Parkinson's And Alzheimer's Diseases PDF

Parkinson’s and Alzheimer’s Diseases By: Dr. Maisa NABULSI Wednesday, April 17, 2024  Cells in certain parts in the brain ( basal ganglia) became damaged. We do not know why?? Only up to 15% of cases is genetic, the rest is idiopathic Pakinson’s: Etiology ...

Parkinson’s and Alzheimer’s Diseases By: Dr. Maisa NABULSI Wednesday, April 17, 2024  Cells in certain parts in the brain ( basal ganglia) became damaged. We do not know why?? Only up to 15% of cases is genetic, the rest is idiopathic Pakinson’s: Etiology  Drugs in Parkinson’s Dse increase Dopamine signaling Tx: 1. Levodopa & Carbidopa Tx: 1. Levodopa & Carbidopa N,V, and hypotension Tx: 1. Levodopa & Carbidopa Tx: 1. Levodopa & Carbidopa 1. about 20% is adequate ( levodopa to dopamine). 2. therapeutic response to levodopa is consis tent, and the patient rarely complains that the drug effects “wear off 3. With time, no. neurons decreases, and fewer cells are capable of converting exogenously administered levodopa to dopamine. Consequently, motor control fluctuation develops. Unfortunately, with time, Relief provided by levodopa is only symptomatic, and it lasts only while the drug is present in the body. ++ carbidopa lowers the dose of levodopa needed by four- to fivefold decreases the severity of the side effects Tx: 1. Levodopa & Carbidopa Tx: 1. Levodopa & Carbidopa ✔ severity of symptoms for the first few years of treatment. ✔ decline in response after 3-4 yrs. ✔ Withdrawal from the drug must be gradual.  PK: Levodopa 1. Absorption: rapidly from the small intestine (when empty of food). ✔ short half-life (1 to 2 hours), which causes fluctuations in plasma concentration. ✔ Ingestion of meals, particularly if high in protein, interferes with the transport of levodopa into the CNS. Thus, levodopa should be taken on an empty stomach, typically 30 minutes before a meal.  Adverse effects Peripheral effects CNS effects 1.Visual and auditory hallucinations and abnormal involuntary movements (dyskinesias) may occur. 2.Mood changes, depression & anxiety.  Interactions: 1. pyridoxine (B6) = diminishes effectiveness. 2. Concomitant administration of levodopa and non-selective MAOIs can produce a hypertensive crisis caused by enhanced catecholamine production. 3. Cardiac patients should be carefully monitored for the possible development of arrhythmias.. Tx: 2 Amantadine ✔ less efficacious than levodopa, and tolerance develops more readily. However, amantadine has fewer side effects. Tx: 3. Dopamine agonists ✔ Dopamine agonists may delay the need to use levodopa in early Parkinson’s disease and may decrease the dose of levodopa in advanced Parkinson’s disease. ✔ Hallucinations, insomnia, dizziness, constipation, and orthostatic hypotension are among the more distressing side effects of these drugs Dopamine agonists: Adverse effects  Drugs in Parkinson’s Dse Inhibit Dopamine degradation Tx: 2. Selegiline Selective MAOI type B inhibit monoamine oxidase (MAO) type B. NO MAOI type A (metabolizes norepinephrine and serotonin) unless given above recommended doses, where it loses its selectivity. When selegiline is administered with levodopa, it enhances the actions of levodopa and substantially reduces the required dose. Metabolites: methamphetamine & amphetamine (CNS stimulants === produce insomnia if the drug is administered later than midafternoon. Tx: 3. COMT inhibitors Pharmacokinetics: ✔ Oral absorption occurs readily & not influenced by food. ✔ They are extensively bound to plasma albumin, with a limited volume of distribution. ✔ Tolcapone has a relatively long duration of action (probably due to its affinity for the enzyme) compared to entacapone, which requires more frequent dosing. ✔ Both drugs are extensively metabolized and eliminated in feces and urine. ✔ Dose adjustments?/??. ✔ S/E: fulminating hepatic necrosis is associated with tolcapone use. ✔ Entacapone does not exhibit this toxicity and has largely replaced tolcapone Miscellaneous…… Quick Recap…. Alzheimer’s Disease:  Fragment is Not soluble and creates a monomer called amyloid beta. Sticky and form plaques either between neurons and may start immune resposnse. Areas of brain affected ……  Hippocampus is a cognitive map!!!!!!!!!!! Learning and storing information referring to portions of space, in the form of cognitive maps. Alzheimer’s Disease: Symptoms  Is their a treatment?????? Numerous studies have linked the progressive loss of cholinergic neurons and, presumably, cholinergic transmission within the cortex to the memory loss that is a hallmark symptom of Alzheimer’s disease. ❖ AChE inhibitors within the CNS will improve cholinergic transmission, at least at those neurons that are still functioning. Aim of Treatment: Provide a modest reduction in the Rate of Loss of cognitive Functioning  Available Drugs: ✔ Reversible AChE inhibitors approved for the treatment of mild to moderate Alzheimer’s disease include: 1. Donepezil 2. Galantamine 3. Rivastigmine ✔ All of them have some selectivity for AChE in the CNS, as compared to the periphery. ✔ Galantamine may also augment the action of acetylcholine at nicotinic receptors in the CNS. Possible Side Effects NMDA receptor antagonist Memantine is an NMDA receptor antagonist indicated for moderate to severe Alzheimer’s disease. It acts by blocking the NMDA receptor and limiting Ca2+ influx into the neuron, such that toxic intracellular levels are not achieved. Memantine is well tolerated, with few dose-dependent adverse events. Expected side effects, such as confusion, agitation, and restlessness. Is often given in combination with an AChE inhibitor.