antipsychotic drugs joseph de soto md, phd, faic

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  • Slide 1
  • Antipsychotic Drugs Joseph De Soto MD, PhD, FAIC
  • Slide 2
  • Schizophrenia Schizophrenia is a mental disorder characterized by abnormal social behavior and failure to recognize what is real. Common symptoms include false beliefs, unclear or confused thinking, auditory hallucinations, reduced social engagement and emotional expression, and lack of motivation. Symptoms begin typically in young adulthood, and about 0.30.7% of people are affected during their lifetime. The disorder is thought to mainly affect the ability to think, but it also usually contributes to chronic problems with behavior and emotion. People with schizophrenia are likely to have additional conditions, including major depression and anxiety disorders.
  • Slide 3
  • Positive & Negative Symptoms Schizophrenia can be described in terms of positive and negative symptoms. Positive symptoms are those that most individuals do not normally experience but are present in people with schizophrenia. They can include delusions, disordered thoughts and speech, and tactile, auditory, visual, olfactory and gustatory hallucinations, typically regarded as manifestations of psychosis. Negative symptoms are deficits of normal emotional responses or of other thought processes, and are less responsive to medication. They commonly include flat expressions or little emotion, poverty of speech, inability to experience pleasure, lack of desire to form relationships, and lack of motivation.
  • Slide 4
  • Antipsychotic Drugs First Generation The first generation antipsychotic drugs exert their antipsychotic effects by blocking the D2 receptor. The first generation drugs are good against the positive symptoms of psychosis but not the negative symptoms. Among the stronger first generation antipsychotics are: Haloperidol, Fluphenazine, Loxapine, Thiothixene, Prochlorperazine and Perphenazine. Among the weaker first generation antipsychotics are: Chlorpromazine and Thioridazine (discontinued).
  • Slide 5
  • Extrapyramidal Symptoms First generation antipsychotics are more likely to be associated with movement disorders known as extrapyramidal symptoms. The strong first generation antipsychotics are more likely to have extrapyramidal symptoms than the The extrapyramidal symptoms include: 1) Dystonia (continuous spasms and muscle contractions) 2) Akathisia (motor restlessness, inability to sit still), 3) Parkinsonism (characteristic symptoms such as rigidity, bradykinesia, and tremor), and 4) Tardive Dyskinesia (irregular, jerky movements). A fifth disorder which is not considered extrapyramidal but is associated with antipsychotics is malignant hyperthermia.
  • Slide 6
  • Antipsychotic Drugs Second Generation The second generation antipsychotics also know as atypical antipsychotics have a much lower incidence of extrapyramidal side effects. These drug however may effect the metabolism. In addition, these medications work on the negative symptoms of psychosis which are thought to be mediated by serotonin in addition to the positive symptoms. Some of the atypicals are: Aripiprazole, Risperidone, Ziprasidone, Quetiapine, Clozapine, Olanzapine and Asenapine.
  • Slide 7
  • Mechanism of Action All of the first generation and most of the second generation antipsychotics block the D2 receptor limiting the positive symptoms of psychosis. D2 blockage in the mesolimbic system is most important. Most of the second generation antipsychotic medications which are useful against the negative symptoms mediate this effect through blocking the 5-HT2A receptors of the mesocortical system. Depending on the particular medication other receptors may be blocked such as the muscarinic receptor, -adrenergic receptor and the histamine receptor. We can take advantage of this for specific comorbidities or conditions. For instance, the weak first generation antipsychotics bind the muscarinic receptors and hence are particularly useful for sedation of agitated psychotic patients.
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  • Selected First Generation Antipsychotics Haloperidol: is a typical antipsychotic medication. It is used in the treatment of schizophrenia, acute psychosis, mania, delirium, Tourette syndrome, choreas, agitation and severe anxiety. A long- acting form called haloperidol decanoate is used as an injection every four weeks in people with schizophrenia or related illnesses who either forget or refuse to take the oral form. Side Effects: Severe extrapyramidal side effects. Hypotension or hypertension, sedation, Anticholinergic side effects such as ; dry mouth, constipation, paralytic ileus, difficulties in urinating, decreased perspiration. Overdose: Coma in severe cases, accompanied by respiratory depression and massive hypotension, shock
  • Slide 10
  • Selected First Generation Antipsychotics Chlorpromazine: is a dopamine antagonist of the typical anti- psychotic class of medications possessing additional anti-adrenergic, anti-serotonergic, anti-cholinergic and anti-histaminergic properties used to treat schizophrenia. Clinically it is used to treat: acute and chronic psychoses, the manic phase of bipolar disorder, as well as amphetamine-induced psychoses. Side effects: Extrapyramidal movement disorders, sedation, weight gain. The drug should never be discontinued suddenly, as this will induce agitation, sleeplessness, states of anxiety, stomach pain, dizziness, nausea and vomiting.
  • Slide 11
  • Acute Dystonia Dystonia may occur with the first dose of antipsychotic medication. It is associated with a mutation of the D2 receptor. In most cases, dystonia tends to lead to abnormal posturing, in particular on movement. Many sufferers have continuous pain, cramping, and relentless muscle spasms due to involuntary muscle movements. Dystonia is often initiated or worsened by voluntary movements. Diphenhydramine, and benzatropine can be used to treat this disorder.
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  • Akathisia Akathisia a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet, inability to keep still, inability to sit or keep still, complaints of restlessness, fidgeting, and rocking from foot to foot. Akathisia may begin during the course of therapy and is usually but not always reversible
  • Slide 14
  • Tardive Dyskinesia Tardive Dyskinesia is a disorder resulting in involuntary, repetitive body movements. In this form of dyskinesia, the involuntary movements are tardive, meaning they have a slow or belated onset. This neurological disorder most frequently occurs as the result of long-term or high-dose use of antipsychotic drugs. The symptoms may include lip smacking, grimacing, lip puckering, lip smacking. Often these side effects are often misconstrued as indicating that the patient is mentally ill due to them. Tardive dyskinesia is often irreversible.
  • Slide 15
  • Parkinsonism Is characterized by tremor, bradykinesia, rigidity, and postural instability. However, unlike Parkinsons disease drug induced Parkinsonism does not progress. In about 25% f the patients the condition is permanent. Benadryl, benztropine, amantadine have been used to limit the symptoms of Parkinsonism.
  • Slide 16
  • Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome is a non-extrapyramidal life- threatening neurological disorder caused by an adverse reaction to antipsychotic drugs. typically consists of muscle rigidity, fever, autonomic instability, and cognitive changes such as delirium, and is associated with elevated plasma creatine phosphokinase. The criteria are as follows: Increased body temperature >38C (>100.4F), or Confused or altered consciousness Diaphoresis "sweat shock" Rigid muscles Autonomic imbalance
  • Slide 17
  • Treatment of Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome is a medical emergency, and can lead to death if untreated. The first step is to stop the antipsychotic medication and treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Dantrolene has been used when needed to reduce muscle rigidity, bromocriptine has been shown to help. Amantadine is another treatment option due to its dopaminergic and anticholinergic effects.
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  • Selected Atypical Antipsychotics Aripiprazole - is used in the treatment of schizophrenia, schizoaffective disorder and bipolar disorder. It is also an add-on treatment in major depressive disorder, tic disorders, and irritability associated with autism. Side effects include: serious: neuroleptic malignant syndrome, tardive dyskinesia, and hyperglycemia. Other: weight gain, headache, agitation, anxiety, insomnia, nausea, constipation, and lightheadedness In the elderly there is an increased risk of death. It is thus not recommended for use in those with psychosis due to dementia.
  • Slide 20
  • Selected Atypical Antipsychotics Clozapine: is an atypical antipsychotic medication used in the treatment of schizophrenia, and is also sometimes used off- label for the treatment of bipolar disorder and borderline personality disorder. This medication is a drug of last resort due to the side effects: including agranulocytosis, seizures, and myocarditis. Additionally, it also often causes less serious side effects such as hypersalivation and weight gain.
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