Drugs for Neurodegenerative Diseases Flashcards by Jonathan Chin

Parkinson’s Disease

Drugs that Increase Dopamine Levels

Levodopa/Carbidopa (Sinemet)
Entacapone (Comtan)
with Ldopa/Cdopa (Stalveo)
Carbidopa (Lodosyn)
Tolcapone (Tasmar)
Rasagiline (Azilect)
Selegeline (Eldepryl)
Amantadine (Symmetrel)

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Parkinson’s Disease

Dopamine Receptor Agonists

Apomorphine (Apokyn)
Bromocriptine (Parlodel)
Pramiprexole (Mirapex)
Ropinirole (Requip)
Rotigotine (Neupro)

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Parkinson’s Disease

Cholinergic Receptor Antagonists

Benztropine (Cogentin)
Trihexyphenidyl

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Alzhimer’s Disease

Central Acetylcholinesterase Inhibitors

Donepezil (Aricept)
Galantamine (Razadyne)
Rivastigmine (Exelon)

offset EP side effects

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Alzhimer’s Disease

Other Agents

Caprylidene (Axona)
Dextromethorphan and Quinidine (Nuedexta)
Memantine (Namenda)

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Drugs for Huntington’s Disease

Diazepam (Valium)
Haloperidol (Haldol)
Tetrabenazine (Xenazine)
Sertraline (Zoloft)

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Drugs for Multiple Sclerosis

Dalfampridine (Ampyra)
Fingolimod (Gilenya)
* Interferon beta B-1b (Betaseron)
Prednisone (Deltasone)
Teriflunomide (Aubagio)
Dimethyl fumarate (Tecfidera)

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Drugs for Amyotrophic Lateral Sclerosis (ALS) (Lou Gehrig’s Disease)

Gabapentin (Neurontin)
Riluzole (Rilutek)

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Anti-Spastic Drugs

* Baclofen (Lioresal)
* Cyclobenzaprine (Flexeril)
* Carisoprodol (Soma)
* Orphenadrine (Norflex)
* Tizanidine (Zanaflex)
* Methocarbamol (Robaxin)
* Dantrolene (Dantrium)
* Botulinum toxin A (Botox)

ine = muscle relaxants = drowiness (anticholinergic aka no pee, no spit)

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PARKINSON’S DISEASEDrugs that increase dopamine levels

Levodopa

Biosynthetic precursor to dopamine
Used to alleviate motor dysfunction
Ingestion of high protein levels can impede response to levodopa
Most common side effect is nausea and vomiting followed by orthostatic hypotension, and cardiac dysrhythmias caused by B-adrenoceptor activation (B-agonist effect)
Dyskinesia (involuntary movements) occurs as a result of excessive dopamine concentrations
Psychotic effects including hallucinations, or distorted thinking may also occur
Other side effects include sedation, agitation, delirium, vivid dreams, euphoria
Drug interaction with MAO Inhibitors (anti-psychotics) may lead to over accumulation of dopamine and cause HTN
Metabolized by L-amino acid decarboxylase (LAAD) (requires B6)
and Catechol-O-methyltransferase (COMT)

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PARKINSON’S DISEASE Drugs that increase dopamine levels

Carbidopa

Structural analog of levodopa and inhibits LAAD thereby reducing the conversion of levodopa to dopamine in peripheral tissues thereby increasing the amount of levodopa that enters the brain
Highly ionized and does not cross the blood brain barrier
Substantially reduces the GI and CV side effects of levodopa and allows for a 75% reduction in the dose of levodopa
Used in combination with levodopa in different concentrations both in immediate release and sustained release formulations to reduce wear off of the drug
Does not inhibit the formation of dopamine in the CNS

INCREASES Levadopa

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PARKINSON’S DISEASE Drugs that increase dopamine levels

Entacapone/Tolcapone

Drugs used to enhance the effectiveness of levodopa in the treatment of PD
Inhibits the COMT enzyme that metabolizes levodopa to 3OMD in the gut and liver
3OMD competes for transport with levodopa into brain tissue
Produces a twofold increase in the oral bioavailability and half life of levodopa
Contributes to more sustained improvement in motor function
Found to increase efficacy of levodopa while reducing the dosing requirement
Side effects include nausea, diarrhea, and in rare cases hepatitis
Entacapone has no reports of hepatic toxicity and is available in a Ldopa/Cdopa combination

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PARKINSON’S DISEASE Drugs that increase dopamine levels

Selegiline (Eldepryl) and Rasagiline (Azilect)

* MOA Inhibits MOA-B and prevents oxidation of dopamine to dihydroxyphenylacetic acid and hydrogen peroxide
* Increases dopamine levels in the basal ganglia and decreases the formation of hydrogen peroxide
* Inhibits the progression of PD by inhibiting the formation of free radicals or by inhibiting the formation of an active metabolite of an environmental toxin
* Does not inhibit MAO-A an enzyme that catalyzes degradation of catecholamines
* Can cause adverse effects if administered with meperidine or with other selective serotonin reuptake inhibitors (Fluoxetine)
* Used in early PD as a single drug and in combination with ldopa/cdopa in moderate or progressive advanced disease

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PARKINSON’S DISEASE Dopamine Receptor agonists

Pramipexol/Ropinirole

*** Act as selective D2 receptor agonists
* May delay the need for levodopa when used in early stages of **PD
* Also indicated for the treatment of Restless Leg Syndrome
* Rotigotine a newer agent is also selective for D2 receptors as well as D3 receptors and is used as an adjunct to ldopa/cdopa
* Available as a patch formulation
* Apomorphine is available as an injection for intermittent hypomobility or freezing episodes
* Acts as a dopamine receptor agonist even though it is structurally related to morphine

Restless leg syndrome

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PARKINSON’S DISEASE Dopamine Receptor agonists

Bromocriptine

Ergo alkaloid in same class as LSD used to treat migraine headaches
D2 receptor agonist and D1 receptor angagonist
Used as an adjunct to ldopa/cdopa in patients with wearing off effects and on off motor fluctuations
New diagnosis in formulation (Cycloset) to treat type 2 diabetes
Adverse effects include nausea, diarrhea, confusion, dyskinesias, sedation, vivid dreams and hallucinations

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Management of Parkinson’s disease
(Early disease of mild intensity)

Exercise, Nutrition, Education
Speech, Occupational, Physical Therapy

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Management of Parkinson’s disease
(Mild tremor and slowness)

Anticholinergic drugs like amantadine may be helpful

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Management of Parkinson’s disease
(More severe functional disabilities)

Dopaminergic drugs are the most effective treatment
Combination therapy with levodopa/carbidopa is usually prescribed
Drugs have a delayed onset of action and improvement may not be noted for 2-3 weeks

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ALZHEIMER’S DISEASE (Central Acetylcholinesterase Inhibitors)

Rivastagimine (Exelon)

Significantly delays the global cognitive impairment associated with AD
Available in a patch formulation
*

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ALZHEIMER’S DISEASE (Central Acetylcholinesterase Inhibitors)

Donepezil (Aricept)

Slow the deterioration of cognitive function
They do not affect the underlying neuro-degenerative process
Donepezil demonstrates a better cognitive function in comparative studies at 24 weeks
Reversible cholinesterase inhibitor that selectively inhibits cholinesterase in the CNS and increases Acetylcholine levels in the cerebral cortex
Side effects include diarrhea, nausea, and vomiting

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Alzheimer’s Disease Treatment

Quinidine with Dextromethorphan

Used to treat pseudobulbar affect of emotional lability seen in patients with neurodegenerative diseases

Alzheimer’s Disease Treatment

Caprylidene

Is a medical food that replaced depleted glucose levels to treat patients with neurodegenerative diseases

Alzheimer’s Disease Treatment

Memantine (Namenda)

Low potency non-competitive antagonist at the NMDA receptor
Attenuates the ex ectocytotoxic effects of glutamate
Combination of memantine extended release with donepezil is also available and has shown increased efficacy as a combination in more of a synergist effect that either agent alone

HUNTINGTON’S DISEASE Treatment

Diazepam

potentiates GABA and can also reduce excess movements in patients with HD

# HUNTINGTON’S DISEASE Treatment Haloperidol (Haldol)

blocks dopamine receptors as does other anti-psychotic drugs

# HUNTINGTON’S DISEASE Treatment Tetrabenazine

is the only drug for the treatment of chorea in HD and acts as a monoamine depletory by reversibly inhibiting the human vesicular monoamine transporter type 2 (VMAT2)

# HUNTINGTON’S DISEASE Treatment SSRIs

have been incorporated as primary treatment for patients with Huntington’s disease particularly Sertraline (Zoloft)

# MULTIPLE SCLEROSIS Treatment Interferon B-1b

* the first drug to demonstrate an ability to halt and even reverse the progression of the disease * Effects are postulated to be from its immunomodulating properties. * Shown to reduce the frequency of relapses and the number of new lesions detected by MRI * Interferon B-1a is also approved to treat the relapsing forms of MS

# MULTIPLE SCLEROSIS Treatment Peginterferon B-1a

provides a longer duration of action

# MULTIPLE SCLEROSIS (Other Treatments) Mitoxantrone

an antineoplastic agent approved for MS suppresses the activity of T cells, B cells, and macrophages thought to lead the attack on the myelin sheath

# MULTIPLE SCLEROSIS (Other Treatments) Glatiramer acetate

acetate is a synthetic protein that mimics the structure of myelin basic protein

# MULTIPLE SCLEROSIS (Other Treatments) Dalfampridine

has been shown to improve walking in patients with MS

# MULTIPLE SCLEROSIS (Other Treatments) Teriflunomide

a new agent used to treat relapsing forms and is believed to reduce the proliferation of overactive immune cells and has major risk of hepatic toxicity

# MULTIPLE SCLEROSIS (Treatment acute exacerbations) Prednisone

* Acute exacerbations are treated with adrenal corticosteroid drugs mostly prednisone * Prednisone shortens the duration of exacerbations and ameliorates the symptoms

# AMYOTROPHIC LATERAL SCLEROSIS (ALS) Baclofen

* GABA B receptor agonist * controls spastity

# AMYOTROPHIC LATERAL SCLEROSIS (ALS) Gabapentin

may slow decline in muscle strength

# AMYOTROPHIC LATERAL SCLEROSIS (ALS) Riluzole

has been shown to prolong the time before patients require a tracheotomy and have prolonged life by approximately 3 months and has been more effective in patients with bulbar onset disease

# Antispastic Agents Baclofen (Lioresal)

Most effective in treating spasticity from MS as a GABA b receptor agonist

# Antispastic Agents Cyclobenzaprine (Flexeril)

MOA unknown but has significant Anticholinergic properties and sedation

# Antispastic Agents Orphenadrine (Norflex)

MOA unknown but has significant Anticholinergic properties and sedation

# Antispastic Agents Methocarbamol (Robaxin)

CNS depressant with a sedative and musculoskeletal relaxant property

# Antispastic Agents Carisoprodol (Soma)

Meprobamate Barbiturate derivative with active metabolites

# Antispastic Agents Tizanidine (Zanaflex)

MOA unknown but has significant Anticholinergic properties and sedation

# MYASTHENIA GRAVIS Thymectomy

This operation to remove the thymus gland (which often is abnormal in individuals with myasthenia gravis) can reduce symptoms and may cure some people, possibly by rebalancing the immune system. A NINDS-funded study found that thymectomy is helpful both for people with thymoma and those with no evidence of the tumors. The clinical trial followed 126 people with myastenia gravis and no visible thymoma and found that the surgery reduced muscle weakness and the need for immunosuppressive drugs.

# MYASTHENIA GRAVIS Monoclonal antibody

This treatment targets the process by which acetylcholine antibodies injure the neuromuscular junction. In 2017, the U.S. Food and Drug Administration approved the use of eculizumab for the treatment of generalized myasthenia gravis in adults who test positive for the antiacetylcholine receptor (AchR) antibody.

# MYASTHENIA GRAVIS Anticholinesterase medications

Medications to treat the disorder include anticholinesterase agents such as mestinon or pyridostigmine, which slow the breakdown of acetylcholine at the neuromuscular junction and thereby improve neuromuscular transmission and increase muscle strength.

# MYASTHENIA GRAVIS Immunosuppressive drugs

These drugs improve muscle strength by suppressing the production of abnormal antibodies. They include prednisone, azathioprine, mycophenolate mofetil, and tacrolimus. The drugs can cause significant side effects and must be carefully monitored by a physician.

# MYASTHENIA GRAVIS Plasmapheresis and intravenous immunoglobulin

These therapies may be options in severe cases of myasthenia gravis. Individuals can have antibodies in their plasma (a liquid component in blood) that attack the neuromuscular junction. These treatments remove the destructive antibodies, although their effectiveness usually only lasts for a few weeks to months.

# MYASTHENIA GRAVIS Plasmapheresis

is a procedure using a machine to remove harmful antibodies in plasma and replace them with good plasma or a plasma substitute.

# MYASTHENIA GRAVIS Intravenous immunoglobulin

is a highly concentrated injection of antibodies pooled from many healthy donors that temporarily changes the way the immune system operates. It works by binding to the antibodies that cause myasthenia gravis and removing them from circulation.