Psychopharmatherapy Case Studies
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Psychiatry Report YL8 Clerkship Psychiatry Rotation Presented by: Barcelona, Kathlene Marie and Laquindanum, Cristal Ann
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Psychopharmatherapy Case Studies
- 1. Psychopharmatherapy Barcelona, Kathlene Marie Laquindanum, Cristal Ann
- 2. Mood Stabilizers Antidepressants Anxiolytics Antipsychotics Psychopharmatherapy by Barcelona&Laquindanum
- 4. According to the mother, he asked his son to be admitted because “nagigingmainitinangulonya”
- 5. The patient is previously known to be kind and hard-working, but known to have a temper and gets verbally abusive and would throw things around in the heat of his anger.Psychopharmatherapy by Barcelona&Laquindanum
- 8. Axis I: Bipolar MRE Manic episodes
- 9. Axis II: T/c narcissistic personality traits
- 10. Axis III: defer
- 11. Axis IV: GAF 11-20
- 13. Divalproate Na (Depakote) 500 mg/tab
- 14. Olanzapine PRN (Zyprexa) 10 mg/vial 1 vial as needed for agitation
- 15. Quetiapine (Seroquel) 25 mg/tab BID
- 16. Clonazepam (Rivotril) 2 mg/tab ¼ tab BID
- 17. Biperiden (Akineton) 2 mg/tab ODPsychopharmatherapy by Barcelona&Laquindanum
- 18. Mood Stabilizers Psychopharmatherapy by Barcelona&Laquindanum
- 19. Mood Stabilizers NE Psychopharmatherapy by Barcelona&Laquindanum
- 20. Mood Stabilizers Psychopharmatherapy by Barcelona&Laquindanum
- 21. Mood Stabilizers Dopamine Psychopharmatherapy by Barcelona&Laquindanum
- 22. Mood Stabilizers Psychopharmatherapy by Barcelona&Laquindanum
- 23. Mood Stabilizers Psychopharmatherapy by Barcelona&Laquindanum
- 25. NOT bound to plasma proteins
- 26. NO metabolism
- 27. Slow onset of action
- 28. Eliminated entirely through renal route
- 29. Proportional to:
- 30. Sodium
- 31. Level of body hydrationTherapeutic range: 0.7 to 1.2 Mild to moderate intoxication (1.5 to 2.0 mEq/L) Moderate to severe intoxication (2.0 to 2.5 mEq/L) Severe lithium intoxication (>2.5 mEq/L) Psychopharmatherapy by Barcelona&Laquindanum
- 32. Mood Stabilizers Symptoms of Lithium Toxicity Psychopharmatherapy by Barcelona&Laquindanum
- 33. Mood Stabilizers Drug interactions Psychopharmatherapy by Barcelona&Laquindanum
- 35. Useful in treating mixed manic episodes and rapid-cycling bipolar disorder
- 36. Increases CNS levels of GABAPsychopharmatherapy by Barcelona&Laquindanum
- 38. Stimulates glutamate release in mouse cerebral cortex (Dixon & Hokin, 1997)
- 39. ↑ glutamine concentration in neuronal cultures and in animal brains by regulation of glutaminase and glutamine synthetase (Collins et al, 1994)Psychopharmatherapy by Barcelona&Laquindanum
- 41. Side effects
- 42. tremor, weight gain, sedation, hair loss, teratogenicity, gastrointestinal problems, liver toxicity, pancreatitisPsychopharmatherapy by Barcelona&Laquindanum
- 44. Mixed episodes and rapid-cycling bipolar disorder
- 45. Also used in the management of trigeminal neuralgia
- 46. Acts by blocking sodium channels and inhibiting action potentials
- 47. Onset of action: 5-7 daysPsychopharmatherapy by Barcelona&Laquindanum
- 49. ataxia, cognitive dulling, allergic skin reactions, teratogenicity, leucopaenia, liver toxicity, pancreatitis, pharmacokinetic interactionsPsychopharmatherapy by Barcelona&Laquindanum
- 50. Which of the following would patients with bipolar disorder identify as the greatest problem? Depressive symptoms Manic symptoms
- 51. Bipolar depression is the predominant symptom in bipolar disorder Up to 70% of patients with bipolar disorderinitially present with a depressive episode In treated patients with bipolar I disorder depressive episodes outnumber manicepisodes by 3:1 Goodwin & Jamison 1990; Judd et al 2003
- 54. A subgroup of patientsmay do well
- 55. Few trials have systematically assessed efficacy
- 56. Switching to mania / hypomania occurs in up to 25% of patients; risk is lower with concomitant lithium or anticonvulsant
- 57. Cycle acceleration may occur, particularly with TCA use, and may not be fully prevented by concomitant lithium or anticonvulsant treatmentAntidepressant treatment in bipolar depression Altshuler et al 1995; Bottländer et al 1998 Altshuler et al 2003; Ghaemi et al 2003; Post et al 2003
- 60. risk of inducing rapid cyclingAtypical antipsychotics are emerging as a first-line treatment option variable efficacy and tolerability
- 61. Mood Stabilizers 5 out of 10: Antipsychotics!
- 62. Case 2 Tom is a 28 year old S.B.M. government employee referred by his family physician for evaluation. He reports 3 month history of worsening anxiety that is especially bad early in the morning. “I wake up at 3 in the morning and I can’t get back to sleep. My thoughts torment me.” He also reports decreased energy, inability to concentrate at his job, decreased appetite with a 10 pound weight loss, and suicidal ideation. “I feel so hopeless that suicide seems like an option.” He also states, “There is nothing in my life that I enjoy.” Psychopharmatherapy by Barcelona&Laquindanum
- 63. Case 2 Tom is tearful during evaluation. He lacks animation and his mood is quite depressed. He denies prior hypomanic or manic episodes. Mental status exam reveals slowed thinking and no evidence of psychosis. He does report two previous depressive periods, one in late adolescence and another during his senior year in college. During the latter episode, his symptoms were severe enough that he was unable to attend classes. “I almost failed that semester.” Both depressive episodes remitted in a few months without treatment; he “felt like normal” during remission. He denies drug abuse or use and has no medical problems. The family history is positive for depression in a paternal grandfather, and in his father, and he reports that a depressed uncle committed suicide about 10 years ago. Psychopharmatherapy by Barcelona&Laquindanum
- 64. Antidepressants:Biochemical basis The Monoamine Hypothesis: Depression arises as a consequence of a disturbance of one or more of the biogenic amine neurotransmitters in the brain. This forms the basis of the monoamine hypothesis of depression, which suggests that a relative deficit in NA, 5HT and DA is responsible for the symptoms of depression. The monoamine hypothesis postulates that the changes in mood (possibly linked to a deficit in 5-HT), deficit in drive and motivation (possibly linked to DA and NE) are the results of hypoactivity of these neurotransmitters. Psychopharmatherapy by Barcelona&Laquindanum
- 65. Antidepressants:Biochemical basis The Monoamine Hypothesis: Antidepressants act on various biochemical processes in the brain by which the amine neurotransmitters prolong their physiologic actions and thereby attenuate the main symptoms of depression Psychopharmatherapy by Barcelona&Laquindanum
- 66. Antidepressants:Biochemical basis Other neurotransmitters disturbances: Acetylcholine Abnormal levels of choline (precursor to Ach), have been found in the brains of some depressed patients Cholinergic agonists produce lethargy, anergia, psychomotor retardation in healthy subjects; exacerbate sx of depression and reduce sx in mania GABA GABA has an inhibitory effect on ascending monoamine pathways, particularly the mesocortical and mesolimbic systems. Reductions of GABA have been observed in plasma, CSF, and brain GABA levels in depression. Animal studies have also found that chronic stress can reduce and eventually can deplete GABA levels. By contrast, GABA receptors are upregulated by antidepressants, and some GABAergic medications have weak antidepressant effects. Psychopharmatherapy by Barcelona&Laquindanum
- 68. Monoamine oxidase inhibitors (MAOIs)
- 69. Selective serotonin reuptake inhibitors (SSRIs)
- 70. Atypical antidepressantsPsychopharmatherapy by Barcelona&Laquindanum
- 71. TCAs – Tricyclic antidepressants MAOIs – Non-selective MAO inhibitors NARIs – Noradrenalin reuptake inhibitors SSRIs – Selective Serotonin Reuptake Inhibitors RIMAs – Reversible inhibitor of MAO SNRIs – Serotonin/NA reuptake inhibitor NASSA – NA/selective 5-HT Selective NARIs – selective NA reuptake inhibitor Antidepressants:Historical perspective 1957 1960 1970 1980 1990 2000 Psychopharmatherapy by Barcelona&Laquindanum
- 72. Antidepressants:TCAs Psychopharmatherapy by Barcelona&Laquindanum
- 73. Antidepressants:MOA: TCAs 5HT TERMINAL NA TERMINAL TCAs act here Serotonin Receptor (5-HT1A, 5-HT2) NA receptor 1, 2, 1 Psychopharmatherapy by Barcelona&Laquindanum
- 77. Nortriptyline (Pamelor)—least likely to cause orthostatic hypotension
- 78. Desipramine (Norpramin)—least sedating, least anticholinergicsideeffects
- 79. Clomipramine (Anafranil)—most serotonin specific, useful in treatment of OCD
- 80. Doxepin (Sinequan)Psychopharmatherapy by Barcelona&Laquindanum
- 82. Significant metabolism occurs from first pass effect.
- 83. Peak plasma concentrations occur within 2 to 8 hours, and the half-lives of the TCAs vary from 10 to 70 hours
- 84. Although they are more likely to cause constipation, sedation, dry mouth, or lightheadedness than the SSRIs, the TCAs are less likely to cause sexual dysfunction, significant long-term weight gain, and sleep disturbances than the SSRIs.Psychopharmatherapy by Barcelona&Laquindanum
- 86. Whereas the TCAs are effective in the treatment of depression in persons with bipolar I disorder, they are more likely to induce mania, hypomania, or cycling than newer antidepressants, most notably the SSRIs
- 87. panic disorder with agoraphobia
- 88. generalized anxiety disorder
- 89. obsessive compulsive disorder
- 90. neuropathic pain and prophylaxis of migraine headachePsychopharmatherapy by Barcelona&Laquindanum
- 92. antihistaminic properties – sedation
- 93. antiadrenergic properties – orthostatic hypotension, tachycardia, arrhythmia
- 94. antimuscarinic effects – dry mouth, constipation, urinary retention, blurred vision, tachycardia
- 95. weight gain
- 96. lethal in overdose - hallmark of TCA toxicity is a widened QRS (>100msec), used as threshold to treatment
- 97. major complications: 3Cs (Convulsions, coma, cardiotoxicity) Psychopharmatherapy by Barcelona&Laquindanum
- 98. Antidepressants:MAOIs Psychopharmatherapy by Barcelona&Laquindanum
- 99. Antidepressants:MOA: MAOIs x x Noradrenaline or 5-HT receptor Psychopharmatherapy by Barcelona&Laquindanum
- 100. Antidepressants:MAOIs MAOIs are not used as first-line agents because of the increased safety and tolerability of newer agents. However, MAOIs are considered very effective for certain types of refractory depression and in refractory panic disorder. Examples: Phenelzine (Nardil) tranylcypromine (Parnate) isocarboxazid (Marplan) Psychopharmatherapy by Barcelona&Laquindanum
- 102. Because they irreversibly inactivate MAOs, the therapeutic effect of a single dose of irreversible MAOIs may persist for as long as 2 weeks. Psychopharmatherapy by Barcelona&Laquindanum
- 104. panic disorder
- 105. social phobia
- 106. PTSD
- 107. bulimia
- 108. attention deficit disorder
- 109. anginal pain
- 110. atypical facial pain Psychopharmatherapy by Barcelona&Laquindanum
- 112. drowsiness
- 113. weight gain
- 114. sexual dysfunction
- 115. dry mouth
- 116. sleep dysfunction
- 117. Serotonin syndrome
- 118. hypertensive crisisPsychopharmatherapy by Barcelona&Laquindanum
- 120. Initially characterized by lethargy, restlessness, confusion, flushing, diaphoresis, tremor, and myoclonic jerks.
- 121. May progress to hyperthermia, hypertonicity, rhabdomyolysis, renal failure, convulsions, coma, and death.
- 122. discontinue medication once serotonin syndrome is suspected Psychopharmatherapy by Barcelona&Laquindanum
- 124. Foods with tyramine (red Chianti wine, cheese, chicken liver, fava beans, cured meats) cause a buildup of stored catecholamines.
- 125. The amino acid tyramine is normally transformed via GI metabolism. MAOIs, however, inactivate GI metabolism of dietary tyramine, thus allowing intact tyramine to enter the circulation.
- 126. A hypertensive crisis may subsequently occur as a result of a powerful pressor effect of the amino acid.
- 127. allow resynthesis of adequate concentrations of MAOs that tyramine-containing foods be avoided until 2 weeks after the last dose of an irreversible MAOI. Psychopharmatherapy by Barcelona&Laquindanum
- 128. Antidepressants:SSRIs Psychopharmatherapy by Barcelona&Laquindanum
- 129. Antidepressants:MOA: SSRIs 5HT TERMINAL x 5-HT uptake site 5-HT2A, 5-HT2C, 5-HT1A Psychopharmatherapy by Barcelona&Laquindanum
- 130. Antidepressants:SSRIs SSRis are the most commonly prescribed antidepressants. Examples of SSRIs include: Fluoxetine (Prozac)—longest half-life with active metabolites Sertraline (Zoloft)—highest risk for gastrointestinal (GI) disturbances Paroxetine (Paxil)—most serotonin specific, most activating (stimulant) Fluvoxamine (Luvox)—currently approved only for use in OCD Citalopram (Celexa)—used in Europe for 12 years prior to FDA ap-proval in the United States Escitalopram (Lexapro)—levoenantiomer of citalopram; similar efficacy, fewer side effects, much more expensive Psychopharmatherapy by Barcelona&Laquindanum
- 132. The most significant difference among the SSRIs is their broad range of serum half-lives. Fluoxetine has the longest half-life: 4 to 6 days; its active metabolite has a half-life of 7 to 9 days. The half-life of sertraline is 26 hours, and its less active metabolite has a half-life of 3 to 5 days. The half-lives of the other three, which do not have metabolites with significant pharmacologic activity, are 35 hours for citalopram, 27 to 32 hours for escitalopram, 21 hours for paroxetine, and 15 hours for fluvoxamine.
- 133. All SSRIs are metabolized in the liver by the cytochrome P450 (CYP) enzymesPsychopharmatherapy by Barcelona&Laquindanum
- 135. suicide
- 136. OCD
- 137. Panic disorder
- 138. PTSD
- 139. GAD
- 140. bulimiaPsychopharmatherapy by Barcelona&Laquindanum
- 142. Sexual dysfunction (25 to 30%)
- 143. GI disturbance
- 144. Insomnia
- 145. Headache
- 146. Anorexia, weight loss
- 147. Serotonin syndrome when used with MAOIsPsychopharmatherapy by Barcelona&Laquindanum
- 148. Antidepressants:Atypicals Psychopharmatherapy by Barcelona&Laquindanum
- 149. Antidepressants:Atypicals Serotonin/norepinephrine reuptake inhibitors (SNRIs) Norepinephrine/dopamine reuptake inhibitors (NDRIs) Serotonin antagonist and reuptake inhibitors (SARIs) Norepinephrine and serotonin antagonists (NASAs) Psychopharmatherapy by Barcelona&Laquindanum
- 150. Antidepressants:Atypicals SNRIs Venlafaxine (Effexor): Venlafaxine is especially useful in treating refractory depression. It has a very low drug interaction potential. Side effect profiles similar to SSRIs. In addition, venlafaxine can increase BP. Psychopharmatherapy by Barcelona&Laquindanum
- 151. Antidepressants:Atypicals NDRIs Bupropion (Wellbutrin): Bupropion is commonly used to aid in smoking cessation, and also useful in the treatment of seasonal affective disorder and adult attention deficit hyperactivity disorder (ADHD). Its most significant advantage is its relative lack of sexual side effects as compared to the SSRIs. Bupropion’sdopaminergic effect in higher doses can exacerbate psychosis. They are not optimal for patients with significant anxiety and are contraindicated in patients with seizure or active eating disorders and in those currently on an MAOI. Psychopharmatherapy by Barcelona&Laquindanum
- 152. Antidepressants:Atypicals SARIs Nefazodone (Serzone) and Trazodone (Desyrel): These are especially useful in treatment of refractory major depression, major depression with anxiety, and insomnia (secondary to its sedative effects). Side effects include nausea, dizziness, orthostatic hypotension, cardiac arrhythmias, sedation, and priapism (sedation and priapism especially with trazodone). Psychopharmatherapy by Barcelona&Laquindanum
- 153. Antidepressants:Atypicals NASAs Mirtazapine (Remeron): Useful in the treatment of refractory major depression, especially in patients who need to gain weight. Side effects include sedation, weight gain, dizziness, somnolence, tremor, and agranulocytosis. Psychopharmatherapy by Barcelona&Laquindanum
- 155. informant/s: patient (poor reliability); guardian (good reliability)
- 156. Patient came in with chief complaint of “I don’t know.” (according to the patient)
- 157. Patient was brought in due to behavioral changes. (according to the guardian)Psychopharmatherapy by Barcelona&Laquindanum
- 159. 3 years PTC, patient’s daily activities consisted of drugs, alcohol and women. Patient had active hallucinations (visual and auditory, persecutory) and paranoid ideations (people were talking about him, people out to hurt him). Patient displayed self-injurious behavior (anger outbursts, punch himself repeatedly on face, usually following hallucinations and self-isolation (lock himself in room).
- 160. 1 year PTC, consulted at our institution, brought in by father (became unmanageable). Patient’s appearance likened to “taonggrasa.”Psychopharmatherapy by Barcelona&Laquindanum
- 162. Easily agitated
- 163. Provoking other patients to fight
- 164. Verbally but not physically violent to others
- 165. Restless (pace back and forth)
- 167. Various people
- 168. Persecutory
- 169. Talks to self
- 170. Bathes self but doesn’t regularly change his clothes
- 171. Paranoid ideations
- 172. doesn’t allow others to clean his room
- 173. Believes that watcher is taking his food
- 174. Believes that people talk about him
- 175. Risk for self-injury
- 176. Punch walls in his room
- 177. Punch self repeatedlyPsychopharmatherapy by Barcelona&Laquindanum
- 179. Family history
- 180. Political family
- 181. Separated parents
- 182. 3rd of 8 children, 5 frstepmom
- 183. Strained relationship with stepmomPsychopharmatherapy by Barcelona&Laquindanum
- 185. Early childhood
- 186. Mother was always away for business
- 187. Taken care of by nanny
- 188. Middle childhood
- 189. Friendly, loud
- 190. 7 yo, see ghost, punched it to make it go away
- 191. Closer to older people than kids of his age
- 192. Late childhood
- 193. Popular in school
- 194. Honor student, generally good grades
- 195. Computer games, magic cards, soccer
- 196. Small business in hs, candy businessPsychopharmatherapy by Barcelona&Laquindanum
- 199. Masturbation – grade 2
- 200. Started date in grade school
- 201. 1st coitus – grade 6 (12 yo) with hs girlfriend
- 202. Attracted to opposite sex
- 204. No sexual problems, no sexual abuse
- 205. Adulthood
- 207. Dropped out during 2nd year
- 208. Lots of money
- 210. Never applied for a job
- 211. Had 3 girlfriends
- 212. Last girlfriend, live in partner
- 213. Left him for his barkadaPsychopharmatherapy by Barcelona&Laquindanum
- 215. Appearance
- 216. Slightly agitated
- 217. Fairly kempt, wearing shirt, shorts, socks and slippers
- 218. Poor eye contact
- 219. Speech
- 220. Hypoproductive
- 221. Mood
- 222. Euthymic
- 223. Affect
- 228. With preoccupations – wants to get out
- 229. No delusions, hallucinations, illusionsPsychopharmatherapy by Barcelona&Laquindanum
- 231. Sensorium
- 232. Alert
- 233. Oriented in 3 spheres
- 234. Unable to do serial 7 or simple math
- 235. Intact recent, recent past and remote memory
- 236. Poor immediate memory, unable to recall 3 objects
- 238. “Aanhin pa angdamo.” – “Aware of the dog, not the cat”
- 239. Good fund of knowledge
- 240. Poor insight
- 241. Good judgmentPsychopharmatherapy by Barcelona&Laquindanum
- 243. Axis 1 – Schizophrenia, disorganized type vs paranoid type
- 244. Axis 2 - defer
- 245. Axis 3 – hepatic steatosis
- 246. Axis 4 – problems with primary support group, social environment
- 247. Axis 5 – 31-40Psychopharmatherapy by Barcelona&Laquindanum
- 249. Seratonergic hypothesis of Psychosis
- 250. Glutamatergic hypothesis of Psychosis
- 251. NMDA receptor hypofunction hypothesis of PsychosisPsychopharmatherapy by Barcelona&Laquindanum
- 253. hyperactivity of dopaminergic systems in schizophrenia
- 254. The major support for this hypothesis is that all effective antipsychotic drugs bind to dopamine receptors
- 255. The clinical potency of antipsychotic drugs is closely correlated with their binding affinity to D2 receptors
- 256. The administration of amphetamine or levodopa exacerbates the symptoms of some schizophrenic patients Psychopharmatherapy by Barcelona&Laquindanum
- 257. Dopamine and Psychosis MESOCORTICAL SYSTEM involved in the NEGATIVE symptoms of Schizophrenia MESOLIMBIC SYSTEM involved in the POSITIVE symptoms of Schizophrenia Basal ganglia Nigrostriatal dopamine pathway Mesolimbicdopamine pathway Substantia nigra Mesocortical dopamine pathway Hypothalamus Tegmentum Tuberoinfundibulardopamine pathway Psychopharmatherapy by Barcelona&Laquindanum
- 259. Mesocortical pathway: Hypoactivity- related to Negative/Cognitive Syndrome (cognitive blunting, social isolation)
- 260. Nigrostriatal pathway: Hypoactivity- related to EPS/Movement disorder (Akathisia, Dystonia, Dyskinesia)
- 261. Tuberoinfundibular pathway: Hypoactivity- related to HyperprolactinemiaPsychopharmatherapy by Barcelona&Laquindanum
- 263. Median raphe nucleus projects to the limbic system
- 264. 5-HT2A receptors, which mediate hallucinogenic effects play modulatory roles within local cortical circuits.
- 265. 5-HT projections inhibit DA at two levels:
- 266. At the midbrain, 5-HT inhibits the firing of DA cells from the substantianigra
- 267. At the cortex and striatum, 5-HT inhibit synaptic release of DA
- 269. Phencyclidine, an NMDA receptor antagonist mimics many positive and negative symptoms of schizophrenia
- 271. This closely parallels the undifferentiated and disorganized subtypes of schizophrenia.
- 273. Traditional antipsychotics are classified according to potency and work by blocking dopamine receptors.
- 274. Atypical (newer) antipsychotics block both dopamine and serotonin receptors; however, their effect on dopamine is weaker, so they are associated with fewer side effects.
- 276. Peak plasma concentrations are usually reached 1 to 4 hours after oral administration and 30 to 60 minutes after parenteral administration.
- 277. Smoking, coffee, antacids, and food interfere with absorption of these drugs. Steady-state levels are reached in approximately 3 to 5 days.
- 278. The half-lives of these drugs are approximately 24 hours.
- 279. Parenteral formulation of DRAs results in more rapid and more reliable onset of action.
- 280. Bioavailability is also up to tenfold higher with parenteral administration.
- 281. Pharmacology
- 283. Antipsychotic activity derives from inhibition of dopaminergic neurotransmission.
- 284. The DRAs are effective when approximately 60 percent of D2 receptors in the brain are occupied.
- 285. At 80 percent one sees the beginning of extrapyramidial signs.
- 286. The DRAs also block noradrenergic, cholinergic, and histaminergic receptors, with different drugs having different effects on these receptor systems.
- 288. High potency
- 290. lower affinity for dopamine receptors and so, higher dose is required
- 291. potency, in this case, refers to action on dopamine receptors
- 294. High potency
- 296. High potency
- 297. greater affinity for dopamine receptors, relatively low dose needed
- 298. higher incidence of EPS and neuroleptic malignant syndrome
- 299. lower incidence of anticholinergic and antihistaminic side effects
- 300. Haloperidol (Haldol)
- 304. Pimozide (Orap)
- 306. Fever (most common presenting sx)
- 307. Autonomic instability (tachycardia, labile hypertension, diaphoresis)
- 308. Leukocytosis
- 309. Tremor
- 312. Rapid neuroleptization
- 313. Early treatment
- 314. Intermittent medications
- 315. Maintenance treatment
- 316. Long-acting depot medications
- 318. Rapid neuroleptization
- 319. Early treatment
- 320. Intermittent medications
- 321. Maintenance treatment
- 322. Long-acting depot medications
- 323. The equivalent of 5 to 20 mg of haloperidol is a reasonable dose for an adult person in an acute state. A geriatric person may benefit from as little as 1 mg of haloperidol.
- 324. Administration of the antipsychotic IM results in peak plasma levels in about 30 minutes, versus 90 minutes using the oral route. Doses of drugs for IM administration are about half those given by the oral route.
- 325. In a short-term treatment setting, the person should be observed for 1 hour after the first dose of medication.
- 326. After that time, most clinicians administer a second dose or a sedative agent (e.g., a benzodiazepine) to achieve effective behavioral control.
- 328. Rapid neuroleptization
- 329. Early treatment
- 330. Intermittent medications
- 331. Maintenance treatment
- 332. Long-acting depot medications
- 333. Rapid neuroleptization (also called psychotolysis) is the practice of administering hourly IM doses of antipsychotic medications until marked sedation of the person is achieved.
- 334. Several research studies have shown, however, that merely waiting several more hours after one dose yields the same clinical improvement as is seen with repeated doses.
- 335. Clinicians can help prevent violent episodes by using adjuvant sedatives or by temporarily using physical restraints until the persons can control their behavior.
- 337. Agitation and excitement usually improve quickly with antipsychotic treatment
- 338. Psychotic symptoms, both positive and negative, usually continue to improve 3 to 12 months after the initiation of treatment.About 5 mg of haloperidol or 300 mg of chlorpromazine is the usual effective daily dose.
- 340. Rapid neuroleptization
- 341. Early treatment
- 342. Intermittent medications
- 343. Maintenance treatment
- 344. Long-acting depot medications
- 346. Rapid neuroleptization
- 347. Early treatment
- 348. Intermittent medications
- 349. Maintenance treatment
- 350. Long-acting depot medications
- 351. Clinicians may choose to use small doses for the p.r.n. doses (e.g., 2 mg of haloperidol) or use a benzodiazepine instead (e.g., 2 mg of lorazepam IM).
- 352. If p.r.n. doses of an antipsychotic are necessary after the first week of treatment, the clinician may want to consider increasing the standing daily dosage of the drug.
- 354. Rapid neuroleptization
- 355. Early treatment
- 356. Intermittent medications
- 357. Maintenance treatment
- 358. Long-acting depot medications
- 359. The first 3 to 6 months after a psychotic episode is usually considered a period of stabilization. After that time, the dosage of the antipsychotic can be decreased about 20 percent every 6 months until the minimal effective dosage is found.
- 360. A person is usually maintained on antipsychotic medications for 1 to 2 years after the first psychotic episode.
- 361. Antipsychotic treatment is often continued for 5 years after a second psychotic episode, and lifetime maintenance is considered after the third psychotic episode, although attempts to reduce the daily dosage can be made every 6 to 12 months
- 363. Rapid neuroleptization
- 364. Early treatment
- 365. Intermittent medications
- 366. Maintenance treatment
- 367. Long-acting depot medications
- 368. Long-acting depot preparations may be needed to overcome problems with compliance. IM preparations are typically given once every 1 to 4 weeks.
- 369. before initiating the depot form, it is good practice to give at least one oral dose of the drug to assess the possibility of an adverse effect, such as severe extrapyramidal symptoms or an allergic reaction.
- 371. These drugs include:
- 373. Olanzapine (Zyprexa)
- 375. Clozapine (Clozaril)
- 376. Ziprasidone (Geodon)
- 378. The SDAs also appear to be more specific for the mesolimbic than striatal dopamine system and, in some cases, are associated with rapid dissociation from the D2 receptor. It is hypothesized that these properties account for the improved tolerability associated with the SDAs.
- 380. In particular, they rarely cause EPS, tardivedyskinesia, or neuroleptic malignant syndrome.
- 381. They are more effective in treating negative symptoms of schizophrenia than traditional antipsychotics.
- 382. These drugs are now first-line in the treatment of schizophrenia.
- 386. Olanzapine is also approved for maintenance treatment of bipolar disorder.
- 388. Olanzapine
- 389. Quetiapine
- 390. Clozapine
- 392. Risperidone undergoes extensive first-pass hepatic metabolism to 9-hydroxyrisperidone, a metabolite with equivalent antipsychotic activity.
- 393. Peak plasma levels of the parent compound occur within 1 hour for the parent compound and 3 hours for the metabolite.
- 394. Risperidone is an antagonist of the serotonin 5-HT2A, dopamine D2, and histamine H1 receptors.
- 396. Olanzapine
- 397. Quetiapine
- 398. Clozapine
- 400. Peak concentrations are reached in 5 hours, and the half-life averages 31 hours (range 21 to 54 hours).
- 401. It is given in once-daily dosing.
- 402. In addition to 5-HT2A and D2 antagonism, olanzapine is an antagonist of the D1, D4, 5-HT1A, muscarinic M1 through M5, and H1 receptors.
- 403. Other than clozapine, olanzapine consistently causes a greater amount and more frequent weight gain than other atypicals
- 405. Olanzapine
- 406. Quetiapine
- 407. Clozapine
- 409. It is rapidly absorbed from the GI tract, with peak plasma concentrations reached in 1 to 2 hours. Steady-state half-life is about 7 hours, and optimal dosing is two or three times per day.
- 410. Quetiapine, in addition to being an antagonist of D2 and 5-HT2, also blocks 5-HT6, Dl and HI, receptors.
- 412. Olanzapine
- 413. Quetiapine
- 414. Clozapine
- 416. It is rapidly absorbed, with peak plasma levels reached in about 2 hours. Steady state is achieved in less than 1 week if twice-daily dosing is used.
- 417. Clozapine is an antagonist of 5-HT2A, D1, D3, D4 receptors. It has relatively low potency as a D2-receptor antagonist.
- 419. Olanzapine
- 420. Quetiapine
- 421. Clozapine
- 423. Olanzapine
- 424. Quetiapine
- 425. Clozapine
- 426. During the first 6 months of treatment, weekly WBC counts are indicated to monitor the patient for the development ofP.1096agranulocytosis. If the WBC count remains normal, the frequency of testing can be decreased to every 2 weeks.
- 427. Myocarditis is also a serious risk in the use of clozapine.
- 429. 1% incidence of agranulocytosis and 2-5% seizures with clozapine, therefore, there should be weekly WBC monitoring
- 430. Olanzapine can cause hyperlipidemia, glucose intolerance, weight gain and liver toxicity, so there should be regular liver function monitoring
- 431. Quetiapine has less propensity for weight gain but has been shown to cause cataracts in beagles, therefore, periodic slit lamp examination is recommended
- 433. This started 20 years PTC when he had an violent altercation with his boss who is part of a syndicate. This made him file AWOL and he doesn’t want to leave the house for about a year.
- 434. He always had a sudden intense wave of fear whenever he sees other people, fearing that they are thinking something bad about him.
- 435. He was brought by his auntie in a psychiatric facility in Pasig, given unrecalled meds with poor compliance since he felt the meds weren’t “working” Psychopharmatherapy by Barcelona&Laquindanum
- 437. MMSE: unremarkablePsychopharmatherapy by Barcelona&Laquindanum
- 439. Anxiety Disorder
- 440. Current Treatment:
- 441. Clonazepam ¼ tab OD at bedtime
- 442. Past Treatment:
- 443. Sertraline
- 444. Fluoxetine
- 446. Anxiolytics Potentiating effects of GABA Psychopharmatherapy by Barcelona&Laquindanum
- 448. Diazepam (Valium)—rapid onset, used in treatment of anxiety and seizure control
- 450. Clonazepam (Klonopin)—treatment of panic attacks, anxiety
- 451. Lorazepam(Ativan)—treatment of panic attacks, alcohol withdrawal
- 452. Temazepam(Restoril)—treatment of insomniaPsychopharmatherapy by Barcelona&Laquindanum
- 454. Anxiolytics Alprazolam (XANOR) Triazolo compound Limited active metabolites, shorter half-life Also indicated for anxiety associated with depression Proven effective for ALL TYPES of anxiety In the brain, there are specific receptor sites coupled to gamma aminobutyric acid (GABA) receptor sites; this explains the anxiolytic, sedative and anticonvulsant properties Have effects on noradrenergic systems, causing down regulation of post-synaptic receptors: this explains the anti-panic and antidepressant properties Psychopharmatherapy by Barcelona&Laquindanum
- 455. Anxiolytics Side effects Avoid BDZs if pCO2 is increased Lorazepam is preferred BDZ in patients w/ respiratory diseases BDZs are contraindicated in pts w/ sleep apnea BDZs may induce “sleep apnea” Benzodiazepines sedation & drowsiness Benzodiazepines can cause amnesia confusion disinhibition Psychopharmatherapy by Barcelona&Laquindanum
- 457. Found in TCAs and low-potency antipsychotics
- 458. Serotonin syndrome: Confusion, flushing, diaphoresis, tremor, myoclonic jerks, hyperthermia, hypertonicity, rhabdomyolysis, renal failure, and death
- 459. Occurs when SSRIs and MAOIs are combined
- 461. Hypertensive crisis: Caused by a buildup of stored catecholamines
- 462. MAOIsplus foods with tyramine (red wine, cheese, chicken liver, cured meats) or plus sympathomimeticsPsychopharmatherapy by Barcelona&Laquindanum
- 464. Parkinsonism—masklike face, cogwheel rigity, pill-rolling tremor
- 466. Dystonia—sustained contraction of muscles of neck, tongue, eyes
- 467. Occurs with high-potency traditional antipsychotics
- 468. Reversible, occurs within days
- 469. Can be life threatening (example—dystonia of the diaphragm causing asphyxiation)
- 470. Hyperprolactinemia
- 471. Occurs with high-potency traditional antipsychoticsPsychopharmatherapy by Barcelona&Laquindanum
- 473. Occurs after years of antipsychotic use (particularly high-potency typical antipsychotics); can be irreversible
- 474. Patients on antipsychotics should be monitored for this with various screening exams (abnormal involuntary movement scale [AIMS], DISCUS) every 6 months.
- 475. Neuroleptic malignant syndrome: Fever, tachycardia, hypertension, tremor, elevated CPK, “lead pipe” rigidity
- 476. Can be caused by all antipsychotics after short or long time (increased with high-potency traditional antipsychotics)
- 477. A medical emergency with 20% mortality ratePsychopharmatherapy by Barcelona&Laquindanum
- 478. Psychopharmatherapy Barcelona, Kathlene Marie Laquindanum, Cristal Ann
- 488. Sertraline (Zoloft)
- 490. Fluvoxamine (Luvox)
- 495. Diazepam (Valium)
- 496. Flurazepam (Dalmane)
- 499. Lorazepam (Ativan)
- 500. Temazepam (Restoril)
- 501. Oxazepam(Serax)
- 502. Triazolam(Halcion)
- 505. Haloperidol (Haldol)
- 511. Olanzapine (Zyprexa)
- 513. Clozapine (Clozaril)
- 514. Ziprasidone (Geodon)
Notas del editor
- STUDY THE LAST THREE SLIDES DOC SAID STUDY THE FOLLOWING CPGS: TIMA, CANMAT, AND APA
- Of the biogenic amines, norepinephrine and serotonin are the two neurotransmitters most implicated in the pathophysiology of mood disorders.
- NE: When levels of this chemical are too high, mania occurs. When levels of norepinephrine drop below normal levels, a person may experience depression. Other evidence has also implicated the presynaptic β2-receptors in depression, because activation of these receptors results in a decrease of the amount of norepinephrine released. Presynaptic β2-receptors are also located on serotonergic neurons and regulate the amount of serotonin released
- SEROTONIN:Depletion of serotonin may precipitate depression, and some patients with suicidal impulses have low cerebrospinal fluid (CSF) concentrations of serotonin metabolites and low concentrations of serotonin uptake sites on platelets.
- DOPAMINE:dopamine has also been theorized to play a role. The data suggest that dopamine activity may be reduced in depression and increased in mania.
- Other neurotransmitters are: ach - Abnormal levels of choline, which is a precursor to ACh, have been found at autopsy in the brains of some depressed patients, perhaps reflecting abnormalities in cell phospholipid composition.(GABA) has an inhibitory effect on ascending monoamine pathways, particularly the mesocortical and mesolimbic systems. Reductions of GABA have been observed in plasma, CSF, and brain GABA levels in depressionThe amino acids glutamate and glycine are the major excitatory and inhibitory neurotransmitters in the CNS.
- Lithium Complete absorptionNOT bound to plasma proteinsNO metabolismEliminated entirely through renal routeProportional to:SodiumLevel of body hydration
- controls acute mania and prevents relapse in about 80 percent of persons with bipolar I disorder and in a somewhat smaller percentage of persons with mixed (mania and depression) episodes, rapid-cycling bipolar disorder, or mood changes in encephalopathy.Lithium Complete absorptionNOT bound to plasma proteinsNO metabolismEliminated entirely through renal routeProportional to:SodiumLevel of body hydration
- an anticonvulsant that is especially useful in treating mixed manic episodes and rapid-cycling bipolar disorder. Its mechanism of action is unknown, but it has been shown to increase central nervous system (CNS) levels of gamma-aminobutyric acid (GABA).
- inhibition of the transamination of GABA (by inhibiting GABA transaminase, then GABA would increase in concentrationStimulates glutamate release in mouse cerebral cortex (Dixon & Hokin, 1997)↑ glutamine concentration in neuronal cultures and in animal brains by regulation of glutaminase and glutamine synthetase (Collins et al, 1994)
- n anticonvulsant that is especially useful in treating mixed episodes and rapid-cycling bipolar disorder. It is also used in the management of trigeminal neuralgia. It acts by blocking sodium channels and inhibiting ac- tion potentials. Its onset of action is 5 to 7 days.Carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to subsequently open, making brain cells less excitable (less likely to fire). Carbamazepine has also been shown to potentiate GABA receptors made up of alpha1, beta2, gamma2 subunits
- n anticonvulsant that is especially useful in treating mixed episodes and rapid-cycling bipolar disorder. It is also used in the management of trigeminal neuralgia. It acts by blocking sodium channels and inhibiting ac- tion potentials. Its onset of action is 5 to 7 days.
- increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the noradrenaline and dopamine transporter.
- The monoamine oxidase inhibitors (MAOIs), which were introduced as antidepressants in 1957, are effective in treating both depression and panic disorder. The first of these drugs were hydrazine derivatives developed as treatments for tuberculosis. Their antidepressant properties were discovered by chance, when some of the patients were observed to experience elevation of mood during treatment.The first selective serotonin reuptake inhibitor (SSRI), fluoxetine (Prozac), which was introduced in 1987, altered attitudes about pharmacologic treatment of depression. The reasons for this included that initial side effects of fluoxetine were generally better tolerated than those of existing treatments, such as the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), and the simplicity of dosing of fluoxetine.
- TCAs inhibit the reuptake of norepinephrine and serotonin, increasing availability in the synapse. They are rarely used as first-line agents because they have a higher incidence of side effects, require greater monitoring of dosing, and can be lethal in overdose.
- Imipramine is the TCA most studied for panic disorder with agoraphobia, but other TCAs are also effective when taken at the usual antidepressant dosages. Because of the potential initial anxiogenic effects of the TCAs, starting dosages should be small, Obsessive-compulsive disorder appears to respond specifically to clomipramine, as well as the SSRIsOther DisordersChildhood enuresis is often treated with imipramine. Peptic ulcer disease can be treated with doxepin, which has marked antihistaminergic effects. Other indications for TCAs are narcolepsy, nightmare disorder, and PTSD. The drugs are sometimes used for treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD), sleepwalking disorder, separation anxiety disorder, and sleep terror disorder. Clomipramine has also been used to treat premature ejaculation, movement disorders, and compulsive behavior in children with autistic disorders; however, because TCAs have caused sudden death in several children and adolescents, their use is best avoided in this population.
- MAOIs prevent the inactivation of biogenic amines such as norepinephrine, serotonin, dopamine, and tyramine (an intermediate in the conversion of tyro- sine to norepinephrine). By irreversibly inhibiting the enzymes MAO-A and -B, MAOIs increase the amount of these transmitters available in synapses. MAO-A preferentially deactivates serotonin, and MAO-B preferentially de- activates norepinephrine/epinephrine. Both types also act on dopamine and tyramine.The MAO enzymes are found on the outer membranes of mitochondria where they degrade cytoplasmic and extraneuronal monoamine neurotransmitters, such as norepinephrine, serotonin, dopamine, epinephrine, and tyramine. MAOIs act in the central nervous system (CNS), the sympathetic nervous system, the liver, and the gastrointestinal (GI) tract.
- Ssri inhibitpresynaptic serotonin pumps,leading to increased availability of serotonin in synaptic clefts
- All SSRIs cause sexual dysfunction, and it is the most common adverse effect of SSRIs associated with long-term treatment. It has an estimated incidence of between 50 percent and 80 percent. The most common complaints are anorgasmia, inhibited orgasm, and decreased libido.Gastrointestinal (GI) side effects, which are very common, are mediated largely through effects on the serotonin 5HT3 receptor. The most frequent GI complaints are nausea, diarrhea, anorexia, vomiting, flatulence, and dyspepsia.
- Traditional anti-psychoticsChlorpromazine (Thorazine) Class: conventional antipsychotic (neuroleptic, dopa2antagonist, antiemetic)Indication: schizophrenia, psychosis, nausea and vom, restlessness and apprehension before surgery, acute intermittent porphyria, manifestations of manic type of manic-depressive illness, intractable hiccups, combativeness and/or explosive hyperexcitable in children, hyperactive children who show excessive motor activity with accompanying conduct disorders,How the drug works: blocks dopa2receptors, reducing positive sx of psychosis; combination of dopa d2, histamine H1 and cholinergic M1 blockade in the vomiting centerHow long until it works: psychotic sx can improve within 1 week, but may take several weeks for full effect on behaviorPearls: one of the earliest classical conventional antipsychoticsLow potency phenothiazines like chlorpromazine have a greater risk of cardiovascular side effects2. HaloperidolPrior to the introduction of atypical antipsychotics, one of the most preferred antipsychoticsLess sedating than many other conventional antipsychotics, especially low potency phenothiazinesLong acting IM formulation lasts up to 4 weeks, while other long acting IM antipsychotics may only last up to 2 weeksPatients receiving atypicals may occasionally require a top up of a conventional antipsychotic such as haloperidol to control aggression or violent behaviorAtypical antipsychoticsClozapine (clozaril, leponex)Atypical antipsychotic, serotonin-dopamine antagonist, mood stabilizerCommonly prescribed for tx resistant schizophrenia, reduction in risk of recurrent suicidal behavior in patients with schiz or schizoaffective disorder2. Risperidone (risperdal)Well acceptdtx of agitation and aggression in elderly demented pxWell accepted for tx of behavioral sx in children and adolescents but may have more sedation and wgt gain in pedia populations than in adult populations3. Quetiapine (Seroquel)4. Olanzapine (zyprex)Documented utility in tx refractory cases, especially at higher dosesDocumented efficacy as aumenting agent to ssri’s (especially fluoxetine) in nonpsychotictxresitant major depressive disorderDocumented efficacy in bipolar depression, especially with fluoxetine
- Traditional anti-psychoticsChlorpromazine (Thorazine) Class: conventional antipsychotic (neuroleptic, dopa2antagonist, antiemetic)Indication: schizophrenia, psychosis, nausea and vom, restlessness and apprehension before surgery, acute intermittent porphyria, manifestations of manic type of manic-depressive illness, intractable hiccups, combativeness and/or explosive hyperexcitable in children, hyperactive children who show excessive motor activity with accompanying conduct disorders,How the drug works: blocks dopa2receptors, reducing positive sx of psychosis; combination of dopa d2, histamine H1 and cholinergic M1 blockade in the vomiting centerHow long until it works: psychotic sx can improve within 1 week, but may take several weeks for full effect on behaviorPearls: one of the earliest classical conventional antipsychoticsLow potency phenothiazines like chlorpromazine have a greater risk of cardiovascular side effects2. HaloperidolPrior to the introduction of atypical antipsychotics, one of the most preferred antipsychoticsLess sedating than many other conventional antipsychotics, especially low potency phenothiazinesLong acting IM formulation lasts up to 4 weeks, while other long acting IM antipsychotics may only last up to 2 weeksPatients receiving atypicals may occasionally require a top up of a conventional antipsychotic such as haloperidol to control aggression or violent behaviorAtypical antipsychoticsClozapine (clozaril, leponex)Atypical antipsychotic, serotonin-dopamine antagonist, mood stabilizerCommonly prescribed for tx resistant schizophrenia, reduction in risk of recurrent suicidal behavior in patients with schiz or schizoaffective disorder2. Risperidone (risperdal)Well acceptdtx of agitation and aggression in elderly demented pxWell accepted for tx of behavioral sx in children and adolescents but may have more sedation and wgt gain in pedia populations than in adult populations3. Quetiapine (Seroquel)4. Olanzapine (zyprex)Documented utility in tx refractory cases, especially at higher dosesDocumented efficacy as aumenting agent to ssri’s (especially fluoxetine) in nonpsychotictxresitant major depressive disorderDocumented efficacy in bipolar depression, especially with fluoxetine
- Nigrostriatal pathway – from substantianigra to corpus striatum - responsible for parkinsonism - parkinsoniansx – bradykinesia, rigidity of extremitiesTuberoinfundibular pathway – prolactin release from hypothalamus to the infundibulum and the anterior pituitary dopamine inhibits the release of prolactin from the anterior pitprolactin for lactationThe ventral tegmentum (tegmentum is Latin for covering), better known as the ventral tegmental area (VTA), is a group of neurons located close to the midline on the floor of the midbrain (mesencephalon). The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and is widely implicated in the drug and natural reward circuitry of the brain. It is important incognition, motivation, drug addiction, and several psychiatric disorders. The VTA contains neurons that project to numerous areas of the brain, from the prefrontal cortex (PFC) to the caudal brainstem and everywhere in between.Mesocortical pathway – from the ventral tegmental area, to the dorsolateral and ventrolateral prefrontal cortexMesolimbic pathway – from ventral tegmental areaIn schizophrenia – there is excess dopamine release in mesolimbic system, and paucity of release in mesocortical(reduction of dopa in the prefrontal cortex, responsible for cognitive sx and negative sx of schiz)(excess of dopa in mesolimbic, responsible for psychosis and positive sx of schiz)
- Nigrostriatal pathway – from substantianigra to corpus striatum - responsible for parkinsonism - parkinsoniansx – bradykinesia, rigidity of extremitiesTuberoinfundibular pathway – prolactin release from hypothalamus to the infundibulum and the anterior pituitary dopamine inhibits the release of prolactin from the anterior pitprolactin for lactationThe ventral tegmentum (tegmentum is Latin for covering), better known as the ventral tegmental area (VTA), is a group of neurons located close to the midline on the floor of the midbrain (mesencephalon). The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and is widely implicated in the drug and natural reward circuitry of the brain. It is important incognition, motivation, drug addiction, and several psychiatric disorders. The VTA contains neurons that project to numerous areas of the brain, from the prefrontal cortex (PFC) to the caudal brainstem and everywhere in between.Mesocortical pathway – from the ventral tegmental area, to the dorsolateral and ventrolateral prefrontal cortexMesolimbic pathway – from ventral tegmental areaIn schizophrenia – there is excess dopamine release in mesolimbic system, and paucity of release in mesocortical(reduction of dopa in the prefrontal cortex, responsible for cognitive sx and negative sx of schiz)(excess of dopa in mesolimbic, responsible for psychosis and positive sx of schiz)
- Partial agonist – A compound which (even when fully occupying a receptor) possesses affinity for a receptor, but elicits a partial pharmacological response at the receptor involved. Partial agonists are often structural analogs of agonist molecules. If neurotransmitter concentrations are low, partial agonists may behave as an agonist. This is why these medications are sometimes called mixed agonists
- Partial agonist – A compound which (even when fully occupying a receptor) possesses affinity for a receptor, but elicits a partial pharmacological response at the receptor involved. Partial agonists are often structural analogs of agonist molecules. If neurotransmitter concentrations are low, partial agonists may behave as an agonist. This is why these medications are sometimes called mixed agonists
- Partial agonist – A compound which (even when fully occupying a receptor) possesses affinity for a receptor, but elicits a partial pharmacological response at the receptor involved. Partial agonists are often structural analogs of agonist molecules. If neurotransmitter concentrations are low, partial agonists may behave as an agonist. This is why these medications are sometimes called mixed agonists
- Partial agonist – A compound which (even when fully occupying a receptor) possesses affinity for a receptor, but elicits a partial pharmacological response at the receptor involved. Partial agonists are often structural analogs of agonist molecules. If neurotransmitter concentrations are low, partial agonists may behave as an agonist. This is why these medications are sometimes called mixed agonists
- Partial agonist – A compound which (even when fully occupying a receptor) possesses affinity for a receptor, but elicits a partial pharmacological response at the receptor involved. Partial agonists are often structural analogs of agonist molecules. If neurotransmitter concentrations are low, partial agonists may behave as an agonist. This is why these medications are sometimes called mixed agonists
- Partial agonist – A compound which (even when fully occupying a receptor) possesses affinity for a receptor, but elicits a partial pharmacological response at the receptor involved. Partial agonists are often structural analogs of agonist molecules. If neurotransmitter concentrations are low, partial agonists may behave as an agonist. This is why these medications are sometimes called mixed agonists
- Chlorpromazine - control of psychosis, to resolve hallucinations and delusionsHaloperidol - 1970sChlorpromazine, halop, thioridazone - dopa antagonist - wparkinsoniansxClozapine - 1990s - first effective antipsychotic with neglibigbleeps side effects - prototype for 2nd gen antipsychotics - less eps - control of both positive and negative sx - but noted to have side effect of agranulocytosis therefore use was restricted to px who responded poorly to other agentsRisperidone - modification of haloperidol - greater affinity to serotonin - less eps side effects
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosis
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosis
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosis
- Traditional anti-psychoticsChlorpromazine (Thorazine) Class: conventional antipsychotic (neuroleptic, dopa2antagonist, antiemetic)Indication: schizophrenia, psychosis, nausea and vom, restlessness and apprehension before surgery, acute intermittent porphyria, manifestations of manic type of manic-depressive illness, intractable hiccups, combativeness and/or explosive hyperexcitable in children, hyperactive children who show excessive motor activity with accompanying conduct disorders,How the drug works: blocks dopa2receptors, reducing positive sx of psychosis; combination of dopa d2, histamine H1 and cholinergic M1 blockade in the vomiting centerHow long until it works: psychotic sx can improve within 1 week, but may take several weeks for full effect on behaviorPearls: one of the earliest classical conventional antipsychoticsLow potency phenothiazines like chlorpromazine have a greater risk of cardiovascular side effects
- 2. HaloperidolPrior to the introduction of atypical antipsychotics, one of the most preferred antipsychoticsLess sedating than many other conventional antipsychotics, especially low potency phenothiazinesLong acting IM formulation lasts up to 4 weeks, while other long acting IM antipsychotics may only last up to 2 weeksPatients receiving atypicals may occasionally require a top up of a conventional antipsychotic such as haloperidol to control aggression or violent behavior
- 1. Antidopaminergic effects: Extrapyramidal side effectsarkinsonism—masklike face, cogwheel rigidity, pill-rolling tremor. Akathisia—subjective anxiety and restlessness, objective fidgeti-nessystonia—sustained contraction of muscles of neck, tongue, eyes(painful) Hyperprolactinemia—leading to decreased libido, galactorrhea,gynecomastia, impotence, amenorrhea, osteoporosisTreatment of EPSEs includes reducing dose of antipsychotic and administer- ingantiparkinsonian, anticholinergic, or antihistaminic medications, such as amantadine (Symmetrel), Benadryl, or benztropine (Cogentin).2. Anti-HAM effects: Caused by actions on histaminic, adrenergic, and muscarinic receptors: Antihistaminic—results in sedation Anti–alpha adrenergic—results in orthostatic hypotension, cardiac ab-normalities, and sexual dysfunction Antimuscarinic—anticholinergic effects: Dry mouth, tachycardia, uri-nary retention, blurry vision, constipation3. Weight gain 4. Elevated liver enzymes, jaundice 5. Ophthalmologic problems (irreversible retinal pigmentation with highdoses of Mellaril, deposits in lens and cornea with chlorpromazine) 6. Dermatologic problems, including rashes and photosensitivity (blue-gray skin discoloration with chlorpromazine) 7. Seizures: Antipsychotics lower seizure thresholds. Low-potency more likely cause seizure8. Tardivedyskinesia: Choreoathetoid (writhing) movements of mouth and tongue that may occur in patients who have used neuroleptics for more than 6 months. It most often occurs in older women. Though 50% of cases will spontaneously remit, untreated cases may be perma- nent.Neuroleptic Malignant SyndromeA potentially fatal side effect of DRA treatment, neuroleptic malignant syndrome, can occur at any time during the course of DRA treatment. Symptoms include extreme hyperthermia, severe muscular rigidity and dystonia, akinesia, mutism, confusion, agitation, and increased pulse rate and blood pressure (BP) leading to cardiovascular collapse. Laboratory findings include increased white blood cell (WBC) count, creatininephosphokinase, liver enzymes, plasma myoglobin, and myoglobinuria, occasionally associated with renal failure. The symptoms usually evolve over 24 to 72 hours, and the untreated syndrome lasts 10 to 14 days. The diagnosis is often missed in the early stages, and the withdrawal or agitation may mistakenly be considered to reflect increased psychosis. Men are affected more frequently than are women, and young persons are affected more commonly than are elderly persons. The mortality rate can reach 20 percent to 30 percent or even higher when depot medications are involved. Rates are also increased when high doses of high-potency agents are used.Ifneuroleptic malignant syndrome is suspected, the DRA should be stopped immediately and the following done: medical support to cool the person; monitoring of vital signs, electrolytes, fluid balance, and renal output; and symptomatic treatmentP.1047of fever. Antiparkinsonian medications may reduce some of the muscle rigidity. Dantrolene (Dantrium), a skeletal muscle relaxant (0.8 to 2.5 mg/kg every 6 hours, up to a total dosage of 10 mg a day) may be useful in the treatment of this disorder. Once the person can take oral medications, dantrolene can be given in doses of 100 to 200 mg a day. Bromocriptine (20 to 30 mg a day in four divided doses) or amantadine can be added to the regimen. Treatment should usually be continued for 5 to 10 days. When drug treatment is restarted, the clinician should consider switching to a low-potency drug or an SDA, although these agents—includingclozapine—can also cause neuroleptic malignant syndrome.Seizure ThresholdThe DRAs may lower the seizure threshold. Chlorpromazine, thioridazine, and other low-potency drugs are thought to be more epileptogenic than are high-potency drugs. Molindone may be the least epileptogenic of the DRA drugs. The risk of inducing a seizure by drug administration warrants consideration when the person already has a seizure disorder or brain lesion.SedationBlockade of histamine H1 receptors is the usual cause of sedation associated with DRAs. Chlorpromazine is the most sedating typical antipsychotic. The relative sedative properties of the drugs are summarized in Table 36.18-3. Giving the entire daily dose at bedtime usually eliminates any problems from sedation, and tolerance for this adverse effect often develops.Central AnticholinergicEffectsThe symptoms of central anticholinergic activity include severe agitation; disorientation to time, person, and place; hallucinations; seizures; high fever; and dilated pupils. Stupor and coma may ensue. The treatment of anticholinergic toxicity consists ofP.1048discontinuing the causal agent or agents, close medical supervision, and physostigmine (Antilirium, Eserine), 2 mg by slow intravenous (IV) infusion, repeated within 1 hour as necessary. Too much physostigmine is dangerous, and symptoms of physostigmine toxicity include hypersalivation and sweating. Atropine sulfate (0.5 mg) can reverse the effects of physostigmine toxicity.Cardiac EffectsTheDRAs decrease cardiac contractility, disrupt enzyme contractility in cardiac cells, increase circulating levels of catecholamines, and prolong atrial and ventricular conduction time and refractory periods. Low-potency DRAs are more cardiotoxic than are high-potency drugs. Chlorpromazine causes prolongation of the QT and PR intervals, blunting of the T waves, and depression of the ST segment. Thioridazine and mesoridazine, in particular, are associated with substantial QT prolongation and risk of torsade de pointes. These drugs, thus, are indicated only when other agents have been ineffective.Sudden DeathOccasional reports of sudden cardiac death during treatment with DRAs may be the result of cardiac arrhythmias. Other causes may include seizure, asphyxiation, malignant hyperthermia, heat stroke, and neuroleptic malignant syndrome. An overall increase in the incidence of sudden death linked to the use of antipsychotics does not appear to exist, however.Orthostatic (Postural) HypotensionOrthostatic (postural) hypotension is most common with low-potency drugs, particularly chlorpromazine, thioridazine, and chlorprothixene. When using intramuscular (IM) low-potency DRAs, the clinician should measure the person's BP (lying and standing) before and after the first dose and during the first few days of treatment.Orthostatic hypotension is mediated by adrenergic blockade and occurs most frequently during the first few days of treatment. Tolerance often develops for this side effect, which is why initial dosing of these drugs is lower than the usual therapeutic dose. Fainting or falls, although uncommon, can lead to injury. Patients should be warned of this side effect and instructed to rise slowly after sitting or reclining. Patients should avoid all caffeine and alcohol; they should drink at least 2 L of fluid a day and, if not under treatment for hypertension, should add liberal amounts of salt to their diet. Support hose may help some persons.Hypotension can usually be managed by having patients lie down with their feet higher than their heads, and pump their legs as if bicycling. Volume expansion or vasopressor agents, such as norepinephrine (Levophed), may be indicated in severe cases. Because hypotension is produced by α-adrenergic blockade, the drugs also block the α-adrenergic stimulating properties of epinephrine, leaving the β-adrenergic stimulating effects untouched. Therefore, the administration of epinephrine results in a paradoxical worsening of hypotension and is contraindicated in cases of antipsychotic-induced hypotension. Pure α-adrenergic pressor agents, such as metaraminol (Aramine) and norepinephrine, are the drugs of choice in the treatment of the disorder.Hematologic EffectsA temporary leukopenia with a WBC count of about 3,500 is a common, but not serious problem. Agranulocytosis, a life-threatening hematologic problem, occurs in about 1 of 10,000 persons treated with DRAs. Thrombocytopenic or nonthrombocytopenicpurpura, hemolytic anemias, and pancytopenia may occur rarely in persons treated with DRAs. Although routine complete blood counts (CBCs) are not indicated, if a person reports a sore throat and fever, a CBC should be done immediately to check for the possibility. If the blood indexes are low, administration of DRAs should be stopped, and the person should be transferred to a medical facility. The mortality rate for the complication may be as high as 30 percent.Peripheral AnticholinergicEffectsPeripheralanticholinergic effects, consisting of dry mouth and nose, blurred vision, constipation, urinary retention, and mydriasis, are common, especially with low-potency DRAs, for example, chlorpromazine, thioridazine, mesoridazine (Serentil). Some persons also have nausea and vomiting.Constipation should be treated with the usual laxative preparations, but severe constipation can progress to paralytic ileus. A decrease in the DRA dosage or a change to a less anticholinergic drug is warranted in such cases. Pilocarpine (Salagen) can be used to treat paralytic ileus, although the relief is only transitory. Bethanechol (Urecholine) (20 to 40 mg a day) may be useful in some persons with urinary retention.Weight gain is associated with increased mortality and morbidity and with medication noncompliance. Low-potency DRAs can cause significant weight gain but not as much as is seen with the SDAsolanzapine (Zyprexa) and clozapine (Clozaril). Molindone (Moban) and, perhaps, loxapine (Loxitane) appear to be least likely to cause weight gain.Endocrine EffectsBlockade of the dopamine receptors in the tuberoinfundibular tract results in the increased secretion of prolactin, which can result in breast enlargement, galactorrhea, amenorrhea, and inhibited orgasm in women and impotence in men. The SDAs, with the exception of risperidone, are not particularly associated with an increase in prolactin levels and may be the drugs of choice for persons experiencing disturbing side effects from increased prolactin release.Sexual Adverse EffectsBoth men and women taking DRAs can experience anorgasmia and decreased libido. As many as 50 percent of men taking antipsychotics report ejaculatory and erectile disturbances. Sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) are often used to treat psychotropic-induced orgasmic dysfunction, but they have not been studied in combination with DRAs. Thioridazine is particularly associated with decreased libido and retrograde ejaculation in men. Priapism and reports of painfulP.1049orgasms have also been described, both possibly resulting from α1-adrenergic antagonist activity.Skin and Eye EffectsAllergic dermatitis and photosensitivity can occur, especially with low-potency agents. Urticarial, maculopapular, petechial, and edematous eruptions can occur early in treatment, generally in the first few weeks, and remit spontaneously. A photosensitivity reaction that resembles a severe sunburn also occurs in some persons taking chlorpromazine. Persons should be warned of this adverse effect, spend no more than 30 to 60 minutes in the sun, and use sunscreens. Long-term chlorpromazine use is associated with blue-gray discoloration of skin areas exposed to sunlight. The skin changes often begin with a tan or golden brown color and progress to such colors as slate gray, metallic blue, and purple. These discolorations resolve when the patient is switched to another medication.Irreversible retinal pigmentation is associated with use of thioridazine at dosages above 1,000 mg a day. An early symptom of the side effect can sometimes be nocturnal confusion related to difficulty with night vision. The pigmentation can progress even after thioridazine administration is stopped, finally resulting in blindness. It is for this reason that the maximal recommended dosage of thioridazine is 800 mg per day.Patients taking chlorpromazine can develop a relatively benign pigmentation of the eyes, characterized by whitish brown granular deposits concentrated in the anterior lens and posterior cornea and visible only by slit-lens examination. The deposits can progress to opaque white and yellow-brown granules, often stellate. Occasionally, the conjunctiva is discolored by a brown pigment. No retinal damage is seen, and vision is almost never impaired. This condition gradually resolves when the chlorpromazine is discontinued.JaundiceElevations of liver enzymes during treatment with a DRA tend to be transient and not clinically significant. When chlorpromazine first came into use, cases of obstructive or cholestatic jaundice were reported. It usually occurred in the first month of treatment and was heralded by symptoms of upper abdominal pain, nausea, and vomiting. This was followed by fever, rash, eosinophilia, bilirubin in the urine, and increases in serum bilirubin, alkaline phosphatase, and hepatic transaminases. Reported cases are now extremely rare, but if jaundice occurs, the medication should be discontinued.
- Neuroleptic Malignant SyndromeA potentially fatal side effect of DRA treatment, neuroleptic malignant syndrome, can occur at any time during the course of DRA treatment. Symptoms include extreme hyperthermia, severe muscular rigidity and dystonia, akinesia, mutism, confusion, agitation, and increased pulse rate and blood pressure (BP) leading to cardiovascular collapse. Laboratory findings include increased white blood cell (WBC) count, creatininephosphokinase, liver enzymes, plasma myoglobin, and myoglobinuria, occasionally associated with renal failure. The symptoms usually evolve over 24 to 72 hours, and the untreated syndrome lasts 10 to 14 days. The diagnosis is often missed in the early stages, and the withdrawal or agitation may mistakenly be considered to reflect increased psychosis. Men are affected more frequently than are women, and young persons are affected more commonly than are elderly persons. The mortality rate can reach 20 percent to 30 percent or even higher when depot medications are involved. Rates are also increased when high doses of high-potency agents are used.Ifneuroleptic malignant syndrome is suspected, the DRA should be stopped immediately and the following done: medical support to cool the person; monitoring of vital signs, electrolytes, fluid balance, and renal output; and symptomatic treatmentP.1047of fever. Antiparkinsonian medications may reduce some of the muscle rigidity. Dantrolene (Dantrium), a skeletal muscle relaxant (0.8 to 2.5 mg/kg every 6 hours, up to a total dosage of 10 mg a day) may be useful in the treatment of this disorder. Once the person can take oral medications, dantrolene can be given in doses of 100 to 200 mg a day. Bromocriptine (20 to 30 mg a day in four divided doses) or amantadine can be added to the regimen. Treatment should usually be continued for 5 to 10 days. When drug treatment is restarted, the clinician should consider switching to a low-potency drug or an SDA, although these agents—includingclozapine—can also cause neuroleptic malignant syndrome.Seizure ThresholdThe DRAs may lower the seizure threshold. Chlorpromazine, thioridazine, and other low-potency drugs are thought to be more epileptogenic than are high-potency drugs. Molindone may be the least epileptogenic of the DRA drugs. The risk of inducing a seizure by drug administration warrants consideration when the person already has a seizure disorder or brain lesion.SedationBlockade of histamine H1 receptors is the usual cause of sedation associated with DRAs. Chlorpromazine is the most sedating typical antipsychotic. The relative sedative properties of the drugs are summarized in Table 36.18-3. Giving the entire daily dose at bedtime usually eliminates any problems from sedation, and tolerance for this adverse effect often develops.Central AnticholinergicEffectsThe symptoms of central anticholinergic activity include severe agitation; disorientation to time, person, and place; hallucinations; seizures; high fever; and dilated pupils. Stupor and coma may ensue. The treatment of anticholinergic toxicity consists ofP.1048discontinuing the causal agent or agents, close medical supervision, and physostigmine (Antilirium, Eserine), 2 mg by slow intravenous (IV) infusion, repeated within 1 hour as necessary. Too much physostigmine is dangerous, and symptoms of physostigmine toxicity include hypersalivation and sweating. Atropine sulfate (0.5 mg) can reverse the effects of physostigmine toxicity.Cardiac EffectsTheDRAs decrease cardiac contractility, disrupt enzyme contractility in cardiac cells, increase circulating levels of catecholamines, and prolong atrial and ventricular conduction time and refractory periods. Low-potency DRAs are more cardiotoxic than are high-potency drugs. Chlorpromazine causes prolongation of the QT and PR intervals, blunting of the T waves, and depression of the ST segment. Thioridazine and mesoridazine, in particular, are associated with substantial QT prolongation and risk of torsade de pointes. These drugs, thus, are indicated only when other agents have been ineffective.Sudden DeathOccasional reports of sudden cardiac death during treatment with DRAs may be the result of cardiac arrhythmias. Other causes may include seizure, asphyxiation, malignant hyperthermia, heat stroke, and neuroleptic malignant syndrome. An overall increase in the incidence of sudden death linked to the use of antipsychotics does not appear to exist, however.Orthostatic (Postural) HypotensionOrthostatic (postural) hypotension is most common with low-potency drugs, particularly chlorpromazine, thioridazine, and chlorprothixene. When using intramuscular (IM) low-potency DRAs, the clinician should measure the person's BP (lying and standing) before and after the first dose and during the first few days of treatment.Orthostatic hypotension is mediated by adrenergic blockade and occurs most frequently during the first few days of treatment. Tolerance often develops for this side effect, which is why initial dosing of these drugs is lower than the usual therapeutic dose. Fainting or falls, although uncommon, can lead to injury. Patients should be warned of this side effect and instructed to rise slowly after sitting or reclining. Patients should avoid all caffeine and alcohol; they should drink at least 2 L of fluid a day and, if not under treatment for hypertension, should add liberal amounts of salt to their diet. Support hose may help some persons.Hypotension can usually be managed by having patients lie down with their feet higher than their heads, and pump their legs as if bicycling. Volume expansion or vasopressor agents, such as norepinephrine (Levophed), may be indicated in severe cases. Because hypotension is produced by α-adrenergic blockade, the drugs also block the α-adrenergic stimulating properties of epinephrine, leaving the β-adrenergic stimulating effects untouched. Therefore, the administration of epinephrine results in a paradoxical worsening of hypotension and is contraindicated in cases of antipsychotic-induced hypotension. Pure α-adrenergic pressor agents, such as metaraminol (Aramine) and norepinephrine, are the drugs of choice in the treatment of the disorder.Hematologic EffectsA temporary leukopenia with a WBC count of about 3,500 is a common, but not serious problem. Agranulocytosis, a life-threatening hematologic problem, occurs in about 1 of 10,000 persons treated with DRAs. Thrombocytopenic or nonthrombocytopenicpurpura, hemolytic anemias, and pancytopenia may occur rarely in persons treated with DRAs. Although routine complete blood counts (CBCs) are not indicated, if a person reports a sore throat and fever, a CBC should be done immediately to check for the possibility. If the blood indexes are low, administration of DRAs should be stopped, and the person should be transferred to a medical facility. The mortality rate for the complication may be as high as 30 percent.Peripheral AnticholinergicEffectsPeripheralanticholinergic effects, consisting of dry mouth and nose, blurred vision, constipation, urinary retention, and mydriasis, are common, especially with low-potency DRAs, for example, chlorpromazine, thioridazine, mesoridazine (Serentil). Some persons also have nausea and vomiting.Constipation should be treated with the usual laxative preparations, but severe constipation can progress to paralytic ileus. A decrease in the DRA dosage or a change to a less anticholinergic drug is warranted in such cases. Pilocarpine (Salagen) can be used to treat paralytic ileus, although the relief is only transitory. Bethanechol (Urecholine) (20 to 40 mg a day) may be useful in some persons with urinary retention.Weight gain is associated with increased mortality and morbidity and with medication noncompliance. Low-potency DRAs can cause significant weight gain but not as much as is seen with the SDAsolanzapine (Zyprexa) and clozapine (Clozaril). Molindone (Moban) and, perhaps, loxapine (Loxitane) appear to be least likely to cause weight gain.Endocrine EffectsBlockade of the dopamine receptors in the tuberoinfundibular tract results in the increased secretion of prolactin, which can result in breast enlargement, galactorrhea, amenorrhea, and inhibited orgasm in women and impotence in men. The SDAs, with the exception of risperidone, are not particularly associated with an increase in prolactin levels and may be the drugs of choice for persons experiencing disturbing side effects from increased prolactin release.Sexual Adverse EffectsBoth men and women taking DRAs can experience anorgasmia and decreased libido. As many as 50 percent of men taking antipsychotics report ejaculatory and erectile disturbances. Sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) are often used to treat psychotropic-induced orgasmic dysfunction, but they have not been studied in combination with DRAs. Thioridazine is particularly associated with decreased libido and retrograde ejaculation in men. Priapism and reports of painfulP.1049orgasms have also been described, both possibly resulting from α1-adrenergic antagonist activity.Skin and Eye EffectsAllergic dermatitis and photosensitivity can occur, especially with low-potency agents. Urticarial, maculopapular, petechial, and edematous eruptions can occur early in treatment, generally in the first few weeks, and remit spontaneously. A photosensitivity reaction that resembles a severe sunburn also occurs in some persons taking chlorpromazine. Persons should be warned of this adverse effect, spend no more than 30 to 60 minutes in the sun, and use sunscreens. Long-term chlorpromazine use is associated with blue-gray discoloration of skin areas exposed to sunlight. The skin changes often begin with a tan or golden brown color and progress to such colors as slate gray, metallic blue, and purple. These discolorations resolve when the patient is switched to another medication.Irreversible retinal pigmentation is associated with use of thioridazine at dosages above 1,000 mg a day. An early symptom of the side effect can sometimes be nocturnal confusion related to difficulty with night vision. The pigmentation can progress even after thioridazine administration is stopped, finally resulting in blindness. It is for this reason that the maximal recommended dosage of thioridazine is 800 mg per day.Patients taking chlorpromazine can develop a relatively benign pigmentation of the eyes, characterized by whitish brown granular deposits concentrated in the anterior lens and posterior cornea and visible only by slit-lens examination. The deposits can progress to opaque white and yellow-brown granules, often stellate. Occasionally, the conjunctiva is discolored by a brown pigment. No retinal damage is seen, and vision is almost never impaired. This condition gradually resolves when the chlorpromazine is discontinued.JaundiceElevations of liver enzymes during treatment with a DRA tend to be transient and not clinically significant. When chlorpromazine first came into use, cases of obstructive or cholestatic jaundice were reported. It usually occurred in the first month of treatment and was heralded by symptoms of upper abdominal pain, nausea, and vomiting. This was followed by fever, rash, eosinophilia, bilirubin in the urine, and increases in serum bilirubin, alkaline phosphatase, and hepatic transaminases. Reported cases are now extremely rare, but if jaundice occurs, the medication should be discontinued.
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosisAtypical antipsychoticsClozapine (clozaril, leponex)Atypical antipsychotic, serotonin-dopamine antagonist, mood stabilizerCommonly prescribed for tx resistant schizophrenia, reduction in risk of recurrent suicidal behavior in patients with schiz or schizoaffective disorder2. Risperidone (risperdal)Well acceptdtx of agitation and aggression in elderly demented pxWell accepted for tx of behavioral sx in children and adolescents but may have more sedation and wgt gain in pedia populations than in adult populations3. Quetiapine (Seroquel)4. Olanzapine (zyprex)Documented utility in tx refractory cases, especially at higher dosesDocumented efficacy as aumenting agent to ssri’s (especially fluoxetine) in nonpsychotictxresitant major depressive disorderDocumented efficacy in bipolar depression, especially with fluoxetine
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosisAtypical antipsychoticsClozapine (clozaril, leponex)Atypical antipsychotic, serotonin-dopamine antagonist, mood stabilizerCommonly prescribed for tx resistant schizophrenia, reduction in risk of recurrent suicidal behavior in patients with schiz or schizoaffective disorder2. Risperidone (risperdal)Well acceptdtx of agitation and aggression in elderly demented pxWell accepted for tx of behavioral sx in children and adolescents but may have more sedation and wgt gain in pedia populations than in adult populations3. Quetiapine (Seroquel)4. Olanzapine (zyprex)Documented utility in tx refractory cases, especially at higher dosesDocumented efficacy as aumenting agent to ssri’s (especially fluoxetine) in nonpsychotictxresitant major depressive disorderDocumented efficacy in bipolar depression, especially with fluoxetine
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosis
- The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin–dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosis
- clozapine, which causes adverse hematologic effects that require weekly blood sampling.
- clozapine, which causes adverse hematologic effects that require weekly blood sampling.
- clozapine, which causes adverse hematologic effects that require weekly blood sampling.
- . During the first 6 months of treatment, weekly WBC counts are indicated to monitor the patient for the development ofP.1096agranulocytosis. If the WBC count remains normal, the frequency of testing can be decreased to every 2 weeks.
- TardivedyskinesiaInvoluntary movements of tongue, jaw, arms, or trunk due to chronic use of antipsychotic meds
- first-line anxiolyticsAdvantages include safety at high doses (as opposed to barbiturates). A significant limitation is imposed on the duration of BDZ use due to their potential for tolerance and dependence after prolonged use. Benzodiazepines work by potentiating the effects of GABA.Can be lethal when mixed with alcohol