PD- Khan

What disease results from the loss of dopaminergic neurons in the substantia nigra?

Parkinson’s disease

The D1 receptor is the ___________ pathway and ____________ movement.

a. direct, inhibits

b. indirect, inhibits

c. direct, enables

d. indirect, enables

c.

The D2 receptor is the ___________ pathway and ____________ movement.

a. direct, inhibits

b. indirect, inhibits

c. direct, enables

d. indirect, enables

b.

Which of the following receptors is inhibited in PD?

a. D1

b. D2

a.

The majority of Parkinson’s cases are ______________.

a. genetic

b. idiopathic

c. caused by drugs

d. caused by environmental toxins

b.

What are some causes linked to parkinson’s?

• Infectious diseases (viral encephalitis)

• Drugs (antipsychotics, antiemetics)

• Environmental toxins

• genetics

What are the symptoms of PD?

• bradykinesia

• muscle rigidity

• tremor

• postural instability

What are the 2 proposed MOAs of Amantadine?

1. Promotes release of DA from remaining striatal dopaminergic terminals

2. Antagonism of NMDA receptor of Glutamate

What is the MOA of Levodopa? Carbidopa?

• levo: dopamine precursor, converted to dopamine in the brain and Increases dopamine synthesis in the striatum

• carb: Inhibit dopa decarboxylase (DCC) in the periphery and makes levodopa more available to the CNS

What is the MOA of COMT inhibitors?

• does it work centrally or peripherally?

• what does it do to DA?

Inhibits COMT in the periphery —> Increases DA and levodopa levels in the brain

What is the MOA of MAO-B inhibitors? What conversion does it prevent?

Selective inhibitor of MAO-B —> MAO-B converts DA to DOPAC

What is the MOA of anticholinergic agents used in PD?

Prevents activation of cholinergic receptors in CNS

Side effects of Amantadine?

• Somnolence (drowsy)

• Psychosis

• Dizziness

• Orthostatic hypotension

Side effects of Carbidopa/Levodopa?

• n/v

• dyskinesia

• CV effects (postural hypotension)

• Psychiatric effects (hallucinations, psychosis)

• Positive Coomb’s test (d/c the drug)

• Dark discoloration of urine, sweat, saliva

• priapism

Side effects of COMT inhibitors?

• Diarrhea

• Confusion

• hallucination

Side effects of MAO-B Inhibitors?

• C/I with hepatic impairment

• Visual changes

Side effects of Dopamine agonists?

• n

• Hallucinations

• Confusion

• Sudden sleep attacks

• Orthostatic hypotension

Side effects of anticholinergic agents?

Intense anticholinergic SEs (dry mouth, blurred vision, urinary retention, tachycardia, confusion)

98% of the oral dose of levodopa is converted to dopamine in the peripheries. What’s the consequence of this?

less levodopa gets to brain, DA SEs in the periphery

Does levodopa have a long or short t ½ ?

What enzyme inactivates levodopa in the peripheries?

• short t ½

• COMT enzyme

Carbidopa/levodopa is contraindicated in what condition?

glaucoma

What are the drug interactions with carbidopa/levodopa?

• nonselective MAO inhibitors

• antipsychotic drugs

• pyridoxine

Before initiating carbidopa/levodopa what drug should be discontinued at least 2 weeks prior due to hypertension?

nonselective MAO inhibitors

Why does levodopa interact with pyridoxine?

pyridoxine stimulates decarboxylase activity= decrease levodopa therapeutic effects

In some pts. what develops near the end of the dosing interval with carbidopa/levodopa?

gradual loss or “wearing off”

What is the on-off phenomenon seen in pts. taking carbidopa/levodopa?

• randomly occurring event

• off times can be minutes—> hours

• off times increase in frequency/intensity as disease progresses

What are the advantages and disadvantages of the carbidopa/levodopa combination?

Advantages

• Daily requirement of Levodopa may be reduced

• Decrease GI and cardiac SEs

• More rapid onset

• Improved control

• Enhanced efficacy

Disadvantages

• Dyskinesia and psych disturbances may be more intense and occur sooner

Be able to recognize the structures of dopamine AND levodopa

Apomorphine must be given concomitantly with what and why?

with antiemetic (ex: trimethobenzamide) bc apomorphine is a POTENT emetic (stimulates CTZ-vomiting center)

Apomorphine is what dosage form?

a. IV
b. SQ

c. oral

d. patch

b.

When is apomorphine C/I?

with 5HT3 antagonists (severe hypotension, loss of consciousness)

What enzyme converts levodopa to dopamine?

l-aromatic amino acid decarboxylase also called DDC-dopa decarboxylase

What conversions are catalyzed by COMT?

• Dopamine—> 3-methoxytyramine

• DOPAC—> HVA

• Levodopa—> 3-O-methyldopa

What drug interactions are associated with MAOIs?

• combining a SSRI/SNRI with MAOI (results in serotonin syndrome)

• do not take with other MAOIs or opioids

An SSRI should be discontinued ___ weeks before starting MAOIs?

a. 1

b. 2

c. 3

d. 4

b.

MAOIs should be avoided with what food?

tyrosine containing foods (sausage, sauerkraut, cheese, airdried meat)

Anticholinergics are contraindicated in what 3 conditions? why?

1. narrow-angle glaucoma—> mydriasis, increase IOP, retinal damage

2. GI obstruction—> further decrease in GI tone/secretion

3. BPH—> aggravation of urinary hesitancy, dribbling

What drugs can cause Parkinson’s symptoms?

• 1st and 2nd gen antipsychotics

• Antiemetics: metoclopramide, promethazine

What drugs can be used to treat Parkinson’s symptoms caused by drugs?

• preferred: QUETIAPINE

• pimavanserin

What are the ADRs of quetiapine?

• metabolic comp. (increase blood sugar and cholesterol)

What drug is used to treat “off” condition? class?

safinamide—> MAO-B inhibitor

ADRs of Selegiline?

insomnia, jitters