Transcript PowerPoint_Chapter7x

Chapter 7
The Nervous System and Drug
Therapy
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Chapter 7
Topics
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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
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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 cord
Processes information received outside the body
 Peripheral nervous system
Is all the nerves outside the brain and spinal cord
Brings signal to the CNS for interpretation
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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
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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
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Anatomy and Physiology of the Nervous System
Anatomy
of the
Nervous
System
Anatomy of
the Brain
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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
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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
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Anatomy and Physiology of the Nervous System
Neurotransmission
Nerve signals are carried from cell to cell by neurotransmitters
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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
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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
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Anatomy and Physiology of the Nervous System
Autonomic
Nervous System
• Autonomic nerves
 Are located
close to the
spinal column
 Regulate
involuntary
body functions
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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
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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
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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
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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
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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
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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
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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 zeroorder 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
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Seizure Disorders
Antiepileptic Drugs: Cautions
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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
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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 .
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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 antiinflammatory drugs, theophylline, and nicotine.
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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
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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
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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
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Attention-Deficit Hyperactivity Disorder (ADHD)
Controlled
Substances
The CII on the
label indicates
that the agent is a
controlled
substance that
must be stored
separately from
other inventory
and locked
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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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