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

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Flashcards in Ch.22: Drugs for Parkinson's Disease Deck (15)
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1
Q

Cardinal Symptoms of PD

A
  • dyskinesia: tremor at rest, rigidity, postural instability, bradykinesia
  • autonomic disturbances
  • depression
  • psychosis and dementia
2
Q

Initial Treatment

A
  • 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
3
Q

Levodopa

A
  • 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
4
Q

Levodopa: Mechanism

A
  • 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
5
Q

Levodopa: Adverse Effects

A
N/V:
- low initial doses and admin with food can reduce therapeutic effects by decreasing absorption
- giving additional carbidopa without levodopa can help reduce N/V
CV:
- alpha-adrenergic agonist
- postural hypotension
- increase intake of salt and water
psychosis:
- visual hallucinations
- vivid dreams or nightmares
- paranoid ideation
CNS:
- anxiety and agitation
- memory/cognitive impairment
- insomnia
- behavioural changes (gambling, binge eating, alcohol abuse)
dyskinesias: 
- activates malignant melanoma (perform careful skin assessment)
6
Q

Levodopa: Interactions

A
  • 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
7
Q

Levodopa: Food Interactions

A
  • 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
8
Q

Carbidopa/Levopdopa

A
  • 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
    disadvantage:
  • no adverse effect of its own
  • abnormal movements can occur sooner and be more intense than with levodopa alone
9
Q

Dopamine Agonists

A
  • 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
10
Q

Pramipexole

A
  • 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
11
Q

Bromocriptine

A
  • 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
12
Q

COMT Inhibitors

A
  • inhibit metoblism of levodopa in periphery
  • no direct therapeutic response on its ow
  • entacpone (safer and more effective) then Tolcapone
13
Q

Entacapone (Comtan)

A
  • 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
14
Q

Selegiline (Eldpryl)

A
  • 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
15
Q

Benztropine

A
  • 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