Drugs for Mvmt Disorders Flashcards by Leah Ritter

What drug is unable to cross the BBB and is thus used in combo w/ levodopa to ensure that more levodopa makes it into the brain?

Carbidopa

-decarboxylase inhibitor in the periphery

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How does botulinum toxin A work in Parkinson’s Dz patients?

–binds w/ high affinity to presynaptic cholinergic neurons to decrease Ach release, thus causing a neuromuscular-blocking effect

ex: injected into salivary glands to prevent sialorrhea

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What are some potential toxicities of MAO-B inhibitors such as selegiline and rasagiline?

exacerbate HTN

- when paired w/ antidepressants, increased risk of suicidal thoughts in pediatrics and young adults

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True or False: palliative care and end-of-life decisions should be discussed early in the disease process of patients w/ Parkinson’s

True; conversations while the patient is still ambulatory are more productive than conversations that are made bedside in the hospital under crisis

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True or False: the motor symptoms of Huntington Disease can be treated

False; only treatments for the non-motor symptoms (depression, irritability) exist.

ex: fluoxetine for depression and irritability
ex: carbamazepine for depression

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What kinds of drugs should be avoided in patients w/ Huntington Disease?

-anticholinergics b/c they can exacerbate chorea

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What drug can be used to treat tremor, dystonia, and sialorrhea in younger patients w/ Parkinson’s Dz?

benztropine (antimuscarinic, cholinergic antagonist)

- contraindicated in elderly and cognitively impaired

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What are symptoms seen in Parkinson’s patients when they walk?

decreased arm swing

- shuffling, festinating gait

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What is a major toxicity in the use of tolcapone (a catechol-O-methyltransferase inhibitor)?

risk of potentially fatal acute fulminant liver failure

- tolcapone is used a last resort

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What is the inheritance pattern of Wilson Dz?

autosomal recessive

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What builds up in the serum on patients w/ Wilson Disease?

copper

avoid eating calf liver, spinach, cashews, molasses

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What two body systems are affected by Wilson Disease?

hepatic

neuro

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What is the mechanism of action of ropinirole?

dopamine agonist (non-ergot)

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What are the side effects of ropinirole (a dopamine antagonist)?

dyskinesia
impulse control disorder (gambling, hypersexuality)
increased melanoma risk
orthostatic hypotension
somnolence
N/V, constipation
HA

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What is the hallmark symptom of Parkinson’s Disease?

“pill-rolling” resting tremor

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Besides benztropine, what is another antimuscarinic, cholinergic antagonist used to treat Parkinson’s Disease?

trihexyphenidyl

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What is a complication of long-term levodopa use in treating restless leg syndrome?

augmentation of the symptoms

ex: symptom spread, shorter duration of drug action

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True or False: autonomic dysfunction is a common complication of Parkinson Disease?

True; includes cardiovascular, GIGU, and thermoregulatory problems

-however, there is a limited ability to treat/manage the autonomic dysfunction

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What is a complication when MAO-B inhibitors (such as selegiline or rasagiline) are used simultaneously with serotonergic agents?

serotonin syndrome (potentially life-threatening)

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What is the mechanism of action of penicillamine?

copper chelation that makes a stable complex that is readily excreted by the kidney
used to treat Wilson Dz

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What class of enzymes metabolizes catecholamine-like NTR’s, and thus can be inhibited pharmacologically in the treatment of Parkinson’s Disease?

monoamine oxidases

MAO’s

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What is a clinical application of amantidine, other than just as adjunctive therapy for dyskinesias in Parkinson patients?

-treats drug-induced extrapyramidal symptoms
(ex: dystonia, rigidity, bradykinesia, tremor)

-useful to tx of tremor when other symptoms are mild

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What are the side effects of amantidine?

CNS depression (decreased alertness)
impulse control disorders
psychosis (hallucinations, paranoia, delusions)
suicidal ideation
livedo reticularis

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What class of drugs contains members that are noteworthy of causing drug-induced movement disorders?

anti-emetics

ex: metoclopramide

What are two components of non-pharmacological treatment in Parkinson's Disease?

- rehabilitation | - occupational therapy

What is a class of enzyme that metabolizes dopamine and is inhibited by tolcapone and entacapone?

catechol-O-methyltransferase

What treatment is considered in select Parkinson patients to treat motor complications when other optimized medical treatments have failed?

Deep Brain Stimulation - subthalamic nucleus - globus pallidus interna

What electrolyte imbalance can mimic Parkinson's dementia?

hypoNa+ | confusion, disorientation, drowsiness

What is the typical age of onset for Parkinson's Disease?

60 yrs

What two drugs can be used to treat a Parkinson's tremor that is causing a disability?

- propranolol (beta blocker) | - primidone (barbiturate)

What is a class of enzymes that metabolizes dopamine and is inhibited by selegiline and rasagiline?

MAO-B | monoamine oxidase B

What are the characteristics of entacapone?

- COMT inhibitor (catechol-O-methyltransferase) - cannot cross BBB (restricted to periphery) - blocks levodopa degradation - used to treat "off" symptoms

In regards to the MAO-B inhibitors, how does the binding of selegiline and rasagiline differ from the binding of safinamide?

- safinamide binds reversibly | - selegiline and rasagiline bind irreversibly

What is the most potent anti-Parkinson therapy that patients are fearful of starting?

levodopa

In Parkinson's Disease, what is one way to administer levodopa-carbidopa that can reduce off-times when compared w/ standard oral levodopa?

-intrajejunal enteric gel (levodopa-carbidopa) through percutaneous gastrostomy - -substantially reduces "off-time" - -reduces dyskinesia

What type of cancer at Parkinson's patients more at risk of developing?

melanoma -risk exacerbated by Tx w/ ropinirole (DA agonist)

What is Parkinson's Disease?

-neurodegenerative disorder that predominantly affects dopaminergic neurons in the substantia nigra -70-80% loss of dopaminergic neurons in Parkinson's (some loss during aging is normal, but not this much!)

What drugs can be used to treat psychosis in Parkinson patients?

- atypical antipsychotics (ex: quetiapine, clozapine) | - also pimavanserin, serotonin 5-HT2a inverse agonist

What is the mechanism of action of amantidine?

- unknown - direct and indirect effects of DA neurons - weak NMDA receptor antagonist

Of the MAO-B inhibitors, which is the most highly selective for the receptor?

safinamide (which binds reversibly)

What NTR stimulates GABAergic neurons?

Ach

What is the mechanism of action of gabapentin and one movement disorder it can be used to treat?

- -alpha-2-delta calcium channel ligand | - -restless leg syndrome

What class of drugs should be used to treat arterial HTN in Parkinson's patients (who tend to have orthostatic hypotension)?

angiotension receptor blockers (ARB's) | --ex: (valsartan, losartan)

What is dystonia?

- sustained involuntary muscular contractions/spasms | - abnormal postures

What is akathisia?

- subjective: feeling of restlessness - objective: pacing, foot shaking, toe tapping, rocking - get distressed if restrained - symptoms may improve when asleep or supine

In what region of the brain does dopaminergic stimulation generate reward, pleasure, euphoria, motivation, perseverance, etc?

frontal cortex

True or False: treatments for Parkinson's alter the progression of the disease

False

What dopamine agonist (same category as ripinirole) has decreased risk of hypotension, but increased risk of hallucinations?

pramipexole

True or False: restless leg syndrome may resolve when a co-existing iron-deficiency anemia is corrected

True

True or False: tyramine in conjunction w/ MAO-B inhibitors can cause a HTN crisis

False

What is the only drug that has any impact on survival (or time to tracheostomy) in ALS (amyotrophic lateral sclerosis) patients?

riluzole (inhibits glutamate release, blocks post-synaptic NMDA receptors, and inhibits voltage-dependent Na+ channels) -side effects: nausea, weakness

True or False: parkinsonism can be induced by typical antipsychotics

True

What is a major risk factor for drug-induced dyskinesias?

age

What dopamine agonist (same class as ropinirole) can be administered in the form of a 24hr transdermal patch?

rotigotine

How can apomorphine be used to treat Parkinson patients?

- dopamine agonist - sublingual or subQ - quickly treats "off" episodes

How can potassium disulfide be used to treat Wilson Disease?

-reduces intestinal absorption of copper | can be prescribed in addition to penicillamine

What type of neuron are lost in Huntington Disease?

GABA-ergic

What is an ergot-derivative dopamine agonist that was used early on in the treatment of Parkinson's Disease, but is now declining in use?

bromocriptine