Pharmacology 203 Windward Community College

Neurodegenerative Diseases

We will cover a number of conditions in

this series, starting with….

NDD we cover

Dementia

Alzheimer’s (ALZ)

Amyotrophic lateral

sclerosis (ALS)

Huntington’s (HC)

Multiple sclerosis (MS)

Parkinson’s (PD)

Attention Deficit

Hyperactivity Disorder

(ADHD)

Narcolepsy

Epilepsy

The Beers Criteria recommends avoiding all TCAs, anticholinergics, benzodiazepines,

chlorpromazine, corticosteroids, H2 receptor blockers, meperidine, sedative

hypnotics and thioridazine to treat dementia. http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf

There are many types of dementia affecting a number of

mental functions. Dementia is not curable, but may be

treatable.

For cognitive and functional losses

AChE inhibitors like Donepezil (Aricept)

For psychosis and agitation

Antipsychotics (which increase the risk of death)

Benzodiazepines (which are on Beer’s list)

Buspirone (BuSpar)

For depression

Antidepressants

Psychostimulants like methylphenidate (Ritalin)

For sleep disturbances

Trazodone (Desyrel)

Zolpidem (Ambien)

BZD, antipsychotics, diphenhydramine (Benadryl)

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Pharmacology 203 Windward Community College

Alzheimer’s is a type and leading cause of dementia. For

some reason, cholinergic neurons die off in the CNS. The

treatment, at least initially, attempts to restore the levels of

acetylcholine. All the other medications mentioned under

“dementia” may also be used.

Donepezil (Aricept) is an acetyl cholinesterase (AChE)

inhibitor that is active in the CNS. This is important. We

covered Neostigmine (Prostigmin) in the peripheral nervous

system, it is also an AChE inhibitor, but only active in the PNS.

Donepezil has a number of important drug interactions,

remember not to give with aspirin or other CNS active

anticholinergics (e.g., diphenhydramine, TCAs...).

Memantine (Namenda) is an NMDA antagonist. The NMDA

receptor is one of the three glutamate receptors. Glutamate

is a neurotransmitter used to modulate other neurons.

Memantine is used in mild to moderate Alzheimer’s.

AChE agents

Chronic use of the AChE agents

leads to hallucinations, nightmares

and confusion.

HC is a genetic disease that leads to excess

glutamate (which is toxic). The mutation is

autosomal dominant, which means the kids born

to a parent with the disease have a 50% of

acquiring the trait themselves. Onset of

symptoms is usually around age 40 and causes a

progressive loss of 1st motor, and then other CNS

functions.

Tetrabenazine (Xenazine) is an anti chorea drug

used to suppress the wild, jerky, unintentional,

uncoordinated movements characteristic of HC.

George Huntington, an American physician

who described the disease when he was

only 22 years old in 1872. He was able to

accomplish this in no small part to the work

done by his father and grandfather.

Dopamine Agonists

Dopamine agonists used in PD or

restless leg therapy can lead to a

decrease in impulse control and an

increase in compulsive behavior

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Pharmacology 203 Windward Community College

MS is an autoimmune condition in which

the myelin is stripped from random CNS

neurons. There appear to be at least 2

forms of the disease. In 2/3 of cases,

gamma interferon is the dominant

cytokine; in 1/3 of cases, interleukin 17F

dominates. The patients expressing

interleukin 17F don’t respond to interferon

therapy.

To slow the progression of MS, interferon-

beta 1a (Rebif, Avonex) and/or glatiramir

acetate (Copaxone) are often used.

To treat the spasticity associated with MS,

a variety of antispasmodics are used

including, Baclofen (Kemstro), Tizanidine

(Zanaflex) and Dantrolene (Dantrium).

To treat the neuropathic pain of MS a

number of drugs may be tried including,

Gabapentin (Neurontin), Carbamazepine

(Tegretol), Phenytoin (Dilantin),

Lamotrigine (Lamictal), Capsaicin (Zostrix)

or a tricyclic antidepressant such as

Amitriptyline (Elavil) which may also be

useful to treat co-morbid depression.

Most MS patients will be taking a number

of drugs at any given time to control

symptoms associated with the progression

of the disease. Because most people

have a remitting relapsing form of MS, it

may be difficult for them to keep track of

their medications.

Parkinson’s disease is a result of the death of

dopaminergic neurons in a small area of the

brain called the substantia nigra. Loss of the

functionality of these neurons results in the

typical signs and symptoms of Parkinson’s,

easily remembered by the acronym: TRAP.

Tremors (“pill rolling” and hand tremors

especially), Rigidity (moving “en block”),

Akinesia (slowed movements), and Postural

instability (impaired balance).

Parkinson’s disease (PD) does not affect

cognition, but patients may have co-

morbidities that include dementia.

One strategy to treat PD is to increase the

levels of dopamine in the brain. To do this a

patient is given Levodopa (Levopa, Biodal)

along with drugs like Carbidopa (Lodosyn)

and/or Entacapone (Comtan) that block the

break down of Levodopa in the periphery.

The fixed dose combination of levodopa,

carbidopa and entacapone is called Stalevo

Another strategy is to use drugs that are

dopamine agonists. Drugs in this class include

Bromocriptine (Parlodel) and Ropinirole

(Requip).

A third strategy is to increase endogenous

dopamine levels by giving a monoamine

oxidase inhibitor like Selegiline (Eldepryl,

Emsam).

A final strategy is to alter the modulation of

the dopaminergic neurons to increase their

activity by giving anticholinergic drugs like

Amantadine (Symmetrel), Benztropine

(Cogentin), Diphenhydramine (Benadryl) or

Trihexyphenidyl (Artane). The anticholinergics

act as antispasmodics.

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Pharmacology 203 Windward Community College

ADHD has numerous co-morbidities including:

Mood disorders including depression and/or

anxiety

Substance abuse

Learning disorders

Conduct disorders

Tourette’s and/or tics

The 1st line drugs for ADHD are CNS stimulants (see

side bar). 2nd line medications include the non-

stimulant drugs Atomoxetine (Strattera), alpha 2

agonists (Clonidine and Guanfacine), and in adults -

Imipramine, Bupropion, and Modafinil.

The benefits of using CNS stimulants include:

1. Decreased overactivity

2. Decreased impulsivity

3. Decreased inattention

4. Increased on task behavior

5. Increased academic performance

6. Increased ability to function socially

Common problems associated with the CNS

stimulants include:

1. Abuse/addiction

2. Increased blood pressure

3. Decreased seizure threshold

4. Decreased linear growth

5. Worsening of tics

6. Unmasking of bipolar mania or schizophrenia

Narcolepsy is treated with the same drugs

as ADHD for the most part. Most

commonly used is Modafinil (Provigil,

Nuvigil), which is only for adults, and NOT

for KIDS.

The CNS stimulant ADHD drugs are all controlled (C-

II) with 19 Different Formulations! CONFUSING!

i. 1. IMMEDIATE RELEASE (IR) - Duration 4-6 hours

a. Amphetamines

Adderall (mixed amphetamine salts),

Dexedrine, Dextrostat and ProCentra

(are dextroamphetamine)

b. Methylphenidate

Ritalin, Methylin(dosed BID or TID)

c. Focalin (dexmethylphenidate)

2. 1ST GENERATION SUSTAINED RELEASE (Slow

Release) - Duration 6-8 hours

a. Methylphenidate

Ritalin SR, Metadate ER, Methylin ER

ii. 3. BIPHASIC RELEASE

a. Amphetamines

Adderall XR, Dexedrine Spansules

Duration 10-12 hours (Adderall XR), 6+

hours (Dexedrine Spansules)

Adderall XR can be sprinkled.

b. Methylphenidate

Ritalin LA, Metadate CD

SID dosing simulates BID dosing

Ritalin LA composed of 50% IR and

50% delayed release beads

4. TRIPHASIC RELEASE

a. Methylphenidate (Concerta)

5. NOVEL DELIVERY SYSTEMS

a. Amphetamines

Vyvanse (lisdexamfetamine)

b. Methylphenidate

Daytrana patch

See handout for more details!

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Pharmacology 203 Windward Community College

We are not going to get into the details of

epilepsy other than to say this is a multi-

factoral disease resulting in hyper-

excitability of neurons. In your notes, a

few types of epilepsy are mentioned.

All the antiepilepsy drugs (AEDs) share an

increased risk for suicidal ideation and

behaviors. They also typically cause

sedation, weakness and alter the synthesis

of steroid hormones.

Carbamazepine (Tegretol, Equetro and

others) is used to treat epilepsy,

neuropathic pain and bipolar disorder. It

can cause a toxic epidermal reaction

called SJS in patients who express the HLA-

B 1502 phenotype, so genetic typing may

be done to improve safety. It also causes

blood dyscrasias.

Divalproex (Depakote), Valproate

(Depacon) and Valproic Acid (Depakene)

are all related. Divalproex is a 50:50

combination of valproate and valproic

acid. Valproate is a prodrug converted to

valproic acid in the stomach. All have a

fairly narrow therapeutic margin.

Divalproex is used to treat epilepsy,

bipolar disorder and migraines. It has a

number of serious side effects & boxed

warnings, as well as many off label uses.

Ethosuximide (Zarontin) is important due to

the fact it is the drug of choice to treat

absence seizures, a common epilepsy in

kids. It can cause considerable GI upset

which may lead to growth failure.

Gabapentin (Neurontin) is an AED, it can

be used for neuropathic pain, bipolar

disorder, dementia, alcohol withdrawal,

anxiety disorders and cleaning the kitchen

sink. The sink part is just a joke, but

gabapentin has many off label uses.

Pregabalin (Lyrica) is a C-V AED indicated

for fibromyalgia and neuropathic pain.

Note it is controlled.

Lamotrigine (Lamictal) is an AED with

indications for epilepsy and bipolar

disorder and used off label for

neuropathic pain and major depressive

disorder.

Phenobarbital (Luminal, Gardenal) is a C-

IV barbiturate that has long been used to

treat epilepsy, especially grand mal

seizures. It is also part of the therapeutic

protocol for status epilepticus. It is a

potent P450 inducer. Patients taking it

chronically will become tolerant to its

effects and will require periodic dose

increases.

Phenytoin (Dilantin) is an important AED

with a huge list of serious adverse effects.

Make sure to read through the notes!

Phenytoin is also an antiarrhythmic.

Topiramate (Topamax) is an unusual AED.

It is indicated for epilepsy and migraines.

It is used off label for PTSD, neuropathic

pain, and to prevent alcoholics from

drinking.

Pharmacology 203 Windward Community College

St. Anthony’s Fire St. Anthony’s Fire is the medieval name for ergotism, first

described in the 1600’s and treated by monks from the

order St. Anthony the Great.

The fungus, Claviceps purpurea, produces a group of toxins

called ergot alkaloids. Human consumption of

contaminated rye and other cereal grain containing the

ergot alkaloids leads to severe vasoconstriction. The

vasoconstriction then leads to gangrene in the hands and

feet (preceded by a terrible burning sensation, or St.

Anthony’s Fire).

The ergot alkaloids cause LSD-like hallucinations and strong

uterine contractions that will cause abortion.

The ergot alkaloids have been used for centuries to cause

abortion, stop bleeding after childbirth and to treat

headaches. They are still used to treat migraine.

Bromocriptine is an ergot alkaloid. It is used to treat PD,

acromegaly, hyperprolactinemia and DMT2.

Homework and Exercises

1. Read the “START HERE” announcement in Laulima for updates and instructions.

2. Read about Neurodegenerative diseases in Chapter 25, Pharmacology of Degenerative

Diseases of the CNS. Adams & Urban, PHARMACOLOGY Connections to Nursing Practice.

3. Review the Powerpoints and listen to the audio from the face-to-face lecture. You may opt to

watch the appropriate videos for this lecture. Review any handouts available for this lecture in

the Course Index.

4. Complete the SLO practice set for Neurodegenerative diseases in Tasks, Tests and Surveys.

5. Use “Chat,” “Discussions and Private Messages” or the lecture “Forum” to ask questions and find

answers or to seek assistance.

6. Complete the online quiz in Laulima, Tasks, Tests and Surveys.

If you have any questions, email me at abeale@hawaii.edu