Estimation of Serum Levels of Alanine Transaminase, Aspartate Transaminase, Alkaline Phosphatase in Donepezil Therapy of Alzheimer’s Patients in a Tertiary Care Hospital

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells. This causes problems with movement (called ataxis), or mental functioning (called dementia). Alzheimer’s is a chronic neurodegenerative disease of the brain that causes problems with memory, thinking and behavior. It is not a normal part of aging. The cause of Alzheimer’s disease is poorly understood. The risk factors include a history of head injuries, depression or hypertension. The medications used to treat Alzheimer’s disease are acetyl cholinesterase inhibitors and NMDA receptor antagonists. Donepezil is a cholinesterase inhibitor. It works by increasing the amount of acetylcholine in the brain, which may help to reduce the symptoms of dementia in patients with Alzheimer’s disease. The administration of Donepezil causes marked elevation in the serum liver enzymes like alanine transaminase, aspartate transaminase, alkaline phosphates. Mathew George 1 , Lincy Joseph 2 , Jeenu Joseph 3 , Sneha Aney Jose 4 * 1. Department of Pharmacology, Pushpagiri College of Pharmacy, Thiruvalla, Kerala, India 2. Department of Pharmaceutical Chemistry, Pushpagiri College of Pharmacy, Thiruvalla, Kerala, India 3. Department of Pharmacognosy, Pushpagiri College of Pharmacy, Thiruvalla, Kerala, India 4. Department of Pharmacy Practice, Pushpagiri College of Pharmacy Thiruvalla, Kerala, India Submission: 7 July 2017 Accepted: 12 July 2017 Published: 25 July 2017 www.ijsrm.humanjournals.com Citation: Mathew George et al. Ijsrm.Human, 2017; Vol. 7 (1): 128-137. 129 INTRODUCTION Alzheimer's is a type of dementia that causes problems with memory, thinking, and behavior. Symptoms usually develop slowly and get worse over time becoming severe enough to interfere with daily tasks. Alzheimer’s disease accounts for 60-80 percent of dementia cases. Alzheimer’s is not a normal part of aging, although the greatest known risk factor is increasing age and the majority of people with Alzheimer’s are 65 and older [1] . The most common early symptom of Alzheimer’s is difficulty in remembering newly learned information. Because Alzheimer’s changes typically begin in the part of brain that affects learning. As Alzheimer’s advances through the brain it leads to increasingly severe symptoms, including disorientation, mood and behavior changes, deepening confusion about events, time and places; unfounded suspicions about family, friends, and professional caregivers; more serious memory loss and behavior changes; and difficulty speaking, swallowing and walking [2] .  There are two types of medications used to treat Alzheimer's disease: Acetyl cholinesterase inhibitors and NMDA receptor antagonists. Cholinesterase inhibitors are a type of drug that boosts the amount of acetylcholine available to nerve cells by preventing its breakdown in the brain. The generic names for the cholinesterase inhibitors are donepezil, rivastigmine and galantamine. o Donepezil was originally patented as the brand name Aricept, but is more widely available now as just generic Donepezil [3] . The NMDA receptor antagonist is memantine. It was originally patented as Ebixa and is now also available as generic memantine. Other UK brand names for memantine include Maruxa and Nemdatine. Donepezil is used to treat confusion (dementia) related to Alzheimer’s Disease. It does not cure Alzheimer’s disease, but it may improve memory, awareness, and the ability to function. This medication is an enzyme blocker that works by restoring the balance of natural substance (neurotransmitter) in the brain [4] . Alzheimer disease is associated with a cholinergic deficiency in the cerebral cortex, and the increase in concentration of acetylcholine with acetyl cholinesterase inhibition is associated with improvement in cognitive function in patients with Alzheimer dementia. Donepezil has www.ijsrm.humanjournals.com Citation: Mathew George et al. Ijsrm.Human, 2017; Vol. 7 (1): 128-137. 130 selective activity for acetyl cholinesterase in the central nervous system with little effect on the enzyme in peripheral tissue. Donepezil was approved for use in the United States in 1996 and is currently the most commonly used acetyl cholinesterase inhibitor used for management of Alzheimer disease. Donepezil is available as regular tablets of 5 and 10 (and recently 23 mg) and as orally disintegrating tablets of 5 and 10 mg in generic forms and under the brand name Aricept. Donepezil is also available as a solution of 1 mg/mL for oral administration. The usual maintenance dosage is 5 to 10 mg once daily. Patients who tolerate the 10 mg daily dose may benefit from a higher dose of 23 mg daily [5] . Common side effects include diarrhea, nausea, vomiting, dizziness, fatigue, insomnia, vivid dreams, anxiety, restlessness, blurred vision, dry mouth and pruritus, symptoms common to cholinergic stimulation. Donepezil binds and inactivates reversibly the cholinesterase, thus inhibiting hydrolysis of acetylcholine. This results in increased acetylcholine concentrations at cholinergic synapses [6] . Donepezil marketed under the trade name Aricept is a medication used in the palliative treatment of Alzheimer’s disease. Donepezil is used to improve cognition and behavior of people with Alzheimer’s but does not slow the progression of or cure the disease [7] . Donepezil binds and reversibly inactivates the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This results in an increased acetylcholine concentrations at cholinergic synapses [8] . MATERIALS AND METHODS Study Design: A prospective experimental study. Study Population: Patient diagnosed with Alzheimer's. Study Setting: Neurology Department Pushpagiri Medical College Hospital, Thiruvalla. IEC NO: PCP/E3/01A/14/2016 Study Period: 6 months