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Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
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Antipsychotic : Dr Rahul Kunkulol's Power point preparations

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Dr Rahul Kunkulol's Power point preparations

Dr Rahul Kunkulol's Power point preparations

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  1. DRUG TREATMENT OF PSYCHOSIS
  2. Psychiatric Nosology (Classification of disease) • Psychosis • Cognitive disorders: confusion, disorientation, memory disturbances and behavioral disorganization (delirium and dementia) • Mood disorders • Anxiety disorders • Personality disorders
  3. Psychosis • Psychosis is a thought disorder characterized by : • Disturbances of reality and perception • Impaired cognitive functioning • Inappropriate or diminished affect (mood) • Psychosis denotes many mental disorders.  Schizophrenia is a particular kind of psychosis characterized mainly by a clear sensorium but a marked thinking disturbance.
  4. Schizophrenia • Pathogenesis is unknown. • Onset of schizophrenia is in the late teens early twenties. • Genetic predisposition -- Familial incidence. • Multiple genes are involved. • Afflicts 1% of the population worldwide. • May or may not be present with anatomical changes.
  5. Schizophrenia • It is a thought disorder. • The disorder is characterized by a divorcement from reality in the mind of the person (psychosis). • It may involved visual and auditory hallucinations, delusions, intense suspicion, feelings of persecution or control by external forces (paranoia), depersonalization, and there is attachment of excessive personal significance to daily events, called “ideas of reference”.
  6. Schizophrenia Positive Symptoms. Hallucinations, delusions, paranoia, ideas of reference. Negative Symptoms. Apathy, social withdrawal, anhedonia (Loss of the capacity to experience pleasure), emotional blunting, cognitive deficits, extreme inattentiveness or lack of motivation to interact with the environment. These symptoms are progressive and non-responsive to medication.
  7. Etiology of Schizophrenia Idiopathic Biological Correlates 1) Genetic Factors 2) Neurodevelopmental abnormalities. 3) Environmental stressors.
  8. Psychosis Producing Drugs 1) Levodopa 2) CNS stimulants a) Cocaine b) Amphetamines c) Khat, cathinone, methcathinone 3) Apomorphine 4) Phencyclidine
  9. Dopamine Theory of Schizophrenia Many lines of evidence point to the aberrant increased activity of the dopaminergic system as being critical in the symptomatology of schizophrenia.
  10. Dopamine Theory of Schizophrenia Dopamine Correlates: • Antipsychotics reduce dopamine synaptic activity. • These drugs produce Parkinson-like symptoms. • Drugs that increase DA in the limbic system cause psychosis. • Drugs that reduce DA in the limbic system (postsynaptic D2 antagonists) reduce psychosis. • Increased DA receptor density (Post-mortem, PET). • Changes in amount of homovanillic acid (HVA), a DA metabolite, in plasma, urine, and CSF.
  11. Dopamine Theory of Schizophrenia Evidence against the hypothesis • Antipsychotics are only partially effective in most (70%) and ineffective for some patients. • Phencyclidine, an NMDA receptor antagonist, produces more schizophrenia-like symptoms in non- schizophrenic subjects than DA agonists. • Atypical antipsychotics have low affinity for D2 receptors. • Focus is broader now and research is geared to produce drugs with less extrapyramidal effects.
  12. Dopamine System There are four major pathways for the dopaminergic system in the brain: I. The Nigro-Stiatal Pathway: Voluntary movements II. The Mesolimbic Pathway.: Behaviour III. The Mesocortical Pathway: Behaviour IV. The Tuberoinfundibular Pathway: Prolactin release
  13. THE DOPAMINERGIC SYSTEM •THE DOPAMINERGIC SYSTEM
  14. Catecholamines Tyrosine  Tyrosine hydroxylase L-Dopa  Dopa decarboxylase Dopamine (DA)  Dopamine  hydroxylase Norepinephrine (NE) (Noradrenaline) Phenylethanolamine-  -N-methyltransferase Epinephrine (EPI) (Adrenaline)
  15. Dopamine Synapse DA L-DOPA Tyrosine Tyrosine
  16. Dopamine System • DOPAMINE RECEPTORS There are at least five subtypes of receptors: Receptor D1 D2 D3 D4 D5
  17. Dopamine Reuptake System
  18. Antipsychotic treatments SCHIZOPHRENIA IS FOR LIFE There is no remission
  19. Antipsychotic treatments Schizophrenia has been around perhaps, since the beginning of humankind, however, it was not until the last century that it was established as a separate entity amongst other mental disorders. Many treatments have been devise:  Hydrotherapy: “The pouring of cold water in a stream, from a height of at least four feet onto the forehead, is one of the most certain means of subsiding violent, maniacal excitement that we have ever seen tried”... wrote an anonymous physician in the early 1800’s.
  20. Antipsychotics treatment Antipsychotics/Neuroleptics • Antipsychotics are the drugs currently used in the prevention of psychosis. • They have also been termed neuroleptics, because they suppress motor activity and emotionality. ** These drugs are not a cure ** • Schizophrenics must be treated with medications indefinitely, in as much as the disease is lifelong and it is preferable to prevent the psychotic episodes than to treat them.
  21. Antipsychotics/Neuroleptics Although the antipsychotic/neuroleptics are drugs used mainly in the treatment of schizophrenia, they are also used in the treatment of : – Psychoses associated with depression – Manic-depressive illness – Psychosis associated with alzheimer’s disease. These conditions are life-long and disabling.
  22. Antipsychotics/Neuroleptics NON-compliance is the major reason for relapse.
  23. Antipsychotic/Neuroleptics Three major groups : 1. Phenothiazines 2. Thioxanthine 3. Butyrophenones OLDER DRUGS
  24. Antipsychotic/Neuroleptics 1) Phenothiazines Chlorpromazine Thioridazine Fluphenazine Trifluopromazine Piperacetazine Perfenazine Mesoridazine Acetophenazine Carphenazine Prochlorperazine Trifluoperazine • Aliphatic Piperidine Piperazine* * Most likely to cause extrapyramidal effects.
  25. Antipsychotic/Neuroleptics 2) Thioxanthines Thiothixene Chlorprothixene Closely related to phenothiazines
  26. Antipsychotic/Neuroleptics 3) Butyrophenones Haloperidol Droperidol* *Not marketed in the USA
  27. Atypical Antipsychotic Pimozide Atypical Antipsychoitcs Loxapine Clozapine Olanzapine Qetiapine Indolones Sertindole Ziprasidone Olindone Molindone Risperidone
  28. Antipsychotics/Neuroleptics • Old antipsychotics /neuroleptics are D2 dopamine receptor antagonists. Although they are also effective antagonists at ACh, 5-HT, NE receptors. Dopamine Synapse DA L-DOPA Tyrosine Tyrosine dopamine receptor antagonist D2
  29. Antipsychotics/Neuroleptics • It appears that the specific interaction of antipsychotic drugs with D2 receptors is important to their therapeutic action. • The affinities of most older “classical” agents for the D2 receptors correlate with their clinical potencies as antipsychotics.
  30. Antipsychotics/Neuroleptics • Both D1 and D2 receptors are found in high concentrations in the striatum and the nucleus accumbens. • Clozapine has a higher affinity for the D4 receptors than for D2. • Recently it has been found that most antipsychotic drugs may also bind D3 receptors (therefore, they are non-selective).
  31. Antipsychotics/Neuroleptics • Antipsychotics produce catalepsy (reduce motor activity). – BLOCKADE OF DOPAMINE RECPTORS IN BASAL GANGLIA. • Antipsychotics reverse hyperkinetic behaviors (increased locomotion and stereotyped behavior). – BLOCKADE OF DOPAMINE RECPTORS IN LIMBIC AREAS. • Antipsychotics prevent the dopamine inhibition of prolactin release from pituitary. – BLOCKADE OF DOPAMINE RECEPTORS IN PITUITARY.  hyperprolactinemia
  32. Antipsychotic/Neuroleptics [Drug dose] Piperazine Aliphatic Piperidine
  33. Antipsychotic/Neuroleptics [Drug dose] Phenothiazine d. Thioxanthene d. Butyrophenone d.
  34. Antipsychotics/Neuroleptics • Newer drugs have higher affinities for D1, 5- HT or -AR receptors. • NE, GABA, Glycine and Glutamate have also been implicated in schizophrenia.
  35. Antipsychotics/Neuroleptics The acute effects of antipsychotics do not explain why their therapeutic effects are not evident until 4-8 weeks of treatment. Blockade of D2 receptors  Short term/Compensatory effects:  Firing rate and activity of nigrostriatal and mesolimbic DA neurons.  DA synthesis, DA metabolism, DA release
  36. Antipsychotics/Neuroleptics Presynaptic Effects Blockade of D2 receptors  Compensatory Effects  Firing rate and activity of nigrostriatal and mesolimbic DA neurons.  DA synthesis, DA metabolism, DA release. Postsynaptic Effects Depolarization Blockade Inactivation of nigrostriatal and mesolimbic DA neurons.  Receptor Supersensitivity
  37. Antipsychotic/Neuroleptics Clinical Problems with antipsychotic drugs include: 1) Failure to control negative effect 2) Significant toxicity a) Neurological effects b) Autonomic effects c) Endocrine effects d) Cardiac effects 3) Poor Concentration
  38. Neurological effects • Acute dystonia- Spasms of muscles of tongue, neck and face • Akasthisia – Uncontrolled motor restlessness • Parkinsonism • Neuroleptic Mallignant Syndrome • Rabbit syndrome (perioral tremors) • Tardive dyskinesia Piperazines Butyrophenones
  39. Acute dystonia
  40. Tardive Dyskinesia (TD) • Repetitive involuntary movements, lips, jaw, and tongue • Choreiform quick movements of the extremities • As with Parkinson’s, movements stop during sleep • No effective treatment
  41. The Nigro-Striatal Pathway Inhibition of Motor Activity DA neuron ACh neuron GABA neuron GABA neuron Substantia Nigra + - - - - Striatum
  42. Antipsychotic/Neuroleptics  Some antipsychotics have effects at muscarinic acetylcholine receptors: • Dry mouth • Blurred vision • Urinary retention • Constipation Clozapine Chlorpromazine Thioridazine
  43. Antipsychotic/Neuroleptics  Some antipsychotics have effects at - adrenergic receptors: • orthostatic hypotension Chlorpromazine Thioridazine  Some antipsychotics have effects at H1- histaminergic receptors: • sedation Risperidone Haloperidol
  44. Antipsychotic/Neuroleptics  Blockade of D2 receptors in lactotrophs in breast increase prolactin concentration and may produce breast engorgement and galactorrhea.
  45. Blood Dyscrasias • Clozapine 1-3 % incidence agranulocytosis • Monitor WBC weekly – WBC < 3,000 hold tx, check for infection – Restart when reach 3,500 – WBC < 2,000 discontinue treatment, do not rechallange
  46. Antipsychotic/Neuroleptics Neuroleptic Malignant Syndrome Is a rare but serious side effect of neuroleptic (antipsychotic) therapy that can be lethal. It can arise at any time in the course of treatment and shows no predilection for age, duration of treatment, antipsychotic medication, or dose.
  47. Antipsychotic/Neuroleptics Neuroleptic Malignant Syndrome • Occurs in pts. hypersensitive to the Ex.Py. effects of antipsychotics. • Due to excessively rapid blockade of postsynaptic dopamine receptors. • The syndrome begins with marked muscle rigidity. • If sweating is impaired, a fever may ensue. The stress leukocytosis and high fever associated with this syndrome may be mistaken for an infection. • Autonomic instability with altered blood pressure and heart rate is another midbrain manifestation. • Creatine kinase isozymes are usually elevated, reflecting muscle damage.
  48. Antipsychotic/Neuroleptics Neuroleptic Malignant Syndrome Treatment Vigorous treatment with antiparkinsonian drugs is recommended as soon as possible. Muscle relaxants such as diazepam, dantrolene or bromocriptine may be helpful.
  49. XVI. Anti-Manic Drugs Lithium (Li+) remains the drug of choice for the treatment and prophylaxis of mania. • Acute manic episodes are managed with lithium salts (carbonate or citrate) alone, or in combination with: 1) Antipsychotics (carbamazepine, similar in structure to TCAs but not effective in depression). 2) Valproic acid 3) Calcium-channel blockers (nifendipine, diltiazem, verapamil).
  50. XVI. Anti-Manic Drugs Li+ • Helps alleviate the depressive phase of bipolar illness. • Useful in refractory depression when added to SSRIs or TCAs, but not a good antidepressant alone.
  51. XVI. Anti-Manic Drugs Li+ Mechanism of action: • Does not alter receptor numbers but alters the coupling of the receptors with their second messengers by reducing coupling of G-proteins. • Regulation of -AR and DAR. • Can reduce release of NTs (5-HT) and affinity of binding to receptor.
  52. XVI. Anti-Manic Drugs Li+ Mechanism of action (Con’t): Inhibits breakdown of IP2 to IP1 (during PIP hydrolysis) => depletion of DAG and IP3 and  [Ca2+] in response to receptor activation (i.e. from 5-HT2R, 1-AR, muscarinic receptors and others). • Alterations in adenylate cyclase and phospholipase C.
  53. XVI. Anti-Manic Drugs PIP PIP2 G IP3 IP2 IP1 InositolPI X Li+ PLC DAG Ca 2+

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