ND drugs

Levodopa

• metabolic precursor of dopamine

• MOA: restores dopaminergic neurotransmission in the neostriatum by enhancing the synthesis of dopamine

• actively transported into the CNS and converted to dopamine

carbidopa

The effects of levodopa on the CNS can be greatly enhanced by coadministering _____

carbidopa

• dopamine decarboxylase inhibitor that does not cross the blood–brain barrier

• MOA: diminishes the metabolism of levodopa in the periphery, thereby increasing the availability of levodopa to the CNS

• nausea

• vomiting

• cardiac arrhythmias

• hypotension

4 side effects of levodopa without carbidopa

30

levodopa should be taken on an empty stomach, typically

____ minutes before a meal.

protein

Ingestion of meals, particularly if high in _____, interferes with the transport of levodopa into the CNS

vitamin pyridoxine (B6)

vitamin that increases the peripheral breakdown of levodopa and diminishes its effectiveness

MAOIs (phenelzine)

Concomitant administration of levodopa and ____ can produce hypertensive crisis caused by enhanced catecholamine production

Antipsychotic drugs

drugs generally contraindicated in Parkinson’s disease, because they potently block dopamine receptors and may augment parkinsonian symptoms

atypical antipsychotics

low doses of _____ are sometimes used to treat levodopa-induced psychotic symptoms.

Selegiline

• selectively inhibits monoamine oxidase (MAO) type B (metabolizes dopamine) at low to moderate doses

• does not inhibit MAO type A (metabolizes norepinephrine and serotonin) unless given above recommended doses, where it loses its selectivity

• increases dopamine levels in the brain by decreasing the metabolism of dopamine

selegiline

When _____ is administered with levodopa, it enhances the actions of levodopa and substantially reduces the required dose

• methamphetamine & amphetamine

• insomnia

selegiline is metabolized to _____ and _____, whose stimulating properties may produce ____ if the drug is administered later than mid-afternoon.

rasagiline

• irreversible and selective inhibitor of brain MAO type B

• 5 times the potency of selegiline

• not metabolized to an amphetamine-like substance

• catechol-O-methyltransferase (COMT)

• 3-O-methyldopa

methylation of levodopa by _____ to _____ is a minor pathway for levodopa metabolism

• entacapone

• tolcapone

• 2 drugs that selectively and reversibly inhibit COMT

• leads to decreased plasma concentrations of 3-O-methyldopa

• increased central uptake of levodopa

• greater concentrations of brain dopamine

• reduce the symptoms of “wearing-off” phenomena

tolcapone

fulminating hepatic necrosis is associated with ____ use

Dopamine receptor agonists

• these agents have a longer duration of action than that of levodopa and are effective in patients exhibiting fluctuations in response to levodopa

• may delay the need to use levodopa in early Parkinson’s disease and may decrease the dose of levodopa in advanced Parkinson’s disease

• does not exacerbate peripheral vascular disorders or cause fibrosis

• Bromocriptine

• pramipexole

• ropinirole

• apomorphine

• rotigotine

• 5 dopamine agonists effective in patients with Parkinson’s disease complicated by motor fluctuations and dyskinesias

• ineffective in patients who have not responded to levodopa

apomorphine

• injectable dopamine agonist that is used in severe and advanced stages of Parkinson’s disease to supplement oral medications

• used for acute management of the hypomobility “off” phenomenon n advanced Parkinson’s disease

bromocriptine

• ergot derivative; potential to cause pulmonary and retroperitoneal fibrosis

• may cause the mental condition to worsen

• caution in patients with history of myocardial infarction or peripheral vascular disease

• apomorphine

• pramipexole

• ropinirole

• rotigotine

4 nonergot dopamine agonists that alleviate the motor deficits in patients who have never taken levodopa and also in patients with advanced Parkinson’s disease who are treated with levodopa

• Pramipexole & ropinirole

• Apomorphine & rotigotine

____ and ____ are orally active agents

____ and ____ are available in injectable and transdermal delivery systems

Rotigotine

nonergot dopamine agonist administered as a once-daily transdermal patch that provides even drug levels over 24 hours

Cimetidine

• inhibits renal tubular secretion of organic bases

• may significantly increase the half-life of pramipexole

• fluoroquinolone

• cytochrome P450 (CYP450) 1A2

____ antibiotics and other inhibitors of the _____ isoenzyme (fluoxetine) may inhibit the metabolism of ropinirole

Amantadine

• antiviral drug used to treat influenza

MOAs:

• increasing the release of dopamine

• blocking cholinergic receptors

• inhibiting the N-methyl-D-aspartate (NMDA) type of glutamate receptors

antimuscarinic agents

• benztropine

• trihexyphenidyl

• procyclidine

• biperiden

• less efficacious than levodopa

• only adjuvant role in antiparkinsonism therapy

• MOAs: Blockage of cholinergic transmission

• accumulation of senile plaques (β-amyloid accumulations)

• formation of numerous neurofibrillary tangles

• loss of cortical neurons (cholinergic neurons)

3 features of dementia of the Alzheimer type

memory loss

hallmark symptom of Alzheimer’s disease

• donepezil

• galantamine

• rivastigmine

3 reversible AChE inhibitors approved for the treatment of mild to moderate Alzheimer’s disease

Galantamine

• has selectivity for AChE in the CNS

• augments the action of acetylcholine at nicotinic receptors in the CNS

Rivastigmine

• the only agent approved for the management of dementia associated with Parkinson’s disease

• the only AChE inhibitor available as a transdermal formulation

• hydrolyzed by AChE to a carbamylate metabolite

glutamate (NMDA)

overstimulation of _____ receptors (____ type) may result in excitotoxic effects on neurons and is suggested as a mechanism for neurodegenerative or apoptotic processes

Memantine

NMDA receptor antagonist indicated for moderate to severe Alzheimer’s disease

acts by blocking the NMDA receptor and limiting Ca2+ influx into the neuron

Multiple sclerosis

autoimmune inflammatory demyelinating disease of the CNS

corticosteroids

• dexamethasone

• prednisone

used to treat acute exacerbations of MS

• white blood cell

• myelin sheath

major target of MS medications is to modify the immune response through inhibition of ______–mediated inflammatory processes that eventually lead to ______damage and decreased or inappropriate axonal communication between cells

Interferon (β1a, β1b)

MS drug used to help to diminish the inflammatory responses that lead to demyelination of the axon sheaths

Glatiramer

MS drug that is a synthetic polypeptide that resembles myelin protein and may act as a decoy to T-cell attack

Fingolimod

• MS drug which alters lymphocyte migration, resulting in fewer lymphocytes in the CNS

• may cause first-dose bradycardia

Teriflunomid

• MS drug which is an oral pyrimidine synthesis inhibitor that leads to a lower concentration of active lymphocytes in the CNS

• cause elevated liver enzymes

• avoided in pregnancy

Dimethyl fumarate

MS drug that may alter the cellular response to oxidative stress to reduce disease progression

Natalizumab

monoclonal antibody indicated for MS in patients who have failed first-line therapies

Mitoxantrone

cytotoxic anthracycline analog that kills T cells and may also be used for MS

Dalfampridine

• oral potassium channel blocker

• improves walking speeds in patients with MS

• first drug approved for this use

Amyotrophic lateral sclerosis (ALS)

characterized by progressive degeneration of motor neurons,

resulting in the inability to initiate or control muscle movement.

Riluzole

• NMDA receptor antagonist which is the only drug indicated for the management of ALS

• acts by inhibiting glutamate release and blocking sodium channels

• may improve survival time and delay the need for ventilator support

B. Levodopa, carbidopa, and entacapone

Which one of the following combinations of antiparkinsonian drugs is an appropriate treatment plan?

A. Amantadine, carbidopa, and entacapone

B. Levodopa, carbidopa, and entacapone

C. Pramipexole, carbidopa, and entacapone

D. Ropinirole, selegiline, and entacapone

E. Ropinirole, carbidopa, and selegiline

C. Carbidopa.

Peripheral adverse effects of levodopa, including nausea, hypotension, and cardiac arrhythmias, can be diminished by including which of the following drugs in the therapy?

A. Amantadine

B. Ropinirole

C. Carbidopa

D. Tolcapone

E. Pramipexole

B. Bromocriptine

Which of the following antiparkinsonian drugs may cause vasospasm?

A. Amantadine

B. Bromocriptine

C. Carbidopa

D. Entacapone

E. Ropinirole

B. Cholinergic

Modest improvement in the memory of patients with Alzheimer’s disease may occur with drugs that increase transmission at which of the following receptors?

A. Adrenergic

B. Cholinergic

C. Dopaminergic

D. GABAergic

E. Serotonergic

D. Memantine

Which medication is a glutamate receptor antagonist that can be used in combination with an acetylcholinesterase inhibitor to manage the symptoms of Alzheimer’s disease?

A. Rivastigmine

B. Ropinirole

C. Fluoxetine

D. Memantine

E. Donepezil

A. Rivastigmine

Which of the following agents is available as a patch for once-daily use and is likely to provide steady drug levels to treat Alzheimer’s disease?

A. Rivastigmine

B. Donepezil

C. Memantine

D. Galantamine

E. Glatiramer

D. Riluzole

Which of the following is the only medication that is approved for the management of amyotrophic lateral sclerosis?

A. Pramipexole

B. Selegiline

C. Galantamine

D. Riluzole

E. Glatiramer

C. Teriflunomid

Which of the following medications reduces immune system–mediated inflammation via inhibition of pyrimidine synthesis to reduce the number of activated lymphocytes in the CNS?

A. Riluzole

B. Rotigotine

C. Teriflunomid

D. Dexamethasone

C. Rivastigmine

Which of the following agents may cause tremors as a side effect and, thus, should be used with caution in patients with Parkinson’s disease, even though it is also indicated for the treatment of dementia associated with Parkinson’s disease?

A. Benztropine

B. Rotigotine

C. Rivastigmine

D. Dimethyl fumarate

A. Dalfampridine

Which of the following agents exerts its therapeutic effect in multiple sclerosis via potassium channel blockade?

A. Dalfampridine

B. Donepezil

C. Riluzole

D. Bromocriptine