CHAPTER 12: CENTRAL NERVOUS SYSTEM DEPRESSANTS AND MUSCLE RELAXERS

CNS Depressants
• Sedatives
– Drugs that have an inhibitory effect on the CNS to the degree that they reduce:
⋅ Nervousness
⋅ Excitability
⋅ Irritability without causing sleep
• Hypnotics
– Calm or soothe the CNS to the point that they cause sleep
– A sedative can become a hypnotic if it is given in large enough doses
• Sedative-hypnotics—dose 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

Sleep
• Normal sleep is cyclic and repetitive
• A sleeping person is unaware of sensory stimuli within the immediate environment
• Rapid eye movement (REM)
• Non–rapid eye movement (non-REM)
• Sleep stages

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

Barbiturates: Four Categories

• Ultrashort
– thiopental
• Short
– pentobarbital
• Intermediate
– amobarbital
• Long
– phenobarbital

Therapeutic Index
• Dosage range within which the drug is
effective but above which is rapidly toxic
• Barbiturates have a narrow therapeutic
index
Barbiturates:
• Mechanism of Action
– Site of action
⋅ Brainstem (reticular formation)
– By inhibiting GABA, nerve impulses travelling in the cerebral cortex are also inhibited
• Drug Effects
– Low doses: sedative effects
– High doses: hypnotic effects (also lowers respiratory rate)
– Notorious enzyme inducers
⋅ Stimulate liver enzymes that cause the metabolism or breakdown of many drugs
• Indications
– Hypnotic
– Sedative
– Anticonvulsant
– Anaesthesia for surgical procedures
• Side Effects
– CNS: Drowsiness, lethargy, vertigo, mental depression, coma
– Respiratory: Respiratory depression, apnea, bronchospasms, cough
– GI: Nausea, vomiting, diarrhea, constipation
– Other: Agranulocytosis, vasodilation, hypotension, Stevens-Johnson syndrome
– Reduce REM sleep, resulting in:
⋅ Agitation
⋅ Inability to deal with normal stress

Barbiturates: Toxicity and Overdose

• Overdose frequently leads to respiratory depression, and subsequently, respiratory arrest
• Overdose produces CNS depression (sleep to coma and death)
• Can be therapeutic
– Anaesthesia induction
– Uncontrollable seizures: “phenobarbital coma”

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

Common Barbiturates
• pentobarbital
• phenobarbital

CNS Depressants: Benzodiazepines

• Most frequently prescribed sedative-hypnotics
• Most commonly prescribed drug classes
• Favourable side effect profiles
• Efficacy
• Safety
Benzodiazepines: Classification
• Classified as either:
– Sedative-hypnotic
– Anxiolytic (medication that relieves anxiety)

Benzodiazepines: Sedative-Hypnotic Types

• Long acting
– chlordiazepoxide, clorazepate, flurazepam
• Intermediate acting
– alprazolam, clonazepam, lorazepam, oxazepam
• Short acting
– midazolam (IV), triazolam

Benzodiazepines:
• Mechanism of Action
– Depress CNS activity
– Affect hypothalamic, thalamic, and limbic systems of the brain
– Benzodiazepine receptors
– Do not suppress REM sleep as much as barbiturates do
– Do not increase metabolism of other drugs
• Drug Effects
– Calming effect on the CNS
– Useful in controlling agitation and anxiety
– Reduce excessive sensory stimulation, inducing sleep
– Induce skeletal muscle relaxation
• Indications
– Sedation
– Sleep induction
– Skeletal muscle relaxation
– Anxiety relief
– Treatment of alcohol withdrawal
– Agitation
– Depression
– Epilepsy
– Balanced anaesthesia
• 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
• 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
• Clients should be instructed to avoid alcohol and other CNS depressants
• 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
• Rebound insomnia may occur for a few nights after a 3- to 4-week regimen has been
discontinued
• Safety is important
– Keep side rails up or use bed alarms
– Do not permit smoking
– Assist client with ambulation (especially the elderly)
– Keep call light within reach
• Monitor for side effects
• 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

Muscle Relaxants
• Act to relieve pain associated with skeletal muscle spasms
• Majority are central acting
– CNS is the site of action
– Similar in structure and action to other CNS depressants
• Direct acting
– Acts directly on skeletal muscle
– Closely resembles GABA

Muscle Relaxants: Indications

• Relief of painful musculoskeletal conditions
– Muscle spasms
– Management of spasticity of severe chronic disorders
– Multiple sclerosis, cerebral palsy
• Work best when used along with physical therapy
• dantrolene
– Malignant hyperthermia crisis

Muscle Relaxants: Side Effects

• Extension of effects on CNS and skeletal muscles
– Euphoria
– Lightheadedness
– Dizziness
– Drowsiness
– Fatigue
– Muscle weakness

Common Muscle Relaxants

• baclofen
 • cyclobenzaprine
• dantrolene
• tizanidine
Muscle Relaxants: Nursing Implications
• See others listed for CNS depressants

Lilley: Pharmacology and the Nursing Process in Canada

Student Worksheets

1. Benzodiazepines work by enhancing the action of the inhibitory neurotransmitter gamma-

aminobutyric acid, producing hypnotic effects and central nervous system depression. An example
of a benzodiazepine is flurazepam hydrochloride (Dalmane).

2. Chloral hydrate is used as a sedative–hypnotic. Side effects include gastrointestinal upset and
gastric irritation with vomiting, nausea, and diarrhea.

3. Larger doses of sedative–hypnotics result in a hypnotic effect. Smaller doses have a calming, or
sedating, effect.

4. Phenobarbital is a barbiturate sedative–hypnotic agent.

5. Flurazepam is a benzodiazepine sedative–hypnotic agent.

6. Zolpidem is a short-acting, non-benzodiazepine hypnotic agent.

7. Dantrolene is the only skeletal muscle relaxant that works directly on the skeletal muscle.

Answers to Critical Thinking Activities

1.
a. The medication is to be taken only as prescribed. If the recommended dose does not work, the
dose is not to be doubled; contact the physician instead. The client should avoid any other type
of central nervous system (CNS) depressants, such as tranquilizers, other sleep agents,
narcotics, and alcohol. The client should always read the labels on over-the-counter medicines
for possible drug interactions. Explain that a “hangover” effect is more common in elderly
clients. It results in the client feeling more tired and less rested but seems to occur less often
than with other sedative–hypnotics, as is seen with the use of benzodiazepines or barbiturates.
The client should not stop taking the medication abruptly and should report to the physician
excessive sedation or dizziness.
b. Chloral hydrate is preferred because it does not suppress rapid eye movement sleep and has
fewer severe side effects and lower toxicity. However, it is useful only for short-term therapy
and (as with all medications) could be associated with idiosyncratic reactions.

2. For individuals diagnosed with seizure disorders who are on anticonvulsant therapy, emphasize
the importance of taking the medication at the same time every day, as well as taking it
consistently to control seizures adequately. Also emphasize that alcohol is contraindicated with
these medications because of the risk of possible exacerbation of seizures.

3. Liver function studies (aspartate transaminase, alanine transaminase, bilirubin, lactate

dehydrogenase), as well as blood urea nitrogen and other renal function studies, need to be
monitored because of the risk of liver and renal dysfunction with long-term barbiturate use (these
 are the main organs of metabolism and excretion). In addition, long-term use may precipitate
various blood dyscrasias and/or bleeding, so complete blood count, hemoglobin, hematocrit, and
bleeding studies also need monitoring.

4. Flurazepam, a benzodiazepine, is associated with physiological and psychological dependence.

An abrupt discontinuance is discouraged to prevent withdrawal symptoms. Also, abruptly stopping
the medication could pose a risk to the client’s safety and cause further complications. The client
needs instruction about weaning off the medicine and the rationale for slow withdrawal of the drug.

Intravenous (IV) diazepam as a sedative–hypnotic, or even as an anti-epileptic drug, cannot be used

without concern. One main concern with IV diazepam is the occurrence of tachychardia,
electrocardiographic changes, hypotension, and CNS depression, including respiratory depression,
especially if given parenterally. In fact respirations, blood pressure, and pulse should be taken every
5 to 15 minutes when diazepam is given IV. In addition, IV diazepam may cause thrombosis or
phlebitis and should be administered only into a large vein; continuous infusion is not recommended.
IV doses should be 5 mg or less and should be administered over at least 1 full minute in adults and
over no less than 3 minutes in children. There are also many incompatibilities in syringes, such as
atropine, chlorpromazine, codeine, droperidol, fentanyl, glycopyrrolate, hydroxyzine, meperidine,
metoclopramide, morphine, nalbupine, pentazocine, pentobarbital, prochlorperazine, promazine,
promethazine, scopolamine HBr, and secobarbital. Parenteral incompatibility occurs when two or
more drugs are mixed in a syringe, causing a reaction such as precipitation