Title: Nursing 220: Pharmacology Module V: Central Nervous System and Psychotropic

Drugs
1
Nursing 220 PharmacologyModule V Central
Nervous System and Psychotropic Drugs

Presented by

Ronda M. Overdiek MSN CCRN RNC

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Overview

Chapters 20-35

CNS Pharmacology (20)

Parkinsons Disease (21)

Alzheimers Disease (22)

Epilepsy (23)

Muscle spasm/Spasticity (24)

Local Anesthetics (25)

Opioid (Narcotic) Analgesics (27)

Sedative/Hypnotic Drugs (33)

Antipsychotic Agents (30)

Antidepressants (31)

Bipolar Drugs (32)

CNS Stimulants (35)

Introduction to Central Nervous System

Pharmacology

CNS Drugs

Agents that act on the brain and spinal cord

Medical Purposes

Psychiatric disorders

Suppression of seizures

Relief of pain

Production of anesthesia

Non Medical purposes

Stimulant

Depressant

Euphoriant

Mind altering abilities

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Introduction to Central Nervous System
Pharmacology

Peripheral Nervous System Neurotransmitters

Acetylcholine norepinephrine epinephrine

Central Nervous System Neurotransmitters (Table

20-1 page 168)

Norepinephrine epinephrine dopamine serotonin

aspartate glutamate GABA glycine dynorphines
endorphins enkaphalins neurotensin
somatostatin substance P oxytocin vasopressin
acetylcholine histamine

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Introduction to Central Nervous System
Pharmacology

Blood Brain Barrier

Impedes the entry of drugs into the brain

Passage is limited to lipid-soluble agents and to

drugs that are able to cross by way of specific
transport systems

Drugs cannot cross if they are protein bound and

are highly ionized

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Introduction to Central Nervous System
Pharmacology

Adaptation of CNS to prolonged drug exposure

Increased therapeutic effects

Decreased side effects

Tolerance

Physical dependence

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Chapter 21Parkinsons Disease Drugs

Parkinson Disease

Degenerative disorder of the basal ganglia

involving the depletion of the inhibitory
neurotransmitter dopamine.

Imbalance of dopaminergic (inhibitory) and

cholinergic (excitatory) activity causes
symptoms. Balance of the two produced normal
motor function.

Possible Causes

Genetic viral and toxic.

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Chapter 21Parkinsons Disease Drugs

Parkinson Disease

Clinical Manifestations

Tremors at rest rigidity (muscle stiffness)

akinesia (decrease in voluntary
movements-disturbance in time it takes to make a
movement) postural abnormalities.

Associated with depression and dementia.

Treatment Drug therapy

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Chapter 21Parkinsons Disease Drugs

Goal of drug treatment

Improve the patients ability to carry out

activities of daily life.

Only provide symptomatic relief they do not cure

PD nor do they alter disease progression.

Give drugs that restore the functional balance

between dopamine and ACh.

Dopaminergic agents activate dopamine receptors

Anticholinergic agents drugs the block receptors

for ACh.

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Chapter 21Parkinsons Disease Drugs

Table 21-1 Dopaminergic Agents

Dopamine Replacement

Promotes dopamine synthesis

Levodopa/Carbidopa

Dopamine Agonists

Stimulate dopamine receptors directly

COMT Inhibitors

Enhance the effects of levodopa by blocking its

degradation

Dopamine Releaser

Promotes dopamine release

MAO-B Inhibitors

Inhibits dopamine breakdown

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Chapter 21Parkinsons Disease
DrugsDopaminergic Agents

Levodopa

Reduces symptoms

Beneficial effects of the drug diminish over time

Conversion of levodopa to dopamine takes place

following the uptake in the dopaminergic nerve
terminals after it crosses the blood brain
barrier and enters the brain.

Dopamine itself cannot cross the blood brain

barrier

Side Effects Nausea/vomiting dyskinesias

(movement disorders-head bobbing tics
grimacing) hypotension dysrhythmias psychosis
(visual hallucinations nightmares paranoid
ideation) darken sweat and urine.

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Chapter 21Parkinsons Disease
DrugsDopaminergic Agents

Levodopa plus Carbidopa Sinemet

Carbidopa is used to enhance the effects of

levodopa

Inhibits decarboxylation of levodopa at the

intestine and peripheral tissues making levodopa
more available to the CNS.

Carbidopa allows the dosage of levodopa to be

reduced by 75

Reduces cardiovascular and other side effects of

levodopa

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Chapter 21Parkinsons Disease DrugsDopamine
Agonists

Used in younger patients (first-line drugs)

For patients with mild/moderate symptoms

Contrast to levodopa

Dont depend on enzymatic conversion to become

active

Are not converted to potentially toxic

metabolites

Dont compete w/ dietary proteins for uptake from

intestine or transport across the blood-brain
barrier

Lower incidence of response failures

Less likely to cause disabling dyskinesias

However do cause more serious side effects

Hallucinations daytime sleepiness postural

hypotension

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Chapter 22Alzheimers Disease Drugs

Alzheimer Disorder

Cause is unknown

Loss of neurotransmitter stimulation chromosomal

mutations viral causes etc.

Pathophysiology

Neuronal proteins become distorted and twisted

causing degeneration and development of plaques
(senile plaques) causing decrease in neuronal
transmission.

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Chapter 22Alzheimers Disease Drugs

Alzheimer Disease

Clinical Manifestations

Forgetfulness emotional upset disorientation

confusion behavioral changes (irritability
agitation restlessness) deterioration of
language rigidity posturing.

Treatment

Memory aids assisting with ADLs.

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Chapter 22Alzheimers Disease Drugs

Patients w/advanced AD have acetylcholine levels

that are 90 below normal.

Drug treatment

Cholinesterase Inhibitors

Prevent breakdown of ACh by acetyl

cholinesterase increasing the availability of
ACh at cholinergic synapses.

Patients w/mild to moderate symptoms only 25-30

respond

Vitamin E / Selegiline (antioxidant properties)

Nonsteroidal Anti-inflammatory Drugs

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Chapter 23Drugs for Epilepsy

Epilepsy

Refers to a group of disorders characterized by

excessive excitability of neurons within the CNS
producing a variety of symptoms ranging from
brief periods of unconsciousness to violent
convulsions.

Treatment

Antiepileptic drugs

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Chapter 23Drugs for Epilepsy

Antiepileptic Drugs work by three mechanisms

Suppression of sodium influx

AEDs bind to sodium channels while they are in

an inactivated state prolonging channel
inactivation thereby delaying return to the
active state which decreases the ability of the
neurons to fire at high frequency.

Suppression of calcium influx

Inhibit calcium influx through T-type calcium

channels which are large enough in the
hypothalamus to cause an action potential which
can result in absent (Petit Mal) seizures.

Potentiation of GABA

GABA is an inhibitory neurotransmitter that is

widely distributed throughout the brain.
Augmentation of GABA decreases neuronal
excitability and suppresses seizure activity.

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Chapter 23Drugs for Epilepsy

Drug Administration Considerations

Goal reduce seizures to an extent that enables

the patient to live a normal or near-normal life.

Proper drug selection for specific seizure

disorders

Drug evaluation for effectiveness

Monitoring plasma drug levels

Promoting compliance

Withdrawing antiepileptic drugs

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Chapter 23Drugs for Epilepsy

Phenytoin (Dilantin)

Most widely used AED

Used for partial seizures and primary generalized

tonic-clonic seizures

Causes selective inhibition of sodium channels

Capacity of the liver to metabolize phenytoin is

very limited. Plasma levels need to be
monitored-narrow therapeutic range.

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Chapter 23Drugs for Epilepsy

Carbamazepine (Tegretol)

Active against partial and tonic-clonic seizures

Causes selective inhibition of sodium channels

Valproic Acid (Depakote)

Used to treat all major seizure types as well as

bipolar disorder and prevention of migraine
headaches.

Acts by all three mechanisms inhibition of

sodium channels suppresses calcium influx
augments inhibitory influence of GABA

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Chapter 23Drugs for Epilepsy

Ethosuximide (Zarontin)

Drug of choice for absent seizuresused only for

absent seizures

Inhibition of low-threshold calcium currents

Phenobarbital

Classified as an anticonvulsant barbiturate

Active against partial seizures and generalized

tonic-clonic seizures

Potentiates the effects of GABA

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Chapter 24Drugs for Muscle Spasm and Spasticity

Muscle spasm

Involuntary contraction of a muscle or muscle

group (resulting from muscle injury)

Drug therapy

Analgesic anti-inflammatory agents

Centrally acting muscle relaxants

Used to treat localized spasm resulting from

muscle injury decreasing local pain and
tenderness and increasing range of motion

Treatment is almost always associated w/sedation

No studies indicating the superiority of one drug

over another drug selection is based on
prescribers preference and patients response.

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Chapter 24Drugs for Muscle Spasm and Spasticity

Spasticity

Refers to a group of movement disorders of CNS

origin characterized by heightened muscle tone
spasm and loss of dexterity.

Causes include multiple sclerosis and cerebral

palsy

Drug Treatment

Baclofen/Diazepam act in the CNS

Dantrolene acts on the skeletal muscle

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Chapter 25Local Anesthetics

Local anesthetics

Drugs that suppress pain by blocking impulse

conduction along axons (by blocking sodium
channels)

Pain can be suppressed w/o causing generalized

depression of the entire nervous system

Administration

Topical applying directly to skin or mucous

membranes

Injection Infiltration nerve block intravenous

(regional) epidural spinal anesthesia.

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Chapter 25Local Anesthetics

Two major groups Amides / Esters

Amide Prototype Lidocaine

Administered topically and by injection

Can be administered w/epinephrine

Amount of drug monitored toxicity can result

Ester Prototype Procaine (Novocain)

Administered by injectionnot effective topically

Poses a greater risk of allergic type reactions

Ester Cocaine

Excellent local anestheticadministration is

topical

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Chapter 27 Narcotic Analgesics

Analgesics

Drugs that relieve pain without causing loss of

consciousness

Opioid Analgesics

Name derived from opium

Morphine Codeine oxycodone

Opioid is a general term defined as any drug

natural or synthetic that has actions similar to
those of morphine.

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Chapter 27 Narcotic Analgesics

Opioid Receptors

Mu Receptors

Responses to activation of mu receptors include

analgesia respiratory depression euphoria and
sedation.

Opioid analgesics act primarily through

activation of mu receptors

Kappa receptors

Responses to activation of kappa receptors can

produce analgesia and sedation.

Opioid analgesics produce weak activation of

kappa receptors

Delta receptors

Opioid analgesics do NOT interact with delta

receptors

Endogenous opioid peptides (enkephalins

endorphins and dynorphins) react w/ all three
receptors

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Chapter 27 Narcotic Analgesics

Classifications of Drugs

Analgesics are classified on the basis of how

they affect receptor function

At each type of receptor a drug can act in one

of three ways

Agonist

Partial Agonist

Antagonist

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Chapter 27 Narcotic Analgesics

Pure Opioid Agonists

Activate mu and kappa receptors producing

analgesia euphoria sedation respiratory
depression etc. Can be subdivided into moderate
or strong opioid agonists.

Agonist-Antagonist Opioid

When administered alone produce analgesia

When administered w/ opioid agonist it can

antagonize analgesia caused by the pure agonist.

Pure Opioid Antagonists

Act as antagonists at mu and kappa receptors

Used for reversal of respiratory and CNS

depression caused by overdose with opioid agonists

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Chapter 27 Narcotic Analgesics

Pure Opioid Agonist (Strong) Prototype

Morphine

Therapeutic use pain

Mimics the actions of endogenous opioid peptides

primarily at mu receptors.

Adverse effects respiratory depression

constipation orthostatic hypotension urinary
retention elevation of ICP sedation etc.

Considerations

Tolerance and physical dependence

Other Strong Opioid Agonists

Fentanyl Meperidine (Demerol) Heroin.

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Chapter 27 Narcotic Analgesics

Pure Opioid Agonist (Moderate to Strong)

Similar to morphine they produce analgesia

sedation euphoria and can cause respiratory
depression constipation urinary retention etc.

Differences are primarily quantitativethey

produce less analgesia and respiratory depression
than morphine and have a lower potential for
abuse.

Prototypes

Codeine oxycodone (percodan percocet)

hydrocodone (Vicodin) propoxyphene (Darvon).

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Chapter 27 Narcotic Analgesics

Agonist-Antagonist Opioids

Prototype Pentazocine (Talwin)

Acts as an agonist at kappa receptors

Acts as an antagonist at mu receptors

Respiratory depression is limited

If a patient is physically dependent on a pure

opioid agonist administration of an
agonist-antagonist opioid will cause withdrawal.

Nalbuphine (Nubain) Butorphanol (Stadol)

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Chapter 27 Narcotic Analgesics

Opioid Antagonists

Block the effects of opioid agonists

Used for overdose reversal of postoperative

opioid effects and management of opioid
addiction.

Naloxone (Narcan)

It is a competitive antagonist at opioid

receptors reversing analgesia sedation
euphoria respiratory depression.

Need to know pharmacokinetics to monitor patients

Naltrexone (Re Via Depade)

Pure opioid antagonist approved for treating

opioid abuse and alcohol abuse. Blocks euphoria
experienced by the abuser

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Chapter 27 Narcotic Analgesics

Nursing Considerations

Assessment of pain

Dosage determination

Dosing schedule

Avoiding withdrawal

Physical dependence abuse and addiction as

clinical concerns

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Chapter 33Sedative-Hypnotic Drugs

Sedative-hypnotic drugs

Depress CNS function

Primarily used to treat anxiety and insomnia

Before benzodiazepines

General CNS depressants (barbiturates) were

utilized to treat anxiety and insomnia.

Powerful respiratory depressants-prove fatal in

overdose

Have a high potential for abuse

With prolonged abuse they produce significant

tolerance and physical dependence

Induce synthesis of hepatic drug-metabolizing

enzymes decreasing responses to other drugs

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Chapter 33Sedative-Hypnotic Drugs

Benzodiazepines

Drugs of choice for treating anxiety/insomnia

Used to induce general anesthesia and manage

seizure disorders muscle spasms panic
disorders and alcohol withdrawal.

Prototypes Diazepam (Valium) Lorazepam

(Ativan) Alprazolam ( Xanax).

Potentiate (amplify) the actions of

GABA-inhibitory neurotransmitter found in the CNS

Pharmacologic Effects

Effects progress from sedation to hypnosis to

stupor. Reduce anxiety promote sleep induce
muscle relaxation.

Considerations produce confusion amnesia

hypotension cardiac arrest (IV administration).
They are weak respiratory depressants.

Overdose

Treatment w/Flumazenil (Romazicon) competitive

benzodiazepine receptor antagonistadverse effect
is precipitation of convulsions.

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Chapter 33Sedative-Hypnotic Drugs

Barbiturates

Cause nonselective depression of CNS function and

are the prototypes of the general CNS
depressants.

Used for sedation induction of sleep

suppression of seizures general anesthesia.

Have a high abuse potential are subject to

multiple drug interactions cause tolerance and
dependence and are powerful respiratory
depressants.

Barbiturates directly mimic GABAtherefore there

is no ceiling to the degree of CNS depression
they can produce.

Examples Phenobarbital secobarbital thiopental.

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Chapter 30Antipsychotic Agents Schizophrenia

Antipsychotic Agents

A chemically diverse group of compounds employed

to treat a broad spectrum of psychotic disorders.

Schizophrenia delusional disorders acute mania

depressive psychoses drug induced psychoses.

Two major groups

Conventional Antipsychotics

Block receptors for dopamine in the CNS

Atypical Antipsychotics

Only produce moderate blockage of receptors for

dopamine and much stronger blockade of receptors
for serotonin

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Chapter 30Antipsychotic Agents Schizophrenia

Schizophrenia

Chronic psychotic illness characterized by

disordered thinking and a reduced ability to
comprehend reality.

Positive symptoms

Hallucinations delusions disordered thinking

disorganized speech combativeness agitation
paranoia

Negative symptoms

Social/emotional withdrawal lack of motivation

poverty of speech blunted affect poor insight
poor judgment poor self-care

Etiology is unknown

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Chapter 30Antipsychotic Agents Schizophrenia

Conventional Antipsychotic Group Properties

Because of extrapyramidal side effects (serious

movement disorders- Page 286) they are known as
neuroleptics.

Classified by potency (low medium high) or by

chemical structure.

Mechanism of Action

Varying degrees these drugs block receptors for

dopamine acetylcholine histamine and
norepinephrine.

Relief of positive symptoms respond better to

conventional antipsychotic drugs less effect on
negative symptoms

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Chapter 30Antipsychotic Agents Schizophrenia

Conventional Antipsychotics

Low potency Prototype Chlorpromazine

(Thorazine)

Use Schizophrenia and other psychotic disorders

manic phase of bipolar disorder suppression of
emesis and relief of intractable hiccups.

High Potency Prototype Haloperidol (Haldol)

Can cause more early extrapyramidal symptoms

(EPS) but less sedation orthostatic hypotension.
Preferred for initial therapy.

Use Schizophrenia and acute psychosis

Tourettes syndrome.

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Chapter 30Antipsychotic Agents Schizophrenia

Atypical Antipsychotic Agents

Cause few or no EPS can relieve both positive

and negative symptoms of schizophrenia.

Prototype Clozapine (Clozaril)

Use Schizophrenia

Blocks receptors for dopamine and serotonin

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Chapter 31Antidepressants

Antidepressants

Used to relieve symptoms of depression as well as

help patients with anxiety disorders

Four major groups

Tricyclic antidepressants

Selective serotonin reuptake inhibitors

Monoamine oxidase inhibitors

Atypical antidepressants

Depression

Symptoms depressed mood and loss of pleasure or

interest in all or nearly all of ones usual
activities and past times. Can include insomnia
anorexia weight loss weight gain mental
slowing loss of concentration feelings of
guilt worthlessness and helplessness thoughts
of death and suicide and overt suicidal behavior.

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Chapter 31Antidepressants

Tricyclic Antidepressants (TCAs)

Prototype Imipramine

Mechanism of Action

Block neuronal reuptake of norepinephrine and

serotonin which intensifies their effects

Uses Depression bipolar disorder

Considerations onset of the blockade and the

onset of therapeutic response can be lengthy.
Initial responses develop in 1-3 weeks maximal
responses over 1 to 2 months.

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Chapter 31Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs)

Most commonly prescribed group of antidepressants

As effective as TCAs but do not cause

hypotension sedation or anticholinergic effects
(dry mouth blurred vision photophobia
constipation urinary hesitancy tachycardia).

Use major depression/ Table 31-4

Prototype Fluoxetine (Prozac Sarafem)

Mechanism of action

Produces selective inhibition of serotonin

reuptake

Blockade of transmitter uptake occurs quickly

therapeutic effects are the result of adaptive

cellular changes that take place in response to

prolonged uptake blockade

Other SSRIs Celexa Paxil Zoloft

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Chapter 31Antidepressants

Monoamine Oxidase Inhibitors (MAOIs)

Most dangerous risk of triggering hypertensive

crisis by eating foods rich in tyramine (Table
31-5 page 312)

MAO is an enzyme found in the liver the

intestinal wall and terminals of
monoamine-containing neurons. Their function is
to convert NE serotonin and dopamine into
inactive products. MAO inhibitors block this
process.

Uses depression bulimia obsessive-compulsive

disorder reduce panic attacks

Caution many drug interactions

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Chapter 31Antidepressants

Atypical Antidepressants

Bupropion (Wellbutrin)

Stimulant actions and also suppresses appetite

Mechanism by which depression is relieved is

unclear but appears to blockade dopamine uptake.

Others Effexor Serzone Remeron Trazadone.

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Chapter 32Drugs for Bipolar Disorder

Bipolar Disorder

Severe biologic illness characterized by

recurrent fluctuations in mood either the mood
is abnormally elevated or depressed.

Drug therapy

Mood stabilizers

Antidepressants (used w/mood stabilizer)

Antipsychotics (used w/mood stabilizer)

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Chapter 32Drugs for Bipolar Disorder

Mood Stabilizing Drugs

Provide relief from an acute manic or depressive

episode preventing symptoms from recurring.

Prototype Lithium

Low therapeutic index so levels MUST be monitored

(toxicity can occur at blood levels that are only
slightly greater than therapeutic).

Although lithium has been studied extensively

the precise mechanism by which it stabilized mood
is unknown.

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Chapter 32Drugs for Bipolar Disorder

Mood Stabilizing Anticonvulsants

Prototype Valproic acid (Depakene Depakote)

It is the only antiseizure agent that has been

approved by the FDA for treatment of BPD.

It is as effective as lithium works faster and

has a higher therapeutic index and more desirable
side effect profile.

First line treatment for BPD

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Chapter 35CNS Stimulants

CNS stimulants

Increase the activity of CNS neurons.

In sufficient doses all CNS stimulants can cause

convulsions.

Indications

Attention deficit/hyperactivity disorder (ADHD)

Narcolepsy

Groups

Amphetamines

Methyphenidate

Methylxanthines

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Chapter 35CNS Stimulants

Amphetamines

Act primarily by promoting release of and partly

by inhibiting reuptake of both norepinephrine and
dopamine.

Effects increase wakefulness and alertness

reduce fatigue elevate mood augment
self-confidence and initiative. Augment euphoria

talkativeness and increased motor activity.

Stimulate respiration and suppress appetite and
perception of pain.

Physical dependence can resulthigh potential for

abuse

Uses ADHD narcolepsy obesity.

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Chapter 35CNS Stimulants

Methylphenidate (Ritalin)

Promote NE and dopamine release and inhibition of

NE and dopamine reuptake

Uses ADHD and narcolepsy

Chemically structured different from amphetamines

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Chapter 35CNS Stimulants

Methylxanthines

Prototype Caffeine

Decreases drowsiness and fatigue and increases

capacity for prolonged intellectual exertion

Uses

Neonatal apnea promoting wakefulness relief of

headaches