Show Menu

Pharmacology of Parkinson's Disease Cheat Sheet by

Pharmacology of Parkinson's Disease

Parkin­sonism Charac­ter­istics

Neurod­ege­ner­ative Disease
Symptoms include: tremor, postural instab­ility, slowed movement (brady­kin­esia), rigidity, shuffling
Combin­ation of rigidity, bradyk­inesia, tremor, and postural instab­ility
Non-motor symptoms: anxiety, depres­sion, confusion, cognitive impair­ment, person­ality changes, apathy, fatigue, sleep disorders, autonomic function abnorm­ali­ties, dysphagia, choking, sweating, sphincter dysfun­ction.
The disease is incurable, generally progre­ssive, and increased disability with time.
**Phar­mac­ologic treatment is used to treat symptoms and improve quality of life.

Importance of Tapering Off Therapy

Anti-P­ark­inson drugs must be tapered. Not tapering leads to a syndrome that resembles "­neu­rol­eptic malignant syndro­me" due to sudden "­dop­amine antagonist effect­s"
A 4 week tape is suggested
Signs similar to NMS: fever, severe "­pip­eli­ne" rigidity, tachyc­ardia, sweating

Drug Catego­rie­s/M­ech­anisms of Action

-COMT inhibition (Entac­apone, Tolcapone, Opicapone) DOPA DC Inhibitors (Carbi­dopa) Levodopa
-MAO-B Inhibitors (Seleg­iline, Rasagi­line) COMT Inhibitors (Tolca­pone) Dopamine Receptor Agonists (Prami­pexole, Ropinirole non erogt) (Bromo­cri­ptine ergot not used)
Amantadine (mechanism unknown) Antimu­sca­rinics (benzt­ropine, trihex­yph­enidyl, biperiden, ect)

Parkinson Dyskinesia

A compli­cation of L-Dopa therapy is dyskin­esi­as-­abn­ormal, chorei­form, and involu­ntary movements usually involving the neck, trunk, and upper extrem­ities. Dyskin­esias are often associated with peak antipa­rki­nsonian benefit, although they can also develop during the rise and fall of L-dopa effects. They are too much movement secondary to the extension of pharma­cologic effect or too much striatal dopamine receptor stimul­ation. They are much more likely to occur with L-dopa therapy than with dopamine agonist therapy.

Adenosine Antagonist

*Adenosine is a G protein receptor in the striatum that modulates the body's response to dopamine
Drug: Istrad­efy­lline (Nourianz)
MOA: adenosine antagonist interferes with GABA release and releases dopamine (gives patients a better voluntary movement capabi­lity)
Indica­tions: adjunct to levodo­pa/­car­bidopa for treatment of "off episod­es"
Formul­ation: oral
Side Effects: consti­pation, dizziness, nausea, little chance of insomnia, dyskinesia is the most common side effect even though the risk is relatively low
Consid­era­tions: once daily dosing, reduces "off time" by an hour and seems to be better tolerated than COMT-I and DA agonists in regard to dyskin­esias and compulsive behavior. Lower risk of psychotic symptoms reported.
Drug integr­ations with CYP3A4 inhibi­tors, dose adjust­ments required (max of 20 mg with from inhibi­tors)

Levodo­pa-­Car­bidopa (Dhivy)

MOA: Levodopa replen­ishes dopamine levels, carbidopa is a dopa decarb­oxylase inhibitor
Indica­tions: Triple scored for ease of titration (IR product)
Side Effects: Dyskin­esias, motor fluctu­ations, nausea, confusion, consti­pation, dry mouth, headaches, loss of appetite, orthos­tatic hypote­nsion, discolored sputum and cough (Inbrija)
Contra­ind­ica­tions: CI in patients with suspicious undiag­nosed skin lesions or history of melanoma.

Dopamine Agonists

Drugs: Pramip­exole (Mirapex, Mirape­xER), Ropinirole (Requip, Requip XL), Rotigotine (Neupro)
MOA: Agonists of dopamine
Indica­tions: better for younger patients, first line in those less than 50 (still less effective than levodopa), can be added to levodopa to reduce off time and improve symptoms or to help with dyskin­esias that are sometimes caused by levodopa
Formul­ation: Oral, Rotigotine is a skin patch (used for early Parkin­son's more continuous DA stimul­ation)
Side Effects: halluc­ina­tions, somnol­ence, may impair impulse control, other side effects are similar to levodo­pa-­car­bidopa
Contra­ind­ica­tions: Avoid in patients with a history of addict­ions, impaired impulse control, psychosis, cognitive impair­ment, recent MI
Consid­era­tions: Lower risk of dyskin­esias with these agents, Bromoc­riptine falls in this category, but is rarely used anymore (D2 agonis­t)-> it is an ergot. DA agonists have higher risk of neurop­syc­hiatric symptoms, BUT less risk of motor symptoms.

Levodopa Inhaler (Inbrija)

Not for patients with lung disease
Onset in 10 minutes
Duration of 1 hour

Treatment of Essential Tremor

Dysfun­ction of beta receptors has been implicated in some instances of essential tremor and this is evident by the fact that they may respond well to beta blockers such as metoprolol and propra­nolol.
The most useful is propra­nolol, metoprolol can be used in patients with concom­itant pulmonary disease that prevents them from using propra­nolol.
Propra­nolol (higher doses required at least 120 mg/daily divided) long acting version preferred with patients for less dosing.
CAUTION in patients with asthma, CHF, depres­sion, or hypogl­ycemia (just due to BB side effects)

Amantadine (Symme­trel)

MOA: antiviral medication (not used for the flu anymore) also potent­iates DA functi­onality by influe­ncing synthe­sis­/re­lease and reuptake, also a NMDA receptor type antagonist (decreases glutamate, antidy­ski­netic effect)
Indica­tions: can be used to target tremor, or added to levodopa in progressed disease for dykinesias
Formul­ations: Oral
Side Effects: confusion, insomnia, halluc­ina­tions, depres­sion, dizziness, orthos­tatic hypote­nsion, livedo reticu­laris (cosmetic problem only, due to spasms of blood vessels or blood flow problem near the surface of the skin)
Contra­ind­ica­tions: CI in severe renal impair­ment, caution in suicidal ideation D/C at the first sign of psychotic symptoms
Consid­era­tions: Gocovri is the ER version. Efficacy may wane after weeks or months, only used for later disease for dyskin­esia. Taken once at bedtime.


Drugs: Selegiline (zelapar), Rasagiline (Azilict), Safinamide (Xadago)
MOA: MAO-A breaks down NE, 5HT, and dopamine, MAO-B breaks down dopamine only. MAOIs stop the action of MAO A/B. This helps to preserve level of dopamine.
Indica­tions: Mild benefit in early disease (must have DA left to worry about rate of breakd­own), not beneficial as a monoth­erapy ->works best in combin­ation (Safin­amide is NOT effective alone at all, only in combo to reduce response fluctu­ations)
Formul­ations: Oral, Selegiline now has a transd­ermal patch (achieves higher plasma levels than oral)
Side Effects: halluc­ina­tions, orthos­tatic hypote­nsion, nausea, HTN, dry mouth, vivid dreams, HA, insomnia. May worsen dyskin­esias when used with levodopa. Agitation and insomnia are most common with selegi­line, Safinamide has less nausea.
Consid­era­tions: can be added to levodopa to reduce off time, keeps DA around longer, increases duration of action of levodopa. Drug intera­ctions (antid­epr­ess­ants, tramadol, meperi­dine, dextro­met­hor­phan, amphet­amines, and other MAOIs pose a risk for serotonin syndrome) Selegiline is most "­Act­iva­tin­g" so consider taking in the morning first thing
Overall lower risk of neurop­syc­hiatric effects compared to DA agonists, and less risk of dyskinesia compared to levodopa

Levodopa gel (Duopa)


Levodopa: Why can't we just give Dopamine

Dopamine is unable to cross the blood brain barrier by itselt.
However, the precursor levodopa crosses the BBB where it is then converted to Dopamine
There is also the peripheral inacti­vation of L-Dopa by COMT
So, Levodopa must be admini­stered with Carbidopa (DDC Inhibitor) or Entaca­pon­e/T­olc­apone (COMT Inhibitor) to prevent the breakdown in the periphery.
When levodopa is used alone, it has to be given in large doses to overcome metabo­lism.
This is why it is often given with another agent such as Carbidopa (a dopa decarb­oxylase inhibitor) or a COMT inhibitor to overcome its metabolism to DA so more is available to cross the BBB
Giving levodopa with carbidopa reduces the daily levodopa requir­ements by 75%
The goal is that Levodopa is converted to Dopamine once in the brain

Drug Catego­rie­s/M­ech­anisms of Action

Tremor Types

Intention Tremor
Involu­ntary contra­ctions that occur during voluntary movement. Most commonly affects the limbs and speech muscles. There is no real treatment, if drug induced then discon­tinue or reduce dose.
Essential Tremor
A tremor without intent­ional movement. Happens all the time. Hands and upper limbs are most commonly affected. Can be worsened with anxiety or intent­ional movement.
Parkin­son's Tremor
Tremor at rest. Gone when moving.

Levodo­pa-­Car­bid­opa­-En­tac­apone (Stalevo)

MOA: Levodopa replen­ishes dopamine levels, carbidopa is a dopa decarb­oxylase inhibitor
Indica­tions: COMPT inhibitor added
Formul­ation: Oral
Side Effects: Dyskin­esias, motor fluctu­ations, nausea, confusion, consti­pation, dry mouth, headaches, loss of appetite, orthos­tatic hypote­nsion, discolored sputum and cough (Inbrija)
Consid­era­tions: Tolcapone better penetrates the BBB and can act both periph­erally and centrally

Levodo­pa-­Car­bidopa (Sinemet, Rytary)

MOA: Levodopa replen­ishes dopamine levels, carbidopa is a dopa decarb­oxylase inhibitor
Indica­tions: First line choice, good for elderly patients
Formul­ation: Oral
Side Effects: Dyskin­esias, motor fluctu­ations, nausea, confusion, consti­pation, dry mouth, headaches, loss of appetite, orthos­tatic hypote­nsion, discolored sputum and cough (Inbrija)
Contra­ind­ica­tions: CI in patients with suspicious undiag­nosed, skin lesions, or history of melanoma
Consid­era­tions: Most effective drug for Parkin­son's motor symptoms, but it has the highest risk for dyskin­esias and motor fluctu­ations. Take 30 minutes before eating to enhance absorption because food can decrease absorp­tion. "Off episod­e"=s­ymptoms like tremor return between carbo/levo doses, this becomes more prominent as the disease progre­sses. There is a lower risk of neurop­syc­hiatric side effects compared with DA agonists. Usually choose IR product for initial therapy due to ease of titration. *Patients should NOT take large doses of B6 because it will cause peripheral conversion of L-dopa to DA

COMT Inhibitors

Drugs: Entacapone (Comtan), Opicapone (Ongen­tys), Tolcapone (Tasmar)
MOA: Inhibit COMT to prevent the breakdown of Dopamine in the periphery
Indica­tions: used as an adjunct to levodo­pa-­car­bidopa for "­wearing off" NEVER as a monoth­erapy
Formul­ation: Oral
Side Effects: discolored urine (reddish brown), nausea, diarrhea, liver toxicity (TOLCA­PONE- requires monito­ring), low blood pressu­re/­diz­ziness (Opica­pone) weight loss (opica­pone)
Consid­era­tions: when added to levodopa to reduce off time, it prolongs the action of levodopa by dimini­shing its peripheral metabolism . Combo product stalevo (levo-­car­bi-­ent­rac­pone), Entaco­apone taken at the same time as levodo­pa-­car­bidopa (up to 6x per day)
Entacapone is generally preferred because it has not been associated with hepato­tox­icity.


Drugs: Trihex­yph­enidyl, Benztr­opine
MOA: antagonist at M receptor in basal ganglia, help antagonize M receptors to help with rigidity and tremors (ensure smooth motor action) Helps to restore balance of ACh and DA.
Indica­tions: Used to target tremor (because unopposed ACh release), especially those <60 years of age
Side Effects: dry mouth, consti­pation, urinary retention, drowsi­ness, confusion, blurry vision, mydriasis
Contra­ind­ica­tion: CI in glaucoma, BPH, and dementia. Caution in the elderly (increased antich­oli­nergic effects)

Apomor­phine (Apokyn)

MOA: non-se­lective dopamine agonist
Indica­tions: used for acute treatment of "off episod­es" in advanced disease, rapid onset. Can reverse "off episod­e" in 10 minutes, used for rescue therapy
Formul­ation: oral, SQ
Side Effects: runny nose, yawing, edema, mouth tissue swelling (SL film), nausea often a complaint (can pre-treat with antiem­etic, not 5HT antago­nist) Warning: hypote­nsion, syncope, QT prolon­gation, psychosis, halluc­ina­tions, impulse control, excessive sleepiness
Consid­era­tions: short duration of action, average SQ dosing was TID in trial, SL can be given 5 times per day (2 hours apart). Can pre-treat with anti-e­metic to prevent N/V (do not use 5HT antagonist med for this like ondans­etron due to increased hypote­nsion risk) Requires initial titration to check BP/pulse because HUGE risk of hypote­nsi­on/­syncope

Pathop­hys­iology of Parkin­son's

In Parkin­son's disease there is loss of the dopami­ne-­con­taining neurons in the substantia nigra (A progre­ssive degene­ration of the Nigro-­Str­iatal tract). DA in normal physiology is present in the brain help to coordinate movement.
These neurons normally project tot he caudate putamen (one piece of the basal ganglia) where the dopamine inhibits firing of the cholin­ergic neurons. These cholin­ergic neurons form excitatory synapses onto other neurons that project out of the basal nuclei. The result of the loss of dopami­ne-­con­taining neurons is that the cholin­ergic neurons are now free to fire without their normal inhibi­tion. This is like a car going down a hill without any brakes.
Striat­um-> receives inform­ation from Neocortex and Substantia Nigra (sends DA to coordi­nate)
Without DA, there is more GABA resulting in increased action of GABA which leads to inhibition of the motor cortex
Without dopamine, there is decreased inhibition of ACh so there is an increase in cholin­ergic activity.
This imbalance between inhibition and excitation leads to the manife­station of symptoms.
Over all the goal, pharma­col­ogi­cally is to replenish dopamine levels, mimic action of dopamine, and to antagonize the excitatory action of ACh on GABA.


No comments yet. Add yours below!

Add a Comment

Your Comment

Please enter your name.

    Please enter your email address

      Please enter your Comment.

          Related Cheat Sheets

          Introduction to Pharmacology Cheat Sheet
          Drug Classes & Actions : NSAIDs Cheat Sheet

          More Cheat Sheets by Bailey_Rickett

          Migraine Pharmacology Cheat Sheet
          Pharmacology of Alzheimer's Disease Cheat Sheet
          Pharmacology of Ischemic Stroke Management Cheat Sheet