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Antipsychotic drugs

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  • 1. Anti-Psychotic DrugsAnti-Psychotic Drugs
  • 2. OverviewOverview  Anti-psychotic drugs-alsoAnti-psychotic drugs-also  known as neuroleptic drugsknown as neuroleptic drugs  anti-schizophrenic drugsanti-schizophrenic drugs  major tranquillizersmajor tranquillizers  Dopamine receptor antagonistsDopamine receptor antagonists  May also act on other targets, particularly 5-May also act on other targets, particularly 5- hydroxytryptamine (5-HT) receptorshydroxytryptamine (5-HT) receptors
  • 3. Types of schizophreniaTypes of schizophrenia TypesTypes PresentationPresentation CatatonicCatatonic Marked psychomotor disturbances. The patient mayMarked psychomotor disturbances. The patient may demonstrate rigidity, immobility, or posturing and may also bedemonstrate rigidity, immobility, or posturing and may also be withdrawn and silent. At the other extreme is characteristicwithdrawn and silent. At the other extreme is characteristic excitement such as pacing and shouting. Fluctuations betweenexcitement such as pacing and shouting. Fluctuations between these two extremes may occur.these two extremes may occur. DisorganizedDisorganized Marked incoherence with inappropriate responses orMarked incoherence with inappropriate responses or unresponsiveness. Delusions or hallucinations are disorganizedunresponsiveness. Delusions or hallucinations are disorganized and fragmented. The patient may giggle, grimace, and act in anand fragmented. The patient may giggle, grimace, and act in an incongruous or silly manner. Hypochondriacal behavior may beincongruous or silly manner. Hypochondriacal behavior may be presentpresent ParanoidParanoid Most prominent characteristics are delusions of grandeur orMost prominent characteristics are delusions of grandeur or persecution, during which the patient may be extremely anxious,persecution, during which the patient may be extremely anxious, aggressive, and/or argumentative.aggressive, and/or argumentative.
  • 4. Type of schizophreniaType of schizophrenia TypesTypes PresentationPresentation ResidualResidual The patient is not currently acutely psychotic, but has aThe patient is not currently acutely psychotic, but has a history of at least one acute psychotic break and currentlyhistory of at least one acute psychotic break and currently experiences residual symptoms such as vague associations,experiences residual symptoms such as vague associations, illogical thinking, withdrawal, or inappropriate affect. Livingillogical thinking, withdrawal, or inappropriate affect. Living skills may be impaired.skills may be impaired. UndifferentiatedUndifferentiated May incorporate prominent delusions, hallucinations,May incorporate prominent delusions, hallucinations, incoherence, or grossly disorganized behavior. But overall,incoherence, or grossly disorganized behavior. But overall, clinical presentation either does not meet the criteria for oneclinical presentation either does not meet the criteria for one of the specific types or meets the criteria for more than oneof the specific types or meets the criteria for more than one type of schizophrinea.type of schizophrinea.
  • 5. Positive and negative symptoms of schizophreniaPositive and negative symptoms of schizophrenia HallucinationsHallucinations Affective flatteningAffective flattening DelusionsDelusions AlogiaAlogia Thought disordersThought disorders ApathyApathy Disorganized speechDisorganized speech AmotivationAmotivation Bizarre behaviorBizarre behavior AnhedoniaAnhedonia insomniainsomnia Asocial behaviorAsocial behavior CombativenessCombativeness InattentivenessInattentiveness
  • 6. Delusions and HallucinationsDelusions and Hallucinations Psychotic symptomPsychotic symptom DelusionDelusion HallucinationHallucination DefinitionDefinition Belief not based onBelief not based on fact or realityfact or reality Perception disturbancePerception disturbance in sensory experiencesin sensory experiences of the environmentof the environment TypesTypes GrandioseGrandiose ReligiousReligious SomaticSomatic NihilisticNihilistic SexualSexual PersecutoryPersecutory AuditoryAuditory VisualVisual OlfactoryOlfactory TactileTactile
  • 7. Mechanism of Action of Anti-Mechanism of Action of Anti- psychotic Drugspsychotic Drugs  Antagonists at dopamine D2 receptorsAntagonists at dopamine D2 receptors  Also block other monoamine receptors,Also block other monoamine receptors, especially 5-HT2.especially 5-HT2.  Clozapine also blocks D4-receptors.Clozapine also blocks D4-receptors.  Anti-psychotic potency generally runs parallel toAnti-psychotic potency generally runs parallel to activity on D2-receptorsactivity on D2-receptors  Anti-psychotics take days or weeks to work,Anti-psychotics take days or weeks to work, suggesting that secondary effectssuggesting that secondary effects  (e.g. increase in number of D2-receptors in limbic(e.g. increase in number of D2-receptors in limbic structure) may be more important than direct effect ofstructure) may be more important than direct effect of D2-receptor block.D2-receptor block.
  • 8. Clinical Efficacy ofClinical Efficacy of Anti-psychotic DrugsAnti-psychotic Drugs Effective in controlling symptoms of acuteEffective in controlling symptoms of acute schizophreniaschizophrenia Long-term treatment is often effective inLong-term treatment is often effective in preventing recurrence of schizophrenicpreventing recurrence of schizophrenic attacksattacks this is a major factor in allowing schizophrenicthis is a major factor in allowing schizophrenic patients to lead normal lives.patients to lead normal lives. Not generally effective in improvingNot generally effective in improving negative schizophrenic symptomsnegative schizophrenic symptoms
  • 9. TYPICAL vs ATYPICALTYPICAL vs ATYPICAL TYPICAL ATYPICAL Haloperidol, chlorpromazine, thioridazine Thiothixene Fluphenazine Prochloroperazine Risperidone Clozapine Olanzapine Quietiapine ziprasidone Blocks D2 receptors Blocks D2 and 5-HT2 (risperidone) Blocks D1 and 5-HT2 (clozapine) Treats positive symptoms only Treats both positive and negative symptoms Causes movement disorders Little or no movement disorders
  • 10. Atypical Anti-psychoticsAtypical Anti-psychotics  RisperidoneRisperidone  11stst line agent fewer movement disorders than any of theline agent fewer movement disorders than any of the typical agentstypical agents  Higher doses cause movement disordersHigher doses cause movement disorders  OlanzapineOlanzapine  11stst line agent fewer movement disorders than any of theline agent fewer movement disorders than any of the typical agentstypical agents  QuetiapineQuetiapine  11stst line agent fewer movement disorders than any of theline agent fewer movement disorders than any of the typical agentstypical agents  ClozapineClozapine  Last line of choiceLast line of choice  May result to idiosyncratic granulosisMay result to idiosyncratic granulosis  No movement disorders but has marked anti-cholinergicNo movement disorders but has marked anti-cholinergic effectseffects
  • 11. Typical Anti-psychoticsTypical Anti-psychotics  High PotencyHigh Potency  HaloperidolHaloperidol  minimal anti-cholinergic but major movementminimal anti-cholinergic but major movement disordersdisorders  Has a depot for prolonged intramuscular dosingHas a depot for prolonged intramuscular dosing  ThiothixeneThiothixene  minimal anti-cholinergic but major movementminimal anti-cholinergic but major movement disordersdisorders  FluphenazineFluphenazine  minimal anti-cholinergic but major movementminimal anti-cholinergic but major movement disordersdisorders  Has a depot for prolonged intramuscular dosingHas a depot for prolonged intramuscular dosing  ProchloroperazineProchloroperazine  Principally used as anti-emeticPrincipally used as anti-emetic
  • 12. Typical Anti-psychoticsTypical Anti-psychotics Low PotencyLow Potency ChlorpromazineChlorpromazine Highly sedatingHighly sedating ThioridazineThioridazine minimal movement effects, non-sedatingminimal movement effects, non-sedating Alpha receptor antagonist- hypotensionAlpha receptor antagonist- hypotension Less tendency for epsLess tendency for eps
  • 13. LOW vs HIGH POTENCYLOW vs HIGH POTENCY Low Potency High Potency Chlorpromazine, thioridazine, clozapine Haloperidol, fluphenazine Sedation, orthostatic hypotension, anticholinergic effects Extrapyramidal symptoms
  • 14. Antipsychotic-induced MotorAntipsychotic-induced Motor DisturbancesDisturbances  Acute dystoniaAcute dystonia  4hrs to 4 days4hrs to 4 days  Sustained muscle spasm anywhere in the bodySustained muscle spasm anywhere in the body  Tx: Diphenhydramine,benztropine,trihexyphenidyl,Tx: Diphenhydramine,benztropine,trihexyphenidyl, amantadineamantadine  ParkinsonismParkinsonism  4 days – 4 mo.4 days – 4 mo.  Resting tremorResting tremor  Tx: benztropine ,anticholinergicTx: benztropine ,anticholinergic  Tradive dyskinesiaTradive dyskinesia  Involuntary movement of lips, head limbs tongue andInvoluntary movement of lips, head limbs tongue and trunktrunk  4mo-4yr4mo-4yr  Typically irreversible once sets inTypically irreversible once sets in  AkathisiaAkathisia  Restlessness, getting up and sitting downRestlessness, getting up and sitting down  Tx: lower medication dose,BB,BZ, anticholinergicsTx: lower medication dose,BB,BZ, anticholinergics  Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome  Life-threatening muscle rigidity, feverLife-threatening muscle rigidity, fever  Tx: cool patient, hydrate with IV fluidsTx: cool patient, hydrate with IV fluids  Dantrolene,bromocriptine, amantadineDantrolene,bromocriptine, amantadine
  • 15. Pharmacotheraphy for TDPharmacotheraphy for TD  ReserpineReserpine  BenzodiazepinesBenzodiazepines  BaclofenBaclofen  Valproic acid and derivativesValproic acid and derivatives  Vitamin EVitamin E
  • 16. Adverse effects by receptor affinitiesAdverse effects by receptor affinities Receptor antagonizedReceptor antagonized Adverse effectAdverse effect Histamine (H)Histamine (H) SedationSedation Serotonin (5-HT)Serotonin (5-HT) Weight gainWeight gain Dopamine (D)Dopamine (D) Extrapyramidal symptomsExtrapyramidal symptoms hyperprolactinemiahyperprolactinemia Muscarinic (M)Muscarinic (M) Anticholinergic effectsAnticholinergic effects Cognitive/memory impairmentCognitive/memory impairment TachycardiaTachycardia Alpha (Alpha (αα)) Orthostatic hypotensionOrthostatic hypotension Reflex tachycardiaReflex tachycardia
  • 17. Unwanted Effects ofUnwanted Effects of Anti-psychotic DrugsAnti-psychotic Drugs  Side-effects (dry mouth, blurred vision,Side-effects (dry mouth, blurred vision, hypotension, etc.)hypotension, etc.)  result from blockade of other receptorsresult from blockade of other receptors  α-adrenoceptors and muscarinic acetylcholineα-adrenoceptors and muscarinic acetylcholine receptors.receptors.  Obstructive jaundice may occur withObstructive jaundice may occur with phenothiazines.phenothiazines.  Cause agranulocytosis as a rare and seriousCause agranulocytosis as a rare and serious idiosyncratic reaction.idiosyncratic reaction.  With clozapine, leucopenia is common andWith clozapine, leucopenia is common and requires routine monitoring.requires routine monitoring.
  • 18. OTHER ADVERSE EFFECTS: Agranulocytosis- clozapine, chlorpromazine Pigmentary retinopathy- thioridazine ECG changes- prolonged QT interval- ziprasidone
  • 19. Other uses of antipsychotics: Antiemetic (blocks dopamine receptors)- prochlorperazine Intractable hiccups- chlorpromazine Pruritus (antihistamine)- promethazine (Zinmet, Thaprozine)
  • 20. CHEMICAL CLASSESCHEMICAL CLASSES PhenothiazinesPhenothiazines Aliphatic- chlorpromazineAliphatic- chlorpromazine Piperazine- fluphenazinePiperazine- fluphenazine Piperidine- thioridazinePiperidine- thioridazine Thioxanthenes- thiothixeneThioxanthenes- thiothixene Butyrophenones- haloperidolButyrophenones- haloperidol Dihydroindolines- molindoneDihydroindolines- molindone Diphenylbutylpiperidines- pimozideDiphenylbutylpiperidines- pimozide

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