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23 Cards in this Set
- Front
- Back
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Causes of Parkinsons
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1) Idiopathic 2) Infections 3) trauma 4) Drugs 5) Endocrine- Wilsons Dz- alatered copper metabolism
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Drug induced parkinsons
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1 )Neuroleptics 2) Metoclclopramide 3) Reserpine 4) Carbamazepine 5) MPTP- Neurotoxin- 1MPP- toxic metbaolite
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4 cardinal features of parkinsons
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1) Tremor 2 )Rigidity 3) Bradykinesia and akinesia 4) Disorders of gait and posture
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Surgical therapies
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1) Pallidotomy, thalamotomy- -remove globus pallidus, VL thalamus, 2) Deep brain stimualtion 3) Fetal nigral transplatnaiton 4) Future- trophic factors, genetically modified cll implants
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Pathophysiology of parinsons .
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ddestruction of dopaminergic neurons in substantia nigra-> reduction of DA in straitum-> Nirostriatal pathway- [art of extrapyramidal system- fegulates fine mvmt, msucle tone, mosture. turns uncoordinated-> finely coordinated
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Direct and Indirect pw of parkisnons
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Direct pathway – GABA released to GPI & SNpr -> excite motor cortex, promote movement
Indirect pathway – GABA released to GPE & STN -> glutamate released to GPI & SNpr -> inhibit movement |
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Levodopa- MOA
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MOA: Pro-drug converted to dopamine-> interacts with D2 in the striatum and in the presynpatic terminals of dopaminergic nigrostraital axons
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Levodopa-Side effects
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Anorexia and NV, tachycardia, postural hypotension, hallucinations, anxiety , dysinesia, orofacial tics (take on empty stomach) , tolerance gradually increases, (Drug holiday not rec. due to withdrawal symptons)
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Levodopa- Fluctuations in reponse
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a) Weaning off effect or end-of-dose akinesia. b) On-off phenomenom- fluctuations may be decr. by taking meds more freq. in smaller doses . End of dose weaning off decr with COMT inhibitors or Stalevo. ABRUBT WITHDRAWAL: severe AKINESIA.
Recommended for advanced parkinsons. |
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Carbidopa/Levodopa (Sinemet)- benefits
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MOST EFFECTIVE- Slower onset, longer duration. Controlled release- Sinemet CR, 1) Decreases levodopa dose 75%, NV much less frequent, less likelihood of tachycrdia. greater efficacy wtih smoother control. Sinemet CR- less fluctuation. Pyroxidine -> increases L-Dopa metabolism
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Carbidopa/Levodopa (Sinemet)-Side effects, and drug intxns
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Dyskinesia and psychiatric distrubances develop earlier and may be more severe. 1) Start with low doses and gradually incr- best on empty stomach. Caution: peptic ulcer, cardiac disease, open angle glaucoma- MYDRIASIS. Contraindications- angle closure glaucoma, psychosis, malignant melanoma. Drug Intxn: Pyridoxine- incr L Dopa metabolism. Non selective MAO inhibitors-> Hypertensive Crisis
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Bromocriptine-MOA
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MOA: to tx hyperprolaactinemia. Binds D2-R & decr Prolactin release in pituitary. (PD: Strong Agonist at D-2).
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Bromocriptine-Side effects
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Erythromelalgia (red tender edematous lower extremities, confusion, hallucinations, delusions, nightmares esp in older patients, Dyskinseases are less than levodopa. Orthostatic hypotension, Anorexia, NV, constiaption
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Pramipexole and Ropinirole- MOA and pharmacokinetics
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D-2 R agonists. Prami- unchanged in urine. ropic is metabolized by CYP1A2- drugs may alter metabolism.
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Pramipexole and Ropinirole- side effects
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Sudden sleep attacks, during daytime- restless leg syndrome. & Nausea, fatigue, hallucinations, dizziness, confusion, postural hypotension
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Selegiline- MOA
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MOA: Type A- norepinephrine and serotonin. Type b- dopamine- brain. MOA: selective MAO-B inhibitor- irreversibly inhibitor- breakdown of DA. Neuroprotective and ANTIAPOPTOIC effects. use alone for early disease
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Selegiline- Side effects
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Dyskineaseia, mental distrubrances (confusion, hallucinations), insominia, anxiety, nausea, hypotension. Drug intxns: tricyclic antidepressants- SSRI's- incr risk of serotonin syndrome-
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Tolcapone - MOA
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MOA: selective inhibitor of COMT- blocks conversion of levodopa to 3-O Methyl Dopa- L Dopa increases
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Tolcapone - side effects
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hepatotoxicity, monitor liver enzymes, ND, hypotension, orthostatic hypotension, vivid treams, hallucinations.
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Amantadine- MOA
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antiviral drug- type A. Increases dopamine release from neurons. blocks Dopamine reuptake. Blocks NMDA Glutamate receptor.
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Amantidine- Side effects
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-'Amanda is a prostitute- wears fishnets- Not My day- NMDA glutamate receptor)- vasospastic -'fishnet' appearance- reddish bluish discoloration in legs and arms. Edema, orthostatic hypotension.
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Trihexyphenidyl, BENztropine mesylate - MOA
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MOA: blocks central MR-1R, decr cholinergic activty from straitoal neurons 'Ben and Trihexy are not cool, block muscarinic
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Trihexyphenidyl, BENztropine mesylate - side effects
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CNS: ANTISLUD -> (not wet)- > dry mouth, cycloplegia, constipation, urinary retension. drowsiness, confusion, delirium. tremor and rigidity are improved. bradykinesia lass so. YOUNGER PATIENTS w disease and pts with drug induced parkinsonism
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