Central Nervous System

Depressants

CNS Depressants
Sedatives
Drugs that have an inhibitory effect on the
CNS to the degree that they reduce:

Nervousness
Excitability
Irritability
without causing sleep

CNS Depressants
Hypnotics
Calm or soothe the CNS to the point that they
cause sleep

CNS Depressants
Sedative-Hypnoticsdose dependent:
At low doses, calm or soothe the CNS
without inducing sleep
At high doses, calm or soothe the CNS
to the point of causing sleep

Sedative-Hypnotics: Barbiturates
First introduced in 1903, standard agents
for insomnia and sedation
Habit-forming
Only a handful commonly used today due
in part to the safety and efficacy of:
BENZODIAZEPINES

Sedative-Hypnotics: Barbiturates
Four categories:
Ultrashort
mephobexital, thiamylal, thiopental

Short
pentobarbital, secobarbital

Intermediate
aprobarbital, butabarbital

Long
phenobarbital

Sedative-Hypnotics: Barbiturates
Barbiturates have a very narrow therapeutic index.

Therapeutic Index
Dosage range within which the drug is effective
but above which is rapidly toxic.

Sedative-Hypnotics: Barbiturates
Mechanism of Action
Site of action:
Brain stem (reticular formation)
Cerebral cortex
By inhibiting GABA, nerve impulses traveling in
the cerebral cortex are also inhibited.

Sedative-Hypnotics: Barbiturates
Drug Effects
Low doses:

Sedative effects

High doses:

Hypnotic effects
(also lowers respiratory rate)

Notorious enzyme inducers

Sedative-Hypnotics: Barbiturates
Therapeutic Uses

Hypnotics
Sedatives
Anticonvulsants
Surgical procedures

Sedative-Hypnotics: Barbiturates
Side Effects
Body System

Effects

CNS

Drowsiness, lethargy, vertigo

mental depression, coma

Respiratory

Respiratory depression, apnea,

bronchospasms, cough

Sedative-Hypnotics: Barbiturates
Side Effects
Body System
GI
Other

Effects
Nausea, vomiting, diarrhea
Agranulocytosis,
vasodilation, hypotension,
Stevens-Johnson syndrome

Sedative-Hypnotics: Barbiturates
Toxicology
Overdose frequently leads to respiratory
depression, and subsequently, respiratory arrest.
Can be therapeutic:
Anesthesia induction
Uncontrollable seizures: phenobarbital coma

Sedative-Hypnotics: Barbiturates
Drug Interactions
Additive effects:
ETOH, antihistamines, benzodiazepines,
narcotics, tranquilizers
Inhibited metabolism:
MAOIs will prolong effects of barbiturates
Increased metabolism:
Reduces anticoagulant response, leading to
possible clot formation

CNS Depressants:
Benzodiazepines
Most frequently prescribed sedative-hypnotics

Most commonly prescribed drug classes

Favorable side effects
Efficacy
Safety

CNS Depressants:
Benzodiazepines
Classified as either:
Sedative-hypnotic or Anxiolytic
(Medication that relieves anxiety)

CNS Depressants:
Benzodiazepines
Sedative-Hypnotic Type
Long-Acting:
flurazepam (Dalmane), quazepam (Doral)
Short-Acting:
estazolam (Prosom), temazepam (Restoril),
triazolam (Halcion)

CNS Depressants:
Benzodiazepines

Anxiolytic Type

alprazolam (Xanax)
chloridiazepoxide (Librium)
diazepam (Valium)
lorazepam (Ativan)
midazolam (Versed)
zolpidem (Ambien) and zaleplon (Sonata)
(nonbenzodiazepine hypnotic agents, share characteristics)

CNS Depressants:
Benzodiazepines
Mechanism of Action
Depress CNS activity
Affect hypothalamic, thalamic, and limbic
systems of the brain
Benzodiazepine receptors

CNS Depressants:
Benzodiazepines
Drug Effects
Calming effect on the CNS
Useful in controlling agitation and anxiety

CNS Depressants:
Benzodiazepines

Therapeutic Uses
Sedation
Sleep induction

Skeletal muscle relaxation

Anxiety relief
Treatment of alcohol withdrawal
Agitation
Depression
Epilepsy
Balanced anesthesia

CNS Depressants:
Benzodiazepines
Side Effects
Mild and infrequent
Headache
Drowsiness
Dizziness
Vertigo
Lethargy
Paradoxical excitement (nervousness)
Hangover effect

CNS Depressants:
Nursing Implications
Before beginning therapy, perform a thorough
history regarding allergies, use
of other medications,health history, and medical
history.
Obtain baseline vital signs and I & O, including
supine and erect BPs.
Assess for potential disorders or conditions that
may be contraindications, and for potential drug
interactions.

CNS Depressants:
Nursing Implications
Give 15 to 30 minutes before bedtime for
maximum effectiveness in inducing sleep.
Most benzodiazepines (except flurazepam)
cause REM rebound and a tired feeling the
next day; use with caution in the elderly.
Patients should be instructed to avoid
alcohol and other CNS depressants.

CNS Depressants:
Nursing Implications
Check with physician before taking any other
medications, including OTC medications.
It may take 2 to 3 weeks to notice improved
sleep when taking barbiturates.
Abruptly stopping these medications,
especially barbiturates, may cause rebound
insomnia.

CNS Depressants:
Nursing Implications
Safety is important
Keep side rails up
Do not permit smoking
Assist patient with ambulation
(especially the elderly)
Keep call light within reach

Monitor for side effects

CNS Depressants:
Nursing Implications
Monitor for therapeutic effects

Increased ability to sleep at night

Fewer awakenings
Shorter sleep induction time
Few side effects, such as hangover effects
Improved sense of well-being because of
improved sleep

Anticonvulsants and Drugs to

Treat Other CNS Disorders

Chapter 8 Topics

Epilepsy
Parkinsons Disease
Myasthenia Gravis
Attention-Deficit Disorders
Amyotrophic Lateral Sclerosis (ALS)
Multiple Sclerosis (MS)
Alzheimers Disease

Learning Objectives
Develop an understanding of the
physiologic processes that occur in
epilepsy.
Classify seizures and the goals of their
therapy.
Understand that specific drugs are used in
different classes of seizures.

Learning Objectives
Be familiar with Parkinsons disease and
the drugs used in its treatment.
Know the symptoms and treatments of
myasthenia gravis
attention-deficit disorders
amyotrophic lateral sclerosis
multiple sclerosis
Alzheimers disease

Epilepsy
Common neurologic disorder with sudden
and recurring seizures
Caused by abnormal electrical impulses in
the brain

Epilepsy
In the U.S., 2.5 million people are affected.
Not all seizure disorders are epilepsy.

Epilepsy
Seizure
Abnormal electrical discharges in the cerebral cortex
caused by sudden, excessive firing of neurons
Result in a change in behavior of which the patient is
not aware
While conscious, the patient may or may not lose
movement control
Loss of body control may affect one area or the entire
body

Epilepsy
Causes of Seizures
Imbalance of excitatory and inhibitory
neurotransmitters:
Glutamate inhibitory
GABA excitatory
Other neurotransmitters can be involved

Neurotransmitter levels are controlled by enzymes

Disruption in enzymes = disruption of
neurotransmitters

Epilepsy
Causes of Seizures

ETOH withdrawal
Cardiovascular disease
High fever
Hypocalcemia
High or low blood
sugar
Hypoxia

Infection (meningitis)
Metabolic
abnormalities
Brain tumor
Toxic substances
Trauma or injury to
the head

Epilepsy
Classes of Seizures
Partial
Generalized

Epilepsy
Classes of Seizures
Partial
Simple-partial
Complex-partial

Generalized

Epilepsy
Classes of Seizures
Partial
Simple-partial
Complex-partial

Generalized

Tonic-clonic or grand mal

Absence or petit mal
Myoclonic
Atonic

Epilepsy
Partial Seizures
Localized in a specific area of the brain
Occurs with 65% of epileptic patients
Can progress to generalized seizures

Epilepsy
Partial Seizures
Simple-Partial
Complex-Partial

Epilepsy
Partial Seizures
Simple-Partial
No loss of consciousness
May have muscle twitching or sensory
hallucinations

Complex-Partial

Epilepsy
Partial Seizures
Simple-Partial
No loss of consciousness
May have muscle twitching or sensory
hallucinations

Complex-Partial
Impaired consciousness
With confusion, blank stare, and postseizure
amnesia

Epilepsy
Generalized Seizures
Involves both hemispheres of the brain, not
one specific location
Types

Tonic-Clonic
Absense
Myoclonic
Atonic

Generalized Seizures
Tonic-Clonic Seizures
Tonic body becomes rigid, lasts a minute
or less
Clonic initiated with muscle jerks, and
may be accompanied by shallow breathing,
loss of bladder control, and excess
salivation

Generalized Seizures
Absence
Interruption of activities by blank stare, rotating
eyes, uncontrolled facial movements, rapid eye
blinking, and/or jerking of an arm or leg
No generalized convulsions
Usually lasts 30 seconds or less
Many times it progresses to tonic-clonic as the
patient gets older

Generalized Seizures
Myoclonic
Occurs with sudden, massive, brief muscle
jerks or non-massive, quick jerks
Consciousness is not lost
Can occur during sleep

Generalized Seizures
Atonic
Begins with sudden loss of muscle tone and
consciousness
Muscles relax, limbs go limp
Lasts a few seconds to a minute, then
patient can resume standing and walking

Generalized Seizures
Status Epilepticus
Continuous tonic-clonic seizures with or
without return to consciousness
High fever and lack of oxygen severe
enough to cause brain damage or death

Discussion
What percentage of status epilepticus
patients die, regardless of treatment?

Discussion
What percentage of patients status
epilepticus patients die, regardless of
treatment?

Answer: 10%

Antiepileptic Drug Therapy

Goals of Therapy
1. Seizure control or lessen the frequency
2. Prevent emotional and behavioral changes

Discussion
Note: 30% of patients are not compliant
due to side effects (sedation and loss of
cognitive processes).
What are some possible strategies health
care providers can use to help improve
drug therapy compliance?

Antiepileptic Drug Therapy

Neuronal Activity
1. Polarized (resting)
2. Depolarized (firing)
1.
2.
3.

Sodium and calcium enter the cell

When sufficient amounts cross, neurotransmitters are
released
Neurotransmitter release leads to firing of the neuron

3. Repolarization (return to resting)

Antiepileptic Drug Therapy

Abnormal Neuronal Activity
Depolarization
If excessive neurotransmitters are released it
leads to uncontrollable firing of the neuron =
seizure

Treatment
Block the firing of the neuron by raising the
threshold of depolarization

Antiepileptic Drug Therapy

Start with monotherapy at a low dose and
titrate up slowly
Medication must be maintained at steady
therapeutic levels (no missed doses)
Polytherapy can be used if sufficient
response is not seen with monotherapy

Antiepileptic Drug Therapy

Problems with Therapy
Wrong medication is used for the seizure
type
Side effects may cause problems with
patient compliance
If doses are missed, there is an increased
risk of seizure activity

Drug List
Anticonvulsants

carbamazepine (Epitol, Tegretol)

clonazepam (Klonopin)
diazepam (Valium)
divalproex (Depakote)
ethosuximide (Zarontin)
Fosphyenytoin (Cerebyx)
gabapentin (Neurontin)

Drug List
Anticonvulsants

lamotrigine (Lamictal)
levetiracetam (Keppra)
lorazepam (Ativan)
oxcarbazepine (Trileptal)
phenobarbital (Luminal Sodium)
phenytoin (Dilantin)

Drug List
Anticonvulsants

primidone (Mysoline)
topiramate (Topamax)
valproic acid (Depakene)
zonisamide (Zonegran)

Therapeutic Regimens for Seizures

Seizure Type

1st Line

2nd Line

3rd Line

Partial

Tegretol or
Dilantin

Neurontin Luminal,
or Lamictal Mysoline, or
Depakene

Absence

Zarontin or
Depakene

Klonopin

Atonic, Atypical
Absence,
Myoclonic

Depakene

Klonopin or
Lamictal

Therapeutic Regimens for Seizures

Seizure Type

1st Line

2nd Line

Tonic-Clonic,
Tonic, Clonic

Tegretol,
Dilantin, or
Depakene

Luminal or
Mysoline

Status Epilepticus

Valium,
Ativan, or
Dilantin

3rd Line

valproic acid (Depakene) and

divalproex (Depakote)
Increases the availability of GABA
(inhibitory)
Take with water, not a carbonated drink
Do not use aspirin

Dispensing Issues
Warning!
Depakote and Depakene can easily be
confused.
Be careful with Depakote and Depakote
ER.
Depakote ER is only once a day.

phenytoin (Dilantin)
May be used to prevent seizures
Promotes sodium outflow from cells
stabilizes the neuronal membrane
Be cautious of drug interactions
Intravenous phenytoin must be mixed
carefully

Phenytoin Side Effects

Dose Related

Ataxia
Diplopia
Dizziness
Drowsiness
Encephalopathy
Involuntary movements

Phenytoin Side Effects

Non-Dose-Related
Gingival hyperplasia
Peripheral neuropathy
Vitamin deficiencies

Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
Cerebyx (anticonvulsant)
Celexa (antidepressant)
Celebrex (for pain and arthritis)

carbamazepine (Epitol, Tegretol)

Has effect on sodium channels which may
alter synaptic transmission.
Blood monitoring must be done regularly.
Be cautious of interactions and side effects.

gabapentin (Neurontin)
Used in conjunction with other medications
No significant drug interactions
Used for many other disorders, particularly
neuropathic pain

Dispensing Issues
Warning!
Neurontin (anticonvulsant) and Noroxin
(antibiotic) are sound-alike drugs, but they
are easy to distinguish by strength.

clonazepam (Klonopin)
Only indication is prophylaxis of seizures
Depresses nerve transmission in the motor
cortex
C-IV controlled substance (benzodiazepine)

Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
Lamictal (anticonvulsant)
Lamisil (antifungal)
Lomotil (for diarrhea)

topiramate (Topamax)
Is thought to alter sodium channels and
thereby increases GABA activity and
decreases glutamine activity
Causes significant cognitive effects
Drink fluids to decrease risk of kidney
stones

Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
Kaletra (antiviral for HIV)
Keflex (antibiotic)
Keppra (anticonvulsant)

Discussion
Which neurotransmitters play
the greatest role in seizures?

Discussion
Which neurotransmitters play the greatest
role in seizures?

Answer
Glutamate (excitatory)
GABA (inhibitory)

Parkinsons Disease
Characteristic Signs
Resting tremor
Rigidity
Akinesia

Usually affects people over 60

Parkinsons Disease
Physiology
Result of pathologic alterations in the
extrapyramidal system (part of the CNS that
controls motor activities)
Distinguishing feature: Lewy bodies
(protein masses) found in the midbrain

Parkinsons Disease
Physiology
Normal muscle movement requires balance of
dopamine (inhibitor) and ACh (stimulator)
In the substantia nigra, enough dopamine is
released to counteract the effects of ACh
In parkinsonism, enough dopamine is not released
which leads to excessive motor nerve stimulation

Cutaway View of the Brain

Substantia Nigra

Parkinsons Disease
Drug Therapy
Improves the functional ability and clinical
status of patients
Aims at symptomatic relief, does not alter
the disease process
Patients may have temporary or prolonged
remission
Side effects can be a problem

Drug List
Anti-Parkinson Agents

amantadine (Symmetrel)
benztropine (Cogentin)
bromocriptine (Parlodel)
entacapone (Comtan)
levodopa (Dopar)
levodopa-carbidopa (Sinemet)

Drug List
Anti-Parkinson Agents

levodopa-carbidopa-entacapone (Stalevo)
pergolide (Permax)
pramipexole (Mirapex)
ropinirole (ReQuip)
selegiline (Eldepryl)
tolcapone (Tasmar)

levodopa (Dopar)
Metabolized to dopamine in the brain, but
the brain does not receive a full dose
Drug has very undesirable effects
After about 5 years of therapy, 2/3 of
patients experience on-off phenomenon

levodopa-carbidopa (Sinemet)
Probably the most common drug used for
parkinsonism
Carbidopa allows for lower doses of
levodopa to be used which decreases side
effects

Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
Amantadine (for Parkinsons)
Ranitidine (for the stomach)
Rimantadine (for the flu)

entacapone (Comtan)
Indicated for patients who have a
deteriorating response to levodopa
Less toxic than tolcapone
Take without regard to food

Discussion
What are the two primary
neurotransmitters involved in
Parkinsons disease and what role do
they play?

Discussion
What are the two primary
neurotransmitters involved in Parkinsons
disease and what role do they play?

Answer
ACh (excitatory)
Dopamine (inhibitory)

Myasthenia Gravis
Autoimmune disorder of the neuromuscular
junction
ACh receptors are destroyed at the motor
end plate
Characterized by weakness and fatigability,
especially of the skeletal muscles

Motor End Plate

Myasthenia Gravis
Presenting Signs
Ptosis (drooping eyelid)
Diplopia (double vision)
Dyarthria (speech)
Dysphagia (swallowing)

Myasthenia Gravis
Treatment
Blocking the destruction of ACh causes
improvement for the patient

Drug List
Myasthenia Gravis Agents

azathioprine (Imuran)
cyclophosphamide (Cytoxan)
edrophonium (Enlon, Reversol)
neostigmine (Prostigmin)
pyridostigmine (Mestinon)

pyridostigmine (Mestinon)
Blocks destruction of ACh
Allows for ACh accumulation at the
synaptic junction

cyclophosphamide (Cytoxan)
Prevents cell division by targeting the autoimmune portion of the disease
Use chemotherapeutic precautions

Attention-Deficit Disorders
Attention-Deficit Hyperactivity Disorder
(ADHD)
Attention-Deficit Disorder (ADD)

Attention-Deficit Disorders
Attention-Deficit Hyperactivity
Disorder (ADHD)
Characterized by purposeless, chronic,
pervasive, driven behavior that affects a child
in social, emotional, and academic settings.

Attention-Deficit Disorders
Attention-Deficit Hyperactivity
Disorder (ADHD)
Characteristics for Assessment
Hyperactivity
Impulsivity
Distractibility

Attention-Deficit Disorders
Attention-Deficit Disorder (ADD)
Has less hyperactivity
Child is more lethargic and more easily
distracted
Both disorders are more common in boys
than girls
Some symptoms can persist into adulthood

Drug List
Attention-Deficit Disorder
Agents

atomoxetine (Strattera)
clonidine (Catapres, Catapres-TTS)
desipramine (Norpramin)
dexmethylphenidate (Focalin), C-II
dextroamphetamine-amphetamine
(Adderall), C-II

Drug List
Attention-Deficit Disorder
Agents
imipramine (Tofranil)
methylphenidate (Concerta, Metadate,
Ritalin, Ritalin-SR), C-II
nortriptyline (Aventyl, Pamelor)
pemoline (Cylert), C-IV

methylphenidate (Concerta,
Metadate, Ritalin, Ritalin-SR)
C-II controlled substance
Drug of choice to treat ADD, ADHD, and
narcolepsy
Increases levels of neurotransmitters in the brain
Concerta is a QD dose outer shell dissolves to
release medication immediately, then drug is
slowly released through pores in the tablet

dextroamphetamine-amphetamine
(Adderall)
C-II controlled substance
Effects last about 6 hours
Primary side effect is depression

Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
Adderall (ADD, ADHD)
Inderal (anxiety, hypertension)

atomoxetine (Strattera)
Nonstimulant inhibitor of norepinephrine
reuptake
Controls impulsivity and activity
Not a controlled substance, so refills can be
called in
Side effects: weight loss and slowed growth

Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
Clonidine (ADD, ADHD)
Klonopin (seizures)

Discussion
Compare and contrast ADHD and
ADD.

Discussion
Compare and contrast ADHD and ADD.
Answer
ADHD hyperactivity, impulsivity, and
distractability
ADD more lethargic and easily
distracted

Amyotrophic Lateral Sclerosis

(ALS)
Known as Lou Gehrigs disease
Progressive degenerative disease of the
nerves
Leads to muscle weakness, paralysis, and
eventually death
Caused by excessive levels of glutamate

Drug List
ALS Agent
riluzole (Rilutek)

riluzole (Rilutek)
First drug approved for ALS
Inhibits release of glutamate
Shown to improve survival rate by 3
months is some patients

Multiple Sclerosis (MS)

Autoimmune disease in which myelin
sheaths degenerate
Patient loses use of muscles and often
eyesight is affected
Some drugs can slow progression, but there
is no cure

Drug List
MS Agents

baclofen (Lioresal)
glatiramer acetate (Copaxone)
interferon beta-1a (Avonex, Rebif)
interferon beta-1b (Betaseron)
mitoxantrone (Novantrone)
tizanidine (Zanaflex)

interferon beta-1a (Avonex, Rebif)

Used for ambulatory patients

Reduces frequency of attacks
Delays disability
Drug should be taken at night with APAP to
prevent flu-like side effects

baclofen (Lioresal)
Skeletal muscle relaxant
Inhibits transmission of reflexes at the
spinal cord
Onset requires three to four days

Alzheimers Disease

Degenerative disorder of the brain that

leads to progressive dementia and changes
in personality and behavior
Progression
1. Minor forgetfulness
2. Inability to complete complex tasks
3. Complete incapacitation, disorientation, and
failure to thrive

Alzheimers Disease
There are no treatments that can reverse this
disease
Depression should be treated according to
symptoms

Drug List
Alzheimers Agents

donepezil (Aricept)
galantamine (Reminyl)
ginkgo
memantine (Namenda)
rivastigmine (Exelon)
tacrine (Cognex)

donepezil (Aricept)
Convenient with few side effects
Improves memory and alertness
Give once a day at bedtime

memantine (Namenda)
May have fewer side effects than other
drugs
Approved for moderate to severe conditions
Evidence that the drug does slow disease

rivastigmine (Exelon)
Has fewer interactions than Aricept
More difficult to dose and administer

Discussion
How does Alzheimers disease affect
patients families? Has the disease
affected someone in your family?

Discussion
Several of the diseases presented in
this chapter are degenerative and
there is yet no known cure. How
might this affect patients with a
diagnosis of one of these conditions?