antipsychotics presentation
Post on 26-Jul-2015
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Dopamine pathways relevant to antipsychotic pharmacology in the treatment of schizophrenia are: Mesolimbic pathway Mesocortical pathway Nigrostriatal pathway Tuberoinfundibular pathway By blocking these pathways, antipsychotics can produce both therapeutic and adverse effects.
Mesolimbic Pathway
This is relevant to positive symptoms of schizophrenia (delusion and hallucination)Anatomy: it is made up of projections from the ventral tegmental area (VTA) to the nucleus accumbens.Physiology: it is the centre for motivation, emotions, pleasure, compulsion.Implication: D2 antagonism reduces positive symptoms of schizophrenia
Mesocortical Pathway
Anatomy: This tract is made up of dopaminergic neurons that projects from the VTA to the pre-frontal cortex.
Physiology: it is relevant to the physiology of cognition, negative symptoms, emotions and affects.
Implications: Hypofunction of this pathway might be related to cognitive and negative symptoms of schizophrenia
Nigrostriatal Pathway
This tract contains about 80% of the brain’s dopamineAnatomy: It projects from the substantia nigra to basal ganglia.
Physiology: It plays a key role in regulating movements.
Implication: D2 antagonism of this tract induces extrapyramidal symptoms (pseudo-parkinsonism, akathisia, acute dystonia) and Tardive dyskinesia (abnormal writhing movement of the tongue, face and body).
Tuberoinfundibular Pathway
This pathway influences prolactin release.
Anatomy: This tract projects from the hypothalamus to the anterior pituitary.
Physiology: Dopamine tonically inhibits prolactin
Implication: D2 antagonism increases prolactin level
Psychosis
Psychosis is a thought disorder characterized by disturbances of reality and perception, impaired cognitive functioning, and 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.
Substances that can induce psychotic symptom
These includes;AlcoholCannabis (Marijuana)CocaineAmphetamines L. dopa
Schizophrenia• It is a thought disorder.• The disorder is characterized by a
divorcement from reality in the mind of the person (psychosis).
• 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
Symptoms
Positive Symptoms :Hallucinations, delusions, paranoia, excited motor behaviour.
Negative Symptoms :Slow thought or speech, social withdrawal, emotional blunting, cognitive deficits, extreme inattentiveness or lack of motivation to interact with the environment.
Antipsychotic Medications (APMs)
Used to treat manifestations of psychosis and other psychiatry disorders
Precise mechanism of action is unknown, however APMs blocks several populations of dopamine (D2, D4) receptors in the brain.
The newer APMs also block serotonin (5-HT2) receptors, a property that may be associated with increased efficacy.
APMs also variably blocks central and peripheral cholinergic, histamine and alpha receptors
Classification of antipsychotic drugs
• PHARMACOLOGICAL CLASSIFICATION
– FIRST-GENERATION ANTIPSYCHOTIC (low potency) • Chlorpromazine • Prochlorperazine • Thioridazine
– FIRST-GENERATION ANTIPSYCHOTIC (high potency)• Fluphenazine (Modecate)• Haloperidol (Haldol)• Pimozide• Thiothixene • Zuclopenthixol (Clopixol)
– SECOND GENERATION ANTIPSYCHOTIC • Aripiprazole • Asenapine • Clozapine • Iloperidone • Lurasidone • Olanzapine • Quetiapine • Paliperidone • Risperidone • Ziprasidone
Division of APMs based on receptor blockade
There are three (3) main groups; Pure D2 antagonist: Typical APMs (low and
high potency). D2-5HT2 antagonist: Risperidone Multireceptor antagonist:
a. Clozapine - D2, D4, 5HT2b. Olanzapine - D2, D4, 5HT2c. Quetiapine - D2, D4, 5HT2d. Ziprasidone - D2, D4, 5HT2e. Aripiprazole - D2, D4, 5HT2
Typical versus Atypical APMs
Typical• Older agents• Dopamine effects• Many side effects• Treatment of
positive symptoms
Atypical• Newer agents• Dopamine and
serotonin effects• Fewer side effects• Treatment of
positive and negative symptoms
Indications for APMs
Psychomotor agitationSchizophreniaOther psychotic disorders – delusional,
brief psychotic, schizophreniform, schizoaffective, substance-induced psychotic disorders
Mood disorders – useful for the treatment of agitation and psychosis during mood episode.
General Adverse effects of APMsWeight gain (olanzapine)
Sedation – due to antihistamine activityHypotension – effect is due to alpha
adrenergic blockade. It is most common with low potency APMs
Anticholinergic symptoms – dry mouth, blurred vision, urinary retention, constipation, etc
Endocrine effects – gynecomastia, galactorrhea, amenorrhea, due to blockade of tuberoinfundibular tract
Hematological problems such as agranulocytosis with atypical APMs (clozapine as the most problematic agent).
Neurologic effects
Pseudoparkinsonism: It is characterized by muscle rigidity, shuffling gait, masklike facial expression, resting tremor.
Acute dystonia: Prolonged muscle spasm. More common in men younger than 40yrs. It may mimic seizure
Akathisia: Subjective feeling of motor restlessness.
Tardive dyskinesia: A disorder that involves involuntary, repetitive movements of the muscles of the tongue, face and body. You treat with low potency or atypical APMs.
Neuroleptic malignant syndrome: A rare but potentially life-threatening reaction to APMs. It causes fever, muscular rigidity, altered mental status, excessive sweating, salivation, increased BP and pulse rate. It is treated by stopping the agent and providing medical support.
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