Antipsychotics
Antipsychotics are a type of psychiatric medication which are available on prescription to treat psychosis.
Anti psychotic drugs are psychiatric drugs used in treatment of mental disorders that are characterized by disturbance of reality and perception, impaired cognitive functioning, and diminished mood
They are licensed to treat certain types of mental health problem whose symptoms include psychotic experiences.
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, mainly schizophrenia but also in a range of other psychotic disorders such as manic states with psychotic symptoms
They are also used together with mood stabilizers in the treatment of bipolar disorder, and they are also used in management of other psychosis associated with depression and manic depressive illness and psychosis associated with Alzheimer’s disease.
Introduction to Psychosis
The term psychosis refers to a variety of mental disorders characterized by one or more of the following symptoms:
- Diminished and distorted capacity to process information and draw logical conclusions
- Hallucinations, usually auditory or visual, but sometimes tactile or olfactory
- Delusions (false believes)
- Incoherence or marked loosening of associations
- Catatonic or disorganized behavior
- Aggression or violence
Antipsychotic drugs lessen these symptoms regardless of the underlying cause or causes ;
Conditions characterized with psychosis include
- schizophrenia,
- mania,
- bipolar disorder,
- schizoaffective disorder,
- depression,
- alcohol withdraw syndrome,
- and delirium.
Factors that may lead to psychosis.
- Genetic factors
- Alcoholism
- Brain tumor
- Brain injures
- Central nervous system stimulants eg cocaine.
Psychosis-Producing Drugs
- Levodopa
- CNS stimulants like
- Cocaine
- Amphetamines
- Khat, cathinone, methcathinone
3. Apomorphine ,Phencyclidine
Neurotransmitters
- Excitatory: dopamine, adrenaline, nor adrenaline, serotonin (5-HT-5-hydroxy tryptamine)
- Inhibitory: Gama Amino Butyric acid (GABA)
SCHIZOPHRENIA
Schizophrenia is a chronic mental disorder (psychotic) characterized by disordered thinking and loss of touch with reality.
In other words, it is a mental disorder characterized by;
- change in personality leading to inability to relate to others ,
- disturbed mood ,
- impaired appreciation and interpretation of environment
The onset of symptoms usually occurs during adolescence and early adulthood.
Schizophrenia is thought to be caused by excessive release of dopamine which leads to over stimulation of the brain cells resulting into abnormal behavior.
DOPAMINE
- it’s a neurotransmitter found in brain
Effects of Dopamine
- Dopamine (DA) plays a critical role in initiation of movement.
- Controls reinforcement and cognitive function.
- Regulates prolactin release
- Plays a major role in vomiting
- Regulates temperature
- Reduces appetite
Signs and symptoms
Symptoms of schizophrenia are classified into two namely positive symptoms (due to distorted function) and negative symptoms (due to diminished function).
Positive and negative symptoms of schizophrenia
Positive symptoms | Negative symptoms |
Hallucinations( Hearing voices, seeing things) | Social withdrawal |
Delusions( False belief) | Emotional withdrawal |
Disorganized speech | Lack of motivation |
Agitations | Poverty of speech |
Flat mood | |
Poor self – care |
- The positive symptons are due to stimulation. If you want to reduce these effects you would use a depressant drug which would worsen the negative symptoms.
- The negative symptoms are due to depression. If you want to treat them, we would use a stimulant drug which would potentiate the positive symptoms.
- The clinical phenotype varies greatly, particularly with respect to the balance between negative and positive symptoms
- The positive symptoms are associated with increase in Dopamine pathway activation whereas the negative symptoms are associated with a decrease in serotonin pathway activation.
Key path ways affected by dopamine in the Brain.
- Meso-cortical: – projects from the brain stem to the cerebral cortex. This path way is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise. Problem here for a psychotic patient, is too little dopamine.
- Meso-limbic: – projects from the dopaminergic cell bodies in the ventral tegmentum (brain stem) to the limbic system. This pathway is where the positive symptoms come from (hallucinations, delusions and thought disorders). Problem here in a psychotic patient, there is too much dopamine.
- Nigro striatal: – projects from dopaminergic cell bodies in the substantia nigra to the basal ganglia. This pathway is involved in movement regulation. Remember that dopamine suppresses acetylcholine activity. Dopamine hypo activity: can cause parkinsonian movements i.e. rigidity, brady kinesia, tremors, akathisia and dystonia
- Tuberoinfundibular: projects from the hypothalamus to the anterior pituitary. Remember that the dopamine release inhibits or regulates prolactin release. Blocking dopamine in this way will predispose your patient to hyper prolactinemia (gynecomastia/galactorrhea/decreased libido/ menstrual dysfunction).
General mechanisms of action antipsychotics
- Blocking the action of dopamine receptors and path ways. Some scientists believe that some psychotic experiences are caused by the brain producing too much of a chemical called dopamine. Dopamine is a neurotransmitter, which passes messages around the brain. Most antipsychotic drugs are known to block some of the dopamine receptors in the brain.
- This reduces the flow of these messages, which can help to reduce psychotic symptoms. By blocking these pathways antipsychotics can produce both therapeutic and adverse effects.
Blockade of dopamine and /or 5HT2 receptors in mesolimbic system.
Blockade of 5HT2 receptor (like the α2 receptors in ANS), which allows constant release of serotonin.
Many of these agents also block cholinergic, adrenergic, and histaminergic receptors. The undesirable side effects of these agents are often a result of actions at these other receptors
Absorption and Distribution
- Most antipsychotics are readily but incompletely absorbed.
- Significant first-pass metabolism.
- Bioavailability is 25-65%.
- Most are highly lipid soluble.
- Most are highly protein bound (92-98%).
- High volumes of distribution (>7 L/Kg).
- Slow elimination.
**Duration of action longer than expected, metabolites are present and relapse occurs, weeks after discontinuation of drug.**
Metabolism
- Most antipsychotics are almost completely metabolized.
- Most have active metabolites, although not important in therapeutic effect, with one exception. The metabolite of thioridazine, mesoridazine, is more potent than the parent compound and accounts for most of the therapeutic effect.
Excretion
• Antipsychotics are almost completely metabolized and thus, very little is eliminated unchanged. Elimination half-life is 10-24 hrs.