Parkinson's, essential tremor, and spasticity drugs Flashcards
What is the mechanism of action of levodopa and carbidopa (sinemet)?
- L-dopa is transported across the blood brain barrier and then into remaining SN DA secreting neurons and converted to DA by aromatic amino acid decarboxylase (AADC)
- Carbidopa blocks peripheral AADC and is always combined with levodopa to allow more L-dopa to reach remaining DA neurons in SN (reduces peripheral AEs)
What is levodopa/carbidopa used for treating?
Parkinson’s disease
What are side effects of levodopa/carbidopa (sinemet)?
N/V, somnolence, headache, dizziness, orthostatic hypotension, cardiac arrhythmias, hallucinations, agitation, confusion, psychosis, dyskinesia, motor fluctuations, discolored urine/sweat/saliva
COMT inhibitors mechanism of action
- Both inhibit peripheral COMT, preventing metabolism of L-dopa to inactive metabolite –> allows more L-DOPA to reach remaining DA neurons in SN
- Combined with L-DOPA/Carbidopa
COMT inhibitors mechanism of action
- Both inhibit peripheral COMT, preventing metabolism of L-dopa to inactive metabolite –> allows more L-DOPA to reach remaining DA neurons in SN
- Combined with L-DOPA/Carbidopa
What two drugs are COMT inhibitors?
Entacapone and tolcapone
What are COMT inhibitors used for?
Added onto therapy for parkinson’s disease (useful extenders w therapy in patients that have motor fluctuations)
What are side effects of COMT inhibitors?
Increases side effects of L-DOPA and causes hepatotoxicity (tolcapone only)
What is the mechanism of action for dopamine agonists?
Stimulate DA receptors in the stiatum (bypasses DA input from the remaining SN neurons)
What two drugs are dopamine agonists?
Pramipexole and ropinirole
What are side effects for dopamine agonists?
- Similar to L-DOPA/Carbidopa but some are less frequent (less n/v, orthostatic htn, motor fluctuations and dyskinesias) or more frequent (adverse behavioral side effects, somnolence)
- Watch out for disorders of impulse control: gambling, shopping, eating, sex
What is the mechanism of action of muscarinic antagonists?
Block muscarinic receptors in striatum
What are dopamine agonists used for?
Parkinsons disease (can be used alone or added tx)
What two drugs are muscarinic antagonists?
Trihexyphenidyl and benztropine
What are muscarinic antagonists used for?
Parkinson’s disease- useful for younger patients who have resting tremor as a predominant finding and preserved cognitive function
What are side effects of muscarinic antagonists?
Xerostomia, blurry vision, constipation, urinary retention, impaired sweating, tachycardia, confusion, impairment of recent memory, hallucinations, delusions
What are some contraindications for muscarinic antagonists?
BPH, narrow angle glaucoma, older patients or patients with congnitive impairment
What is the mechanism of action of MAO-B inhibitors?
Irreversible selective inhibition of MAO-B which decreases the oxidative metabolism of DA; Neuroprotective effects unclear
What two drugs are MAO-B inhibitors?
Selegiline and rasagiline
What are side effects of MAO-B inhibitors?
Nausea, orthostatic hypotension, headache, confusion, hallucinations, insomnia
What are MAO-B inhibitors used for?
Mild symptomatic benefit and often used w L-DOPA/carbidopa and/or DA receptor agonists for treatment of parkinson’s disease
What is the mechanism of action for NMDA receptor antagonists?
Uncertain but blocking NMDA receptors may decrease glutaminergic transmission in BG (reduce L-DOPA dyskinesias) and may increase dopamine release, block DAT, or stimulate DA receptors
What is an example of a NMDA receptor antagonist?
Amantadine
What are side effects of amantadine?
Orthostatic htn, dizziness, confusion, hallucinations, insomnia, n/v, livedo reticularis
What are NMDA receptor antagonists used for?
Weak parkinsons disease drug with low toxicity that is most useful short-term in early mid PD or later to help with dyskinesias from L-DOPA/carbidopa
What is the mechanism of action for essential tremor drugs?
Enhance neurotransmission at the GABA-A receptor
What drugs are used for essential tremor?
- Primidone (barbiturate)
- Topiramate (also prolongs inactivation of Na voltage gated channels and blocks CA)
- Gabapentin (binds ca vg channels and increase gaba + decrease glutamate transmission)
- Alprazolam (benzo)
- Propanolol (bb)
What is the mechanism of action of tizanidine?
alpha 2 agonist and enhances inhibition of muscle stretch reflex
What are side effects of tizanidine?
skeletal muscle weakness, hypotension, bradycardia, drowsiness, xerostomia
What is tizanidine used for?
Spasticity
What is baclofen’s mechanism of action?
GABA-B agonist and enhances inhibition of muscle stretch reflex
What are side effects of baclofen?
skeletal muscle weakness (more than tizanidine), dizziness, drowsiness, depression, fatigue
What is diazepams mechanism of action?
Increases GABA-A activity by enhancing inhibition of muscle stretch reflex
What are side effects seen with diazepam?
Sedation, motor impairment, amnesia, tolerance, physical dependance
What is diazepam used to treat in this case?
Spasticity
