Ch.22: Drugs for Parkinson's Disease Flashcards Preview

Pharmacology > Ch.22: Drugs for Parkinson's Disease > Flashcards

Flashcards in Ch.22: Drugs for Parkinson's Disease Deck (15):

Cardinal Symptoms of PD

- dyskinesia: tremor at rest, rigidity, postural instability, bradykinesia
- autonomic disturbances
- depression
- psychosis and dementia


Initial Treatment

- mild symptoms: MAO-B inhibitor (Selegiline)
- more severe: Levadopa or a dopamine agonist
- levadopa is more effective than dopamine agonists but long-term use carries a higher risk for disabling dyskineslas
- management of motor flucutations: "off" times can be reduced with dopamine agonists, COMT inhibitors and MAO-B inhibitors; drug induced dyskinesias
- neuroprotection: no proven drug yet



- only given in combo with carbidopa (promost BBB entry)
- highly effective but benefits diminish over time
- oral administered; rapidly absorbed from small intestine
- food delays absorption, amino acids compete for intestinal absorption and transport across BBB, high protein food reduce therapeutic effects
- adverse: dyskinesias
- symptoms be controlled for first 2 years- return at end of 5 years
- acute loss of effect: gradual loss develops near end of dosing interval and indicates that drug levels have declined to subtherapeutic value
- can be minimized by: shortening dosing interval, giving a drug that prolongs plasma half-life (entacapone), giving a direct-acting dopamine agonist


Levodopa: Mechanism

- increasing dopamine synthesis in straitum
- enters brain via active transport system carried across BBB
- converted to dopamine
- helps restore a proper balance between dopamine and ACh
- activity of decarboxylases is enhanced by Vit B6 and can prevent levodopa from working


Levodopa: Adverse Effects

- low initial doses and admin with food can reduce therapeutic effects by decreasing absorption
- giving additional carbidopa without levodopa can help reduce N/V
- alpha-adrenergic agonist
- postural hypotension
- increase intake of salt and water
- visual hallucinations
- vivid dreams or nightmares
- paranoid ideation
- anxiety and agitation
- memory/cognitive impairment
- insomnia
- behavioural changes (gambling, binge eating, alcohol abuse)
- activates malignant melanoma (perform careful skin assessment)


Levodopa: Interactions

- first-gen antipsychotic drugs block receptors for dopamine and decrease therapeutic effects
- MAO inhibitors: levodopa can cause a hypertensive crisis if administered to an individual taking a nonselective MAO inhibitor
- anticholinergic drugs: excessive stimulation of cholinergic receptors contributes to the dyskinesias of PD- by blocking these receptors, anticholinergic agents can enhance responses to leodopa
- Pryidoxine (vit B6): decrease amount og levodopa available to reach CNS; reduce effect; carbidopa suppresses decarboxylase


Levodopa: Food Interactions

- high protein content can reduce therapeutic responses to levodopa
- neutral amino acids compete for absorption and transport across BBB
- spread their protein consumption evenly throughout the day



- allows dosage of levodopa to be reduced by 75%
- reduces CV responses to levodopa as well as N/V
- inhibits decarboxylase- eliminates concerns about decreasing the effects of levodopa by taking a vitamin preparation that contains pyridoxine
- no adverse effect of its own
- abnormal movements can occur sooner and be more intense than with levodopa alone


Dopamine Agonists

- first-line of drugs for PD
- direct activation of dopamine receptors in the straitum
- comparision with levodopa: less effective, not dependent on enxymatic conversion to be active, does not compete with dietary proteins, lower inceidence of response failure, less likely to cause dyskinesias
- two types: derivates of ergot and nonergot derivatives



- nonergot dopamine agonist
- used alone in early PD and with levadopa later on
- max benefits take several weeks to develop
- adverse: monotherapy: Nausea, dixxy, saytime somnolence, insomnia, constipation, weakness, hallicuinations
- combined: orthostatic hypotension, dyskinesias, and increase hallucinations
- rare: pathological gambling



- ergot derivative
- approved for PD
- poorly tolerated
- direct-acting dopamine agonist
- activate dopamine receptors
- used alone for early PD and in combo with levodopa for advanced PD
- advantage: prolong therapeutic responses when combines and reduce motor fluctuations; reduced dosage of levodopa
- adverse: Nausea; psychological reactions; retrroperitoneal fibrosis, pulmonary infiltrates


COMT Inhibitors

- inhibit metoblism of levodopa in periphery
- no direct therapeutic response on its ow
- entacpone (safer and more effective) then Tolcapone


Entacapone (Comtan)

- selective and reversible inhibitor of COMT
- inhibits metabolism of levodopa in intestine and peripheral tissues
- prolongs time levodopa is available to brain
- adverse: dyskinesias, orthostatic hypotension, nausea, hallicuinations, sleep disturb, impluse control disorders, vomiting, yellow-orange discoloration of urine


Selegiline (Eldpryl)

- modest improvement in motor function
- causes selective and irreversible inibition of MAO-B
- suppress destruction of dopamine and prolong effects of levodopa
- dramatically decline within 12-24 months



- anticholinergic drug
- reduce tremor and ridigity
- no reduction of bradykinesia
- better tolerated but less effective
- second line defense
- younger patients with mild symptoms
- avoid in elderly who are intolerant to CNS side effects