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69 Cards in this Set
- Front
- Back
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What are drug induced Parkinsonism:
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Neuroleptics, metoclopramide, reserpine, carbamazepine, MPTP
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Ex. of Nueropletpics, metoclopromide, reserpine, carbamazapine, MPTP
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neuroleptics: haloperidol
Metoclopromide: DA antag Reserpine: Depletes DA, NE Carbamazepine: Antiepileptic MPTP: neurotoxin; analog of Meperidine |
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Cardinal Features of Park
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Tremor
Rigidity Bradykinesia/akinesia disorders of gait and posture |
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Top two surgical therapies for parks
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Thalamotomy, pallidotomy
(remove gp and VL thalamus) Fetal nigral transplantation |
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L Dopa get rapidly absorbed from the gut with what type of transport
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Active
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The acid Ph effect absorbtion in what way and what AA competes with its binding site
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decreases
Leucine |
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Does L-dopa go through extensive metabolism and which enzyme is responsible for this
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dopamine decarboxylase
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What are the major metabolites
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DOPAC and HVA
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L- DOPA MOA
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improve parkinsonism
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L-Dopa side effects
GI/ CV |
GI: Anorexia
CV: postural hyptoension tach Tollerance gradually |
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Side effects of L-DOPA are
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GI, CV, Abnormal involuntary movements, behavioral distrubances, flunctuations in response
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LDopa SE: GI
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NV
action of DA on chemoreceptor trigger zone (CTZ). Tolerance gradually increased Carbidopa decreases incidence |
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LDopa SE: CV
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tachycardia, postural hypotension
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L Dopa SE: involuntary movements
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Oralfacial tics: head bobbing and jerking
Dose related: decrease dose and the SE will go away. Carbidopa increases incidence Tolerance does not develop: Dyskinesisas disappear if dosage decrease |
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L Dopa SE: behavior disturbances
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Depression, anxiety, hallucinations
Gets worse with carbidopa |
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L Dopa SE: Flunctuations in response
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Wearing off phenomenon: severe akinesia when you come off
on/off phenomenon: sudden dyskenisia, diet may affect May result from alteration of DA-R and post-R changes to plasma levodopa level Fluctuations may be decreased by taking medication more freq. in smaller doses and prolonged release |
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How can you decrease end of dose wearing off effect
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give COMT inhibitors, a combo of entacapone with 3 different doses of L-Dopa/caridopa
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Why is L-Dopa reserved for advanced Park
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because your best results are obtained in first 3 to 4 years of treatment. After that refractoriness may develop due to disease progression or increase SE due to drug-induced supersensitivity.
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Abrupt Withdrawal of L-dopa
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severe akinesia
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L-dopa + carbidopa=
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Sinemet
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L Dopa SE: Flunctuations in response
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Wearing off phenomenon: severe akinesia when you come off
on/off phenomenon: sudden dyskenisia, diet may affect May result from alteration of DA-R and post-R changes to plasma levodopa level Fluctuations may be decreased by taking medication more freq. in smaller doses and prolonged release |
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How can you decrease end of dose wearing off effect
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give COMT inhibitors, a combo of entacapone with 3 different doses of L-Dopa/caridopa
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Why is L-Dopa reserved for advanced Park
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because your best results are obtained in first 3 to 4 years of treatment. After that refractoriness may develop due to disease progression or increase SE due to drug-induced supersensitivity.
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Abrupt Withdrawal of L-dopa
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severe akinesia
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L-dopa + carbidopa=
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Sinemet
Carbidopa peripheral inhibitor of DOPA decarboxylase DOC for Parkinsons, or can use the First-line drugs |
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What are the properties of Sinemet
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Slower onset longer duration
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What is the most effect combo for Park
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Sinemet
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Compared to Ldopa, Sinemet is better because
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decrease dopa amount by 75%
greater efficacy with smoother control, may result in less flunctuation Pyridonxine no longer antag effect of L-dopa |
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Sinemet SE: CV
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less tachy than L-Dopa
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Sinemet SE: GI
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Less NV
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Sinemet: SE nuero/Psych
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more server psych disturbances and dyskinesias than L-Dopa
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Sinement: caution and contraindications
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start low doses and increase gradually
Caution-peptic ulcer, cardiac disease, open-angle glaucoma-mydirasis Contraindications- angle closure glaucoma, psychosis, malignant melanoma-Ldopa a precursor to melanin |
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Sinemet: Rx interaction
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Pyridoxine
antipsychotic drugs Anticholinergic drugs Non-selective MAO inhibitors --Hypertensive crisis; decrease catechol metab other dopamine agonists |
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Bromocriptine: MOA
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Used to treat prolactenemia: binds to DA2 receptor decreases prolactin release in pituitary
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Bromocroptine: prop
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Ergoline Dopamine agonist
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Bromocroptine: effects
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L-dopa but less effective
Good when used with L-dopa |
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Bromo: combined with L-dopa to reduce what
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on-off phenomena or becomign refractory
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When is bromo ideally used
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When ldopa is contraindicated
Start with low and move up |
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Bromo SE: GI
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NV, anorexia, constipation
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Bromo SE: CV
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orthostatic hypotension, cardiac arrythmias more than Ldopa
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Bromo SE: involuntary movements
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dyskenisias less than L dopa
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Bromo SE: psych and neuro
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mental disturbances: confusion, hallucination, delusions, nightmares
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bromo miscellaneous:
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headache, nasal congestion, erythromelalgia (red lower extremeties)
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Bromo contraindications
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hx: mental illness, CV disease, preg
Low to high |
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nonergot DA agonists
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MOA
Selective D2-R agonists Great FIRST-LINE DRUG over L-dopa$$ Parkinson Used for mild disease: 1st line Combo with L- Dopa RLS |
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Nonergot SE:
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Naus, fatigue, dizziness, confusion, hallucination, postural hypotension, dyskinesia
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Main SE for nonergot
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Sudden sleep attacks, during daytime activity
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Examples of nonergots
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Pramipexolen (mirapex)
Ropinirole (requip) Rotigotine (neupro)-transdermal patch |
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Pharmacokinetics of nonergs
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pramipexole is rapidly absorbed and is excreted unchanged in urine
Ropinirole is metabolized by CYP1A2. Drugs metabolized by the liver may alter its metab |
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MOA of selegiline
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MAO inhibitor type B
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Two type of MAO nhibtors
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type A- serotonin NE
Type B- dopamine |
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MOA of Selegiline
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Lack undesirable effects of non-selective MAO inhibitors
(hypertension following ingestion of foods rich in tyramine) Release NE from sympathetic neurons **LIPID SOLUBLE, GETS INTO CNS*** May have neuroprotective and anti-apoptotic effects |
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Selegiline: Clinical use
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Adjunctive therapy with L-dopa for advanced disease
May prolong the effect of L-dopa and decrease mild on-off or wearing off akinesia |
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Selegiline SE:
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Dyskinesias and mental distrubaces( eg confusion and hallucina greater than l-dopa
Insomina, anxiety, nausea, hyptension |
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drug interaction
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tricyclic antidepressants, SSRI's: increase risk of Serotonin Syndrome- hypertension tremors rigidity, agitation, hyperthermia
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Tolcapone MOA
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COMT inhibitor
Inhibit catechol-o-methyl-transferase (COMT) blocks periphperal conversion of levodopa to 3-o-methyl-DOPA ↑ L-DOPA entering BRAIN |
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Tol pharmocokinetics
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Rapidly absorbed, bound to plasma protein, and metabolized prior to excretion. Half life of both drug is about 2 hrs 4-6x/d
**NOT lipid soluble, CANNOT get into CNS*** (stays in periphery) |
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Tolcapone clinical uses
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adjunct to L-dopa/carbidopa in patients experiencing on-off phenomenon: may produce smooth response
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Tolcapone SE:
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Nausea, hypotension, orthostatic hypotension, vivid dreams, hallucination, DIARRHEA **HEPATOTOXICITY (mainly tolcapone though)***
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Tolcapone where it works compared to selegilline
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*so these are great drugs to give WITH L-dopa b/c Entacapone works in PERIPHERY (COMTi) to prevent brk of L-dopa, allowing more L-dopa to enter CNS and converted to DA, then Selegiline works CENTRALLY (MAO-Bi) to allow Dopamine to work in Basal ganglion (end pt effect).
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Amantadine MOA
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MOA
Old Belief: ↑ DA release & Blocks DA reuptake **NEW findings point more to BLOCKING NMDA Glutamate Receptor **this is MOA** **ORIGINALLY used as anti-viral (NO LONGER used for that), UNPREDICABLE benefit for PARKINSONS$$ |
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Amantadine SE: CNS
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CNS: Dizziness, confusion, insomnia, anxiety, excitement, hallucinations
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Amantadine SE: CV
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Edema; orthostatic hypotension
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Amantadine SE: main
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$$$Livedo reticularis$$ from local release of catecholamines vasospastic disease (FISHNET appearance in legs & arms, Reddish, bluish Discoloration in legs & arms)
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Amantaidien clinical Use
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Mild cases alone
Severe cases: Adjunctive therapy with L dopa or anticholinergic drugs Start low and go up |
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Trihexphynidly
Benztropine mesylate MOA |
Central anticholinergic drug
Blocks Central M1-R Decrease excitatory cholinergic activity from striatal neurons |
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Trihexphynidly
Benztropine mesylate Indication |
Less effective than levodopa
RECOMMENDED over L-dopa only in: **Younger patients w/ mild disease and pts w/ drug-induced parkinsonism$$$ Tremor and rigidity are most improved *bradykinesia less so |
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Anticolingergic MOA continued
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*this works b/c cortex EXCITES CP (striatal neurons) via ACH **so if inhibit this then **REMOVE inhibition on INDIRECT*** path (so GPL is able to inhibit STN, and therefore INCREASE MOTOR b/c no excitation of inhibition on VL thalamus)*** b/c with Parkinsons, then usually the INDRECT path is Hyperexcited **can think of functioning like a D2R agonist (eventhough diff mech)
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Trihexphynidly
Benztropine mesylate SE |
Metabolism Side Effects
**SIMILAR to ATROPINE effects CNS: Drowsiness, confusion, delirium, hallucinations Peripheral: dry mouth, cycloplegia, constipation, urinary retention (anti-SLUD) |
