Antipsychotics

Agenda:

• Introduction

• History of the family

• Disease Defination

• Types of Antipsychotics

• Mechanism of Action

• Kinetic Properties

• Conditions it treat

• Clinical use

• Dose and Adminestration

• Interactions

• Side Effect

• When to call the doctor

• Monographs

Introduction: 

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder.

While some research has shown that use of any antipsychotic is associated with smaller brain tissue volumes, including white matter reduction and that this reduction is dose dependent and time dependent, schizophrenia is itself a neurodegenerative disorder associated with reduced brain tissue volumes.

A more recent controlled trial suggests that second generation antipsychotics combined with intensive psychosocial therapy  may potentially prevent pallidal brain volume loss.

History of Antipsychotics:

The “psychopharmacological revolution” of the 1950-70's yielded the development of a number compounds, such as haloperidol, fluphenazine, loxapine and thioridazine, that were termed first generation “typical” antipsychotics. In 1966, a simple two page document suggested that because chlorpromazine and haloperidol were antagonists of amphetamine and that the hyperlocomotor activity effect of amphetamines was “…probably induced by the activation of dopamine receptors in the brain,” it was possible that dopamine receptor blockade was a mechanism of action of antipsychotic drugs.

What is psychosis?

Psychosis isn’t a medical condition. It’s a collection of symptoms that indicate your brain isn’t processing certain kinds of information as it should. The symptoms all involve a disconnection from reality. The main symptoms are hallucinations and delusions. It can also involve disorganized thoughts and actions, or dampen how you show emotions.

Are there different types of antipsychotics?

There are two main types of antipsychotic medications:

First-generation antipsychotics. Also known as “typical antipsychotics,” these drugs were the first types of medications developed for treating psychosis. Most aren’t commonly used for treating psychosis now. 

Second-generation antipsychotics. Also known as “atypical antipsychotics,” these are now the main drugs for treating psychosis. That’s mostly because they have fewer side effects.

Mechanism of Action:

All antipsychotics have some degree of antagonism at D2 receptors. First-generation antipsychotics (FGAs) produce antipsychotic effects at 60% to 80% D2 occupancy. Second-generation antipsychotics (SGAs) like risperidone exhibit their therapeutic effects through some D2 blockade, but more from the blockade of serotonin receptors like 5HT2A. Second-generation antipsychotics have loose binding to D2 receptors and can quickly dissociate from the receptor, potentially accounting for the lower likelihood of causing extrapyramidal symptoms (EPS).

Moreover, second-generation antipsychotics have agonism at the 5HT1A receptor. Serotonin and norepinephrine reuptake inhibition are potential mechanisms by which risperidone is postulated to produce antidepressant effects. The improvement of positive symptoms is thought to be accomplished through the blockade of D2 receptors, specifically in the mesolimbic pathway. The ability of antipsychotics to block D2 receptors in the prefrontal cortex and nucleus accumbens is important in improving certain psychiatric symptoms. Of note, risperidone does not cause anticholinergic effects, which may benefit patients in certain populations, including the elderly with dementia.

Kinetic Properties:

Antipsychotic drugs (neuroleptics) are candidates for plasma concentration monitoring, but not all agents have the same potential in this respect. The present review analyses the available data on the kinetics and metabolism of fluphenazine, perphenazine, thiothixene, flupenthixol, clopenthixol, haloperidol, pimozide, penfluridol, sulpiride and clozapine. Although some of the drugs described in this review have been in use for many years, knowledge of their pharmacokinetics is still only approximate. This is primarily because determination in biological fluids is not always feasible. Accordingly, analytical methods useful for pharmacokinetic studies or plasma concentration monitoring of these antipsychotic drugs are discussed. With the exception of sulpiride, all the neuroleptics reviewed share some basic pharmacokinetic properties: good gastrointestinal absorption but reduced systemic availability because of hepatic first-pass metabolism, high hepatic clearance and a large apparent volume of distribution leading to an apparent elimination half-life of about 24 hours for most of these compounds. The renal elimination is negligible and it seems that these drugs do not possess active metabolites. The pharmacokinetic properties of antipsychotic drugs are important for the inclusion of a set of drugs in a psychiatric institution where there is a possibility of drug concentration monitoring. In addition, the availability of a depot preparation is of importance. These factors are discussed in view of the experience made during the last years in the University Psychiatric Institutions of Geneva.

What conditions do antipsychotics treat?

Antipsychotics treat conditions that cause or involve psychosis. Those include:

• Schizophrenia (and its related spectrum of disorders, including schizoaffective disorder and schizophreniform disorder)

• Bipolar disorder

• Mania

• Major depressive disorder with psychotic features

• Delusional disorder

• Severe agitation

• Borderline personality disorder

• Dementia

• Delirium

• Substance-induced psychotic disorder

Providers may treat other conditions with antipsychotics, but those drugs aren’t their main treatment. These conditions include:

• Tourette syndrome

• Huntington’s disease

• Parkinson’s disease

• Lesch-Nyhan syndrome

• Obsessive-compulsive disorder

Clinical use :

Typical antipsychotics block the dopamine 2 receptor (D2) receptor, causing a tranquilizing effect.  It is thought that 60–80% of D2 receptors need to be occupied for antipsychotic effect. For reference, the typical antipsychotic haloperidol tends to block about 80% of D2 receptors at doses ranging from 2 to 5 mg per day. On the aggregate level, no typical antipsychotic is more effective than any other, though people will vary in which antipsychotic they prefer to take based on individual differences in tolerability and effectiveness. Typical antipsychotics can be used to treat, e.g., schizophrenia or severe agitation. Haloperidol, due to the availability of a rapid-acting injectable formulation and decades of use, remains the most commonly used antipsychotic for treating severe agitation in the emergency department setting.

Interactions:

Drug-Drug interaction:

• Blood pressure medicines.ACE inhibitors, beta-blockers, calcium channel blockers, and other blood pressure drugs can interact with antipsychotics. Together, they may make your heartbeat in an abnormal rhythm or lower your blood pressure too much.

• Heart rhythm drugs. Doctors may prescribe medicines such as amiodarone (Cordarone), disopyramide (Norpace), and sotalol (Betapace) to treat an abnormal heart rhythm. But when you take them with antipsychotic drugs, these medicines can cause even more serious heart rhythm problems.

• Mood stabilizers and anti-seizure medicines. Medicines such as carbamazepine (Tegretol), phenytoin (Dilantin), and valproate (Depakote) can alter blood levels of antipsychotic medications.

• Parkinson's drugs. Taking levodopa (Sinemet) or other medications to treat Parkinson's disease with an antipsychotic can make both drugs less effective. This interaction could bring abnormal muscle movements and make your schizophrenia symptoms worse.

• Avoid alcohol. Alcohol may potentiate CNS adverse effects and orthostatic hypotension.

• Take with or without food. The absorption of antipsychotic drug is unaffected by food.

Drug-Food interaction:

• Alcohol. Antipsychotic medicines already cause drowsiness as a side effect. Drinking alcohol with your medicine can make you extra sleepy.

• Caffeine. Coffee and other caffeinated drinks and foods like chocolate can raise the amount of Clozaril in your blood. This could lead to more side effects.

• Grapefruit. This fruit and its juice can dangerously raise blood levels of some antipsychotic drugs such as lurasidone (Latuda), quetiapine (Seroquel), and ziprasidone (Geodon).

• Nicotine: Smoking can decrease levels of medicines for schizophrenia which are active in your body. Let your doctor know if you smoke or use nicotine.

Side Effect:

Antipsychotics are useful, but there are possible drawbacks. Antipsychotic medications can have various side effects and complications, including:

Drug-induced movement disorders:

•  First-generation and second-generation antipsychotics can cause an inability to hold still (akathisia) or uncontrolled face muscle movements (tardive dyskinesia). Other symptoms include tremors or parkinsonism-like symptoms. They can also cause neuroleptic malignant syndrome, a possibly deadly complication. 

Scientists developed second-generation antipsychotics to avoid that side effect.

Heart and circulatory problems:

• Antipsychotic drugs may alter your heart rhythm. They can also cause orthostatic hypotension, which is a blood pressure drop when you stand or sit up quickly that can make you fall or pass out.

Metabolism effects.:

•  Antipsychotic drugs can cause high cholesterol (hyperlipidemia) and high blood sugar (hyperglycemia). They can also increase your risk of developing Type 2 diabetes.

• Dizziness and sedation. All antipsychotics can have a sedative effect, meaning they make you tired. They can also cause dizziness, increasing your risk of falls and injuries.

Immune disruption:

•  Some antipsychotics can cause agranulocytosis, a dangerous condition that involves a weakening of your immune system.

Jaundice:

• This is when your skin and the whites of your eyes (sclera) turn yellow because of a problem in your liver.

Other less serious side effects can include:

• Weight gain.

• Dry mouth.

• Constipation.

• Urinary retention.

When To Call the Doctor

When should I call my healthcare provider?

Antipsychotics may cause serious side effects or complications for some people. Your healthcare provider can tell you which symptoms to watch for and what you should do if you notice them.

In general, you should call your healthcare provider as soon as possible if you notice any of the following symptoms:

• Shaking or tremors

• Uncontrolled face movements

• Yellowing of your skin or whites of your eyes

Symptoms of neuroleptic malignant syndrome, including:

•  high fever

• rigid or stiff muscles

•  confusion or unusual/unexpected changes in mental status

Antipsychotics treat mental health conditions that can greatly increase the risk of self-harm, suicidal thoughts and behaviors, or violent behavior toward others.

Monographs :

 For more information about antipsychotics drugs see our monographs now by the buttons below: