2© Paradigm Publishing, Inc. Chapter 7 The Nervous System and Drug Therapy

© Paradigm Publishing, Inc. 2

Chapter 7

The Nervous System and Drug Therapy


Chapter 7

Topics

• Anatomy and Physiology of the Nervous System• Seizure Disorders• Parkinson’s Disease• Dementia and Alzheimer’s Disease• Attention-Deficit Hyperactivity Disorder (ADHD)• Drugs that Affect the Autonomic Nervous System• Herbal and Alternative Therapies


Anatomy and Physiology of the Nervous System

The Nervous System• Senses and interprets surroundings and controls vital

bodily functions• Contains two divisions of the nervous system which are

the CNS and the peripheral nervous system CNS

Is made up of the brain and spinal cordProcesses information received outside the body

Peripheral nervous systemIs all the nerves outside the brain and spinal cordBrings signal to the CNS for interpretation



Peripheral Nervous System• Contains two divisions called the somatic nervous

system and the autonomic nervous system Somatic nervous system

Controls intentional, voluntary movement Autonomic nervous system

Controls involuntary and automatic body functions, like heart rate, respiration, and digestion



Autonomic Nervous System: Two Divisions• Sympathetic nervous system

Uses adrenergic receptors and some cholinergic receptors

• Parasympathetic nervous system Uses cholinergic receptors

The Brain: Two Sections• Cerebrum, including the cerebral cortex

Performs high cognitive functions, such as thinking and memory

• Cerebellum Coordinates movement and balance



Anatomy of the Nervous System

Anatomy of the Brain



Pons and Medulla• Located in the brain stem• Regulate automatic and reflex functions of the body

Thalamus and Hypothalamus• Are in the middle of the brain• Control various functions, including hormone regulation

and body temperature

Pituitary Gland• Helps regulate hormones and controls the growth cycle

throughout life



Blood-Brain Barrier (BBB)• Protects delicate CNS tissue from potentially harmful

chemicals Oxygen, carbon dioxide, small molecules like glucose,

and small lipid-soluble drugs pass easily from blood to CNS

Water-soluble molecules, like drugs and most pathogens, do not easily enter the brain or spinal cord

• Must be overcome so that drug therapy can enter the CNS



Neurotransmission

Nerve signals are carried from cell to cell by neurotransmitters



Six Neurotransmitters and Their Actions• Acetylcholine (ACh)

Used in the parasympathetic nervous system to control blood pressure, digestion, heart rate, and in exocrine glands

• Dopamine (DA) Used in CNS to control mood and coordinated movement

• Epinephrine (adrenaline) Used in the sympathetic nervous system to regulate

cardiac function and bronchodilation• GABA (gamma-aminobutyric acid)

Used in the brain to regulate signal delivery



Six Neurotransmitters and Their Actions (continued)• Norepinephrine

Used in the CNS and sympathetic nervous system Involved in mood and emotion in the brain Acts on receptors to control blood pressure, cardiac

function, and digestion in the periphery• Serotonin (5-HT)

Used in the peripheral nervous system and CNS Acts on receptors in smooth muscle in the periphery Involved in mood and emotions in the brain

• Altered production, release, or metabolic breakdown of neurotransmitters causes many nervous system conditions



Autonomic Nervous System• Autonomic nerves

Are located close to the spinal column

Regulate involuntary body functions



Autonomic Nervous System: Fight or Flight Response• Sympathetic nerves release norepinephrine in scary or

surprising situations; adrenal medulla releases epinephrine Increases heart and respiration rates and blood pressure Sympathetic nerves are called adrenergic

• Parasympathetic nerves release ACh to regulate body functions when relaxed or resting Heart rate and breathing slow, and digestion and

urination can occur Parasympathetic nerves are called cholinergic



Alpha and Beta Adrenergic Receptors• Activated by norepinephrine and epinephrine• Alpha receptors

Found in blood vessels; when stimulated blood vessels constrict, raising blood pressure and when blocked by drugs blood pressure decreases

• Beta-one and beta-two receptors Beta-one mostly in the heart; stimulation increases heart rate

and contraction force Beta-two in smooth muscle; stimulation causes blood vessels

and bronchioles to dilate When blocked by drugs heart rate, blood pressure, and

respiration decrease


Seizure Disorders

About Seizures (Convulsions) • Are uncoordinated bursts of neuronal activity that result in

brain dysfunction• Common causes include alcohol or drug withdrawal, high

fever, stroke, shock, low or high blood sugar, and infection• One in ten individuals will have unprovoked seizure in

lifetime• Epilepsy

Is a chronic seizure disorder All patients with epilepsy have seizures, but not all

patients with seizures have epilepsy


Seizure Disorders

Types of Seizures• Partial seizure

Most common type Affects localized brain area and specific body area Causes twitching or muscle tightness in specific body areas Loss of consciousness usually does not occur and patient

can communicate• Generalized seizures

Loss of consciousness usually occurs Afterward, patient has a period of memory loss, confusion,

and tiredness


Seizure Disorders

Antiepileptic Drugs (AEDs)• Anticonvulsants

Are drugs used to treat seizure disorders Mechanism of Action: varies; can work by multiple

mechanisms at once Affect the influx of sodium, calcium, or chloride ions across

the nerve cell membrane which slows erratic nerve impulses• Glutamate

Excitatory neurotransmitter that affects sodium and calcium influx

• GABA Neurotransmitter inhibitor that affects chloride influx


Seizure Disorders

Antiepileptic Drugs (AEDs) (continued)• Mechanism of Action: some work directly on ion channels;

others inhibit glutamate or enhance GABA Some work in multiple ways, such as topiramate

• Drug therapy regimens are highly individualized for each patient; take up to a month for full benefit from AEDs

• Status epilepticus (an emergency) treatment includes 1 of 2 benzodiazepines (diazepam or lorazepam), plus phenytoin or fosphenytoin Phenobarbital also may be used Storage: this drug combination found in crash cart kits;

pharmacy technicians often maintain


Seizure Disorders

Antiepileptic Drugs: Side Effects• Many are dose-dependent; blood levels monitored for

highest (peak) and lowest (trough) concentrations• Phenytoin, valproate, and carbamazepine undergo zero-order

pharmacokinetics which results in severe toxicity• Can cause drowsiness, dizziness, and mental

confusion, but these effects can improve in time• May have dulling effect on ability to think which is common

in children• Rare and serious effects include Stevens-Johnson syndrome

(severe and sometimes fatal rash) and blood abnormalities• Phenytoin can cause gingival hyperplasia


Seizure Disorders

Antiepileptic Drugs: Cautions• Do not take with alcohol• Avoid abrupt withdrawal• Several anticonvulsants are in pregnancy category D• Do not take zonisamide if allergic to sulfa drugs• Zonisamide and topiramate can cause kidney stones• Phenytoin interacts with many other medications• Routes: all oral (fosphenytoin is IM, IV); others also IV

Valproate and valproic acid swallow whole• Controlled substances are barbiturates (phenobarbital,

amobarbital, and mephobarbital) and primidone


Your Turn

Question 1: What is the function of the parasympathetic nerves?Answer: They regulate restful body functions. When relaxed or resting, the heart and breathing are slow, digestion occurs, and urination is possible.

Question 2: A child took an antiepileptic drug for 3 months during the school year. During that time, his grades began to drop. What could have caused this to happen?

Answer: Antiepileptic drugs can have a dulling effect which affects the ability to think. The child may have experienced this side effect, which impacted his school performance .


Parkinson’s Disease

About Parkinson’s Disease (PD)• Is characterized by tremors, muscle rigidity, difficulty

moving, and balance problems; quite debilitating• Is most common among elderly; 1% over age 60 have

PD in the U.S.• Is a disorder of the CNS in which cells are lost in the

substantia nigra (region in midbrain) These cells produce dopamine, a neurotransmitter used

in initiating and coordinating muscle movement• Is progressive and has no cure• Drug therapy can relieve symptoms, allowing movement



About Parkinson’s Disease (continued)• Symptoms: shuffling gait, lean forward, somewhat

off-balance, tremors, and inability to move• Symptoms (other): anxiety, depression, fatigue, slow

thinking dementia, fragmented sleep, and hallucinations

PD-Type Symptoms• Some drugs cause PD-type symptoms, but the effects are

usually reversible when drug is stopped Antipsychotics, metoclopramide, phenothiazine

antiemetics, pimozide, amoxapine, lithium, and serotonin reuptake inhibitors



Drugs for PD• Initial therapy starts with one drug: an anticholinergic agent

or a dopaminergic agent such as levodopa• Eventually, adjunct therapy added for symptom control

COMT inhibitors, selegiline, apomorphine, amantadine

Drugs for PD: Dopamine Agents• Are mainstay of treatment for PD• Levodopa

Is most effective treatment because it greatly improves movement and significantly restores normal function

Effects wear off over time



Drugs for PD: Dopamine Agents (continued)• Other dopaminergic agents used as an alternative to

levodopa but not always as effective• Will work without significant side effects about five years• Mechanism of Action: replaces dopamine or mimics its

action in the brain• Dopamine itself cannot cross the BBB, so its prodrug,

levodopa is given; the brain breaks it into dopamine Carbidopa is also often given with levodopa to slow its

breakdown before it reaches CNS; more enters brain• Routes: all are oral, except apomorphine is SC injection



Drugs for PD: Dopamine Agents (continued)• Side Effects of Levodopa/Carbidopa (common): nausea and

dyskinesias (involuntary movements of limbs, neck, and mouth)

• Side Effects of Dopamine Agonists (common): dizziness, constipation, nausea, insomnia, daytime sleepiness, “sleep attacks,” yawning, hallucinations, and mood elevations

• Caution: do not take apomorphine with antiemetic agents Self-injected pen used for acute“off” times; not used

regularly; pharmacist needs to teach use how to use Storage: refrigerate prefilled syringes for one day



Drugs for PD: Anticholinergics and Amantadine• Indication (early in PD): mostly for tremors• Indication (later in PD): adjunct for side effects of levodopa• Anticholinergics

Mechanism of Action: block muscarinic receptors in the brain, reducing tremors

Side Effects: anxiety, confusion/memory impairment, drowsiness, dry nose and mouth, blurred vision, constipation, difficulty urinating, and possible heatstroke

• Amantadine Mechanism of Action: inhibits reuptake of dopamine

• Cautions: drowsiness and confusion; do not take with alcohol



Drugs for PD: COMT Inhibitors• Indication: adjunct therapy (not monotherapy)

Help when levodopa starts to wear off at the end of each dosing interval

Are given with levodopa to increase “on” time• Mechanism of Action: block an enzyme that metabolizes

dopamine and boost effects of levodopa and dopamine• Routes: all are oral• Side Effects (Entacapone): dyskinesia worsening , nausea,

diarrhea, abdominal pain, and postural hypotension• Caution (Entacapone): can cause urine discoloration



Drugs for PD: MAOIs• Indication (early in PD): mild dopamine-boosting• Indication (later in PD): adjunct therapy• Mechanism of Action: block MAO, an enzyme that breaks

down dopamine in neurons• Routes: all are oral• Side Effects: insomnia, confusion, hallucinations,

euphoria, dizziness, and postural hypotension• Cautions: limit intake of tyramine-rich foods (beef,

sausage, aged and pickled foods and beverages) Technicians remind patients to limit consumption


Dementia and Alzheimer’s Disease

About Alzheimer’s Disease• Is a form of dementia• Is a degenerative brain disorder leading to loss of memory,

intellect, judgment, orientation, and speech• 250,000 people diagnosed each year• Can cause depression and anxiety• “Failure to thrive” level reached and death results; no cure

Drugs for Alzheimer’s Disease• Goal is to maintain cognitive function and alertness for as

long as possible• Indications: mild symptoms early in disease progression

32

Dementia and Alzheimer’s Disease

Drugs for Alzheimer’s Disease (continued)• Mechanism of Action: inhibit enzymes that break down

acetylcholine• Routes: all are oral; rivastigmine is also transdermal• Later in the disease antidepressants given for depression;

benzodiazepines for anxiety and sleep problems; antipsychotics for hallucinations

• Side Effects (Cholinesterase Inhibitors): nausea, vomiting, agitation, rash, loss of appetite, weight loss, and confusion

• Cautions: tacrine has many drug interactions; if taking donepezil avoid NSAIDs, theophylline, and nicotine

© Paradigm Publishing, Inc.


Your Turn

Question 1: What is the function of carbidopa when administered with levodopa?

Answer: Carbidopa slows the breakdown of levodopa before it reaches CNS, so more of it enters the brain.

Question 2: What is a restriction of donepezil?Answer: Patients with cardiac disease, liver problems, or Parkinson’s disease should not take donepezil. In addition, patients taking donepezil should avoid nonsteroidal anti-inflammatory drugs, theophylline, and nicotine.


Attention-Deficit Hyperactivity Disorder (ADHD)

About ADHD• Is characterized by inattention, impulsivity, and

hyperactivity• Affects 3 to 10% school-aged children, whereas 5% of

adults are affected• Onset occurs by age 3 and is more prevalent in boys

Drugs for ADHD• Public controversy around the overdiagnosis and

overmedication of ADHD• For best results use drugs with behavioral therapy



Drugs for ADHD: CNS Stimulants• Is the first-line drug therapy for children and adults• Immediate-release products usually used first and then

extended products are used for longer effects• Mechanism of Action: enhance the release and block the

reuptake of dopamine and norepinephrine in nerve cells• Routes: all are oral; extended release also transdermal• Side Effects (common): headache, stomachache, loss of

appetite, weight loss, insomnia, and irritability• Side Effects (severe): growth suppression in children, liver

dysfunction (very rare), and jaundice



Drugs for ADHD: CNS Stimulants (continued)• Cautions: Rare but serious (even fatal) cardiac

abnormalities• Caution for Adderall XR: do not use if cardiac abnormalities• Are controlled substances (Schedule II)

No refills and limited supplies given at a time Patients and their parents required to submit new

written prescription for each refill• Pharmacy technicians should remind patients or caregivers

about refill requirements with first prescription



Controlled SubstancesThe CII on the label indicates that the agent is a controlled substance that must be stored separately from other inventory and locked



Drugs for ADHD: Nonstimulant Drugs• Atomoxetine

Is an alternative to CNS stimulants Not a controlled substance Mechanism of Action: increases norepinephrine and/or

dopamine in brain and increases focus and curbs impulsivity Side Effects (common): nausea, heartburn, fatigue, and

decreased appetite Side Effects (severe): liver injury

• Other nonstimulant drugs include antidepressants as well as clonidine and guanfacine for patients with tics or insomnia


Drugs that Affect the Autonomic Nervous System

Adrenergic Inhibitors • Block alpha and beta receptors• Causes increased heart rate and blood pressure,

vasoconstriction, and delayed bladder emptying

Adrenergic Inhibitors: Alpha Blockers• Indications (primary): HTN and useful in men with BPH• Side Effects (common): headache, dizziness, nausea, and

fatigue/tiredness• Side Effects (rare): priapism (erection longer than 4 hours)• Cautions: may cause hypotension and heart palpitations;

avoid alcohol or taking verapamil



Adrenergic Inhibitors: Beta Blockers• Indications: HTN, angina, arrhythmias, and also

recommended for heart attack patients Less commonly used for migraine headaches, mild

anxiety, and glaucoma• Beta blockers make up the entire Class II of anti-arrhythmic

agents• Cardioselective beta blockers

Inhibit only beta-one receptors in the heart Indications: angina and certain arrhythmias

without causing bronchoconstriction



Adrenergic Inhibitors: Beta Blockers (continued)• Side Effects (common): headache, dizziness, lightheadedness,

nausea, and fatigue/weakness Associated with increased incidence of depression If difficulty breathing, seek medical help right away

• Routes: All are oral, except esmolol is IV only• Caution: do not use beta-two blockers if impaired respiratory

function like asthma or COPD• Cautions: do not stop taking abruptly because this can cause

severe cardiac problems; avoid oral decongestants if taking beta blockers for high blood pressure; some take with food or and others no food



Adrenergic Agonists• Stimulate autonomic nervous system to produce sympathetic

activity, such as increased heart rate and blood pressure, and bronchodilation

• Are vasopressors and sympathomimetics

Vasopressors and Sympathomimetics• Sympathomimetics

Mimic effect of stimulating sympathetic nervous system Indications: respiratory distress, allergic reactions, sinus

congestion, and glaucoma Epinephrine

Indication: anaphylactic reactions Routes: SC injection, IV, inhalation, and nasal



Vasopressors and Sympathomimetic (continued) • Vasopressors

Increases the heart rate and blood pressure Indications: cardiac arrest and shock situations

Adrenergic Agonists• Routes: IV, oral, and IM • Side Effects (common): headache, excitability, fast heart rate,

restlessness, and insomnia. • Side Effects (rare): arrhythmia

Use these medications only when needed due to these side effects



Adrenergic Agonists: Cautions• Pharmacy technicians may handle IV forms of these agents

only if they supply the emergency room or critical care unit• Mixed as needed in the unit for cardiac code situations

Mixed in dextrose solution• Stocked in emergency drug kits that technicians maintain• Epinephrine in autoinjector form (for life-threatening

allergies) prescribed and dispensed in outpatient setting Pharmacists should counsel patients how to inject into

the thigh, not the buttocks Do not use medication if expired



Anticholinergic Drug Effects• Includes dry mouth, dry eyes, constipation, urinary

retention, and blood pressure rises Caused by blocking cholinergic activity in the

parasympathetic system• Caution: do not use anticholinergics if patient has urinary

difficulty or bowel problems• Opioid pain medications and bladder spasticity agents

Causes significant constipation and dry mouth• Pharmacy technicians should be aware of interaction

warnings


Herbal and Alternative Therapies

• Ginkgo biloba Has modest benefits for early Alzheimer’s disease Causes serious side effects such as bleeding, seizures,

and coma Do not use if taking warfarin or aspirin for coagulation Interacts with other prescription drugs, particularly

anticonvulsants• Ephedra (ma huang)

Is a dietary supplement banned in the U.S. in 2004 Can cause heart palpitations, tremors, and insomnia Has caused deaths from cardiac arrest


Summary• A variety of antiepileptic drugs are used to control seizures• Dopamine, agonists, anticholinergics, and COMT inhibitors

are used to treat Parkinson’s disease• CNS stimulants are used to treat ADHD• Alpha and beta blockers used for parasympathetic actions• Adrenergic agonists used to stimulate sympathetic actions• Epinephrine is used in anaphylactic reactions• Many drugs cause anticholinergic side effects

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2© Paradigm Publishing, Inc. Chapter 7 The Nervous System and Drug Therapy