Parkinson's Disease
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Parkinson's Disease - Marcador
Parkinson's Disease - Detalles
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What is a progressive neurodegenerative disorder? | Parkinson's Disease |
What is Parkinson's diseases caused by? | By degeneration of substantia nigra in the midbrain, with irreversible loss of DA-containing neurons in the nigrostrial pathway. |
What part does dopamine play in the prevention of Parkinson's disease? | Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus ( ventral intermediate nucleus) |
The symptoms of Parkinson's disease result from what? | Loss of nigrostrial neurons and DA depletion. ACh predominates |
What is the symptomatic triad of Parkinson's disease? | Bradykinesia, rigidity and tremor |
What are the secondary manifestations of Parkinson's disease? | Defective posture and gait, mask-like face and sialorrhoea, dementia ( in some cases) |
What is the etiology of Parkinson's disease? | 1) Genetics: 2) Environmental Factors 3) Toxins 4) Drugs |
What is alpha-synuclein? | Deposited in dopaminergic neurons of substantia nigra with loss of pigmentation leading to the formation of Lewy bodies ( the pathological hallmark of PD) and dopaminergic cell death |
What is Lewy neurite? | Swollen nerve fibers that contain alpha-synuclein and other proteins which interfere with transmission of nerve signals and neuronal functions. |
Does dopamine pass the blood-brain barrier? | NO. Dopamine must be produced within the CNS in order to act in the striatum |
Briefly describe the biosynthesis and metabolsim of dopamine | Please see image attached |
What is the final inactive metabolite of dopamine? | Homovanillic acid by either MAO or COMT |
What are the clinical manifestations of Parkinson's disease? | Tremor- "Resting tremor Rigidity Bradykinesia |
What are the five dopamine receptor subtypes? | D1, D2 ( found in corpus striatum) D3, D4, and D5 |
What is the function of D1 and D5? | Activates adenlyl cylcase to produce cAMP |
What is the function of D2, D3 and D4? | Inhibits adenlyl cyclase to produce less cAMP |
Where is dopamine produced? | Cells in the PARS COMPACTA of the SUBSTANTIA NIGRA. |
What are the two pathways through which striatal information reaches Globus Pallidum Internal? | Direct Pathway ( excitatory) and Indirect Pathway ( inhibitory) |
Explain the mechanism behind the binding of dopamine to the D1 and D2 receptors | Will Discuss Via Google Meets |
What are the objectives of antiparkinsonian pharmacotherapy? | 1) Enhance DA-ergic activity 2) Reduce cholinergic activity |
What are examples of DA agonists? | Bromocriptine and cabergoline |
What are examples of drugs that inhibit the metabolism of dopamine? | Selegiline and rasagiline |
What is LEVODOPA? | Natural AA precursor of DA Crosses the BBB via L-amino acid transporter effective in treating symptoms of rigidity and bradykinesia seen in PD 1-3% only oral dose reaches the brain |
What are the adverse effects of L-DOPA? | Nausea, Vomiting; nearly 80% patients Postural Hypotension Cardiac Arrhythmias Anxiety, Agitation, Hallucinations/ mood changes |
What is the main adverse central adverse reaction of L-dopa? | Athetosis: a condition where the patient experience slow, convulated, involuntary and writhing movements of the hands, fingers, feet and toes |
What is the wearing- off phenomenon? | Increasingly shortened benefit period following each dose of l-dopa due to l-dopa's short half life. |
What is L-Dopa Honeymoon? | Early phase of treatment (lasts 5-6 years typically) |
What is On-Off Fluctuations? | Characterized by sudden, unpredictable shifts of mobility between undertreated and treated states- sudden, unpredictable and very difficult to treat. |
What are examples of COMT inhibitors? | Entacapone and tolcapone |
What are examples of dopamine agonists? | Ropinirole,pramipexole,rotigotine |
What are examples of MAO-B inhibitors? | Selegiline, rasagiline |
What are L-Dopa Interactions? | Avoid high protein meals; AA's compete with L-dopa for entry to the brain. Take on empty stomach or reduce dietary protein. Vitamin B6: metabolizes L-dopa Hypertensive crisis if MAOIs are given concomitantly L-dopa should not be prescribed to treat the extrapyramidal effects of antipsychotics since l-dopa enhances dopamine and its interaction with D2 receptors in the mesolimbic and mesocortical pathways. Antipsychotics block these receptors and their efficacy could be compromised |
What dopamine agonists are ergot-derivatives? | Bromocriptine and Carbergoline |
What dopamine agonists are non-ergot-derivatives? | Pramipexole and Ropinirole and Apomorphine |
What is the difference between dopamine agonists and l-dopa? | 1) They act directly at dopamine receptors, therefore, it does not need metabolic conversion to an active moiety as in the case of L-DOPA 2) They do not undergo oxidation and thus avoid the generation of free radicals that may contribute to neuronal degeneration 3) Their longer half-life causes fewer motor complications as they provide continuous stimulation of striatal dopamine receptors and reduce frequency of dosing required to maintain adequate drug levels 4)DAs do not require carrier-mediated transport for GI absorption or entry into the BBB; thus dietary restrictions are not required 5) DAs usage is associated with more hallucinations, somnolence, and edema than with levodopa therapy. |
What is the triple combination used for patients with end of dose, wearing off? What is the major risk ? | Carbidopa, L-Dopa and Entacapone CVS events |
What is the side effect of tolcapone? | Hepatatoxicity |
What is Bromocriptine? | D2- receptor agonist, but weak alpha-adrenoceptor anatagonist. Commonly used with l-dopa started at low doses at night, titrating up according to clinical response |
What is Bromocriptine also used for? | Prolactin-secreting adenomas,amenorrhea/galactorrhea to hyperprolactinemia, to stop lactation, acromegaly |
What are the adverse reactions of bromocriptine? | Nausea, vomitting which may be prevented by domperidone, postural hypotension |
What is cabergoline | Better than bromocriptine Longer half life. Used once or twice a week Alleviates night -time problems in PD due to lack of l-dopa |
What is pramipexole? | Non-ergot D2 and D3 receptor agonist more effective against tremors Allows dose of LD to be reduced and smoothens out fluctuations |
What is ropinirole? | New non-ergot direct D2 receptor agonist metabolized by CyP450 so clearance may be reduced if used with simultaneous metabolisers |
What are the adverse effects of dopamine agonists? | Drowsiness, nausea, vomiting, dry mouth, dizziness, leg swelling, orthostatic hypotension. sleepiness compulsive behaviors- shopping, binge eating, gambling, sexual activities |
What is apomorphine? | Used in emergency cases "rescue" medication |
What is amantadine? | Antiviral agent used for influenzea |
What are central antimuscarinic drugs? | Shows modest improvement in tremor, rigidity and sialorrhea and muscular stiffness |