Psychopharmacology

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rzand
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152224
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Psychopharmacology
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2012-05-16 23:50:08
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Neurology
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Psychopharmacology
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  1. SSRIs
    citalopram (Celexa), escitalopram (Lexapro),fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine(Paxil), sertraline (Zoloft)

    SSRIs inhibit 5HT reuptake butdo not act on NE or dopamine
  2. Serotonin syndrome
    increased levels of 5HT in CNS --> Altered mental status, agitation, fever, hypotension,ataxia, hyperreflexia, myoclonus

    Concern with combining any agents that increase CNS 5HT levels (SSRIs, MAOIs, TCAs, psycho stimulants,dopamine agonists, buspirone, sumatriptan, meperidine, dextromethorphan)

    and

    MAOI + SSRI, dextromethorphan,meperidine, TCAs, trazodone, lithium,

    or

    SSRI + another SSRI venlafaxine, dextromethorphan,buspirone, carbamazepine, lithium, mirtazapine, tramadol, nefazodone, sumatriptan, or “ecstasy”
  3. Discontinuation syndrome in SSRIs
    Transient dizziness and vertigo, lethargy, paresthesias(paroxetine), nausea, vivid dreams, irritability

    Treat by tapering dose
  4. High-yield facts about SSRIs
    - Fluoxetine: longest half-life and active metabolite with longest half-life, side effects include reduced appetite

    - Fluoxetine and fluvoxamine: best profile inregard to sexual side effects

    - Sertraline: worst profile in regard to sexual side effects, most potent blocker of dopamine transporters, has active metabolite with short half-life

    Fluvoxamine and paroxetine: no active metabolites, more likely to cause discontinuation syndrome with abrupt withdrawal of drug

    Citalopram: most selective for 5HT

    Paroxetine: most potent SSRI, side effects include weight gain and somnolence
  5. MAOIs
    • isocarboxazid (Marplan),
    • phenelzine (Nardil),
    • tranylcypromine (Parnate)
  6. TCAs and Metabolism
    TCAs + alcohol, carbamazepine, phenytoin, cigarette smoking --> increased metabolism of TCAs sub therapeutic levels of TCAs

    • TCA + neuroleptics, SSRIs (especially paroxetine and fluoxetine), cimetidine methylphenidate (Ritalin),quinidine, thyroid medications --> decreased metabolism of
    • TCAs -->potentially toxic levels of TCAs

    Nortriptyline: therapeutic window from 50 to 150 ng/mL, less effective at both very high and very low doses

    Amitriptyline: therapeutic range is 75 to 175 ng/mL
  7. Mixed-mechanism antidepressants
    bupropion, duloxetine,mirtazapine, nefazodone, trazodone, venlafaxine
  8. Bupropion (Wellbutrin)
    DA/NE reuptake inhibitor

    Indications: smoking cessation, MDD, adult ADHD
  9. Duloxetine (Cymbalta)
    5HT/NE reuptake inhibitor

    Indications: MDD, diabetic peripheral neuropathic pain
  10. Mirtazapine (Remeron):
    enhances NE and 5HT release via α2-antagonism, potent histamine antagonist, antagonist of 5HT2, 5HT3 receptors

    Indications: MDD, improves sleep/appetite
  11. Nefazodone
    inhibitor of serotonin uptake and weakly of NE reuptake, antagonist of 5HT2A, may selectively activate 5HT1A

    Indications: MDD
  12. Trazodone (Desyrel)
    blocks 5HT2 receptor, weak inhibitor of 5HT reuptake

    Indications: MDD, insomnia
  13. Venlafaxine (Effexor):
    inhibits 5HT reuptake at lowdoses, NE/DA at higher doses

    Indications: MDD, GAD, social anxiety disorder
  14. Atypicals Antipsychotics:
    clozapine, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone
  15. Atypical Antipsychotics
    Aripiprazole (Abilify): partial agonist D2, 5HT1A receptors and antagonist at 5HT2A receptors

    Clozapine (Clozaril): low potency, EPS/TD nearly absent, good with positive and negative symptoms, Warning—agranulocytosis potential, seizures

    Quetiapine (Seroquel): low potency, few EPS, less sexual dysfunction, no prolactin increase

    Olanzapine (Zyprexa): medium/high potency, fewEPS, high weight gain

    Risperidone (Risperdal): high potency, few EPS,can increase prolactin, more sexual dysfunction

    • Ziprasidone (Geodon): good for positive and negativesymptoms, improves cognition and depression,low EPS, not associated with weight gain
    • Warning—can lead to QT prolongation


    Indications:Psychotic disorders, schizophrenia, mood disorderwith psychotic features, delirium, acute mania, aggressive behaviors, psychosis due tomedical condition or substances
  16. Akathisia
    (subjective feelings of anxiety, tension, agitation): treat by lowering dose of antipsychotic, try β-blocker, clonidine, amantadine, or benzodiazepine
  17. Preferred benzodiazepines for the elderly
    oxazepam,lorazepam, temazepam (“out the liver”)

    • 1) have no active metabolites
    • 2) Relatively short acting
  18. Buspirone (BuSpar)
    • -Other anxiolytics, sedative-hypnotics
    • - Used for generalized anxiety disorder: effects seenafter 1 to 2 weeks

    - Relatively nonsedating, no abuse potential
  19. Clinical use in Parkinson’s disease: ECT
    ECT may improve both mood and motor symptoms of patients with advanced Parkinson’s disease, but effects may be short lived from days to weeks to 6 months, according to variousstudies
  20. Possible contraindications of ECT:
    • -active pulmonary infection,
    • -recent MI,
    • -unstable CAD,
    • -CHF,
    • -uncontrolled hypertension,
    • -space-occupying brain lesion,
    • -increased ICP,
    • -recent cerebrovascular accident,
    • -history of anesthesia complications,
    • -seizure,
    • -reflux,
    • -aneurysms,
    • -venous thrombosis,
    • -recent bone fracture (especiallycervical spine)
  21. Adverse effects of ECT
    • -brief episode of hypotension or hypertension,
    • -bradyarrhythmia or tachyarrhythmia,
    • -prolonged seizures,
    • -prolonged apnea (due to pseudocholinesterase deficiency),
    • -postictal confusion,
    • -headache,
    • -nausea,
    • -muscle pain,
    • -memory impairment (retrograde amnesia forshort time surrounding hospitalization)
  22. Responce rate of ECT
    80%
  23. Lithium:
    inhibits inositol-1-phosphatase

    Indications: mania, augmentation of antidepressants, prophylaxis of mania/depression,schizoaffective disorder, aggression, impulsivity

    Concerns: thyroid/kidney, pregnancy (Ebstein’sanomaly)
  24. Valproate
    enhances GABA Indications: mania, augmentation of antidepressants, alcohol withdrawal states, rapid cycling
  25. Neurasthenia
    Neurasthenia is a psycho-pathological term first used by George Miller Beard in 1869[1] to denote a condition with symptoms of fatigue, anxiety, headache,neuralgia and depressed mood.

    Neurasthenia is currently a diagnosis in the World Health Organization's International Classification of Diseases (and in the Chinese Classification of Mental Disorders, translated as 神经衰弱). However, it is no longer included as a diagnosis in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders.

    Americans were said to be particularly prone to neurasthenia, which resulted in the nickname "Americanitis"[2] (popularized by William James). Today, the condition is still commonly diagnosed in Asia.
  26. Amphetamine
    introduced in 1930s, dextroamphetamine (Dexedrine), combination of amphetamine and dextroamphetamine (Adderall)

    • Clinical use:
    • 1) Narcolepsy and other sleep disorders, attentiondeficit/ hyperactivity disorder in children, obesity
    • 2) Has also been used for depression by augmenting antidepressant effects, neurasthenia, AIDS dementia, encephalopathy from brain injury

    • b. Mechanism of action
    • 1) Causes direct release of dopamine and NE from neurons
    • 2) Blocks reuptake of catecholamines
    • 3) Peak plasma levels in 1 to 3 hoursc.

    Effects: CNS stimulation, appetite suppression, vasoconstriction, hypothermia, tolerance can developd.

    Adverse effects: stomach pain, anxiety, irritability, insomnia, tachycardia, arrhythmias, dysphoria, may worsen tics, psychosis, paranoia, delusions, delirium, seizurese.

    Monitor: blood pressure and pulse initially and after changes in dose, weight and height initially and several times annually
  27. Methylphenidate (Concerta, Ritalin):
    related toamphetamine, but milder stimulant (little or no abusepotential)
  28. Modafinil
    Modafinil (Provigil): novel stimulant for narcolepsy

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