Drugs for Parkinsons

Question 1

DRUGS FOR PARKINSONS

Answer 1

Normally have balance of acetylcholine and dopamine.
Decrease in dopamine → increase in acetylcholine.
Bringing acetylcholine level back to normal can bring dopamine level up.
Bringing dopamine level up gets acetylcholine level down.

Question 2

ANTICHOLINERGICS

Answer 2

AKA cholinergic blocking agents, parasympatholytics, antimuscarinics. – have been used for >150 yrs.

Question 3

ANTICHOLINERGICS

Action

Answer 3

Action – Block the action of acetylcholine at the muscarinic receptors in the PSNS. Competitive antagonists which compete with acetylcholine at the muscarinc receptor site → inhibition of nerve transmission.

Question 4

ANTICHOLINERGICS

causes

Answer 4

Causes: mydriasis and cycloplegia (eye stuff); decreased GI motility, decreased secretions; increased HR; decreased bladder contraction; decreased sweating; decreased bronchial secretions

Question 5

ANTICHOLINERGICS

uses

Answer 5

Uses – decrease muscle rigidity and tremors. Tx heart block and sinus bradycardia. Tx bronchospasm. Tx ulcers, IBD, and GI hypersecretory states. Tx pancreatitis.

can produce a little improvement in functional capacity. Usefulness limited by SE and get less effective with continued use. Also used to control EPS.

Parkinson’s drugs are only effective for a little while and then they stop working and you have to change the drug class to get better symptom control. By the time most patients cycle through all the classes of drugs they have had decent symptom control for about 20 years.

Question 6

ANTICHOLINERGICS

interventions

Answer 6

Interventions: elderly can respond to usual doses c agitation, sleepiness, and altered thought processes. Get memory problems. Also paradoxical excitability, confusion, hallucinations.

Question 7

ANTICHOLINERGICS

interventions

Answer 7

Precipitate glaucoma because mydriatic (pupil gets bigger which blocks the angle the fluid has to go through?)

Dec GI motility and GU function so careful with pts with GI disorders, and tendency to urinary retention or BPH.

Inc HR, so careful is pt has CV disease.

Careful with COPD pts, can dry secretions and → mucus plugs. Start with low doses and build up gradually, also stop same way.

Give before meals [30-60min] to maximize absorption. No antacids or antidiarrheal within 1 hr.

Question 8

Benztropine [Cogentin]

Anticholinergic

Answer 8

Benztropine [Cogentin]*** – suppresses tremor and rigidity. PO, IM, IV.
SE: drowsiness, confusion, constipation , N/V, blurred vision, mydriasis, photophobia, dry skin, urinary retention, decreased sweating
OD: resp depression, circulatory collapse, shock, coma. Antidote = physostigmine.

Question 9

Trihexyphenidyl [Artane]

Answer 9

Trihexyphenidyl [Artane] - same as Cogentin. In older males, may → prostatic hyperplasia.

Question 10

Atropine

Answer 10

Atropine is used a lot in emergency hospital settings (OD causes resp depression, circulatory collapse, shock, and coma. Antidote for anticholinergics is physostigmine.)

Question 11

DOPAMINE INCREASERS

Answer 11

DRUGS THAT INCREASE BRAIN DOPAMINE LEVELS
levodopa [L-Dopa]*** – THEY SAVE THIS FOR THE END AFTER THE OTHERS STOP WORKING.
Small percentage crosses blood-brain barrier intact. Decarboxylated to dopamine, replacing missing brain dopamine and balancing dopamine-acetylcholine concentrations

Takes 2-3 weeks to get effect. Sometimes much longer.

Question 12

DOPAMINE INCREASERS SE

Answer 12

SE: anxiety, nervousness, confusion, nightmares, tremors and involuntary movements, insomnia, dystonias (head bobbing, jerking movements – require lowering of dose), flushed skin, dark urine or sweat. Depression, mood changes, increased aggressiveness (Psychosis in about 20% of pts on ldopa) irregular heart beat, orthostatic hypotension. Severe nausea and vomiting. And HA.

Question 13

DOPAMINE INCREASERS SE

Answer 13

Not recommended for kids, preggies, pts with skin lesions or malignant melanoma.

Question 14

Interventions

DOPAMINE INCREASERS

Answer 14

Interventions – give before meals because food impedes drug’s action.
Orthostatic hypotension can be real problem. Call MD if Sx of OD eg involuntary muscle twitching and winking.
Must have 2 weeks off before giving MAOI. Must have 12 hrs between levodopa dose and start of carbidopa-levodopa combo pill.

Question 15

Dietary counseling

Answer 15

Dietary counseling: proteins may be metabolized into amino acids, which compete with levodopa for transport to the brain, making the response to levodopa unpredictable. Divide protein intake evenly throughout day.

Question 16

Dietary counseling II

Answer 16

Vitamin compounds and foods high in pyridoxine (Vit B6), such as pork, beef, liver, bananas, ham, and egg yolks, may decrease the effects of l-dopa and should be avoided.

Take high fiber and fluid intake to minimize SE of constipation.

Question 17

LevoDopa ON-OFF SYNDROME

Answer 17

Comes after long term Tx [2 years or more]. Pt fluctuates from being Sx free “on” to demonstrating full blown Parkinson’s Sx “off” during therapy. May last from a few minutes to hrs and may be 2O to a decease in delivery of dopamine centrally; an alteration in sensitivity of the dopamine receptors; variation in amount and rate of drug absorption; a dopamine metabolite interference; or a combination of effects.

Question 18

ON-OFF SYNDROME treatment

Answer 18

Rx: 1) give more frequently, 2) add bromocriptine, 3) give new drug – apomorphine HCL [Apokyn] – approved as an orphan drug to Tx the off syndrome.

Question 19

Wearing off effect

Answer 19

seen at end of duration as serum level may fall below therapeutic. Need more frequent dosing.

Question 20

Levodopa-carbidopa [Sinemet]

Answer 20

see this or L-dopa most often.

Question 21

Levodopa-carbidopa [Sinemet]

Answer 21

Carbidopa is a decarboxylase inhibitor. Competes c the enzyme dopa decarboxylase, thus retarding the peripheral breakdown of l-dopa [and minimizing SE like N/V]. Carbidopa does not cross blood-brain barrier and does not interfere with the intracerebral transformation of l-dopa to dopamine. Because of peripheral action get less SE. Combining the 2 drugs allows the use of much lower doses of Ldopa. Do not get pyridoxine interaction. But, because more ldopa gets to brain - get more CNS SE, such as involuntary movements, eyelid spasms, mental changes.

Question 22

Parcopa

Stalevo

Answer 22

Parcopa = levodopa and carbidopa – a dissolving tablet
Stalevo = levodopa, carbidopa and entacapone.

Question 23

DOPAMINE AGONISTS

Answer 23

Used alone with mild disease or with ldopa with advanced disease. No dietary restrictions. Even when used long term, they have less wearing off effect and less dystonias. But they can cause more orthostatic hypotension, hallucinations, and sudden attacks of sleep.

Question 24

2 classes

Answer 24

Ergot alkaloids and non-ergot alkaloids.

Question 25

Non-ergot: DOPAMINE AGONISTS

Pramipexole [Mirapex]

Answer 25

Pramipexole [Mirapex]
Used alone early on and with ldopa later on.
Also used for restless leg syndrome
Agonizes dopamine receptors at both presynaptic and postsynaptic sites
SE – Hallucinations, dizziness, drowsiness, nausea. Orthostatic hypotension (>50% or pts). Sleep attacks. Blood dyscrasias.

Question 26

Non-ergot: DOPAMINE AGONISTS

Apomorphine [Apokyn]

Answer 26

Apomorphine [Apokyn]
SC injection
Not routine use – just a dose for off episodes
Does not bind to morphine receptors – no analgesia
SE – Sleep attacks. Circulatory failure. Severe N/V – use Tigan for 3 days prior to injection. Orthostatic hypotension, anorexia, agitation, erections.

Question 27

Non-ergot: DOPAMINE AGONISTS

Ropinirole [Requip]

Answer 27

Ropinirole [Requip] - also for restless leg syndrome

SE – Syncope, drowsiness, fatigue.

Question 28

Ergot Dopamine Agonists:

Bromocriptine [Parlodel]

Answer 28

Bromocriptine [Parlodel] - has many other uses also.

SE – Seizures, shock, MI. Psych reactions – confusion, hallucinations, paranoia, nightmares

Question 29

Amantadine [Symmetrel]

Other drugs for PD

Answer 29

Amantadine [Symmetrel]*** – Releases dopamine from neuronal storage sites. Blocks uptake of dopamine into presynaptic neurons, thus permitting peripheral and central accumulation of dopamine.

Used as antidyskinetic [and antiviral]. Effectiveness is usually limited to about 6 - 12 months because functioning nerves decrease as disease progresses.

SE: Impaired concentration, dizziness, increased irritability, N/V/A, nervousness, purple-red skin spots, blurred vision, constipation, HA, dry mouth, hallucinations, mood changes

Can make edema, CHF, psych illness, and seizures worse.

Question 30

Catechol-O-methyltransferase

Answer 30

COMT inhibitors enhance the effectiveness of levodopa by blocking COMT, one of the main enzymes responsible for breakdown of levodopa in the bloodstream before it reaches the brain. By preventing breakdown in peripheral tissues, more is available for the brain. Their entire effect is from the increase in ldopa in brain.

Question 31

Catechol-O-methyltransferase

Answer 31

Tolcapone [Tasmar]*** – Preg cat C – may cause liver failure
entacapone [Comtan] – Preg cat D

SE – dyskinesia (due to higher levels of dopamine), N/V, orthostatic hypotension, psych S/S, urine discoloration.

Question 32

MAO-B Inhibitors

Answer 32

MAO-B inactivates dopamine.

Drugs – Selegiline [Eldepryl] - PO, disintegrating tab, patch.
Rasagiline [Azilect] – PO

SE – Orthostatic hypotension, dyskinesias, confusion , N/V, HA, arthralgia, dyspepsia. Don’t need tyramine restriction unless high doses used.