Parkinson's Disease (part one)
Parkinson's Disease (part one) 333
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This 3 page Class Notes was uploaded by Sarah Kincaid on Monday October 10, 2016. The Class Notes belongs to 333 at 1 MDSS-SGSLM-Langley AFB Advanced Education in General Dentistry 12 Months taught by Caine in Fall 2016. Since its upload, it has received 25 views. For similar materials see Drugs and Behavior in Psychology at 1 MDSS-SGSLM-Langley AFB Advanced Education in General Dentistry 12 Months.
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Date Created: 10/10/16
Parkinson’s Disease (PD) *Exam 1: Tuesday October 18 (one class more class on PD before the exam)* Material covered: OL 1-4 (I will also be posting a comprehensive study guide that ties the information together coherently) What we know about PD and why its important - Brain mechanisms of the disorder (neuropathology) - Drug actions that treat disorder (how drug works to treat the disease) - Start-up mechanism won’t work in PD – need dopamine - PD is very prevalent – you will know at least one person with PD in your life - This is unusual bc for most diseases we do not know why the drug necessarily works or how to map out the neuropathology (e.g. anti-anxiety meds, anti-schizophrenic meds) Motor control of body uses the pathway of substantia nigra to dorsal striatum - 95% of brain’s dopamine is in striatum - In PD, this pathway degenerates - Visible in PET scans – trace a single neuron (dopamine) and count transporters in the dorsal striatum (sending end) - If only 10,000 or 20,000 transporters (reuptake sites) = patient has PD - Visible after death in stained horizontal brain slices where you count # of dark spots/dots (cell nuclei) in the substantia nigra (receiving end) - No dark spots = cell degenerated - 20,000 dots = healthy - 1,000/2,000/3,000 dots = PD (unhealthy) Note: VTA to ventral striatum is the pathway used for Adderall, too much cocaine/crystal meth Most important symptom of PD: akinesia (loss/lack of motor function) Other symptoms of PD (of decreasing importance) - poor posture (esp. in later stages) - rigidity (if they are sitting and doctor tries to turn their head, it does not turn much) - resting tremors: shaking when they are not using their hands/feet (unimportant) l. dopa - Restores patients to near normal movement in the “honeymoon” phase - Tx: voluntary movement - Side effect: involuntary movement - Problem: Over time (after several years of taking it - Tx decrease: ED of Tx increases (tolerance); shifts right 50 - Side effects increase: ED of 50de effects decreases (sensitization); shifts left Sinemet Parkinson’s Disease (PD) - l.dopa (precursor for dopamine) - carbidopa (enzyme inhibitor for AAAD, aromatic L-amino acid decarboxylase) - Problem: l. dopa is converted to dopamine which is metabolized quickly (mouth, stomach, mostly intestines) before it even reaches the brain and dopamine cannot cross BBB - Pharmacokinetics (pK) - carbidopa inhibits DDC from converting l. dopa into dopamine and from being metabolized elsewhere in the body - Pharmacodynamics (pD) - carbidopa cannot pass BBB, but l.dopa can, so l.dopa crosses BBB and the is converted into dopamine If you were to insert PD medicine into brain where and what? - Put it in the dorsal striatum 1. l.dopa 2. direct dopamine D2 agonist 3. pure dopamine (we cannot insert meds directly into dorsal striatum yet) Most Common Meds for PD 1. Sinemet 2. Direct dopamine D2 agonist Why can’t we use a dopamine reuptake inhibitor (same as Alzheimer’s) - Don’t have enough dopamine - Not enough reuptake sites either - Use precursor, direct agonist, or dopamine (eventually) What causes idiopathic PD? - Idiopathic = w/o known cause - 99.9% of cases - genes might increase or decrease risk for PD but don’t cause it - certain genes are more likely to increase risk or protect you from PD when you are exposed (manganese, for example) in environment - genes and environmental factors interact!!! Encephalitis-caused PD - 0.01% cases - Brain regions infected: dorsal striatum & cells in substantia nigra - Rare - Move: Awakening Familial PD - 2 confirmed cases (early onset PD w/ the gene that caused it) - Extremely rare PD Stats - 1 in 1,000 out of everyone in world - Over 60 or 70 y. o., 1 in 100 - 1 in 40 chance for you to get it in your liftetime Major Neurodegenerative Diseases Parkinson’s Disease (PD) 1. Parkinson’s 2. Alzheimer’s 3. Huntington’s Review of old material - Hydrocodone & oxycodone (95% of prescribed drugs) - Hydromorphone & oxymorphone (~5%) - 19% of HS seniors have taken opioid w/o opioid Rx (he keeps changing this number, but just know that between 10-20% of HS seniors have done opioids w/o the Rx) - 50% chance you will get Alzheimer’s Disease
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