Parkinson’s Disease, Essential Tremor, and Spasticity Flashcards
Parkinson’s Disease
-Degenerative
-Diffuse, asymmetric
-Substantia nigra (DA secreting)
-Years of normal function then insidious onset after safety factor is exceeded
Parkinson’s disease: Pathophysiology
- Loss of DA input to striatum from SN results in decreased direct pathway (“gas”) and increased indirect pathway (“brake”)
- Unopposed ACh activity at muscarinic receptors in the striatum contributes to the pathophysiology
Parkinson’s disease: Clinical Features
Cardinal Motor Features
1. Resting tremor
2. Bradykinesia, Akinesia
3. Rigidity
4. Postural instability
*Skeletal muscle strength is preserved in PD patients!
Levodopa (MOA/AE)
MOA: L-dopa -> BBB -> SN DA secreting neurons -> converted into DA by AADC
-Carbidopa blocks peripheral AADC
AE: (SHOC DD NBM)
-Nausea/vomiting
-Sleepiness/drowsiness
-Headache, Dizziness
-Orthostatic hypotension
-Cardiac arrhythmias
-Behavioral/psychiatric changes
-Dyskinesia
-Motor fluctuations
-Discoloration of urine, saliva, and sweat
Levodopa: Considerations
- If pt doesn’t respond, probably not PD
- Drug of choice, especially in older patients (e.g., > 65 years old) or patients with more severe symptoms
- When starting, patients should take with food or snack to minimize N/V
- With more advanced disease and/or motor fluctuations, more effective if take on empty stomach and avoid high protein foods (amino acids compete with L-DOPA for transport)
Entacapone, Tolcapone
CHA
MOA: COMT inhibitors, prevent metabolism of L-dopa
AE:
-Increases L-DOPA AEs
-Hepatotoxicity (tolcapone only)
Consideration:
-Ineffective when given alone but are useful L-DOPA “extenders” in patients with motor fluctuation
Pramipexole, Ropinirole
DIY
MOA: stimulate DA receptors
AE:
-Similar to L-dopa/carbidopa
(Less: N/V, Ortho hypo, dysk, motor fluc
More: behavioral, somnolence)
-Disorders of impulse control
Consideration:
-Used as monotherapy in younger patients (e.g.,<65 years old) or as an adjunct to L-DOPA/carbidopa
Trihexyphenidyl, Benztropine
MOA: block muscarinic receptors
AE:
-Antimuscarinic: dry mouth, BV, tachy, cons, urinary retention, sweating
-CNS: confusion, memory impairment, delusions, hallucinations
Consideration:
-Most useful for younger PD patients who have resting tremor as predominant finding and preserved cognitive function
-Caution with older patients or patients with cognitive impairment
Selegiline, Rasagiline
Giline is in the MOAB with NOHCHI
MOA: irreversible selective inhibition of MAO-B, which decreases the oxidative metabolism of DA
AE: (NOHCHI)
-Nausea
-Orthostatic hypotension
-Headache
-Confusion
-Hallucinations
-Insomnia
Consideration:
-Have mild symptomatic benefit
-Often used in combination with L-DOPA/carbidopa and/or DA receptor agonists
Amantadine
A man and LINH are OCD
MOA: blocking NMDA receptors
AE:
-Orthostatic hypotension
-Dizziness
-Confusion
-Hallucinations
-Insomnia
-Nausea/vomiting
-Livedo reticularis
Consideration:
-Relatively weak PD drug with low toxicity that is most useful for SHORT TERM use in early mild PD or later to help with dyskinesias from L-DOPA/carbidopa therapy
Essential Tremor (ET): Pharmacological Treatment
P TGA P
Many drugs enhance neurotransmission at the GABAA receptor
1. Primidone (barb)
2. Topiramate (prolong Na IA / block CA)
3. Gabapentin (increase GABA / decrease GLUT)
4. Alprazolam (benzo)
5. Propranolol
Spasticity: Pathophysiology
-Upper motor neuron lesions
-Increased muscle tone
-Hyperreflexia, weakness/paralysis of SKM
Tizanidine
AA BD SHX
MOA: alpha2 agonist
AE:
-skeletal muscle weakness
-hypotension
-bradycardia
-drowsiness
-xerostomia
Baclofen
G, SDDDF
MOA: GABAb agonist
AE:
-skeletal muscle weakness (more than tizanidine)
-dizziness
-drowsiness
-depression
-fatigue
Diazepam
G, PSMAT
MOA: increases GABAa activity
AE:
-sedation
-motor impairment
-amnesia
-tolerance
-physical dependence
