Tuesday, August 23-Drugs For Movement Disorders-DSA-Kruse

Question 1

Coadministration of levodopa with this DOPA decarboxylase inhibitor that does not cross the BBB results in increased levodopa available for entry into the brain

Answer 1

Carbidopa

Question 2

Levodopa given in the absence of a peripheral decarboxylase inhibitor may have these adverse effects in the GI tract:

Answer 2

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

Question 3

What are some potential cardiovascular adverse effects with tx of levodopa?

Answer 3

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

Question 4

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

Answer 4

Apomorphine

Question 5

Pts taking __ may experience hypertensive crisis when combined with levodopa

Answer 5

Monoamine oxidase A inhibitors

Question 6

Levodopa is contraindicated in these types of pts:

Answer 6

• psychotic pts
• pts with angle-closure glaucoma
• pts with history of melanoma
• caution in pts with active peptic ulcer d/t possible GI bleeding

Question 7

___ 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

Answer 7

Bromocriptine

Question 8

___ 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)

Answer 8

Pramipexole

Question 9

___ 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

Answer 9

Ropinirole

Question 10

What are some adverse effects of dopamine receptor agonists in the GI tract?

Answer 10

• anorexia, nausea, and vomiting can occur; symptoms reduced if taken with meals
• constipation, dyspepsia, and symptoms of reflux esophagitis

Question 11

This adverse CV effect may occur with the use of dopamine receptor agonists, especially at the initiation of therapy

Answer 11

Postural hypotension

Question 12

This dopamine receptor agonist may cause digital vasospasm during long-term tx.

Answer 12

Bromocriptine

Question 13

In terms of adverse CV effects with the use of dopamine receptor agonists, the presence of ___ may indicate the need to discontinue therapy

Answer 13

Peripheral edema and cardiac arrhythmias

Question 14

Headache, nasal congestion, increased arousal, pulmonary infiltrates, and pleural and retroperitoneal fibrosis have been reported with the use of this dopamine receptor agonist

Answer 14

Bromocriptine

Question 15

What are some contraindications to using dopamine receptor agonists?

Answer 15

Pts with history of psychotic illness, recent MI, or with active peptic ulceration

Question 16

This dopamine receptor agonist drug is contraindicated in pts with peripheral vascular disease (vasoconstricting effects)

Answer 16

Bromocriptine

Question 17

There are 2 forms of monoamine oxidase:
___ preferentially metabolizes phenylethylamine and benzylamine

___ preferentially metabolizes norepinephrine and serotonin

Answer 17

MAO-B

MAO-A

Question 18

These compounds are metabolized equally by MAO-A and MAO-B

Answer 18

Dopamine and tryptamine

Question 19

__ 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

Answer 19

Selegiline

10% bioavailability with peak [plasma] within an hr

Question 20

You should use caution when prescribing Selegiline to pts who are taking ___

Answer 20

Caution recommended or contraindicated in pts taking Mepiridine, tricyclic antidepressants, or 5-HT reuptake inhibitors

Question 21

___ 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

Answer 21

Rasagiline

Question 22

The coadministration of levodopa and a ___ must be avoided because it may lead to a hypertensive crisis (due to peripheral accumulation of norepinephrine)

Answer 22

Non-selective MAO inhibitor

Question 23

___ metabolizes levodopa to 3-O-methyldopa, which competes with levodopa for transport across the intestinal mucosa and BBB

Answer 23

COMT

Question 24

___ prolong the activity of levodopa by inhibiting its peripheral metabolism, which decreases clearance and increases bioavailability

Answer 24

COMT inhibitors –> Tolcapone and Entacapone

Question 25

___ may be helpful in pts receiving levodopa who have developed response fluctuations

Answer 25

COMT inhibitors such as Tolcapone and Entacapone

Question 26

Regarding COMT inhibitors:

__ may has both central and peripheral effects, whereas ___ has peripheral effects only

Answer 26

Tolcapone=central and peripheral

Entacapone=peripheral only

Question 27

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)

Answer 27

Tolcapone

Question 28

Side effects associated with COMT are often due to levodopa but include:

Answer 28

Orange discoloration of urine, diarrhea, abdominal pain, and sleep disturbances

Question 29

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)

Answer 29

Apomorphine

Question 30

Adverse effects of apomorphine include nausea, which can be pretreated with this antiemetic ____

Answer 30

Trimethobenzamide

Other adverse effects of apomorphine include dyskinesias, drowsiness, sweating, hypotension, and injection site bruising

Question 31

__ 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

Answer 31

Amantadine

Question 32

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.

Answer 32

Amantadine

Question 33

Benztropine, biperidin, orphenadrine, procycladine, and trihexyphenidyl are examples of these drugs that are available to treat pts with PD.

Answer 33

Centrally acting mAChR antagonists

Question 34

mAChR antagonists may improve tremor and rigidity associated with PD but have little effect on ___

Answer 34

Bradykinesia

Question 35

B1-receptors have been implicated in some tremors and these tremors respond well to ___

Answer 35

Metoprolol and propanolol

Question 36

Symtpomatic tremor can be controlled by the antiepileptic drug __ in smaller doses than those used to treat seizures

Answer 36

Primidone

Question 37

This 5-HT receptor agonist has shown to be effective in the tx of tremors

Answer 37

Topirimate

Question 38

Alprazolam (benzodiazepine) and IM injections of __ have been effective in treating some pts with tremor

Answer 38

Botulinum toxin A

Question 39

___ is the immediate metabolic precursor to dopamine and an agonist at D receptors

Answer 39

Levodopa (L-dopa)

Question 40

These drugs that impair dopaminergic neurotransmission often alleviate chorea associated with Huntington disease

Answer 40

Reserpine, tetrabenzine

Question 41

___ are markedly reduced in the basal ganglia of pts with Huntington disease

Answer 41

GABA, glutamic acid decarboxylase, and choline acetyltransferase

Question 42

Reserpine (irreversible) and tetrabenzine (reversible) are agents that block ___ and deplete cerebral dopamine stores

Answer 42

Vesicular monoamine transporter

The effects of tetrabenzine resemble reserpine but with less peripheral activity and a shorter DOA

Question 43

The most predictive and effective pharmacological approach to the tx of tics are neuroleptic antipsychotics such as ___

Answer 43

Pimozide

Because of their tendency to cause extrapyramidal syndromes, weight gain, sedation, irritability, and various phobias, they are not awlays the first choice

Question 44

Alpha-adrenergic agonists such as __ are effective at treating tics and cause fewer long-term adverse effects

Answer 44

Clonidine and guanfacine

Question 45

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

Answer 45

Pramipexole and ropinirole

Question 46

__ is the only drug to have any impact on survival in ALS, which has been shown to prolong survival by a few months

Answer 46

Riluzole

Question 47

What is the MOA of Riluzole for the tx of ALS?

Answer 47

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

Question 48

What are major adverse effects associated with Riluzole in tx of ALS?

Answer 48

Nausea and weakness

Question 49

This chelating agent is used in tx of wilson disease that forms a stable complex with copper and is readily excreted by the kidney

Answer 49

Penicillamine

Adverse effects: nausea, vomiting, nephritic syndrome, myasthenia, optic neuropathy, and various blood disorders

Question 50

___ reduces intenstinal absorption of copper and can be prescribed in addition to penicillamine in tx of wilson disease

Answer 50

Potassium disulfide

Question 51

Aside from penicillamine and potassium disulfide, what other agents are useful in tx of wilson disease?

Answer 51

Trientine (chelating agent), zinc acetate and zinc sulfate (increase fecal excretion of Cu by decreasing GI absorption)