Etiology of Parkinsons
Dopamin deficiency OR Ach excess
Feature of Parkinsons
- Resting tremor
- Rigidity
- Bradykinesia
- Postural instability
Amyotrophic Lateral Sclerosis (ALS)
Sporadic or familial progressive neurodegenerative disease
Essential Tremor
Nerve disorder characterized by uncontrollable shaking while moving
Guillan-Barre
Immune system attack the nerves with weakness and tingling in the feet and legs–>ascending paralysis
Huntington’s Disease
Inherited adult-onset neurologic disease with dementia and bizarre involuntary movements
Myasthenia Gravis
Chronic autoimmune neuromuscular disorder with fluctuating weakness
Restless Leg Syndrome (RLS)
Urge to move the legs
Associated with iron deficiency
Tourettes Syndrome
Repetitive movements or unwanted sounds (tics) that can’t be easily controlled
Inherited (genetic) and environmental factors
Wilsons disease
Inherited autosomal recessive disorder of copper accumulation in liver, brain, kidneys, and eyes
List a monoamine Oxidase Inhibitor (MAO-B)
Rasagline
Rasagline ADEs
- Confusion
- Insomnia
- Hallucinations
- Nausea
- Orthostatic hypotension
Rasagline Drug interactions with Meperidine
Serotonin Syndrome
- N/V
- Tremor
- Agitation/restlessness
What would be the best treatment of choice in a 71-year-old PD patient?
Amantadine
Amantadine MOA
- Enhances Dopamine release
2. Blocks glutamatergic NMDA receptors
Amantadine Benefits
Decreases:
- Tremor
- Rigidity
- Bradykinesia
Amantadine ADEs
Anti-cholinergic effects:
- Dry as a bone-Dry mouth, urinary retention
- Blind as a bat-Dilated pupils/Mydriasis
- Mad as a hatter-Confused/hallucinations
- Red as a beet-Flushing
List the prototype Dopamine Agonist
Pramipexole
Pramipexole MOA
Stimulate dopamine activity on the nerves in the substantial nigra and striatum
Pramipexole ADE’s
- Postural Hypotension
- Impulsive Behavior-Tend to gamble
- Psychosis- Confusion, hallucinations, sedation, vivid dreams
Levodopa MOA
Dopamine Precursor
- Crosses the blood brain barrier
- Once crossed, converted to Dopamine
Carbidopa MOA
Prevents the metabolism of Levodopa in the peripheral blood via dopa decarboxylase
–>higher blood levels and good portion gets into the brain
Levodopa/Carbidopa drug interactions
COMT and MAO type B inhibitors diminish doses and prolongs action= Excess Dopamine
Levodopa/Carbidopa ADEs
- Drowsiness
- Nausea
- Dyskinesias-MOTOR COMPLICATIONS
List the two COMT inhibitors
- Entacapone
2. Tolcapone
COMT inhibitor effect on L-Dopa
1Blocks conversion of L-Dopa into the inactive form of 3-O-Methyldopa (3-OMD) = Greater % that will cross BBB
COMT inhibitor effect on Dopamine
Prevents conversion of Dopamine to 3-methoxytyramine (3-MT)
What are we going to monitor when using COMT inhibitors?
LFTs due to liver toxicity
What drug is the most useful as monotherapy in patients under 70 years of age with disturbing tremor who do not have significant bradykinesia or gait disturbances?
Anticholinergic/Antimuscaranic
List the two Anticholinergic/Antimuscaranic used in PD
- Benztropine
2. Trihexyphenidyl
What is Duopa
Carbidopa/Levodopa in Gel form that goes directly to your intestine through a tube
Benefits of Duopa
- Treat motor sx’s
- Improve absorption
- Reduce off-times by delivering directly to small intestines
End-of-dose “wearing off” (motor fluctuation) treatment
- Increase frequency of carbidopa/L-dopa doses
- Add COMT or MAO-B inhibitor
- Add Dopamine Agonist
“Delayed on” or “no on” response treatment
- Give carbidopa/L-dopa on empty stomach
2. Use carbidopa/L-dopa ODT
Start hesitation (“freezing”) treatment
- Increase frequency of carbidopa/L-dopa doses
- Add MAO-B inhibitor
- Add Dopamine Agonist
- Physical Therapy
- Sensory cues
Peak-dose dyskinesia treatment
- Provide smaller does of carbidopa/L-dopa
- Reduce dose of adjunctive dopamine agonist
- Add Amantadine
What do we want to give to your patients who are on Entcapone/Talcapone (COMT inhibitors) to help avoid one of the SE’s?
Anti-diarrheal agents due to diarrhea SE
What are we going to monitor in Amantadine?
- Mental status
2. Renal function
