Central Nervous System Drugs- Ch. 14

Slows neuronal activity in the brain.
Alters epinephrine and norepinephrine
Continuum ranging from relaxation, to sedation, to anesthesia
1. Sedatives: Relaxes the patient
  1. Hypnotics: Induces sleep in the patient
    1. Sedative-hypnotic: Calms at lower doses, causes sleep at higher doses
      1. Tranquilizers: Produces a calm or tranquil feeling
2. Withdrawal can cause fever; psychosis; seizures; tachycardia; hypotension; anorexia; muscle cramps; memory, concentration, and orientation impairment; abnormal sounds in the ear; blurred vision; and insomnia, agitation, and anxiety
  1. Obvious symptoms last 2-4 wks; subtle can last months
Antidepressants
1. Treats GAD, OCD, panic, social phobia, and PTSD
2. Can reduce the negative thoughts associated w/anticipatory component of panic
  1. Can also suppress ANS, helping pt. remain calm
3. SSRIs: Safer and w/less sympathomimetic & anticholinergic effects
  1. Atypicals, including SNRIs: Side effects include abnormal dreams, sweating, constipation, dry mouth, anorexia, weight loss, tremor, abnormal vision, and loss of sexual desire
    1. TCAs: Annoying anticholinergic effects, such as dry mouth, blurred vision, urine retention, and hypertension
      1. Not recommended for pt. with a history of heart attack,heart blocks, or arrhythmia.
        Most are pregnancy category C or D
        Alcohol or other CNS depressants are off limtis
        Pt. w/ asthma, GI disorders, alcoholism, schizophrenia, or bipolar should be cautious
      2. MAOIs: Can cause orthostatic hypotension, headache, and diarrhea,
        Pt. should strictly avoid foods containing tyramine
        Potentiate effects of insulin & other diabetic drugs
        Rarely used due to potential for severe adverse effects
Benzodiazepines
1. Most widely prescribed in medicine
  1. Act by binding to GABA receptor-chloride channel molecule, which intensifies effects of GABA
    1. Most are metabolized in liver & excreted in urine
      1. Does not cause life-threatening respiratory depression unless taken in large quantities, combined w/other CNS depressions, or given to pt. w/sleep apnea.
        Shortens length of time to get to sleep and reduces frequency of interrupted sleep
        Most increase total sleep time, btut some reduce stage 3 and some affect REM
        Can be used for seizure disorders (Valium), alcohol withdrawal, central muscle relaxation, and general anesthesia.
        Many of these have the same actions and adverse effects, and differ primarily in onset and duration of action.
  2. Preferred for short term treatment of insomnia caused by anxiety.
    1. Class IV drugs
Barbiturates
1. Treatment of choice for anxiety and insomnia prior to introduction of benzos
  1. Rarely, if ever, given for anxiety or insomnia anymore b/c of significant adverse effects and better medications
    1. Risk of dependence is high; withdrawal is severe and sometimes fatal; OD can cause profound respiratory depression, hypotension, and shock
      1. Several are class II
      2. Bind to GABA receptor-chloride channel and intensify effects of GABA
        Capable of depressing CNS function at all levels
        When taken for prolonged periods, they stimulate microsomal enzymes.
        Simulates their own metabolism, as well as that of hundreds of other drugs
        Tolerance can develop to this drug and to other CNS depressants, such as opioids.
Miscellaneous
1. Used mainly for social anxiety:
  1. Valproate (Depakote)
    1. Propranolol (Inderal) and atenolol (Tenormin)
2. Used mainly for insomnia:
  1. Zaleplon (Sonata)
    1. Eszopiclone (Lunesta)
      1. Zolpiden (Ambien)
        Anxiolytic & hypnotic effect
      2. Hypnotic effect
3. Buspirone (BuSpar):
  1. Mechanism unclear, but r/t D2 dopamine receptors in brain
    1. Agonist effects on presynaptic dopamine & high affinity for serotonin
      1. Less likely than benzos to affect cognitive & motor performance
        Rarely interacts w/other CNS depressants
        Common side effects: Dizziness, headache, and drowsiness
        Less of a chance of dependence. May take a couple weeks to work.
        Anxiolytic effect
4. Zolpidem (Ambien, Edluar, Intermezzo):
  1. Class IV, short-term insomnia treatment
    1. Highly specific to GABA
      1. Produces muscle relaxation and anti-convulsant effects when given higher than therapeutic dose
        Rapid onset
        Impaired liver or kidney will increase serum lvl of drug
        Use w/ caution in suicidal patients b/c intentional overdose can happen.
        Adverse effects may include nausea, dizziness, diarrhea, daytime drowsiness, amnesia, and somnambulism
        Rebound insomnia can occur when discontinued
        Long-term use allowed
5. Escopiclone (Lunesta)
  1. Similar properties to zolpidem
    1. Longer elimination half life may give it an advantage over zolpidem in maintaining sleep & decreasing early morning waking
      1. More likely to cause daytime sedation
6. Zaleplon (Sonata)
  1. Useful for ppl who fall asleep but wake early in the morning
    1. Sometimes used for travel
7. Ramelton (Rozerem)
  1. Melatonin receptior agonist
    1. Shown to improve sleep induction
      1. Short onset of action, lasts as long as XR zolpidem
        Long-term use allowed
        Hypnotic effect
8. Tasimelteon (Hetlioz
  1. Melatonin receptor agonist
    1. Treatment of non-24 hour sleep-wake disorder
      1. Most common effects are headaches and uncommon dreams
        Avoid concurrent use w/ fluvoxamine (Luvox) or rifampin (Rifandin)
        Long-term use allowed

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