Drugs for Parkinson Disease (Ch 24) Flashcards
Theraputic uses to Selegiline (MAO-B inhibitor)? and how is it used as an adjunctive agent? what does it allow for? what does is suppress?
-Used in combination with levodopa or levodopa-carbidopa
-Adjunctive agent when response to levodopa is fluctuating (“on-off”) (it can suppress the destruction of dopamine derived from levodopa)
Allows the dose of levodopa to be decreased
Ex of an anticholinergic agent?
Benztropine
Adverse effects of MAO-B selegiline?
Adverse effects usually mild
-nausea, abdominal pain, dry mouth
-lightheadedness, dizziness, insomnia, confusion
-doses higher than 10 mg/day may cause more severe adverse effects
What must we monitor for when treating PD? and what signs and symptoms of PD must we assess for?
Monitor for response to drug therapy
*Masklike expression
Speech problems
*Dysphagia
Rigidity of arms, legs, and neck
Adverse effects to anticholinergic effects?
-Dry mouth
-Blurred vision
-photophobia
-urinary retention
-constipation
-Tachycardia
What MAO-B inhibitor promotes DA release from nerve endings?
Amantadine
What indreict acting dopaminergic therapy causes the relase of dopamine from the stroage sites at the end of nerve cells that are still intact?
amantadine
What do anticholinergic agents also treat?
Also used to treat drug-induced extrapyramidal symptoms (EPS)
Mechanism of action/how does selegiline work? What effect does it not elicit?
-It causes selective, irreversible inhibition of MAO-B, the enzyme that inactivates dopamine in the striatum
-Does not elicit the “cheese effect” of the nonselective MAOIs used to treat depression (cheese, red wine, etc)
What are the two reasons why PD is not treated directly with dopamine?
1.) Because dopamine cant cross the BBB, levodopa crosses the barrier by means of an active transport system (a system that does NOT transport dopamine)
2.) Because dopamine has such a short half life in the blood that it would be impractical to use even if it could cross the BBB
when does the acute loss effect of levodopa therapy begin?
-Between 5 and 10 years after the start of levodopa therapy
-Gradual loss - “wearing off”—develops near the end of the dosing interval and indicates that drug levels have declined to a subtherapeutic value
What levodopa/carbidopa/Entacapone drug is given to newly dignosed patients? What does it do? what kind of inhbitor is it?
Selegilne
-Inhibits DA breakdown in neurones
-It may delay neurodegeneration and hence ,may delay disease progression, however there is no conclusive evidence of this
-MAO-B inhibitor
What is levodopa therapy aimed at?
Aimed at increasing dopamine release from surviving DA neurones (aimed at the remaining neurons in the brain)
what does Selegiline is a MAO-B inhibitor cause in the CNS?
Causes an increase in the levels of dopaminergic stimulation in the CNS
When starting dopaminergic agents why must we assist our client with walking?
Because dizziness may occur (hypotension)
How does levodopa therapy work How long does it take to see therapeutic responses? What does the therapy do?
-Therapy maintains functional mobility for years
prolongs quality of life
prolongs life expectancy
-Full therapeutic response may take several months to develop
-Therapy does not cure or stop progression of disease
How are Anticholinergic Therapy agents used? What are their theraputic effects? WHat do they block?
-Anticholinergics block the effects of ACh
-They are used to reduce tremor and rigidity but not bradykinesa(extremely slow movements)
Muscle tremors
Cogwheel rigidity
Pill-rolling movement of fingers and head bobbing while at rest
What is the main therputic use for amantadine?
Help manage dyskinesias caused by levodopa
(its not considered a first line treatment because responses are much less profound than with levodopa or the dopamine agonists)
What is given in combination levodopa therapy? What does it do? What does it not cross?
-Carbidopa does not cross the blood-brain barrier
-prevents levodopa breakdown in the periphery
What do anticholinergic agents also treat?
Also used to treat drug-induced extrapyramidal symptoms (EPS)
What kind of drug therapy is levodopa focused on?
Most drug therapy focused on DA pathway
As long as there are functioning nerve terminals (focuses on the remaining dopamine pathways)
-They are not a cure but they do extend life to a certain degree
What are some adverse effects of levodopa treatment? What is the main one that is ironic?
*Dyskinesia - (ironically)
involuntary muscle movements eg oral and facial muscles (chewing motion), writhing/flinging movement of arms and legs
-Hypotension and cardiac dysrhythmias
-Psychosis (hallucinations)
-Nausea and vomiting
-Activation of dopamine receptors in the chemoreceptor trigger zone of the medulla
-Low initial doses and administration with food can reduce therapeutic effects by decreasing levodopa absorption
-Giving additional carbidopa (without levodopa) can help reduce nausea and vomiting
Adverse effects to anticholinergic effects?
-Dry mouth
-Blurred vision
-photophobia
-urinary retention
-constipation
-Tachycardia
How does amantadine work? what does it cause? What does it block? What may it help with?
-Causes release of dopamine from the storage sites at the end of nerve cells that are still intact
-Also blocks the reuptake of dopamine into the nerve endings
-May help with levodopa-induced dyskinesias
What are some of the adverse effects to taking dopaminergic therapy?
hallucinations, postural hypotension
Impulse control disorders (pramipexole)
When used long term what are dopamine agonists less likey to cause? What do they reduce?
-They have a lower incidence of response failures and are less likely to cause disabling dyskinesais
Reduce “wearing off” effect of levodopa
less effective than levodopa
What is levodopa converted after uptake?
It is converted into dopamine, its active form
In what ways can the “wearing off” of levodopa be minimized?
-Shortening the dosing interval
-Giving a drug that prolongs levodopa’s plasma half-life (for example, entacapone)
-Giving a direct-acting dopamine agonist
Why is levodopa not given alone?
Most commonly, levodopa not given alone
additional drug to reduce peripheral levodopa metabolism
What kind of therapy is levodopa-carbidopa?
It indirectly works on the dopamine system
Ex of an anticholinergic agent?
Benztropine
Disadvantages of carbidopa treatment?
Carbidopa has no adverse effects of its own
-Any adverse responses from carbidopa/levodopa are the result of the potentiating of the effects of
levodopa
-When levodopa is combined with carbidopa, abnormal movements and psychiatric disturbances can occur
sooner and be more intense than with levodopa alone
How does Levodopa Therapy work?
1.)Levodopa is a precursor of dopamine
2.)Blood-brain barrier does not allow exogenously supplied dopamine to enter but does allow levodopa
3.) Levodopa is taken up by dopaminergic terminal
converted into dopamine, then released
Where is levdopa absorbed?
It is given PO and undergoes rapid absorption from the small intestine
2 cominations therapies?
Combination Therapy:
-Levodopa + Carbidopa
-Levodopa + Carbidopa + Entacapone
What reduces the effectiveness of levdopa therapy
-Food delays absorption
-Neutral amino acids compete with levodopa for intestinal absorption and for transport across blood-brain
barrier
-High-protein foods reduce therapeutic effects
What is levdopa only given in combination with?
Only given in combination with carbidopa or carbidopa/entacapone
What is the first line treatment for PD for patients with mild to moderate symptoms? Why? What are they less effective then?
Dopamine Agonists
-In contrast to levdopa, they are not dependant on enxymic conversion to become active, are not converted to potentially toxic metaboties, and do not compete with dietary proteins for uptake from the intestine or transport across the BBB
-Less effective then levodopa
