Tuesday, August 23-Drugs For Movement Disorders-DSA-Kruse Flashcards
Coadministration of levodopa with this DOPA decarboxylase inhibitor that does not cross the BBB results in increased levodopa available for entry into the brain
Carbidopa
Levodopa given in the absence of a peripheral decarboxylase inhibitor may have these adverse effects in the GI tract:
Anorexia, nausea, and vomiting in roughly 80% of pts
The combo of levodopa/carbidopa causes less frequent and less trouble some GI side effects in only 20% of pts
What are some potential cardiovascular adverse effects with tx of levodopa?
Postural hypotension can occur but often diminishes with continuing tx
HTN can occur with large doses of levodopa or in combo with nonselective MAOI or sympathomimetics
Increases in cardiac arrhythmias are rare and can be attributed to presence of increase peripheral catecholamine synthesis
In the on-off phenomenon, off-periods of marked akinesia alternate over the course of a few hours with on-periods of improved mobility but often marked dyskinesia. Subcutaneous injections of ___ may provide temporary benefit to those pts with severe off-periods
Apomorphine
Pts taking __ may experience hypertensive crisis when combined with levodopa
Monoamine oxidase A inhibitors
Levodopa is contraindicated in these types of pts:
- psychotic pts
- pts with angle-closure glaucoma
- pts with history of melanoma
- caution in pts with active peptic ulcer d/t possible GI bleeding
___ is an ergot alkaloid derivative that is a D2 agonist that is also approved for tx of endocrine disorders. It has extensive 1st-pass metabolism, a t1/2 of 15 hrs, and 28% bioavailability with peak plasma concentration usually attained within 1-3 hrs
Bromocriptine
___ has a preferential affinity for D3 receptors, is approved for tx of moderate-to-severe primary Restless Leg syndrome (RLS), and has a peak plasma concentration reached in 2 hrs with a half-life of 8 hrs. 90% of this drug is excreted unchanged in the urine (individuals with renal insufficiency may require dose adjustment)
Pramipexole
___ has a preferential affinity for D2 receptors and is also approved for tx of Restless Leg syndrome (RLS). It is metabolized primarily by CYP1A2 and coadministration with agents that are also metabolized by CYP1A2 may reduce the clearance of this drug. Its peak plasma concen reached in 1-2 hrs with t1/2 of 6 hrs
Ropinirole
What are some adverse effects of dopamine receptor agonists in the GI tract?
- anorexia, nausea, and vomiting can occur; symptoms reduced if taken with meals
- constipation, dyspepsia, and symptoms of reflux esophagitis
This adverse CV effect may occur with the use of dopamine receptor agonists, especially at the initiation of therapy
Postural hypotension
This dopamine receptor agonist may cause digital vasospasm during long-term tx.
Bromocriptine
In terms of adverse CV effects with the use of dopamine receptor agonists, the presence of ___ may indicate the need to discontinue therapy
Peripheral edema and cardiac arrhythmias
Headache, nasal congestion, increased arousal, pulmonary infiltrates, and pleural and retroperitoneal fibrosis have been reported with the use of this dopamine receptor agonist
Bromocriptine
What are some contraindications to using dopamine receptor agonists?
Pts with history of psychotic illness, recent MI, or with active peptic ulceration
This dopamine receptor agonist drug is contraindicated in pts with peripheral vascular disease (vasoconstricting effects)
Bromocriptine
There are 2 forms of monoamine oxidase:
___ preferentially metabolizes phenylethylamine and benzylamine
___ preferentially metabolizes norepinephrine and serotonin
MAO-B
MAO-A
These compounds are metabolized equally by MAO-A and MAO-B
Dopamine and tryptamine
__ is a selective irreversible MAO-B inhibitor (inhibits MAO-A at high doses) and slows the breakdown of dopamine and prolongs the antiparkinsonian effects of levodopa. It may reduce the on-off or wearing-off phenomenon. It is used as adjunctive therapy in pts with declining or fluctuating response to levodopa
Selegiline
10% bioavailability with peak [plasma] within an hr
You should use caution when prescribing Selegiline to pts who are taking ___
Caution recommended or contraindicated in pts taking Mepiridine, tricyclic antidepressants, or 5-HT reuptake inhibitors
___ is an irreversible inhibitor of MAO-B and is more potent than Selegiline. It is used as a neuroprotective agent and for early symptomatic tx of PD
Rasagiline
The coadministration of levodopa and a ___ must be avoided because it may lead to a hypertensive crisis (due to peripheral accumulation of norepinephrine)
Non-selective MAO inhibitor
___ metabolizes levodopa to 3-O-methyldopa, which competes with levodopa for transport across the intestinal mucosa and BBB
COMT
___ prolong the activity of levodopa by inhibiting its peripheral metabolism, which decreases clearance and increases bioavailability
COMT inhibitors –> Tolcapone and Entacapone
___ may be helpful in pts receiving levodopa who have developed response fluctuations
COMT inhibitors such as Tolcapone and Entacapone
Regarding COMT inhibitors:
__ may has both central and peripheral effects, whereas ___ has peripheral effects only
Tolcapone=central and peripheral
Entacapone=peripheral only
This COMT inhibitor may cause an increase in liver enezyme levels and has been associated, rarely, with death from acute hepatic failure (use in the USA requires signed pt consent)
Tolcapone
Side effects associated with COMT are often due to levodopa but include:
Orange discoloration of urine, diarrhea, abdominal pain, and sleep disturbances
This dopamine agonist appears to act by stimulating postsynaptic D2 receptors in the caudate-putamen. It is injected subQ for quick, temporary relief of off-periods of akinesia in pts on dopaminergic therapy (clinical benefits within 10 mins)
Apomorphine
Adverse effects of apomorphine include nausea, which can be pretreated with this antiemetic ____
Trimethobenzamide
Other adverse effects of apomorphine include dyskinesias, drowsiness, sweating, hypotension, and injection site bruising
__ is an antiviral agent whose MOA in parkinsonism is unknown (may potentiate dopaminergic function by influencing synthesis, release, or reuptake of dopamine). It has a t1/2 of 2-4 hrs; peak [plasma] reached in 1-4 hrs; excreted mostly unchanged in the urine. The benefits may be short-lived
Amantadine
This antiviral agent may cause livedo reticularis, a vascular condition characterized by a purplish mottled discoloration of the skin, usually on the legs. You want to use this drug with caution in pts with a history of seizures or heart failure.
Amantadine
Benztropine, biperidin, orphenadrine, procycladine, and trihexyphenidyl are examples of these drugs that are available to treat pts with PD.
Centrally acting mAChR antagonists
mAChR antagonists may improve tremor and rigidity associated with PD but have little effect on ___
Bradykinesia
B1-receptors have been implicated in some tremors and these tremors respond well to ___
Metoprolol and propanolol
Symtpomatic tremor can be controlled by the antiepileptic drug __ in smaller doses than those used to treat seizures
Primidone
This 5-HT receptor agonist has shown to be effective in the tx of tremors
Topirimate
Alprazolam (benzodiazepine) and IM injections of __ have been effective in treating some pts with tremor
Botulinum toxin A
___ is the immediate metabolic precursor to dopamine and an agonist at D receptors
Levodopa (L-dopa)
These drugs that impair dopaminergic neurotransmission often alleviate chorea associated with Huntington disease
Reserpine, tetrabenzine
___ are markedly reduced in the basal ganglia of pts with Huntington disease
GABA, glutamic acid decarboxylase, and choline acetyltransferase
Reserpine (irreversible) and tetrabenzine (reversible) are agents that block ___ and deplete cerebral dopamine stores
Vesicular monoamine transporter
The effects of tetrabenzine resemble reserpine but with less peripheral activity and a shorter DOA
The most predictive and effective pharmacological approach to the tx of tics are neuroleptic antipsychotics such as ___
Pimozide
Because of their tendency to cause extrapyramidal syndromes, weight gain, sedation, irritability, and various phobias, they are not awlays the first choice
Alpha-adrenergic agonists such as __ are effective at treating tics and cause fewer long-term adverse effects
Clonidine and guanfacine
The non-ergot dopamine agonists ___ are the only drugs approved by the FDA for restless leg syndrome and are considered first-line tx in pts with daily symptoms
Pramipexole and ropinirole
__ is the only drug to have any impact on survival in ALS, which has been shown to prolong survival by a few months
Riluzole
What is the MOA of Riluzole for the tx of ALS?
Inhibits glutamate release and blocks postsynaptic NMDA- and kainite-type glutamate receptors and inhibits voltage-dependent Na channels, though the precise mechanism in tx of ALS is unclear
What are major adverse effects associated with Riluzole in tx of ALS?
Nausea and weakness
This chelating agent is used in tx of wilson disease that forms a stable complex with copper and is readily excreted by the kidney
Penicillamine
Adverse effects: nausea, vomiting, nephritic syndrome, myasthenia, optic neuropathy, and various blood disorders
___ reduces intenstinal absorption of copper and can be prescribed in addition to penicillamine in tx of wilson disease
Potassium disulfide
Aside from penicillamine and potassium disulfide, what other agents are useful in tx of wilson disease?
Trientine (chelating agent), zinc acetate and zinc sulfate (increase fecal excretion of Cu by decreasing GI absorption)
