Drugs for movement disorders Flashcards
What neurons are affected in Parkinson’s
dopaminergic neurons in the substantia nigra
Bradykinesia, muscular rigidity, resting tremor, and impairment of postural balance leading to gait disturbances are cardinal features of what?
Parkinsons
What are the functions of the Dopamine pathways?
- Reward
- pleasure, euphoria
- motor function
- compulsion
- perseveration
What are the functions of the serotonin pathways?
- mood
- memory processing
- sleep
- cognition
Which MAO metabolizes NE, serotonin, dopamine, and tryptamine?
MAO-A (dopamine and tryptamine equal MAO A and B)
Which MAO metabolizes phenylethylamine, benzylamine, dopamine, and tryptamine?
MAO-B
dopamine and tryptamine equal MAO A and B
How does amantadine work?
exact mechanism unknown–> direct and indirect effects on dopamine neurons
weak, non-competitive NMDA receptor antagonists
- has direct and indirect effects on dopamine neurons
What drug in indicated in tx of drug induced extrapyramidal symptoms and Parkinson’s as adjunctive for dyskinesias in pts taking levodopa?
Amantidine
-weak, noncompetitive NMDA receptor antagonist
What NMDA receptor antagonist can cause... -CNS depression -impulse control disorders -psychosis -suidcide ideation levedo reticulares
Amantidine
What is ropinirole MOA?
Post synaptic D2 agonist ( some action on D3)
- increases DA- mediated effects in CNS to treat movement disorders
- Tx of Parkinson’s
- can be given with levodopa/carbidopa
- won’t work if L dopa doesn’t work
What drug’s toxicities include…
- dyskinesias
- impulse control disorders/compulsice behaviors
- increased risk for melanoma
- orthostatic hypotension (from D2 stimulation)
- psychotic events
- somnolence (fall asleep while driving)
- n/v, constipation
- headaches
Ropinirole
Which D2 agonist has decreased risk of hypotension and somnolence but increased risk of hallucinations compared to ropinirole?
Pramipexole
- sounds kinda mystical right? like hallucinations?
What D2 agonist is available in transdermal patch?
Rotigotine
what DA agonist is available in sublingual film or subQ injection?
Apomorphine
What early DA agonist is an ergot alkaloid derivative?
Bromocriptine
What is the MOA of selegiline?
Irrevesible inhibitor of MAO with affinity for MAO- B compared to A(A is found in intestinal tract)
What drug has BBW of antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients?
Selegiline
- IRREVERSIBLE inhibitor of monoamine oxidase
- greater affinity for MAO-B
Could selegiline cause hyper or hypotension?
Hyper as opposed to D2 agonist causing hypo
What is a MAO-B selective irreversible inhibitory that has greater potency, but similar efficacy and adverse effects as selegiline?
Rasagiline
RAAAAAAA — sounds more powerful right?
What is a REVERSIBLE MAO-B inhibitor?
Safinaminde
What is the MOA of tolcapone?
Selective and reversible inhibitor of catechol-o-methyl-transferase (pathway for degradation of levodopa)
When is tolcapone used?
Adjuct to levodopa and carbidopa in tx of Parkinson’s, helps prevent degradation
- tolcapone is a selective and reversible inhibitor of catechol-o-methly transferase (COMT)
- COMT is a major pathway for levodopa degradation
What drug requires patients to acknowledge/sign warning about liver failure?
Tolcapone– This is a LAST RESORT DRUG
- can cause liver failure
- only use if not responding to other agents
Why would someone want to use entacapone?
is a nitrocatechol COMT inhibitor with a short half life.
- can’t cross BBB
- acts in periphery to block Levodopa degradation
- is less toxic to liver than Tolcapone
What type of drug is Carbidopa?
peripheral DOPA decarboxylase inhibitor, can’t cross BBB
Can levodopa cross BBB?
yes
What is given with levodopa?
cabidopa to prevent levodopa degradation
What COMT inhibitor is given with carbidopa and levodopa?
Entacapone
What is MOA of benztropine?
Cholinergic antagonist at muscarinic receptors (like atropine but less activity)
What Parkinson drug can cause dry mouth, blurred vision, cognitive changes, drowsiness, constipation, urinary retention, tachycardia, anorexia, Severe delirium and hallucinations at toxic doses
Benztropine
-cholinergic antagonist at muscarinic receptors like atropine but less activity
What are the 4 main classes of drugs for Parkinson’s tx?
- MAO-B inhibitors
- Amantidine
- Levodopa
- Dopaminergic agonists
MALD was BALD and had Parkinsons
What is the most potent antiparkinson therapy?
levodopa
How is sialorrhea treated in Parkinson’s patients?
Botulinum toxin A into the salivary glands
What should be given to patients on antiparkinsons meds that have a risk of orthostatic HTN?
alpha adrenergic agonist MIDODRINE
-peripheral D2 antagonist DOMPERIDONE
mineral corticoid FLUCORTISONE
Melatonin and clonazepam can be used to treat what?
those with rapid eye movement sleep behavior disorder
What drugs are used to treat cognitive decline of PD?
Cholinesterase inhibitors: Rivastigmine or donepezil
NMDA-antagonist: Memantine
* the only drugs in the dementia lecture*
What are first line agents for treating essential tremor?
Propranolol and primidone (barbiturate anticonvulsant)
What drug can prolong ALS survival for a few months/ prolong time to tracheostomy?
Riluzole
What does penicillamine treat? How?
Wilson’s disease
- copper chelating agent
What does potassium disulfide treat? How?
reduces intestinal absorption of copper, can be
prescribed in addition to penicilamines
How would mild sx of Parkinson’s be treated? (little interference with daily function)
- MAO B inhibitor
2. Amantadine–> useful if tremor is predominant
If PD diminishes daily quality of life, what drug is indicated in pt less than 65?
-DA agonist
or
-levodopa
If PD diminishes daily quality of life, what drug is indicated in pt greater than 65?
initiate with immediate release levodopa
What often proceeds motor symptoms in PD?
Depression
What are standard atypical anti psychosis agents?
quetiapine
clozapine
What are adverse effects to D2 receptor activation in PD?
psychosis
N/V
What is adverse effect to using Ach muscarinic receptors antagonists?
dementia– use restricted to young PD patients
How is restless leg syndrome treated?
-non-ergot dopamine agonist–> like ropinirole
alpha 2 delta calcium channel ligand
