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103 Cards in this Set
- Front
- Back
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Primary PD's cause is?
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idiopathic
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When PD is genetically linked, where is the issue and what does it do?
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Chromosome 4
It leads to the aberrant protein: Alpha-Synuclein |
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What is the pathological hallmark of PD?
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Loss of pigmented dopaminergic neurons in the substantia nigra pars compacta w/ the appearance of Lewy Bodies
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What is a lewy body?
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its an intracellular inclusion
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what % of dopaminergic neurons must be lost to cause PD?
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>70%
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How do pts die of PD?
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Complications of immobility like aspiration pneumonia or pulmonary embolism
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Causes of PD
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Idiopathic
Post-encephalitic Iatrogenic Amine Depleting Agents Head Trauma Arteriosclerosis CO poisoning MPTP-->MPP+ |
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what are lewy bodies made of?
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Alpha-synuclein and parkin
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What's another thing found upon autopsy in some PD pts?
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Neurofibrillary tangles
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Which types of PD exhibit tangles?
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post-encephalitic
the PD-dementia complex |
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Motor Sx's of PD
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1. Tremor at Rest
2. Rigidity 3. Bradykinesia |
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How long does the disease take to progress?
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15-20 years
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what are the Dopamine Receptor Families?
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The D1 Family (D1 and D5)
The D2 Family (D2, D3, and D4) |
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Mech of D1 family?
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stimulate synthesis of cAMP and phosphatidyl inositol hydrolysis
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Mech of D2 Family?
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inhibit synthesis of cAMP
Modulate potassium and calcium currents |
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What is the distribution of the Dopamine Receptors?
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D1 and D2: striatum
D4 and D5: extra-striatal D3: low in caudate and putamen, but more in nucleus accumbens and olfactory tubercle |
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Which dopamine receptors are most important for PD cause and Rx?
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D1 and D2
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Who coordinates my movements?
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1. Pyramidal System
2. Extrapyramidal System 3. Cerebellum |
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What does the Pyramidal System do?
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initiates voluntary movement
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What does the extrapyramidal system do?
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adjusts body posture
maintenance of stable background of movement activates autonomic movements keeps spinal reflexes in ready position |
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What role does the Cerebellum play in movements?
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coordinates various muscles for smooth and precise movements
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How does PD effect the extrapyramidal system?
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There is a loss of both excitatory and inhibitory DA nigro-striatal input-->loss of excitatory output from thalamus to CTX
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What's the number 1 PD drug?
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Levodopa
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Which types of PD is levodopa good for?
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all of them except for iatrogenic PD
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why does levodopa work?
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its a metabolic precursor to dopamine that gets decarboxylated to dopamine
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why can't we just treat them with dopamine?
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it doesn't cross the BBB
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which sx's of PD is levodopa good for?
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all of them
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Issues w/ long term levodopa use?
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"wearing off" phenomenon
-i.e. sx's return earlier and earlier "on/off" phenomenon sometime it works, sometimes it doesn't. If it does work it causes dyskinesias |
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Why not just give more levodopa?
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you start causing dyskinesias
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B/c of the two phenomenon, when is levodopa prescribed?
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when the Sx's cause functional impairment
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What is Carbidopa?
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its a peripheral (doesn't cross BBB) dopa decarboxylase inhibitor
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How is carbidopa used?
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its given in a fixed combo with levodopa
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Role of carbidopa?
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it reduces the required levodopa dosage by up to 75%
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Adverse Effects of Levodopa
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N&V**
Orthostatic Hypotension** Cardiac Arrythmias** Abnormal movements Mental disturbances |
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Contraindications of Levodopa?
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narrow-angle glaucoma
H/O psych disorders H/O cardiac arrythmias or recent infarct |
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Drug-Drug interactions of levodopa?
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non-selective MAO inhibitors
sympathomimetic amines (in OTC decongestants) Pyridoxine (B6) Antipsychotics (except clozapine) and Reserpine-like drugs |
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Drugs used to help with N&V associated with levodopa?
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Domperidone can be used as an anti-emetic
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Drug used to help with cardiac arrythmias associated with levodopa?
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Propanolol
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Drug used to help with mental distrubances/behavioral changes associated with levodopa?
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Clozapine
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Drug used to treat the depression that accompanies PD?
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Trazodone
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What is Selegiline?
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its a MAO-B inhibitor
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what are some other MAO-inhibitors?
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Rasagiline
Safinamide |
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Bad news drug interactions of Selegiline?
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Fluoxetine (prozac) and Meperidine (demerol) can cause a fatal toxic rxn
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Other contraindication of selegilne?
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Tyramine rich foods
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What is Rasagiline?
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Potent, selective, irreversible MAO-B inhibitor
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Why is rasagiline good?
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it is anti-PD
It has motor restoration activities It possesses neuroprotective properties |
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When can you use Rasagiline?
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Idiopathic PD as a monotherapy
With Levodopa in pts with end-of-dose fluctuations |
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Mechanisms of Safinamide?
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1. Reversible MAO-B inhibitor
2. Blocks voltage-dep Na and Ca channels 3. inhibits Glutamate release |
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Besides the MAO-B inhibitors what's another class of drugs used in PD?
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Anticholinergic Drugs
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Who are the anticholinergic drugs that can have benefits in PD patients?
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Trihexiphenidyl
Benztropine Diphenydramine (benadryl) Amantadine |
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How do Trihexiphenidyl and Benztropine work?
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antimuscarinic/antihistaminergic agents
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What Sx's are anticholinergics best for?
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Tremors
Drooling and others |
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SE's of anticholinergics?
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dry mouth
constipation pee retention impaired memory confusion |
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How does benadryl work against PD?
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it has weak central antimuscarinic activity
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when is benadryl used in PD pts?
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when the pts are old and can't tolerate the more potent anti-cholinergics
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How does Amantadine work?
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1. May release dopamine in the CNS presynaptic nerve terminals
2. antimuscarinic activity |
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Enhancer of Amantadine?
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levodopa
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Amantadine is useful in which types of PD?
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all of them
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poor drug-drug interaction of amantadine?
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it greatly enhances SE's of anticholinergics
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Examples of Dopamine Receptor Agonists
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Bromocriptine
Pergolide Pramipexole Ropinirole |
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What are Bromocriptine and Pergolide?
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ergot alkaloid derivatives
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Target for Bromocriptine?
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Full D2 agonist
Partial D1 agonist |
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Target for Pergolide?
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full D1 and D2 agonist
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which is more potent, bromo or pergolide?
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Pergolide
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Purpose of using Bromocriptine or Pergolide?
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treat on/off effect with or w/o levodopa/carbidopa
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SE's of bromo and pergo
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Less dyskinesias, but
Behavioral SE's common Hypotension common Ergot SE's: pleuropulmonary and retroperitoneal fibrosis, etc |
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When in the course of PD do you use Pramipexole and Ropinirole?
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Early (w/o levodopa) or Late (w/ l-dopa)
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Which receptors do Prami and Ropi go after?
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D2
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SE's of Prami and Ropi?
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Syncope w/ bradycardia (3-12%)
Hallucinations with Prami (10-21%) Nausea Exacerbate dyskinesias Compulsive appetities (gambling, food, booze...mostly Prami...probaly do to D3) |
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What is Entacapone?
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Inhibitor of COMT
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When is Entacapone used?
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Used w/ levodopa/carbidopa to fight off "wearing off" Sx's.
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SE's of Entacapone?
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It enhances the SE's of levodopa (dyskinesias, N&V, anorexia, syncope, etc)
Can be an issue if used with other drugs typically metabolized by COMT |
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What surgical interventions can be used for PD?
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Pallidotomy
Deep Brain Stimulation |
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Why Deep Brain Stimulation?
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Safer and just as effective as Pallidotomy
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Brain location of HD?
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Basal Ganglia disease
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The Sx's of HD resemble what?
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Excessive dopamine in the CNS
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Which pathway is affected first in HD?
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the indirect pathway
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why is this important?
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b/c it leads to an increase in excitatory drive to the neocortex-->involuntary choreiform movements
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Rx for HD
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1. If there are large amp movements: Reserpine or Tetrabenazine
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Other drugs used in HD
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Antidepressants and Anxiolytics to help the patient cope
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What is ALS?
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Amyotrophic Lateral Sclerosis
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Pathology of ALS?
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disorder of motor nerves of ventral horn of SC and cortical neurons that provide their afferent input
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Sx's of ALS?
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Rapidly Progressive weakness
muscle atrophy Fasiculations Spasticity Dysarthria Dysphagia Resp Compromise |
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Rx for ALS?
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Rx is symptomatic and focused on spasticity.
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For ALS pts w/ increased extensor tone and clonus, what can you give them?
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Baclofen: GABA agonist
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Length of time till ALS kills you?
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2-3 years
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Inheritance of ALS???
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Most cases are sporadic, though some are Auto Dom or Auto Rec
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Only drug for ALS?
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Riluzole
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Effects of Riluzole?
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extends life by months
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Possible mech of Riluzole?
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may inhibit release of glutamate
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First line of Rx for Tourette's? (general and specific)
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Alpha-2 Adrenergic Agonists
ex: clonidine and guanfacine |
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SE's of Alpha 2 adrenergic agonists?
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mild
sedation dry mouth HA's |
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Other drugs used to Rx tourettes?
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2nd Gen Antipsychotics
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Why?
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Less SE's
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SE's that are present with the 2nd gen antipsychotics
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somnolence
wt. gain depression hepatotoxic DM |
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Of the 2nd gen antipsychotics, which specific drug leads the way?
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Risperidone
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Of the 1st generation which drug is used?
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Pimozide
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For several focal tics, what can be prescribed?
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Botulinum toxin A
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So what are all the drugs you can use for tourettes?
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Guanfacine and Clonidine
Risperidone Pimozide Botox |
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Who are the 2nd Generation, Atypical Neuroleptics?
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Risperidone
Ziprasidone Olanzapine THEY ALL CAUSE WT GAIN! |
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Who are the 1st Gen, Typical Neuroleptics
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Pimozide
Haloperidol Fluphenazine |
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Who are the BDZ's you can use for Tourette's?
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Clonazepam (for anxiety and ADHD)
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What about a GABA agonist?
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Baclofen (may work on anxiety more than tic)
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