgo extract in Alzheimer's disease. Epigallocatechin Gallate and resveratrol, the structure of both of these compounds, which can be pathological factors in the development of Alzheimer's disease, have close similarities. Epigallocatechin Gallate is thought to reduce the formation of toxic Amyloid oligomers. )27) Docosahexaenoic acid is found in fish oil. DHA is the most common Omega-3 Polyunsaturated fatty acid in the human brain. Studies show that they did not have a significant effect in the treatment of this disease, but in one study it was shown that if another additive called Eicosapentaenoic acid. (EPA) is added to DHA, this medicinal compound will have useful and significant effects in the early stages of Alzheimer's patients in its prevention and treatment. Curcumin is an effective substance found in turmeric root. It has an Anti-Inflammatory and preventive effect in preventing the development of colon cancer. Several hypotheses have been proposed regarding the action of Curcumin, that macrophages activated by Curcumin remove Amyloid plaques faster and to a greater extent. Curcumin is also thought to reduce inflammatory processes associated with glial cells and act as a systemic Anti-Inflammatory by inhibiting COX-2 Cyclooxygenase and reducing the expression of Pro-Inflammatory Cytokines, Epigallocatechin Gallate is also thought to reduce the formation of toxic Amyloid oligomers. (32). Drug interactions with drugs and drug interactions with supplements and food are very common in these patients and are associated with high risk. Extensive studies on drug interactions have shown that when the number of drugs used reaches 2, there is at least a 13% chance of unwanted side effects, or when it reaches 3 or more than 8, about 100% of patients will experience an unwanted drug side effects. Cholinesterase inhibitors including (Rivastigmin, Donezepil, Galantamine) prevent the hydrolysis of Acetylcholine. The increased effect of Acetylcholine causes bronchial constriction, increased secretions and bronchial spasm. They can also produce a vagotonic effect on the sinus and vestibular glands, therefore, treatment with cholinesterase inhibitors should be considered in patients with cardiac and respiratory dysfunction, a history of asthma or obstructive lung disease, peptic ulcer, Parkinson's disease, and seizure and tremor disorders. and patients with previous bradycardia or underlying cardiac conduction disorders should be treated with extreme caution (38-40-43-44-47). Before performing any imaging procedure that may be directly or indirectly injected into the spine, injections (Metrizamide, Iopamidol, Iohexol) can sometimes cause seizures, and if the patient is also taking drugs (Galantamine, Donepezil, Rivastigmine) at the same time uses, the risk may increase serious complications for the patient (55-57). Immunosuppressive drugs  (Ozanimod and Siponimod) used to treat multiple sclerosis (RMS) with cholinesterase inhibitors such as (Galantamine, Donepezil, Rivastigmine) can increase the risk of irregular heart rhythms, which may be serious and potentially life-threatening. (60). Supplements containing (Ginkgo Biloba) with antibiotics such as (Ciprofloxacin and Levofloxacin, Ofloxacin) can cause seizures and danger. Taking Ginkgo Biloba together with Aspirin and warfarin can increase the risk of bleeding, and in patients with chronic hypertension, it is associated with an increased risk of unwanted complications. Also, with (Galantamine Donepezil, Rivastigmin) they cause an increased risk of seizures (61, 62).  Also, supplements containing Epigallocatehin Gallate, such as green tea, can interact with Monoamine Oxidase inhibitors, oral contraceptives, Cimetidine, Verapamil, Fluconazole, Ciprofloxacin, Norfloxacin, and Enoxaparin, and also reduce the effects of Warfarin. Resveratrol, which is a Polyphenolic compound of Phthalaxin and its sources include red grapes, red raisins, red wine, red vinegar, raspberries, dark chocolate, etc. Its side effects during pregnancy, if taken as a supplement, can cause major problems in the fetal pancreas. The latest findings and results from Neuro Medicine research centers show that currently, according to the mechanism of action of these monoclonal antibody drugs, there is no expectation for a complete cure, and the reduction of Amyloid beta platelets significantly affects prevention and reduction. Cognitive, functional and behavioral abilities are not affected in Alzheimer patients. The possible interactions of these drugs with other drugs and supplements were investigated in the clinic, so that the unwanted side effects caused by them have a significant effect on the patient's treatment. According to the latest findings as well as the results of Neuro Medicine research centers, it can be concluded that currently, due to the mechanism of action of existing drugs and the use of various supplements, there is no expectation for a complete treatment of Alzheimer's disease, and their prescription can probably be Prevention and treatment or reduction of unwanted side effects are effective. Finding new drugs that can significantly reduce amyloid-beta platelets or affect the cognitive, functional and behavioral abilities of Alzheimer's patients is one of the important goals of researchers.</div> آلزایمر, مهارکننده های کولین استراز, EGCG, پپتید بتا آمیلوئید, رسوراترول, کورکومین, ممانتین, مونوکلونال Abs,MW108 Alzheimer, Cholinesterase inhibitors, EGCG, Amyloid beta peptide, Resveratrol, Curcumin, Memantine, Monoclonal Abs,MW108 280 295 http://rjms.iums.ac.ir/browse.php?a_code=A-10-5593-1&slc_lang=fa&sid=1 Mohammed Mehdi Saghafi محمد مهدی ثقفی Saghafi.mm@iums.ac.ir 3900319475328460074833 0000000344691408 Yes (mag. Phar. PhD), Member of the Scientific Faculty, Pharmaceutical Care Department, Firozabadi Hospital, Iran University of Medical Sciences, Tehran, Iran بخش مراقبت‌های دارویی، بیمارستان فیروزآبادی، دانشگاه علوم پزشکی ایران، تهران، ایران