Central Nervous System Depressants. CNS Depressants Sedatives Drugs that have an inhibitory effect...

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-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

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


Four categories:• Ultrashort

– mephobexital, thiamylal, thiopental

• Short– pentobarbital, secobarbital

• Intermediate– aprobarbital, butabarbital

• Long– phenobarbital


Barbiturates have a very narrow therapeutic index.

Therapeutic Index• Dosage range within which the drug is effective

but above which is rapidly toxic.


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.


Drug Effects• Low doses: Sedative effects

• High doses: Hypnotic effects(also lowers respiratory rate)

Notorious enzyme inducers


Therapeutic Uses• Hypnotics• Sedatives• Anticonvulsants• Surgical procedures


Side Effects

Body System EffectsCNS Drowsiness, lethargy, vertigo

mental depression, coma

Respiratory Respiratory depression, apnea, bronchospasms, cough


Side Effects

Body System EffectsGI Nausea, vomiting,

diarrhea

Other Agranulocytosis, vasodilation, hypotension, Stevens-Johnson

syndrome


Toxicology• Overdose frequently leads to respiratory

depression, and subsequently, respiratory arrest.• Can be therapeutic:

– Anesthesia induction– Uncontrollable seizures: “phenobarbital coma”


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


Classified as either:

• Sedative-hypnotic or Anxiolytic

(Medication that relieves anxiety)


Sedative-Hypnotic Type• Long-Acting:

– flurazepam (Dalmane), quazepam (Doral)

• Short-Acting:– estazolam (Prosom), temazepam (Restoril),– triazolam (Halcion)


Anxiolytic Type

• alprazolam (Xanax)

• chloridiazepoxide (Librium)

• diazepam (Valium)

• lorazepam (Ativan)

• midazolam (Versed)

zolpidem (Ambien) and zaleplon (Sonata)

(nonbenzodiazepine hypnotic agents, share characteristics)


Mechanism of Action• Depress CNS activity• Affect hypothalamic, thalamic, and limbic

systems of the brain• Benzodiazepine receptors


Drug Effects

• Calming effect on the CNS

• Useful in controlling agitation and anxiety


Therapeutic Uses• Sedation

• Sleep induction

• Skeletal muscle relaxation

• Anxiety relief

• Treatment of alcohol withdrawal

• Agitation

• Depression

• Epilepsy

• Balanced anesthesia


Side Effects

• Mild and infrequent

Headache DrowsinessDizziness VertigoLethargyParadoxical 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.

• Patients 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.

• Abruptly stopping these medications, especially barbiturates, may cause rebound insomnia.


• 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


• 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• Parkinson’s Disease• Myasthenia Gravis• Attention-Deficit Disorders• Amyotrophic Lateral Sclerosis (ALS)• Multiple Sclerosis (MS)• Alzheimer’s 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 Parkinson’s disease and the drugs used in its treatment.

• Know the symptoms and treatments of– myasthenia gravis– attention-deficit disorders– amyotrophic lateral sclerosis– multiple sclerosis– Alzheimer’s 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

SeizureAbnormal 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


– Simple-partial– Complex-partial

• Generalized

Epilepsy


– 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


– No loss of consciousness– May have muscle twitching or sensory

hallucinations

• Complex-Partial

Epilepsy


– 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


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


Myoclonic• Occurs with sudden, massive, brief muscle

jerks or non-massive, quick jerks

• Consciousness is not lost

• Can occur during sleep


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


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 Therapy1. 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?


Neuronal Activity

1. Polarized (resting)

2. Depolarized (firing)1. Sodium and calcium enter the cell

2. When sufficient amounts cross, neurotransmitters are released

3. Neurotransmitter release leads to firing of the neuron

3. Repolarization (return to resting)


Abnormal Neuronal Activity

• DepolarizationIf excessive neurotransmitters are released it leads to uncontrollable firing of the neuron = seizure

• TreatmentBlock the firing of the neuron by raising the threshold of depolarization


• 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


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

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)

Drug List

Therapeutic Regimens for Seizures

Seizure Type 1st Line 2nd Line 3rd Line

Partial Tegretol or Dilantin

Neurontin or Lamictal

Luminal, 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 3rd Line

Tonic-Clonic, Tonic, Clonic

Tegretol, Dilantin, or Depakene

Luminal or Mysoline

Status Epilepticus Valium, Ativan, or Dilantin

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

• Depakote and Depakene can easily be confused.

• Be careful with Depakote and Depakote ER.

• Depakote ER is only once a day.

Warning!

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

Look-Alike and Sound-Alike Drugs

– Cerebyx (anticonvulsant)

– Celexa (antidepressant)

– Celebrex (for pain and arthritis)

Warning!

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

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

Warning!

clonazepam (Klonopin)

• Only indication is prophylaxis of seizures

• Depresses nerve transmission in the motor cortex

• C-IV controlled substance (benzodiazepine)

Dispensing Issues


– Lamictal (anticonvulsant)

– Lamisil (antifungal)

– Lomotil (for diarrhea)

Warning!

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


– Kaletra (antiviral for HIV)

– Keflex (antibiotic)

– Keppra (anticonvulsant)

Warning!

Discussion

Which neurotransmitters play the greatest role in seizures?

Discussion

Which neurotransmitters play the greatest role in seizures?

Answer

• Glutamate (excitatory)

• GABA (inhibitory)

Parkinson’s Disease

• Characteristic Signs– Resting tremor– Rigidity– Akinesia

• Usually affects people over 60


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


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


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

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)

Drug List

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


– Amantadine (for Parkinson’s)

– Ranitidine (for the stomach)

– Rimantadine (for the flu)

Warning!

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 Parkinson’s disease and what role do they play?

Discussion

What are the two primary neurotransmitters involved in Parkinson’s 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

Myasthenia Gravis Agents

• azathioprine (Imuran)

• cyclophosphamide (Cytoxan)

• edrophonium (Enlon, Reversol)

• neostigmine (Prostigmin)

• pyridostigmine (Mestinon)

Drug List

pyridostigmine (Mestinon)

• Blocks destruction of ACh

• Allows for ACh accumulation at the synaptic junction

cyclophosphamide (Cytoxan)

• Prevents cell division by targeting the auto-immune portion of the disease

• Use chemotherapeutic precautions

Attention-Deficit Disorders

• Attention-Deficit Hyperactivity Disorder (ADHD)

• Attention-Deficit Disorder (ADD)


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


Attention-Deficit Hyperactivity Disorder (ADHD)Characteristics for Assessment

– Hyperactivity– Impulsivity– Distractibility


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

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

Drug List

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


– Adderall (ADD, ADHD)

– Inderal (anxiety, hypertension)

Warning!

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


– Clonidine (ADD, ADHD)

– Klonopin (seizures)

Warning!

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 Gehrig’s disease

• Progressive degenerative disease of the nerves

• Leads to muscle weakness, paralysis, and eventually death

• Caused by excessive levels of glutamate

ALS Agent

• riluzole (Rilutek)

Drug List

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

MS Agents

• baclofen (Lioresal)

• glatiramer acetate (Copaxone)

• interferon beta-1a (Avonex, Rebif)

• interferon beta-1b (Betaseron)

• mitoxantrone (Novantrone)

• tizanidine (Zanaflex)

Drug List

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

Alzheimer’s Disease

• Degenerative disorder of the brain that leads to progressive dementia and changes in personality and behavior

• Progression1. Minor forgetfulness

2. Inability to complete complex tasks

3. Complete incapacitation, disorientation, and failure to thrive

Alzheimer’s Disease

• There are no treatments that can reverse this disease

• Depression should be treated according to symptoms

Alzheimer’s Agents

• donepezil (Aricept)

• galantamine (Reminyl)

• ginkgo

• memantine (Namenda)

• rivastigmine (Exelon)

• tacrine (Cognex)

Drug List

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 Alzheimer’s 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?

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