PD Drugs Flashcards
Apomorphine
dopamine agonist
Role of Dopamine agonists
important role as first-line therapy for PD
lower incidence of response fluctuations and dyskinesias that occur with long term LD therapy
may also be given to patients who are taking LD and who have end of dose akinesia or on-off phenomenon or becoming resistant to LD
Dopamine Agonists
Apomorphine Bromocriptine Pergolide Pramipexole Ropinirole Rotigotine
why is Pergolide a dopamine agonists no longer available
has been associated with the development of Valvular heart disease
Pramipexole
ergot derivative
preferential affinity for the D3 family of receptors
effective as monotherapy for mild PD but also helpful in patients with advanced disease permitting reduction of LD dose and smoothing out response fluctuations
Readily absorbed after oral administration
Peak plasma after 2 hrs
excreted in the urine
start as dose of 0.125 mg 3x/d
doubled after 1 week and again after another week
Further increments in the daily dose are by 0.75mg weekly intervals depending on response
Most patients require between 0.5 to 1.5mg 3x/d
wof: renal insufficiency may need dose adjustment
Ropinirole
nonergoline derivative
pure D2 receptor agonist effective as monotherapy in patients with mild disease and as a means of smoothing the response to LD in patients with advanced disease
0.25 mg 3x/d and the total daily dose is then increased by 0.75 mg/week until the 4th week then 1.5mg/week thereafter
usually 2 -8mg 3x/d is necessary
metabolized by CYP1A2
Rotigotine
dopamine agonist
delivered thru a skin patch
approved for treatment of early PD
efficacy in more advanced disease is less clear
Adverse effects of dopamine agonists
nausea, vomiting, anorexia
postural hypotension
cardiac arrhythmia is an indication for discontinuation
pergolide - cardiac valvulopathy
dyskinesias
mental disturbances - includes compuslive gambling, shopping, betting, sexual activity
somnolence particularly pramipexole, ropinirole
Contraindications to Dopamine Agonists
psychotic illness
recent myocardial infarction or with active peptic ulceration
Difference of MAO-A and MAO-B inhibitor
MAO A - metabolizes norepinephrine, serotonin and dopamine
MAO B - metabolizes dopamine slectively
MAO B inhibitors
Selegiline
may reduce mild on-off or wearing-off phenomenon
Rasagiline more potent than selefgline in preventing MPTP-induced parkinsonism and is being used for early symptomatic treatment
Standard dose of selegiline
5mg with breakfast and 5mg with lunch, may cause insomnia when taken later during the day
dosing of rasagiline
1mg/d
considerations when giving MAO B inhibitors
not to be given in patients on meperidine, should be used with care in patients receiving tricyclic antidepressants or SSRI - serotonin syndrome
combination of LD and MAOIs must be avoided because it may lead to hypertensive crises because of peripheral accumulation of norepinephrine
COMT
Catechol-O-Methyltransferase Inhibitors
tolcapone and entacapone
diminish peripheral metabolism of LD
Why is Entacapone preferred over tolcapone
it has not been associated with hepatotoxicity
additional info: tolcapone has central and peripheral effects, entacapone - peripheral
Stalevo
LD/CB/entacapone prep 50 : 50mg LD/12.5 CB/200mg entacapone 100: 100mg/25 mg/200mg 150: 150/37.5/200
Potent dopamine agonist effective for teoprary relief of off-periods of akinesia in patients optimized dopaminergic therapy
subcutaneous injection
Apomorphine
leading to cinical benefit that begins within 10 minutes of injection and persists for up to 2 hrs
max 10mg, not be given more than 3x daily
antiviral agent found to have antiparkinsonism properties
amantadine
MOA unclear
reported to antagonize the effects of adenosine at adenosine A2A receptors, which are receptors that may inhibit D2 receptor function
less efficacious than LD
100 mg 2 or 3x daily
Adverse effects of Amantadine
restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, confusion
overdosage ay produce acute toxic psychosis
higher doses - convulsions
Livedo reticularis peripheral edema headache heart failure posturla hypotension urinary retention GI disturbances
<p>dopamine agonistsergot derivatives</p>
<p>ropinirOLE
pramipexOLE
dapat rOLE models pag dopa agonists</p>
glutamate antagonist
amantadineantagonist si Amantadine
<p>anticholinergics</p>
<p>Benztropine
| Trihexyphenidyl</p>
COMT inihibitor
EntacaponeCOMTacapone
<p>MAO inihibitors</p>
<p>Rasagiline
Selegiline
M(AOI) RSe</p>
side effects of this PD drugLeg swelling, congestive heart failure, prostatic outlet obstruction, confusion, hallucinations, insomnia
amantadine
side effects
Atropinic effects: dry mouth, urinary outlet obstruction, confusion, and psychosis
Benztropine
aside from levodopa what PD drug can also cause dyskinesias
Entacapone
<p>decarboxylase inhibitors</p>
<p>carbidopa
| benserazide</p>
True or False
Dopamine agonists are less potent than levodopa.
True
1091
True or False
In PD, the use of a low-protein diet has been advocated as a means of controlling the motor fluctuations.
True
p1093