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Psychotropic Drugs

Psychotropic Drugs. Jeff Hurley MD Martin Luther King Jr. Hospital Emergency Medicine. Objectives. Review common psychiatric drugs Side effects and interactions Signs and symptoms of overdose Treatment of acute overdose . Antipsychotics. Antipsychotics.

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Psychotropic Drugs

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  1. Psychotropic Drugs Jeff Hurley MD Martin Luther King Jr. Hospital Emergency Medicine

  2. Objectives • Review common psychiatric drugs • Side effects and interactions • Signs and symptoms of overdose • Treatment of acute overdose

  3. Antipsychotics

  4. Antipsychotics • Used to treat psychoses whether primary or secondary in nature • Divided into two general classes typical and atypical agents • Side effects generally include extrapyramidal side effects, cardiovascular effects, and anticholinergic effects

  5. TABLE 155-1 -- Selected Antipsychotic Agents Approved or Nearing Approval for Use in the United States

  6. Typical Antipsychotics • Divided into low potency and high potency generally differentiated by side effect profile • Mechanism of action of typical agents are blockade of D2 receptors in the basal ganglia, limbic system, hypothalamus, and chemoreceptor trigger zone

  7. Antipsychotics • Low Potency versus High Potency • Low potency: significant hypotension • Rarely used in the ED • High Potency: few anticholinergic and alpha blocking effects • Choice Drugs in the ED • Haldol is only approved for IM use even though it has been used IV

  8. Atypical Antipsychotics • Developed to minimize the extrapyramidal side effects of typical agents • Atypical agents work by a balanced blockade of D2 and serotonin 5HT2 A receptors

  9. Extrapyramidal Side Effects

  10. Extrapyramidal Side Effects Akinesia lack of movement, Parkinson-like Dystonic Reaction muscle spasms of face, neck, back Dyskinesia Blinking or twitches Akathesia Inability to sit still

  11. Acute Dystonic Reactions • Typically occur in young males during the initiation of therapy • Symptoms include muscle spasms of the back, neck, and face occasionally oculogyric crisis and laryngospasm may occur • Treatment includes diphenhydramine 50-100mg IV/IM or benztropine 1-2mg IV and airway support if severe laryngospasm occurs

  12. Akathisia • Typically characterized by a subjective feeling of restlessness and inability to stay still • Occurs in ~40 % of patients receiving 10mg of haloperidol within an hour or administration

  13. Parkinsonian Syndrome • Symptoms include bradykinesia, cogwheel rigidity, resting tremor, and shuffling gait • Occurs with high and low potency typical agents • Symptoms may be treated with simultaneous administration an anticholingeric medication and lowering the dose of the antipsychotic

  14. Tardive Dyskinesia • Chronic movement disorder characterized by involuntary movements of the face, extremities, and trunk • Occurs in up to 20% of patents receiving long term antipsychotics • Generally once symptoms occur they are permanent however benztropine may help control symptoms

  15. Cardiovascular Effects • Hypotension may occur with low potency typical agents • Prolonged QT and Torsade de Pointes may occur with any antipsychotic medication however they occur primarily with thioridazine, mesoridazine, droperidol, sertindole, and high-dose IV haloperidol • Treatment includes discontinuation of the offending drug, IVF for hypotension, and treatment of torsade de pointes with MgSO4 or overdrive pacing

  16. Anticholinergic side effects • Symptoms include dry mouth, sedation, urinary retention, cardiovascular effects, and altered sensorium • Management is primary supportive and includes discontinuation of the drug and physostigmine 1-2mg IV only in siezure, coma, and arrhythmia

  17. Overdose of Antipsychotics • Experience with acute ingestion of antipsychotics is limited • Given the mechanism of action at the chemoreceptor trigger zone high doses induce nausea and emesis and may aid in elimination of the drug • The most common manifestation is depressed level of consciousness • Protective airway reflexes are impaired at high doses

  18. Overdose of Antipsychotics • Treatment includes the ABCs, IV, O2, cardiac monitoring, administration of activated charcoal • The most common cause of morbidity and mortality is aspiration pneumonia so intubation should highly be considered early in the resuscitation • Hypotension is generally mild and responds to IVFs • The most common cardiac rhythm is sinus tachycardia • Treatment of torsade de pointes include MgSO4 or overdrive pacing if no response to MgSO4 • Most patients recover from isolated antipsychotic overdose

  19. Neuroleptic Malignant Syndrome • Idiosyncratic side effect of antipsychotic medications • Occurs in ~1 in 500 generally within the first two weeks of therapy, but may occur anytime • Cardinal features include altered mental status, muscle rigidity, hyperthermia, and autonomic nervous system dysfunction • Lab: elevated CPK, aldolase, WBC, LFTs

  20. Neuroleptic Malignant Syndrome • NMS is a medical emergency with a mortality rate approaching 20% • Treatment is primarily supportive beginning with the ABCs, discontinuation of the offending drug, and IV hydration • Avoid: anticholinergic meds • Multisystem organ failure may occur with liver and renal dysfunction being the most commonly involved

  21. Treatment

  22. Antidepressants

  23. Tricyclic Antidepressants • Indications: • Major Depression • Dysthmic Disorder • Panic Disorder • Agorophobia • Obscessive Compulsive Disorder • Enuresis • School phobia • Therapeutic Effects: • Related to norepinephrine and serotonin

  24. Major Pharmacodynamic Effects of Cyclic Antidepressents • Sodium channel blockade (quinidine-like effects) • negative inotropism, wide QRS, prolonged QT, AV Block • α1 -Adrenoreceptor blockade • hypotension • Inhibition of reuptake of biogenic amines (norepinephrine, serotonin) • initially hypertensive and tachycardic • Muscarinic receptor blockade • anticholinergic effects Dry mouth • Dry mouth, flushed skin, blurred vision, urinary retention, constipation, dizziness, ALOC, emesis • Histamine receptor blockade • antihistaminic effects

  25. Tricyclic Antidepressants • Anticholinergic side effects are the most common which include dry mouth, blurred vision, constipation, urinary retention, tachycardia, and altered sensorium • Aggitation: treat with benzos, avoid phenothiazines • Pysostigmine (centrally acting cholinergic) is contraindicated in TCA: May cause asystole

  26. Tricyclic Antidepressants • Cardiac effects: EKG changes occur within 6 hours of ingestion • negative inotropism, wide QRS, prolonged QT, AV block, atrial and ventricular dysrhythmias • Treatment: • alkalization and sodium loading • blood to a pH of 7.45-7.55 appears to uncouple TCA from myocardial sodium channels • D5W plus 2 amps of bicarb TRA 100-150 cc/hr • controlled studies have only validated the benefits of the initial bolus of 1-2 mEq/kg of sodium bicarbonate • no controlled studies looking at continuous infusions • Class IA, IC, b-blockers, Ca-channel blockers, Class III contraindicated

  27. Tricyclic Antidepressants • Hypotension: • Treat with IVF. If hypotension persists, bicarb is indicated regardless of QRS width. • Direct acting alpha-agonists (eg, norepinephrine, phenylephrine) are indicated when significant hypotension persists despite adequate volume replacement (as monitored by central venous pressure or pulmonary capillary wedge pressure). • Dopamine may not be as effective because its action is mediated by the release of endogenous catecholamines that may be depleted during TCA toxicity. • In addition, use of dopamine or dobutamine alone may result in unopposed beta-adrenergic activity resulting from TCA-induced alpha blockade and, therefore, may worsen hypotension.

  28. Tricyclic Antidepressants • TCA-induced seizures should be treated aggressively • Acidosis: augmenting cardiovascular toxicity • Goal of 7.45-7.55 pH with Bicarb administration • Benzodiazepines: Drug of Choice • Phenytoin: ineffective / possible prodysrhythmic effects • Phenobarbital second line • Physostigmine is contraindicated • Flumazenil is contraindicated • Bicarb does not stop siezures • Neuromuscular blockers / General

  29. Tricyclic Antidepressants • Overdose of tricyclics accounts for up to 20% of deaths from suicidal ingestion • Poor outcome is associated with QRS>100 msec, hypotension, cardiac dysrhythmias, and acidemia • Treatment includes the ABCs, IVFs, O2, monitor, activated charcoal, and HCO3 if acidemia or QRS>100 is present

  30. Monoamine Oxidase Inhibitors • Although infrequently used MAOIs are indicated for atypical depression and refractory depression unresponsive to TCAs or SSRIs • Mechanism of action related to increased serotonin and norepinephrine in the CNS

  31. Monoamine Oxidase Inhibitors • Side effects include orthostatic hypotension which may be severe, CNS irrability, and anticholinergic side effects • Tyramine/Hypertensive crisis may occur when sympathomimetic drugs, L-dopa, narcotics, TCAs, or tyramine containing foods such as aged cheese, wine, pickled herring, fava beans are ingested • Onset is usually precipitated by a severe headache and may progress to a hypertensive ICH with subsequent death • However most patients have resolution of symptoms within a few hours and their medications may be restarted with counseling concerning drug interactions

  32. Serotonin Selective Reuptake Inhibitors • The most common class of antidepressants prescribed due to their high therapeutic index and lower side effect profile • Indicated for major depressive disorder, panic disorder, generalized anxiety disorder, and OCD

  33. Serotonin Selective Reuptake Inhibitors • Side effects include headache, dizziness, nausea, diarrhea, insomnia, and sexual dysfunction • Sudden withdrawal of SSRIs may present as flu like symptoms including nausea, fatigue, myalgias, vertigo, and headache • Treatment is reinstatement of SSRI and gradual tapering

  34. Serotonin Selective Reuptake Inhibitors • Serotonin syndrome characterized by CNS, GI, and occasionally cardiovascular symptoms (restlessness, tremor, myoclonus, hyperreflexia, and siezures) • It is clinically indistinguishable from NMS • Treatment is mainly supportive including the ABCs, IVF, O2, cardiac monitoring, activated charcoal, and if symptoms persist hemodialysis

  35. Anxiolytics

  36. Anxiolytics • Indicated for short term management of anxiety or acute panic reactions • Mechanism of action is related to binding of to the benzodiazepine receptor • Side effects generally are CNS related such as drowsiness, sedation, and ataxia • In acute overdose of benzodiazepine careful respiratory monitoring should take place with standard therapy initiated with careful attention to possible mixed ingestions • Flumenazil is only indicated with single benzodiazepine overdose and not with mixed overdose • The only time flumenazil should be administered is if the treating physician administers too much benzodiazepine

  37. References • Marx, John MD Rosen's Emergency Medicine: Concepts and Clinical Practice, 5th ed, Mosby, 2002 • Tintinalli, Judith MD Emergency Medicine:A Comprehensive Study Guide, 5th ed, McGraw-Hill, 2000 • Merck Manual

  38. Questions?

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