Pharmacology of Drugs for Neurodegenerative Disorders Flashcards
What anticholinergic drugs are used to treat Parkinson’s?
Benztropine, trihexyphenidyl
What life-threatening ADRs are associated with use of MOA inhibitors?
Hypertensive crisis and serotonin syndrome in patients on TCAs or SSRIs
What is the primary strategy for the use of drugs to treat Parkinson’s disease?
In Parkinson’s disease, less dopamine is present in the synaptic cleft. The target of drugs is to increase or amplify functional dopamine
What is the MOA of Selegiline?
A selective, irreversible inhibitor of MOA-B. This drug cannot be used as a monotherapy
Amantadine should be used cautiously in what patient populations?
Patients with seizures, heart failure, or renal failure
This drug is a dopamine precursor the works to increase the presence of dopamine at the synaptic cleft.
Levodopa
What is the MOA of Riluzole?
Antioxidant that reduces glutamate-induced excitotoxicity of ALS
What antipsychotic does not target D2 receptors and may be used to treat psychosis in a patient with Parkinson’s disease?
Primavanserin
Hallucinations are associated with what MOA inhibitor?
Selegiline
What are the COMT inhibitors used to treat Parkinson’s?
Entacapone & Tolcapone
What is the MOA of Lecanemab?
Monoclonal antibody against amyloid beta plaques
What is the MOA of anticholinergic medications in treating Parkinson’s?
Dampen stimulatory signaling from neurons
What is the most common dopamine agonist used to treat Parkinson’s disease?
Pramipexole
Impulse control disorders are associated with what MOA inhibitor?
Rasagiline
What is the only drug used to treat Alzheimer’s that reduces the rate of disease progression and slows cognitive decline?
Lecanemab
Levodopa is quickly converted to dopamine in circulation and cannot cross the BBB. How can this issue be resolved?
Co-treatment with a DOPA decarboxylase inhibitor. L-DOPA can cross the BBB, where there it can be converted to dopamine by a DOPA decarboxylase
Symptoms of parkinsonism induced by drugs typically resolve within 6 months of drug withdrawal. What drug is the exception?
Synthetic heroin (MPTP) - symptoms are irreversible and progressive degeneration of neurons may occur for years
What drug is used as a rescue therapy for temporary relief of off-periods of akinesia?
Apomorphine
These categories of Parkinson’s drugs work to prevent the breakdown of dopamine.
DOPA decarboxylase inhibitors, Catechol-O-methyltransferase inhibitors (COMTIs), Monoamine oxidase B inhibitors (MOA inhibitors)
What is the MOA of tetrabenazine?
Depletes cerebral dopamine to reduce severity of chorea
True/False. Levodopa may be used as a chronic monotherapy to treat motor symptoms of Parkinson’s disease.
False. The benefits of Levodopa begin to decline after 3-5 years. Other drugs may be added to enhance the effects of Levodopa, but decreased efficacy and response fluctuations will occur
What serious ADR is associated with monoclonal antibody treatment of Alzheimer’s?
Intracerebral hemorrhages
True/False. A patient failed treatment with L-dopa. Treatment with Pramipexole is an effective next treatment option.
False. Dopamine agonists are generally ineffective in patients who did not respond to L-dopa.
What NMDA Antagonist is used to improve cognition in patients with early Alzheimer’s?
Memantine
Anticholinergics should not be used to treat Parkinson’s in what patients?
Elderly and cognitively impaired, patients with bradykinesia
What are the contraindications for the use of L-dopa?
Closed-angle glaucoma, psychosis, melanoma or undiagnosed skin lesions, cardiac disease, gastric ulcer
What DOPA decarboxylase inhibitor is typically administered with Levodopa?
Carbidopa (Benserazide is another inhibitor)
What are the stages of treatment with Levodopa?
Honeymoon phase (dramatic improvement), benign fluctuations in response (wearing-off reactions, end-of-dose akinesia), unpredictable response fuctuations
What is the MOA of Amantadine?
NMDA receptor antagonist that potentiates dopaminergic effects
What is the MOA of donepezil, rivastigmine, and galantamine in treating Alzheimer’s?
Cholinesterase inhibitors that enhance cholinergic functioning in the basal forebrain for cognition and functioning
What MOA inhibitor is a selective, irreversible inhibitor of MOA-B, but may be administered as a monotherapy in early Parkinson’s treatment.
Rasagiline. Selegiline is also an irreversible, selective MOA-B inhibitor, but is always used as an adjunct therapy
What drugs are known to interact with L-dopa?
Vitamin B6, antiemetics, antipsychotics, MAO-A inhibitors
What ADRs are associated with L-dopa?
Dyskinesias (especially twitching of face and extremities), GI disturbances, cardiac arrhythmias, orthostatic hypotension, depression, anxiety, confusion, and psychosis
What is the only Parkinson’s medication that can be used as short-term treatment for bradykinesia, rigidity, and tremor?
Amantadine
What drug is used to treat ALS?
Riluzole
What drugs are known to induce Parkinsonism?
Antipsychotics, antiemetics, synthetic heroin (MPTP)
What ADRs are associated with COMT inhibitors?
Dyskinesias, GI disturbances, confusion, orthostatic hypertension, urine discoloration
What COMT inhibitor is most commonly used, even though it is less effective?
Entacapone - Tolcapone is more effective but has high risk of hepatotoxicity
What drug is used to reduce movement in patients with Huntington’s Disease?
Tetrabenazine
What is the oral form of Riluzole for ALS treatment?
Edaravone
ADRs of dopamine agonists are similar to those of L-dopa. What additional ADRs are present?
Dopamine agonists withdrawal syndrome, dopaminergic dysregulation syndrome, sleep attacks
True/False. L-dopa, dopa decarboxylase inhibitors, and COMT inhibitors may all be administered to treat Parkinson’s and work to increase dopamine presence.
True. The combined drug is called Stalevo. This is commonly useful when patients reach the phase of response fluctuations with L-dopa alone
What ADRs are most commonly associated with cholinesterase inhibitors in treating Alzheimer’s?
GI disturbances, bradycardia, hypotension, sleep distubrances
Dopamine agonists are contraindicated in what patients?
Patients with history of psychosis, myocardial infarction, peptic ulcers
Parkinson’s disease is characterized by demyelination of neurons in the substantia nigra. Where do these neurons project?
Striatum (Caudate & Putamen)
Riluzole and Edaravone have limited effects on the disease progression of ALS. What drugs are used solely for symptomatic treat of ALS?
Baclofen (spasticity) & Gabapentin (slow muscle atrophy)
Peripheral edema and livedo reticularis are ADRs associated with what Parkinson’s medication?
Amantadine
