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Transcript of 2© Paradigm Publishing, Inc. Chapter 7 The Nervous System and Drug Therapy.
© Paradigm Publishing, Inc. 3
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
© Paradigm Publishing, Inc. 4
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
© Paradigm Publishing, Inc. 5
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 6
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 7
Anatomy and Physiology of the Nervous System
Anatomy of the Nervous System
Anatomy of the Brain
© Paradigm Publishing, Inc. 8
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 9
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 10
Anatomy and Physiology of the Nervous System
Neurotransmission
Nerve signals are carried from cell to cell by neurotransmitters
© Paradigm Publishing, Inc. 11
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 12
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 13
Anatomy and Physiology of the Nervous System
Autonomic Nervous System• Autonomic nerves
Are located close to the spinal column
Regulate involuntary body functions
© Paradigm Publishing, Inc. 14
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 15
Anatomy and Physiology of the Nervous System
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
© Paradigm Publishing, Inc. 16
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
© Paradigm Publishing, Inc. 17
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
© Paradigm Publishing, Inc. 18
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
© Paradigm Publishing, Inc. 19
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
© Paradigm Publishing, Inc. 20
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
© Paradigm Publishing, Inc. 21
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
© Paradigm Publishing, Inc. 22
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 .
© Paradigm Publishing, Inc. 23
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
© Paradigm Publishing, Inc. 24
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 25
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 26
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 27
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 28
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 29
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 30
Parkinson’s Disease
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
© Paradigm Publishing, Inc. 31
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.
© Paradigm Publishing, Inc. 33
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.
© Paradigm Publishing, Inc. 34
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
© Paradigm Publishing, Inc. 35
Attention-Deficit Hyperactivity Disorder (ADHD)
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
© Paradigm Publishing, Inc. 36
Attention-Deficit Hyperactivity Disorder (ADHD)
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
© Paradigm Publishing, Inc. 37
Attention-Deficit Hyperactivity Disorder (ADHD)
Controlled SubstancesThe CII on the label indicates that the agent is a controlled substance that must be stored separately from other inventory and locked
© Paradigm Publishing, Inc. 38
Attention-Deficit Hyperactivity Disorder (ADHD)
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
© Paradigm Publishing, Inc. 39
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
© Paradigm Publishing, Inc. 40
Drugs that Affect the Autonomic Nervous System
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
© Paradigm Publishing, Inc. 41
Drugs that Affect the Autonomic Nervous System
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
© Paradigm Publishing, Inc. 42
Drugs that Affect the Autonomic Nervous System
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
© Paradigm Publishing, Inc. 43
Drugs that Affect the Autonomic Nervous System
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
© Paradigm Publishing, Inc. 44
Drugs that Affect the Autonomic Nervous System
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
© Paradigm Publishing, Inc. 45
Drugs that Affect the Autonomic Nervous System
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
© Paradigm Publishing, Inc. 46
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
© Paradigm Publishing, Inc. 47
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