L-dopa
Parkinson's causes a decrease in Dopamine and increased ACH
Normally, there is a balance between Dopamine and ACH in the basal ganglia
How do Dopamine agonists work? What are some problems associated with them?
They can cross the BBB- directly stimulates dopamine receptors
Has longer 1/2 life- possibly more stable responses
Can be used as initial treatment in early PD, might be neuroprotective
Problems: N/v, confusion, hallucinations, postural hypotension, increased dyskinesia
What is the impact Antiparkinson drugs have on rehabilitation? What should we as PTs consider when treating these patients?
Coordinate rehab sessions with drug therapy
Optimal treatment time: 30-60 minutes after medication
Recognize the synergistic effects of PT and drug therapy
What is marijuana classified as? What does this mean for medical treatment?
It is classified as Schedule 1
It is currently not accepted as a medical treatment
What are som adverse systemic effects?
CV: increase HR, BP, myocardial O2 demand, increased risk of ischemic stroke
Pulmonary: airway inflammation, airflow obstruction, wheezing, coughing, increased sputum
GI: Increase N/V (hyperemesis syndrome)
What is the dopamine replacement therapy for Parkinson's called? How does it work?
It is called L-dopa or Levodopa- which is a precursor to dopamine
Since dopamine cannot cross the blood brain barrier, L-dopa is administered instead becasue it can cross the BBB
Carbidopa inhibits premature conversion of L-dopa and is usually combined with L-dopa in the same pill (SInemet)
How do COMT inhibitors work to treat parkinson's? What are some problems with this treatment?
COMT is an an enzyme that breaks down L-dopa in peripheral tissues
COMT inhibitors allows more L-dopa to reach the brain, can be combined with L-dopa and carbidopa (Stalevo)
Specific agents: tolcapone (Tasmar), entacapone (Comtan)
GI distress (diarrhea), orthostatic hypotension, increased dyskinesia, other
What is the goal of antiseizure medications? What are the primary mechanisms?
Goal: selective effect on hyperexcitable neurons. MANY agents with several chemical categories
Mechanisms: decrease sodium entry into rapidly firing neurons, decrease calcium entry into thalamic neurons , increase GABA inhibition, decreased release or effects of excitatory amino acids
What are Cannabinoids? What are the 2 most important ones?
It is the ""Active" ingredient in marijuana
THC: produces psychoactive effects and high
CBD: not as psychoactive, may provide certain medicinal effects
What are some acute and chronic CNS effects of MJ?
Acute: "high", increased perception, euphoria, some users- confusion, hallucinations, paranoia
- decreased cognition, alertness, rx time
- decreased balance, coordination (issue with older population)
Chronic: long term adverse effects are not well understood
What are some possible side effects with L-dopa therapy? What can happen towards the end of a dose cycle?
GI irritation, hypotension, Psychotropic behavioral effects, Dyskinesias, freezing of gait
End of dose akinesia: wearing off effect- decreased response toward end of dose cycle
How do Anticholinergic agents help treat Parkinson's? What limits its use?
Decreases acetylcholine influence, may help decrease rigidity and tremor
Use is limited by side effects
Common agents include: benztropine, mesylate, biperiden, diphenhydramine and trihexyphenidyl
Is there a difference between primary antiseizure drugs and second generation antiseizure drugs?
2nd gen drugs arent more effective but they can have milder side effects and have a more predictable profile.
2nd gen also allows for more drug combos when treating seizures
How do Cannabinoids affect humans?
1. Cannabinoid receptors
- CB1: found throughout NS, esp in pain pathways, produces psychotropic effects
- CB2: found in immune tissues, modulates immune and inflammation, does not produce psychotropic effects
2. Substances produced within the body (endocannabinoids)
- produced by CNS and peripheral tissues when tissues are injured or disturbed
3. Enzymes that synthesize and degrade endocannabinoids
- Anandamide, 2-AG
- drugs that enhance synthesis or inhibit breakdown may be beneficial
What is Cannabis Use Disorder?
Taken in larger amounts, over longer period than intended
Persistent desire, unsuccessful efforts to cut down or control use
A lot of time is spent in activities to obtain, use or recover from effects
Craving/strong desire to use cannabis
Failure to fulfill obligations at work, school or home
ect....
Is L-dopa therapy good for long term use?
Benefits may be lost, or dyskinesias become intolerable after 4-5 years of L-dopa therapy
How do MAO-B inhibitors help in the treatment of Parkinson's? Are there any problems with these?
They inhibit monoamine oxidase type B- prolongs dopamine effects in the brain so it doesn't break down as quickly
It is combined with L-dope to increase and prolong effects
No major problems
Agents: selegiline (Eldepryl, Zelapar), rasagiline (Azilect)
Minor: Sedation, HA, dizziness, incoordination, GI problems
More serious: liver toxicity, aplastic anemia, increased risk of birth defects
What are the different ways to administer medical marijuana? What are positives and negatives of each?
Inhalation: rapid onset and effects, easy to adjust does, may damage respiratory tissue
Oral: edibles- easy, convenient but long delay before onset, tablets- best method for regulating dose, long delay before onset/peak, Oromucosal spray- rapid onset, faily easy to adjust dose, avoids 1st pass effect
Topical/Transdermal: use of CBD products- cream, lotion penetrates through skin to treat subQ structures
Are the withdrawal symptoms from cannabis the same as withdrawal from opioids?
No, withdrawal from cannabis involves much milder symptoms
When is inhaled L-dopa used?
During the "Off" episodes if already treated with levodopa/carbidopa
How does Amantadine (Symmetrel) work to treat Parkinson's? Are there any prolems associated with it?
It is an antiviral agent that was discovered by chance to treat parkinsons
It blocks the NMDA receptors in the brain which decreases the influence of excitatory amino acids (glutamate)
Decreases chance of dyskinesias
Problems: orthostatic hypotension, psychotropic effects, skin discoloration
What is important to understand about D/C anti seizure medications? What are rehab concerns?
Make sure they talk to prescriber before stopping the medication to make sure they are okay to come off of the medication
60-70% can remain seizure free after medication is withdrawn but should be seizure free for 2 years, good seizure control within 1 year after seizures begin, normal neuro exam, initial seizure onset in childhood
Rehab concerns: be aware of patients taking this medication, document seizure activity
What can medical marijuana be used to treat (neuromusculoskeletal indications)?
Pain (cancer, neuropathic pain, fibromyalgia, arthritis, chronic neck/back pain)
Spasticity (MS)
Seizures (esp resistant seizures in children)
Can also be used for Chemo induced N/V, appetite stimulant and glaucoma
What are some rehabilitation issues with MJ?
Assess for positive effects: decreased pain, spasticity, seizures, disability
Assess for adverse effects: decreased balance, coordination, adverse CV/resp. effects, excessive/inappropriate use or concomitant use with other drugs
We CAN'T advise or recommend use, they need to be referred to their MD for more info