{"id":155,"date":"2019-10-07T20:15:49","date_gmt":"2019-10-07T14:45:49","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=155"},"modified":"2019-10-07T20:15:49","modified_gmt":"2019-10-07T14:45:49","slug":"antipsychotic-drugs","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/antipsychotic-drugs\/","title":{"rendered":"Antipsychotic Drugs"},"content":{"rendered":"\n

Drugs\nfor Psychiatric Illness<\/strong><\/p>\n\n\n\n

Two major types of psychiatric disorders are psychosis and\nneurosis.<\/p>\n\n\n\n

Psychosis:<\/strong> The patient\nis not aware of his illness (insight is absent) and refuses to take treatment.\nIt includes major psychosis like schizophrenia as well as mood disorders (like mania,\ndepression and bipolar disorder).<\/p>\n\n\n\n

Neurosis:<\/strong> It is less serious and insight is present. It includes anxiety, obsessive-compulsive disorder (OCD), phobias, eating disorders and post-traumatic stress disorder (PTSD).<\/p>\n\n\n\n

\"\"<\/figure><\/div>\n\n\n\n

Antipsychotic\nDrugs<\/strong><\/p>\n\n\n\n

Schizophrenia<\/strong> is a severe psychiatric illness and is thought to be due to dopaminergic overactivity in the limbic system<\/em><\/strong> of the brain. <\/p>\n\n\n\n

Other\nneurotransmitters like 5-HT and NA also probably play a role in this disorder. <\/p>\n\n\n\n

All drugs for schizophrenia have equal efficacy, these mainly differ in potency<\/em><\/strong> and can be classified as typical (D2 blockers) and atypical (acting via other mechanisms) antipsychotics.<\/p>\n\n\n\n

\"\"<\/figure><\/div>\n\n\n\n

Actions of\nTypical Antipsychotics<\/strong><\/p>\n\n\n\n

\u2022 These\ndrugs act by blocking D2 receptors <\/strong>and differ significantly in potency. Low\npotency drugs (like chlorpromazine) <\/strong>are highly sedative whereas high\npotency drugs cause less sedation.<\/p>\n\n\n\n

\u2022 High\npotency drugs are more likely to cause extrapyramidal symptoms (maximum with\nhaloperidol) <\/strong>whereas it is least common with thioridazine.<\/strong><\/p>\n\n\n\n

\u2022 High\npotency drugs have low anticholinergic and autonomic side effects as compared\nto low potency drugs.<\/p>\n\n\n\n

\u2022 These\ndrugs lower the seizure threshold <\/strong>and can precipitate convulsions in an epileptic\npatient.<\/p>\n\n\n\n

\u2022 All of\nthese agents are potent antiemetic <\/strong>drugs except thioridazine<\/strong>.<\/p>\n\n\n\n

\u2022 Low\npotency drugs <\/strong>possess significant \u03b1 blocking <\/strong>(maximum with chlorpromazine)\nand anticholinergic <\/strong>(maximum with thioridazine) properties.<\/p>\n\n\n\n

High\npotency compounds have less activity on these receptors.<\/p>\n\n\n\n

\u2022 Due to the\nblockade of D2 receptors in the hypothalamus and pituitary, these drugs can increase\nprolactin release <\/strong>resulting in galactorrhoea and amenorrhea<\/em>. <\/p>\n\n\n\n

Actions of\nAtypical Antipsychotics<\/strong><\/p>\n\n\n\n

These\ndrugs act by antagonistic actions at 5-HT2 and <\/em>\u03b1 receptors <\/em>and\nmay or may not possess D2 blocking activity. <\/p>\n\n\n\n

These\ndrugs are less likely to cause\nextrapyramidal symptoms<\/em><\/strong>. <\/em><\/p>\n\n\n\n

However, most of these agents (except ziprasidone and aripiprazole) <\/em>can result in weight gain, hyperlipidemia<\/strong> and new-onset diabetes mellitus.<\/strong><\/p>\n\n\n\n

Tolerance\nand dependence<\/strong><\/p>\n\n\n\n

Tolerance to the sedative and hypotensive actions develops within days or\nweeks, but maintenance doses for therapeutic effect in most psychotics remain\nfairly unchanged over the years, despite increased DA turnover in the brain. <\/p>\n\n\n\n

The antipsychotic, extrapyramidal and other actions based on DA\nantagonism do not display tolerance.<\/p>\n\n\n\n

Neuroleptics are hedonically (pertaining to pleasure) bland drugs, lack\nreinforcing effect so that chronic recipients do not exhibit drug-seeking\nbehavior. Physical dependence is probably absent. <\/p>\n\n\n\n

Individual\nDrugs<\/strong><\/p>\n\n\n\n

\u2022 Thioridazine:\n<\/strong><\/p>\n\n\n\n

  • It has the least incidence of extrapyramidal\nsymptoms among typical antipsychotic <\/em>drugs due to low potency D2 blocking\naction and the presence of central anticholinergic activity.<\/li>
  • It interferes with male sexual\nfunction by inhibiting ejaculation <\/em>(due to \u03b1 blocking action)<\/li>
  • It can cause cardiac arrhythmia\n(Prolongation of QT interval).<\/li>
  • Retinal damage <\/em>limits\nlong term administration.<\/li><\/ul>\n\n\n\n

    Trifluoperazine,\nfluphenazine, and haloperidol<\/strong><\/p>\n\n\n\n

    • These are high potency drugs and have the\nleast <\/em>\u03b1 blocking, anticholinergic, sedative and proconvulsant actions<\/em>.\nHowever, extrapyramidal symptoms are marked.<\/li><\/ul>\n\n\n\n

      \u2022 Penfluridol\n<\/strong>is the longest acting <\/em>antipsychotic drug.<\/p>\n\n\n\n

      \u2022 Pimozide\n<\/strong>selectively blocks D2 receptors without affecting \u03b1 and muscarinic receptors. It also\npossesses a long duration of action. It carries the risk of arrhythmias due to QT\nprolongation.<\/em><\/p>\n\n\n\n

      \u2022 Clozapine<\/strong><\/p>\n\n\n\n

      • an atypical antipsychotic <\/em>drug\nhaving weak D2 blocking action. <\/li>
      • mainly\nacts by blocking 5-HT2, alpha-adrenergic\nand D4 receptors. <\/li>
      • suppresses\nboth positive as well as negative symptoms <\/em>(First\nFDA approved drug for antisuicide indication<\/em>) of schizophrenia. <\/li>
      • It\nis used only as a reserve drug due to the risk of precipitation of seizures <\/em>(even\nin non-epileptics) and agranulocytosis<\/strong> \u00e0 weekly\nmonitoring of leucocyte count required. <\/li>
      • Convulsions are dose-dependent adverse\neffect seen only in high doses whereas agranulocytosis is independent of dose. <\/strong><\/li>
      • Because of association with myocarditis<\/strong>,\nclozapine is contraindicated in patients with severe heart disease<\/em>. <\/li>
      • It\nhas powerful anticholinergic effects (equivalent to chlorpromazine and\nthioridazine). <\/li>
      • Metabolic\ncomplication like weight gain, hyperlipidemia, and precipitation of diabetes is\nanother major limitation. <\/em><\/li>
      • The risk of extrapyramidal symptoms\nis least <\/em>with the use of this drug. <\/li>
      • It\nspecifically has two risks of intestinal dysfunction; potentially severe\nileus and sialorrhea.<\/em><\/li><\/ul>\n\n\n\n

        \u2022 Risperidone<\/strong>:\n<\/p>\n\n\n\n

        • It acts by blocking 5-HT2, \u03b1 adrenergic and D2 receptors. <\/li>
        • A\nmore potent D2 blocker than clozapine and can cause extrapyramidal symptoms at a\nhigh dose. <\/li>
        • The\nrisk of precipitation of seizures is less than clozapine. <\/li>
        • Hyperprolactinemia <\/strong>has\nbeen reported more commonly with risperidone than other atypical antipsychotics.\n<\/li>
        • Its active metabolite (paliperidone)\nhas a lesser risk of causing metabolic adverse effects.<\/li><\/ul>\n\n\n\n

          \u2022 Olanzapine<\/strong>:\n<\/p>\n\n\n\n

          • It has a similar mode of action as\nrisperidone. <\/li>
          • It is also a potent anticholinergic drug\nand can cause dry mouth and constipation. <\/li>
          • can\ncause seizures and weight gain<\/em>. <\/li>
          • Apart from its use in schizophrenia,\nit is also used in acute mania and bipolar disorder<\/em>.<\/strong>\n<\/li>
          • It has been associated with a significantly\nhigher risk of stroke and death <\/strong>in elderly patients.<\/li><\/ul>\n\n\n\n

            \u2022 Ziprasidone<\/strong>:\n<\/p>\n\n\n\n

            • It causes QT prolongation <\/em>and\ncarries the risk of arrhythmias. <\/li>
            • Unlike other atypical antipsychotics,\nit is not associated with weight gain,\nhyperlipidemia or diabetes.<\/strong><\/li><\/ul>\n\n\n\n

              \u2022 Quetiapine:\n<\/strong>Can cause cataract formation. <\/em>It has the shortest half-life.<\/em><\/p>\n\n\n\n

              \u2022 Aripiprazole:\n<\/strong><\/p>\n\n\n\n

              • Acts as a partial agonist at 5-HT1A\nand D2 receptors, and antagonist at 5-HT2A receptors. <\/li>
              • It is also known as dopamine- serotonin stabilizer<\/em>. <\/strong><\/li>
              • It has quite a long half-life. <\/li>
              • It\nhas also been approved for the treatment\nof irritability associated with autistic disorders in children.<\/em><\/strong><\/li><\/ul>\n\n\n\n

                \u2022 Asenapine\n<\/strong>is used sublingually <\/strong>for schizophrenia and acute mania.<\/p>\n\n\n\n

                \u2022 Iloperidone\n<\/strong>has less risk of extrapyramidal adverse effects but causes orthostatic hypotension\nand can prolong QT interval.<\/p>\n\n\n\n

                Adverse\nEffects<\/strong><\/p>\n\n\n\n

                1. CNS <\/strong><\/li>
                2. Drowsiness, lethargy, mental confusion; more with\nlow potency typical antipsychotics Sedation<\/strong>\n(maximum with chlorpromazine) and some\natypical ones like quetiapine and clozapine. <\/li>
                3. Tolerance to sedative effects may develop. <\/li>
                4. Other side effects are increased appetite and weight\ngain (not with haloperidol<\/strong>); aggravation of seizures in epileptics; even\nnonepileptics may develop seizures with high doses of some antipsychotics like\nclozapine and occasionally olanzapine. <\/li>
                5. All atypical antipsychotics may result\nin weight gain, hyperlipidemia and new-onset diabetes <\/strong>except\nziprasidone<\/em>.<\/li>
                6. However high potency, phenothiazines, risperidone,\nquetiapine aripiprazole, and ziprasidone have little effect on seizure threshold.<\/li><\/ol>\n\n\n\n

                  According to their potential to cause adverse metabolic side effects<\/strong>, anti-psychotics can be classified as:<\/p>\n\n\n\n

                  \"\"<\/figure><\/div>\n\n\n\n
                  • CVS<\/strong>\n<\/li>
                  • Postural\nhypotension, palpitation, inhibition of ejaculation (especially with\nthioridazine) are due to \u03b1 adrenergic blockade<\/strong>; more\ncommon with low potency phenothiazines.<\/li>
                  • Q-T prolongation and cardiac\narrhythmias \u00e0\nrisk of overdose with thioridazine, pimozide, and ziprasidone. <\/li><\/ul>\n\n\n\n
                    • Anticholinergic <\/strong><\/li>
                    • Dry mouth, blurring of vision,\nconstipation, urinary hesitancy in elderly males (thioridazine has the highest\npropensity); absent in high potency agents. <\/li>
                    • Some like clozapine induces hypersalivation\ndespite anticholinergic property, probably due to central action.<\/li><\/ul>\n\n\n\n
                      • Endocrine<\/strong>\n<\/li>
                      • Hyperprolactinemia (due to D2 blockade)\nis common with typical neuroleptics and risperidone. <\/li>
                      • amenorrhoea, infertility,\ngalactorrhoea, and gynecomastia occur infrequently after prolonged treatment. <\/li>
                      • The atypical antipsychotics, except\nrisperidone, do not appreciably raise prolactin levels.<\/li><\/ul>\n\n\n\n
                        • Metabolic\neffects<\/strong> <\/li>
                        • Elevation of blood sugar and\ntriglyceride levels as a consequence of chronic therapy with certain\nantipsychotics is a major concern now. <\/li>
                        • Low potency phenothiazines (CPZ,\nthioridazine) and some atypical antipsychotics, particularly olanzapine and\nclozapine have a high risk of precipitating diabetes or worsening it. <\/li>
                        • High potency drugs like trifluoperazine,\nfluphenazine, haloperidol and atypical antipsychotics like risperidone,\naripiprazole and ziprasidone have low\/no risk. <\/li>
                        • The mechanism of this effect is not\nclear; maybe due to weight gain and\/or accentuation of insulin resistance.<\/li><\/ul>\n\n\n\n
                          • Extrapyramidal\ndisturbances<\/strong> <\/li>
                          • major dose-limiting side effects; more\nprominent with high potency drugs like fluphenazine, haloperidol, pimozide,\netc., <\/li>
                          • least with thioridazine, clozapine,\nand all other atypical antipsychotics, except a higher dose of risperidone. The\nextrapyramidal effects may be categorized into:<\/li><\/ul>\n\n\n\n

                            (a) Parkinsonism with typical\nmanifestations\u2014<\/strong><\/p>\n\n\n\n

                            • rigidity, tremor, hypokinesia, mask-like\nfacies, shuffling gait<\/li>
                            • appears between 1\u20134 weeks of therapy\nand persists unless the dose is reduced.<\/li>
                            • If that is not possible, one of the\nanticholinergic antiparkinsonian drugs may be given concurrently.<\/li>
                            • Changing the antipsychotic, especially\nto an atypical agent, may help. <\/li>
                            • Though quite effective, a routine\ncombination of the anticholinergic from the start of therapy in all cases is\nnot justified, because they tend to worsen memory and impair intellect, in\naddition to dry mouth and urinary retention. <\/li>
                            • Amantadine is an alternative. <\/li>
                            • A rare form of extrapyramidal side\neffect is perioral tremors \u2018rabbit\nsyndrome\u2019<\/strong> that generally occurs after a few years of therapy \u00e0 often\nresponds to central anticholinergic drugs.<\/li><\/ul>\n\n\n\n

                              (b) Acute muscular dystonias<\/strong>\n<\/p>\n\n\n\n

                              • Bizarre muscle spasms, mostly\ninvolving linguo-facial muscles \u2014grimacing, tongue thrusting, torticollis,\nlocked jaw; occurs within a few hours of a single dose or at the most in the\nfirst week of therapy. <\/li>
                              • It is more common in children below 10\nyears and in girls, particularly after parenteral administration; overall\nincidence is 2%. <\/li>
                              • It lasts for one to a few hours and\nthen resolves spontaneously.<\/li><\/ul>\n\n\n\n

                                (c) Akathisia<\/strong>\n<\/p>\n\n\n\n

                                • Restlessness, feeling of discomfort, apparent\nagitation manifested as a compelling desire to move about, but without anxiety<\/li>
                                • seen in some patients between 1\u20138\nweeks of therapy: up to 20% incidence. <\/li>
                                • maybe mistaken for exacerbation of\npsychosis. <\/li>
                                • A central anticholinergic may reduce\nthe intensity in some cases, but a benzodiazepine like clonazepam or diazepam\nis the first choice treatment of motor restlessness. <\/li>
                                • Propranolol is more effective; may be given\nto non-responsive cases.<\/li>
                                • Most patients respond to a reduction\nin dose of the neuroleptic or changeover to an atypical antipsychotic like\nquetiapine.<\/li><\/ul>\n\n\n\n

                                  (d) Malignant neuroleptic syndrome<\/strong>\n<\/p>\n\n\n\n

                                  • It occurs rarely with high doses of\npotent agents.<\/li>
                                  • the patient develops marked rigidity,\nimmobility, tremor, hyperthermia, semiconsciousness, fluctuating BP and heart\nrate; myoglobin may be present in the blood. <\/li>
                                  • The syndrome lasts 5\u201310 days after\ndrug withdrawal and may be fatal. <\/li>
                                  • The neuroleptic must be stopped\npromptly and symptomatic treatment instituted. <\/li>
                                  • Intravenous dantrolene may benefit.<\/li><\/ul>\n\n\n\n

                                    (e) Tardive dyskinesia<\/strong>\n<\/p>\n\n\n\n

                                    • occurs late in therapy, sometimes even\nafter withdrawal of the neuroleptic: manifests as purposeless involuntary facial\nand limb movements like constant chewing, pouting, puffing of cheeks, lip\nlicking, choreoathetoid movements.<\/li>
                                    • more common in elderly women, and is a\nmanifestation of progressive neuronal degeneration along with supersensitivity\nto DA. <\/li>
                                    • An incidence of 10\u201320% has been\nreported after long term treatment. <\/li><\/ul>\n\n\n\n
                                      • Miscellaneous<\/strong>\n<\/li>
                                      • Weight gain often occurs due to\nlong-term antipsychotic therapy, <\/li>
                                      • sugar and lipids may tend to rise. <\/li>
                                      • Blue pigmentation of exposed skin,\ncorneal and lenticular opacities, retinal\ndegeneration (more with thioridazine)<\/strong><\/li>
                                      • Hypersensitivity\nreactions<\/strong> <\/li>
                                      • Cholestatic jaundice with portal\ninfiltration; 2\u20134% incidence; occurs between 2\u20134 weeks of starting therapy \u00e0 More common with low potency phenothiazines<\/strong>;\nrare with haloperidol.<\/li>
                                      • Skin rashes, urticaria, contact dermatitis,\nphotosensitivity (more with CPZ).<\/li>
                                      • Agranulocytosis is rare; more common\nwith clozapine.<\/li>
                                      • Myocarditis Few cases have occurred\nwith clozapine.<\/li>
                                      • Cataract formation with\nquetiapine.<\/li><\/ul>\n\n\n\n

                                        Other\nUses<\/strong><\/p>\n\n\n\n

                                        \u2022\nThese agents can be used as an alternative to ECT in severe depression with\npsychotic features.<\/em><\/p>\n\n\n\n

                                        \u2022\nAlcoholic hallucinosis.<\/p>\n\n\n\n

                                        \u2022\nGilles de la Tourette\u2019s syndrome and Huntington\u2019s disease (Haloperidol is the\ndrug of choice<\/em>).<\/p>\n\n\n\n

                                        Note:<\/strong><\/p>\n\n\n\n

                                        1.\nHaloperidol and fluphenazine <\/strong>are the most potent typical <\/strong>antipsychotic\ndrugs whereas risperidone is the most potent atypical antipsychotic agent<\/strong>.<\/p>\n\n\n\n

                                        2.\nThe risk of extrapyramidal adverse effects is negligible with clozapine,\nquetiapine, and aripiprazole.<\/p>\n\n\n\n

                                        3.\nChlorpromazine, thioridazine, and clozapine <\/strong>possess the strongest\nanticholinergic <\/strong>activity.<\/p>\n\n\n\n

                                        4.\nFluphenazine <\/strong>(enanthate and decanoate) and haloperidol <\/strong>(decanoate)\nare long-acting injectable <\/strong>(s.c. or i.m) forms of typical\nantipsychotics. <\/p>\n\n\n\n

                                        Risperidone\n<\/strong>is the first atypical antipsychotic available <\/em>in\nlong-acting injectable <\/strong>form.<\/p>\n\n\n\n

                                        5. The most\ncommonly used antipsychotic by the intravenous route is haloperidol. <\/strong>l Nervous System<\/strong><\/p>\n\n\n\n

                                        6.\nZiprasidone, aripiprazole, asenapine, and iloperidone <\/strong>has negligible\nrisk to cause metabolic adverse effects <\/em>(weight gain, hyperlipidemia, and\nnew-onset diabetes mellitus)<\/p>\n\n\n\n

                                        7. Asenapine, paliperidone, and ziprasidone <\/strong>have\nthe greatest potential to prolong the QT interval<\/em>.<\/p>\n","protected":false},"excerpt":{"rendered":"

                                        Drugs for Psychiatric Illness Two major types of psychiatric disorders are psychosis and neurosis. Psychosis: The patient is not aware of his illness (insight is absent) and refuses to take treatment. It includes major psychosis like schizophrenia as well as mood disorders (like mania, depression and bipolar disorder). Neurosis: It is less serious and insight[…]\n","protected":false},"author":3,"featured_media":157,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/155"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=155"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/155\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media\/157"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=155"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=155"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=155"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}