Pharm - Movement disorders Flashcards
- Describe the two components of Sinemet and their functions.
Sinemet is a combination of L-dopa (Levodopa) and Carbidopa. L-Dopa is the precursor to Dopamine and will increase synthesis. Carbidopa is a DOPA decarboxylase inhibitor that prevents the metabolism of L-Dopa in the periphery. Carbidopa cannot cross the BBB
Give one reason daily doses of L-dopa are decreased over time.
Avoid side effects that are not present when initially taking it. These are due to the reduction of dopaminergic cells, causing an excess of L-dopa to build up.
Explain the “on-off phenomenon” and give one treatment for it.
A treat patient with L-dopa exhibits two different adverse signs while on medication. “Off” periods are marked by akinesia (similar to the “wearing off” effect). Whereas “on” periods improved mobility but marked dyskinesia. The treatment for the off periods are treated with SubQ apomorphine (dopamine agonist).
- Give two reasons COMT inhibitors entacapone and tolcapone improve responsiveness to L-dopa.
They decrease metabolism of levodpa in the periphery and decrease the synthesis of 3-O-methlydopa(3OMD) which competes with L-dopa for the same transporter across the BBB
- Give the 3 components of Stalevo.
Stalevo combines levodopa (L-Dopa and carbidopa) with entacapone (peripheral COMT inhibitor)
- Give two advantages of DA agonists over L-dopa.
Dr. Esper said he’d like to prescribe these first
• Do not require the enzymatic conversion
• Have no toxic metabolites (NE metabolite in the periphery that causes cardiovascular effects)
• Do not compete with other substances to actively cross into blood and the BBB
• Have fewer adverse affects:
Lower incidence of response fluctuations and/or dysknesias
- Give two indications for pramipexole.
A specific D3 receptor agonist or a “dopamine agonist.”
Can be used as a monotherapy for mild forms of PD
Can be used as adjunctive therapy with advanced PD to lower L-dopa dosage or smooth out fluctuations.
- Give the specific indication for apomorphine.
Apomorphine is a subQ injection of a potent dopamine agonist. Given because of its quick acting (~10 min) effects on the “off” period of akinesia in patients on dopamine therapy.
- Give the symptoms of PD that improve with treatment with Ach blockers.
Will improve the tremor and rigidity but will have little effect on bradykinesia
Examples are benztropine mesylate, trihexyphenidyl
- Give the class of drugs given for postural tremor and one in this class not to give.
β- blockers can be given to alleviate postural tremor and one example is propranolol. (But not metoprolol a selective β1 receptor inhibitor). The tremor is mediate through activation of β2 receptors
- Give four drugs to be given for essential tremor.
β-blockers: Propranolol (used with caution with patients with heart failure, heart block, asthma and hypoglycemia) Antiepileptics: Primidone Topiramate Anti-axiety - Benzodiazepine: Alprazolam
- Give three drugs used to treat Huntington’s Disease.
Dopamine receptor antagonists:
Phenothiazines (perphenazine), Butyrophenones (haloperidol)
Reserpine
Prevents intraneuronal storage of dopamine
AE – hypotension, depression, sedation, diarrhea and nasal congestion
Tetrabenzaine
Inhibits monoamine transporter 2 to decrease central monoamines (i.e. dopamine)
- Give the MOA of tetrabenazine and an advantage it has over reserpine.
Dopamine antagonist
1. Inhibits vesicular monoamine transporter 2
1. Depletes central monoamines
2. Precise mechanism of antichorea effects are unknown
Less adverse effects compared to reserpine but patients can become depressed and suicidal
- Give one drug approved for ALS.
Riluzole only drug specifically approved for ALS
Protects motor neurons from toxic effects of excitatory amino acids (inhibits glutamate signaling)
- Explain the inherent difficulty in treating tardive dyskinesia.
Drug induced dyskinesia (from typical antipsychotics). Often trying to treat symptoms by reducing the dopamine receptor blocker often worsens the dyskinesia. You have to use drugs that interfere with dopamine signaling.
Try to switch the patient
Examples: • Reserpine, tetrabenazine, trihexyphenidyl • Phenothiazines, butyyophenones (last resort usage)
- Give one drug used to treat restless leg syndrome.
Unpleasant, creeping discomfort that causes the urge to move
Ropinirole a dopamine agonist
Ropinirole can also treat Wilson’s disease
- Describe the dosing regimen for Sinemet.
Doses start small x 3/day (Sinemet is carbidopa 25 mg/ L-dopa 100 mg)
Dose can be increased but can enhance side effects
Keep low and add additional drug therapies
EX: dopamine agonist/additional enzyme inhibitors
The drug Parcopa has been formulated to disintegrate in saliva.
- Give a class of drugs contraindicated with L-dopa and what the combination can cause.
Dopaminergic (dopamine antagonists) anti-emetics are NOT given as they may exacerbate the parkinsonism
Pyridoxine enhances peripheral breakdown of L-dopa (in absence of carbidopa)
Monoamine oxidase A inhibitors will increase dopamine levels
When given at the same time, or within 2 weeks they may initiate a hypertensive crisis.
- Give a surprising population that should be careful with L-dopa treatment and describe why.
• Psychotic patients – exacerbates mental disturbances (remember typical anti-psychotics mostly block DA2 receptors) Dopaminergic dysregulation syndrome.
o Leads to cyclical mood disorders (hypomania/manic), tolerance, and impulse control disorders (hypersexuality and pathological gambling)
• Angle-closure glaucoma (increased IOP)
• History of melanoma/undiagnosed skin lesions
• L-dopa precursor to skin melanin -> malignant melanoma
- Give the indication for selegiline.
a. A selective irreversible inhibitor of MAO-B
b. Minor therapeutic effect when given alone
Prolongs antiparkinsonism effect of L-dopa (allowing for lower doses) for Parkinson
- Give the specific indication for apomorphine.
SubQ injection – quickly into blood and brain
Effect seen ~10 min and lasts for ~2 hours
Potent dopamine agonist
Temporary relief of off-periods of akinesia in patients on dopamine therapy
AE – nausea; pretreatment with an antiemetic (trimethobenzamide)
