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55 Cards in this Set
- Front
- Back
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Where do movement disorders originate from?
PD mech (long): |
disturbances in basal ganglia
Degen of DA neurons in pars compacta of SN, leading to overactivity of indirect pathway, culminating in inc gluatmate output from subthalamic nuc AND inc GABA in put into the thalamus |
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DA synthesis recap in 3 steps:
What three proteins metab DA? |
Tyrosine --> l-dopa + Dopa decarboxylase --> DA
MAO-A, MAO-B, COMT |
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When do PD sxs usually start?
What are causes of PD-like sxs (5)? |
When 70% of striatal DA is lost.
tumors, trauma, antipsychotics, manganese or CO poisoning, metaclopramide |
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What are the primary sxs of PD (4)?
Secondary sxs (4)? |
stiffness, tremor, slowness, trouble with balance & walking
Depression, dementia, deformity, speech issues |
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How do DA and ACH interact with GABA rls in striatum?
How do DA and ACH interact in PD? |
DA = dec GABA output, ACH = inc
Decreased DA means ACH pathways dominate = huge upreg in GABA = inhibition (?) |
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What are the main methods for tx of PD (2):
Why is l-dopa used instead of straight DA? |
Inc DA levels, dec ACH activity in striatum
DA cannot cross BBB |
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L-dopa
Use: Why problematic when used alone? What overcomes this? |
tx of Parkinson's
l-dopa becomes DA in GI so only 1-3% reaches brain. High doses, but they cause adverse effects |
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L-dopa
Frequently used with: Improves delivery to brain up to: |
carbidopa. Renders more effective at smaller doses
75%! |
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Carbidopa
Mech: Why do we care if it crosses BBB? |
dopa decarboxylase inhibitor that does not cross BBB
It dec DA synth in tissues, but not in brain. |
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L-dopa/carbidopa - PHKs
Abs (2): t1/2: |
Oral: rapid abs but competes with AAs.
short. must take 3-4x/day |
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What is the response rate to L-dopa/carbidopa?
Which PD sx is it best for? |
1/3 respond well, 1/3 less, 1/3 not at all
bradykinesia |
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L-dopa/carbidopa
What does it do in PD?' What does it NOT do? Why is it less efficient over time? |
Dramatic improvement of PD sxs for 3/4 yrs
Does not slow disease progression Fewer DA neurons + higher incidence of side effects with chronic use |
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L-dopa/carbidopa Side Effects
GI (2): CV (2): |
NV in 80% with l-dopa alone - 60% with combo.
tachy, V systole sec to B-rec effects or postural hypotension sec to activation of periph DA recs |
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L-dopa/carbidopa Side Effects
Dyskinesias: Most common with: But, decreasing dose = |
Excessive, involuntary mvmnt in 80% after chronic tx
L-dopa/carbidopa combo decreased mobility. sigh. |
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L-dopa/carbidopa Side Effects
Behavioral (6): Tx of these: |
depression, anxiety, somnolence, confusion, delusions, nightmares
with atypical antipsychotics - classics make worse! |
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L-dopa/carbidopa Side Effects
On-Off Phenom: Tx of this (4): |
Off = akinesia, On = dyskinesia every few hours based on falling drug levels
more freq doses, dec dietary AAs, DA agonist, selegiline |
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L-dopa/carbidopa Side Effects
What is a drug holiday? Why is it not encouraged in PD? |
Drug w/d gradually (3-21 days) then reintroduced at 1/2 dose to dec side effects?
Pneumonia or DVT/PE can result from akinesia |
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L-dopa/carbidopa - CIs
Drugs (2): |
MAOIs (HTN crisis) & pyroxidine/B6 (dec effectiveness of l-dopa)
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L-dopa/carbidopa - CIs
Non-drug (4): |
Psychosis (inc DA is bad)
Closed-angle glaucoma (inc press) Peptic ulcer (inc bleeding) Malignant melanoma (l-dopa precursor to melanin) |
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Selegiline
Drug class: Use: Mech: |
MAOI
Tx of PD Inhibs MAO-B in striatum |
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Selegiline
How does it slow the progression of PD? How does it impact MAO-A metab? |
MAO-B metab causes increased H202, so inhib = less free radial damage
No effect |
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Selegiline
PHKs (2): Side effects (2): |
Oral well abs, BID bkfst/lunch
Insomnia, anxiety sec to its metabolites |
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Selegiline
Only drug CI and results (4): |
Meperidine: causes stupor, rigidity, agitation, hyperthermia
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Tolcapone
Drug Class: Use in PD: |
COMTI
adjunct to sinemet |
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Tolcapone
Biggest risk: Other side effects (3): |
fatal hepatoxicity - requires consent
dyskinesia, confusion, nausea |
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Bromocriptine/pramipexole in PD
Useful for what in PD? Does not: But does: |
On-off phenom
Slow disease progression Remain effective for duration of disease |
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Bromocriptine/pramipexole in PD
How to start dosing? Derivs of: Result of that? |
Slowly over 2-3 months
Ergot derivs. May cause vasospasm. |
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Bromocriptine/pramipexole Side Effects
GI (5): CV (3): |
NVC, anorexia, dyspepsia, GERD, bleeding ulcers
postural hypo (First dose phenom), vasospasm, arrhythmias |
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Bromocriptine/pramipexole Side Effects
CNS (2): Other (3): |
Confusion, hallucs (as seen in ergot poisoning)
Hypoprolactinemia, dyskinesia, erythromelalgia |
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What is erythromelalgia and with what drug does it occur?
Tx? |
red, tender swollen feet/hands secondary to vasospasm. Occurs with bromocriptine. DC of drug usually relieves sxs.
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Apomorphine
Use: Dose: Duration: |
Temp tx of 'Off' period in PD
SubQ, up to 3x/day Up to 2 hrs |
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Apomorphine
Side effects (5): |
Nausea (take anti-emetic), dyskinesias, sweating, sedation, hypotension
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Amantadine
Use: Mech: |
Influenza antiviral that relieves sxs of PD.
Unclear |
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Amantadine
Comparison to l-dopa (2): May cause (3): |
Less potency and duration
agitation, skin spotting, periph edema |
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Amantadine
OD sxs (2): Caution in pts with (2): |
toxic psychosis and convulsions
Hx szs or CHF. |
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Benztropine/Biperiden in PD
Improves (3): Does not improve: |
rigidity, tremor, drooling
bradykinesia not improved |
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Benztropine/Biperiden in PD
Drug class: Mech: |
anticholinergics
Dec ACH to restore balance with DA |
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Benztropine/Biperiden in PD
How to start/stop? What potentiates them (2)? |
Gradually!
TCAs & anti-histamines |
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Huntington's
Sxs: Due to imbalance of (3): |
adult onset of progressive chorea and dementia
DA, ACH, GABA |
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Huntington's
Mech/location: Tx (3): |
Degen of GABA neurons in basal ganglia
Deplete DA with tetrabenzine, reserpine, or haloperidol |
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Tourette's
Tx (5): |
Haloperidol, clonidine, phenothiazines, benzos, carbemazepine
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ALZ
What is the pathogenesis? |
Formation of neuritic plaques with neurofibrillary tanges that contain neurotoxic Beta amyloid and tau protein.
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ALZ
What are two genetic risk factors? |
Presence of APoE4, and genes controlling synth of Beta-amyloid
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ALZ
Risk factors (4)? |
Age, genes, F>M, higher educ = lower risk
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ALZ
What paths are degenerated (2)? What NT is significantly reduced? |
Degen of cholinergic neurons from nuc basalis of Mynert which goes to the cortex & hippocampus. Also, degen of NE & 5HT pathways from locus ceruleus & nuc raphe.
90% reduc of ACH |
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ALZ
Mild sxs (4): |
Confusion, disorientation, issues with routine tasks, personality & judgement changes.
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ALZ
Moderate sxs (6): |
Trouble with daily living tasks, anxiety, paranoia, sleep issues, wandering, recognition degen
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ALZ
Severe sxs (3): Death occurs from: |
Loss of speech, appetite, continence
Usually from issues like pneumonia or infection. |
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Tacrine & Rivastigmine
Drug class: Use/mech: |
Cholinesterase inhibs
Tx of ALZ, because inc ACH improves sxs to a point |
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Tacrine & Rivastigmine
Why should it be started promptly on suspicion of ALZ? Big risk of tacrine? |
It slows course of disease
Hepatotoxicity in 50%. Requires freq blood tests - no longer used. |
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Tacrine & Rivastigmine
Side Effect: |
GI upset in 1%
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Memantine
Drug class: Uses (2): |
non-competitive NMDA rec antagonist
Tx of severe ALZ or mild/mod vascular dementia |
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Memantine
Prevents: CIs (2): |
Neurotoxicity of glutamate on NMDA recs, slowing neurodegeneration.
Meperidine and dextromethorphan (NMDA antags) |
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Memantine PHKs
Excretion: t1/2: Competes for: |
RExc unchanged
60-80 hrs Competes for renal tubular secretion |
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Memantine
Side effects (6): |
agitation, dyskinesia, incontinence, UTI, insomnia, diarrhea
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