Unit 3: The Nervous System

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Unit 3 The Nervous System

• Chapter 16 Drugs for
• Emotional and Mood Disorders

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Case Study

• N.N., a 21-year-old nursing major, is in her 7th
  semester and has maintained a 3.75 GPA. During
  this semester she has missed several classes with
  complaints of extreme fatigue, headaches, and
  generalized joint and muscle pain. When N.N. is
  in class she seems distracted and unable to
  concentrate. Outside of class she is spending
  more and more time alone. It is now mid-term and
  N.N. is failing her nursing course. Her teacher
  has noticed that N.N. gained weight, appears
  extremely sad, and her written work has declined
  in quality. At the suggestion of her teacher
  N.N. makes an appointment with campus health
  services.

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Questions

• What do you suspect is N.N.s problem?
• Why?
• What does the campus health nurse need to possess
  in order to care for N.N.?
• What should happen before assigning the diagnosis
  of a mood disorder?
• Who must N.N. see to receive a diagnosis?

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The Case Unfolds

• The campus nurse suspected depression but wanted
  to rule out physical causes first. She obtained
  information about N.N.s current and recent
  medications and made N.N. an appointment with a
  general practitioner. No physical pathology was
  identified and Dr. J. referred N.N. to the
  psychiatrist in his building. The psychiatrist
  confirmed that N.N. is experiencing a major
  depressive disorder. The psychiatrist plans to
  treat N.N. with medication and psychotherapy.

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More Questions

• What pharmacotherapy would you anticipate?
• What psycotherapies would you anticipate would be
  incorporated into N.N.s plan of care?
• You are the office nurse, how will you respond
  when N.N. asks you how long she will have to take
  the medication?

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Antidepressants

• The FDA this week approved the first-ever
  transdermal patch for the treatment of
  depression. Simply remove the backing and press
  the patch firmly over your mothers mouth.
  ---Tina Fey, on Saturday Night Live (March 2006)

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Mechanism of ActionAntidepressants

• Believed to exert effect through action on
  certain neurotransmitters
• Norepinephrine
• Dopamine
• Serotonin
• Two basic mechanisms of action
• Blocking enzyme breakdown of norepinephrine
• Slowing reuptake of serotonin

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Tricyclic Antidepressants

• Inhibit the reuptake of both norepinephrine and
  serotonin into presynaptic nerve terminals.
• Examples
• amytriptyline (Elavil)
• despiramine (Norpramin)
• doxepin (sinequan)

• Prototype imipramine (Tofranil) p. 187
• Primary use major depression
• Adverse effects
• Orthostatic hypotension
• Cardiac dysrhythmias
• Initial Sedation
• Anticholinergic effects

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Nursing Considerations

• Identify the nursing role in TCA therapy.
• What should be included in client teaching?

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Selective Serotonin Reuptake Inhibitors

• Selectively target serotonin (5-HT) blocks
  reuptake more 5-HT is available in the synaptic
  gap
• Examples
• citalopram (Celexa)
• escitalopram (Lexapro)
• fluoxetine (Prozac)
• paroxetine (Paxil)

• Prototype sertraline (Zoloft) p. 188
• Primary use depression
• Adverse effects
• Nausea, dry mouth, insomnia, somnolence,
  headache, nervousness, anxiety, GI disturbances,
  dizziness, anorexia, fatigue
• Sexual dysfunction

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Serotonin Receptor Facts

• 5-HT1, 5-HT2, 5-HT3, 5-HT4
• Subtypes5HT1A, 1B, 1C, 1D, 5-HT2A, 2B, 2C
• LSD is a famous 5-HT1 and 5-HT2 agonist (booster)
  causing schizophrenic- like effects
• 5-HT1Aif you activate it you will be anxious if
  you block it you will reduce anxietyBuspirone
  (Buspar) is a blocker of this receptor
• 5-HT1Dif you boost it vasoconstriction will
  occur the triptans are 5-HT1D agonists for
  acute migraines

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Serotoninhistorical highlights

• The Italians initially discovered this
  neurotransmitter in the gut in 1933 and called it
  enteramine
• 1st discovered as a protein in serum in 1948, and
  was called sero for serum and tonin for its
  vasoconstricting properties
• 95 of all serotonin in the body is enteric or
  in the GUT

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Digression The Second Brain...

• Serotonin and the gut
• Drugs such as SSRIs that increase serotonin in
  the brain and improve mood, also increase the
  release of serotonin in the GI tractincreasing
  gastric motility and the release of serotonin
  from the duodenum
• Side effectsnausea and diarrhea (use Imodium)
• Irritable bowel syndromebrain-butt connection
• The histologic changes found in the CNS are also
  found histologically in the bowelHUH?

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Functions of serotonin

• Happiness
• Boosts self-esteem/overcomes shyness
• Social phobias
• Makes you full and feel sleepy
• Eating disorders such as bulimia
• Helps to control pain pathways
• Nausea, vomiting, gastric motility
• Generalized anxiety disorder and panic attacks
• Premenstrual dysphoric disorders
• Extreme violence
• Migraines
• Impulse control

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Boosts self-esteem/overcome shyness

• College fraternity members w/ highest ranking and
  most friends had 20-40 higher serotonin levels
• Stroke patients and SRIs (i.e., Prozac)improved
  compliance w/ rehab

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Boosts self-esteem

• Remove dominant chimpanzee from group
• Give a subordinate male fluoxetine (Prozac)
• The subordinate took charge, made friends,
  organized alliances, and became the top banana.

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Eating disorders such as bulimia

• Not enough serotonin in bulimic patients? Use
  SRIs to treat bulimia
• Levels of serotonin activity are abnormally high
  in anorexicslinked to feelings of anxiety and
  obsessional thinking, classic traits of anorexia
  dopamine levels are also high addicted to
  starvation (autoimmune? Genetics?)

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She helps to control pain pathways(norepinephrine
is also involved)
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Premenstrual dysphoric disorder

• A breakdown product of progesterone,
  allopregnanolone, acts on receptors for GABAhas
  a calming effect fluoxetine (Prozac/Sarafem)
  specifically increases allopregnanolone

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Impulse control
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The SRIs

• 1987the first selective serotonin reuptake
  inhibitor was unleashed and we all know that
  drug as fluoxetine, Prozac (Lilly) (longest t½)
• Sertraline (Zoloft)(1992)shortest t½ excellent
  choice for elderly depressed patient may also be
  useful for mild irritability and aggression

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SRIs (Serotonin Reuptake Inhibitors)

• Paroxetine (Paxil)(1992) drug interactions
  adrenergic effectstremor14.7 _at_ 40 mg/d) most
  anticholinergic
• Citalopram (Celexa)(2000)most selective affinity
  for HT receptors useful for mild irritablity and
  aggression
• Escitalopram(2002)(as above) (Lexapro)(12 of the
  top selling drugs in 2008)fewest SE of all SRIs

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Give antidepressants time to work! 3-5 weeksbut
monitor closely

• Why does it take so long for anti-depressants to
  work?
• How long should your patients stay on
  antidepressants?
• (P.S. Lexapro may ease depressive and anxiety
  symptoms more quickly than the other SRIsin some
  cases by the end of week one)

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The SRIsside effects

• If something goes UP, something else must go DOWN
• Increasing serotonin may result in decreased
  dopamine in the libido area
• SRIs may result in anorgasmia, loss of libido
• Specifically ASK your female patients about
  sexual dysfunctionmany wont volunteer the
  information

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Rx of SRI sexual dysfunction

• What can you do? Zoloft/Paxilshort
  half-lifehold for 24 hours prior to planned
  activity
• Add bupropion (Wellbutrin) 75 mg TID or start
  with bupropion in the first place if the
  depression is accompanied by sexual dysfunction
• Amantadine (Symmetrel) to boost dopamine100 mg
  TID
• Buspirone (Buspar)15-30 mg/day
• Yohimbine5 mg TID (not recommended)
• DHEA?
• How about Viagra?

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Two other annoying side effects of SSRIsboth men
and women

• Bruxismlow dopamine/increased serotonin
• Weight gain--at least 7 of body weight
• Paroxetine (Paxil)
• F (18.2) M (10)
• Sertraline (Zoloft)--
• F (8.3) M (0)
• Fluoxetine (Prozac)
• F (8.3) M (9.1)
• (J of Psych 2004 651365-1371)

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Do anti-depressants work for everyone? NO.

• Psychotherapy is definitely beneficial
• Increase the dose of antidepressant if the
  initial dose shows NO improvement after 4 weeks
• Switch therapies
• Does switching in the same class of drugs work?
  Like Prozac to Zoloft? Paxil to Lexipro? YES

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What else can you recommend? TLCs

• Hang around people that make you happy
• Get out in the sun! Boosts serotonin and
  endorphins
• Light therapy even with non-seasonal depression
  (Martiny K et al. Adjunctive bright light in
  non-seasonal major depression Results from
  patient-reported symptom and well-being scales.
  Acta Psychiatr Scan 2005 Jun111453-9)
• Exercise boosts endorphins, serotonin, NE
• Get a pet

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Serotonin Syndrome

• Occurs when another medicine affects the
  metabolism, synthesis, or reuptake of serotonin
  resulting in increased serotonin levels.
• Symptoms
• Mental status changes, Hypertension, Tremors,
  Sweating, Hyperpyrexia, Ataxia
• Treatment
• Discontinue SSRI and provide supportive care

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Nursing Considerations

• Identify the nursing role in SSRI therapy.
• What should be included in client teaching?

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MAO Inhibitors

• Decreases effectiveness of monoamine oxidase and
  limits the breakdown of nor-epinephrine,
  dopamine, and serotonin in the CNS neurons
• Examples
• isocarboxazid (Marplan)
• tranylcypromine (Parnate)

• Prototype phenelzine (Nardil) p. 190
• Uses clients not responsive to other
  antidepressants
• Adverse effects
• Orthostatic hypotension
• Headache
• Insomnia
• Diarrhea
• Drug/food or drug/drug interactions

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Nursing Considerations

• Identify the nursing role in MAOI therapy.
• What should be included in client teaching?

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Case Study

• Judy is a 30 year old mother of three. Over the
  past few years she has experienced some low
  spots but was always able to bounce back.
  Judys husband has become concerned because last
  week she was so depressed she couldnt get out of
  bed and this week she has cleaned the house from
  top to bottom, filled the freezer with prepared
  meals and taken three trips to the gambling boat.
  She has become uncharacteristically talkative
  and impatient with the children. When her
  husband voiced concerns about her behavior she
  stated Theres nothing wrong with me. I feel
  rested and energized after a couple hours of
  sleep. There isnt anything I cant accomplish.

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Questions

• What do you suspect is Judys problem?
• Why?
• How will this be treated?

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Prototype eskalith (Lithium) p. 194

• Monotherapy or in combination with other drugs
• Approved in US in 1970
• Narrow therapeutic range 0.6 1.5 mEq/L
• Contraindicated
• Salt free diet, Hx of cardiac or renal disease
• Adverse effects
• Dizziness, fatigue, short-term memory loss,
  increased urination, n/v, anorexia, abdominal
  pain, diarrhea, dry mouth, muscle weakness, and
  slight tremors

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Lithium Toxicity

• S/S
• Diarrhea
• Lethargy
• Muscle weakness
• Ataxia
• Seizures
• Edema
• Hypotension
• Circulatory collapse

• Treatment
• Hemodialysis
• Supportive care

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Nursing Considerations

• Identify the nursing role in Lithium therapy.
• What should be included in client teaching?

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Attention Deficit Hyperactivity Disorder

• developmentally inappropriate behaviors
  involving difficulty in paying attention or
  focusing on tasks
• Symptoms
• Children distractable, cant focus or stay
  still, impulsive (p. 197 for full list)
• Adults (ADD) similar to mood disorders (anxiety,
  mania, restlessness, depression)
• Diagnosis
• Psychological and medical evaluation

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Causes

• Known correlations
• Exposure to high lead levels
• Exposure to alcohol or drugs in utero
• Genetic predisposition

• Recent evidence
• Suggests that the dysfunction by be related to
  dysfunction of neurtotranmitters
  (nor-epinephrine, dopamine, and serotonin) in the
  RAS

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Traditional Drug Therapy

• CNS stimulants
• Prototype methylphenidate (Ritalin) p. 198)
• Activates the RAS which results in hightened
  awareness in various brain regions, esp. centers
  associated with focus and attention
• Adverse effects
• Insomnia, nervousness, anorexia, weight loss
• Occasionally dizziness, depression,
  irritability, nausea, and abdominal pain.
• Contraindicated in heart disease, hypertension,
  hyperthyroidism, and seizure disorder.

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Drugs for ADHD/ADDfirst line RX

• Methylphenidate
• Short acting--Ritalin, Methylin
• Extended release-- Ritalin SR, Metadate ER,
  Methylin ER
• Long-actingRitalin LA,, Metadate CD, Concerta,
  Daytrana patch (9 hours),
• DexmethylphenidateFocalin (BID)
• Dextroamphetamineshort acting, intermediate
  acting (Adderall, Dexedrine Spansule)
  long-acting (Adderall XR)

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Drugs for ADHD/ADD--second and third-line agents

• Atomoxetine--Strattera
• Bupropion (SR and ER)Wellbutrin
• Imipramine (Tofranil)
• Desipramine (Norpramin)
• Clonidine (Catepres)
• Guanfacine (Tenex)

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Questions

• methylphenidate (Ritalin) and the other CNS
  stimulants are Schedule II and Pregnancy category
  C drugs?
• What are the implications of this information?

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Non-CNS Stimulants

• Clonidine (Catapres)
• Atypical antidepressants
• bupropion (Welbutrin)
• imipramine (Tofranil)
• Newest drug
• atomoxetine (Strattera)
• Exact mechanism of action unknown
• Classified as norepinephrine reuptake inhibitor
• Side effects headache, insomnia, upper abd pain,
  decreased appetite, cough

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Nursing Considerations in ADHD Therapy

• Identify the nursing role in ADHD therapy.
• What should be included in client teaching?