anti psychotic pharma

8/2/2019 Anti Psychotic Pharma

1/4

Antipsychotic An antipsychotic (or neuroleptic) is a tranquilizing psychiatric medication primarily used to

manage psychosis (including delusions or hallucinations, as well as disordered thought), particularly

in schizophrenia and bipolar disorder.

Mechanism of actionAll antipsychotic drugs tend to block D2 receptors in the dopamine pathways of the brain. This

means that dopamine released in these pathways has less effect. Excess release of dopamine in

the mesolimbic pathway has been linked to psychotic experiences. It is the blockade of dopamine

receptors in this pathway that is thought to control psychotic experiences.

Structural effects

Many studies now indicate that chronic treatment with antipsychotics affects the brain at a

structural level, for example increasing the volume of the basal ganglia (especially the caudate

nucleus), and reducing cortical grey matter volume in different brain areas. The effects may differ for

typical versus atypical antipsychotics and may interact with different stages of disorders. Death

of neurons in the cerebral cortex, especially in women, has been linked to the use of both typical andatypical antipsychotics for individuals withAlzheimers.Side effects

Antipsychotics are associated with a range of side effects. It is well-recognized that many

people stop taking them (around two-thirds even in controlled drug trials) due in part to adverse

effects. Extrapyramidal reactions include acute dystonias, akathisia,parkinsonism (rigidityand tremor), tardive dyskinesia, tachycardia, hypotension, impotence, lethargy, seizures, intense

dreams or nightmares, and hyperprolactinaemia. Side effects from antipsychotics can be managed by

a number of different drugs. For example,anticholinergics are often used to alleviate the motor side

effects of antipsychotics. Some of the side-effects will appear after the drug has been used only for a

long time.

Following are details concerning some of the side effects of antipsychotics:

Antipsychotics, particularly atypicals, appear to cause diabetes mellitus and fatal diabetic

ketoacidosis, especially (in US studies) inAfrican Americans.

Antipsychotics may cause pancreatitis.

The atypical antipsychotics (especially olanzapine and clozapine) seem to (due to occupancy of

the histamine receptor) cause weight gain more commonly than the typical antipsychotics. The

well-documented metabolic side effects associated with weight gain include diabetes, which can

be life-threatening.

Antipsychotics increase the likelihood of a fatal heart attack, with the risk of death increasing with

dose and the length of time on the drug. Clozapine also has a risk of inducing agranulocytosis, a potentially dangerous reduction in the

number of white blood cells in the body. Because of this risk, patients prescribed clozapine may

need to have regular blood checks to catch the condition early if it does occur, so the patient is in

no danger.

One of the more serious of these side effects is tardive dyskinesia, in which the sufferer may

show repetitive, involuntary, purposeless movements (that are permanent and have no cure)

often of the lips, face, legs, or torso. It is believed that there is a greater risk of developing tardive


2/4

dyskinesia with the older, typical antipsychotic drugs, although the newer antipsychotics are now

also known to cause this disorder.

A potentially serious side effect of many antipsychotics is that they tend to lower an individual's

seizure threshold. Chlorpromazine and clozapine, in particular, have a relatively high seizurogenic

potential. Fluphenazine, haloperidol, pimozide and risperidone exhibit a relatively low risk.

Caution should be exercised in individuals that have a history of seizurogenic conditions such

as epilepsy, orbrain damage.

Neuroleptic malignant syndrome, in which the drugs appear to cause the temperature regulation

centers to fail, resulting in a medical emergency, as the patient's temperature suddenly increases

to dangerous levels.

Dysphoria.

Drug-induced parkinsonism due to dopamine D2 receptor blockade may

mimic idiopathic parkinsonism. The typical antipsychotics are more prone to cause this, compared

to the atypical antipsychotics.

Sexual dysfunction, which may rarely continue after withdrawal, similar to Post-SSRI sexual

dysfunction (PSSD).

Dystonia, a neurological movement disorder in which sustained muscle contractions cause

twisting and repetitive movements or abnormal postures.

Hyperprolactinaemia. The breasts may enlarge and discharge milk, in both men and women due

to abnormally-high levels of prolactinin the blood. Prolactin secretion in the pituitary is normally

suppressed by dopamine. Drugs that block the effects of dopamine at the pituitary or deplete

dopamine stores in the brain may cause the pituitary to secrete prolactin.

There is evidence that exposure may cause demyelinating disease in laboratory animals.

Following controversy over possible increased mortality (death) related to antipsychotics in

individuals with dementia, warnings have been added to packaging.

Some people suffer few apparent side effects from taking antipsychotic medication, whereas others

may have serious adverse effects. Some side effects, such as subtle cognitive problems, may go

unnoticed.

There is a possibility that the risk of tardive dyskinesia can be reduced by combining the anti-

psychotics with diphenhydramine orbenzatropine, although this remains to be established. Central

nervous system damage is also associated with irreversible tardive akathisia and/or tardive

dysphrenia.

Common antipsychotics

Commonly used antipsychotic medications are listed below by drug group. Trade names appear in

parentheses.

First generation antipsychoticsMain article: Typical antipsychotic

Butyrophenones

Main article: Butyrophenones

Haloperidol (Haldol, Serenace)

Droperidol (Droleptan)


3/4

Phenothiazines

Main article: Phenothiazines

Chlorpromazine (Thorazine, Largactil)

Fluphenazine (Prolixin) - Available in decanoate (long-acting) form

Perphenazine (Trilafon) Prochlorperazine (Compazine)

Thioridazine (Mellaril, Melleril)

Trifluoperazine (Stelazine)

Promazine

Triflupromazine (Vesprin)

Levomepromazine (Nozinan)

Promethazine (Phenergan)

Thioxanthenes

Main article: Thioxanthenes

Chlorprothixene (Cloxan, Taractan, Truxal)

Clopenthixol (Sordinol)

Flupenthixol (Depixol, Fluanxol)

Thiothixene (Navane)

Zuclopenthixol (Cisordinol, Clopixol, Acuphase)

Second generation antipsychotics

Main article: Atypical antipsychotic

Clozapine (Clozaril) - Requires weekly to biweekly complete blood count due to risk

of agranulocytosis. Olanzapine (Zyprexa) - Used to treat psychotic disorders including schizophrenia,

acute manic episodes, and maintenance of bipolar disorder

Risperidone (Risperdal) -Divided dosing is recommended until initial t itration is completed, at

which time the drug can be administered once daily. Used off-label to treat Tourette

syndrome and anxiety disorder.

Quetiapine (Seroquel) - Used primarily to treat bipolar disorder and schizophrenia, and "off-label"

to treat chronic insomnia andrestless legs syndrome; it is a powerful sedative.

Ziprasidone (Geodon) - Approved in 2004 to treat bipolar disorder. Side-effects include a

prolonged QT interval in the heart, which can be dangerous for patients with heart disease or

those taking other drugs that prolong the QT interval.

Amisulpride (Solian) - Selective dopamine antagonist. Higher doses (greater than 400 mg) actupon post-synaptic dopamine receptors resulting in a reduction in the positive symptoms of

schizophrenia, such as psychosis. Lower doses, however, act upon dopamine autoreceptors,

resulting in increased dopamine transmission, improving the negative symptoms of schizophrenia.

Lower doses of amisulpride have also been shown to have antidepressant and anxiolytic effects

in non-schizophrenic patients, leading to its use in dysthymia and social phobias. Amisulpride has

not been approved for use by the Food and Drug Administration in the United States.

Asenapine (Saphris) is a 5-HT2A- and D2-receptor antagonist under development for the

treatment of schizophrenia and acute mania associated with bipolar disorder.


4/4

Paliperidone (Invega) - Derivative of risperidone that was approved in 2006.

Iloperidone (Fanapt) - Approved by the FDA on May 6, 2009.

Zotepine (Nipolept, Losizopilon, Lodopin, Setous)- An atypical antipsychotic indicated for acute

and chronic schizophrenia. It was approved in Japan circa 1982 and Germany in 1990.

Sertindole (Serdolect, and Serlect in Mexico). Sertindole was developed by the Danish

pharmaceutical company H. Lundbeck. Like the other atypical antipsychotics, it is believed to

have antagonist activity at dopamine and serotonin receptors in the brain.

Lurasidone (Latuda), a recently FDA approved once daily antipsychotic with a favorable efficacy

and safety profile.

Third generation antipsychotics

Aripiprazole (Abilify) - Mechanism of action is thought to reduce susceptibility to metabolic

symptoms seen in some other atypical antipsychotics. The extent to which these effects differ

from other atypical antipsychotics is debated.

Partial agonists of dopamine.

Other options

Cannabidiol is one of the main components of Cannabis sativa. Cannabidiol differs from the

active drug in cannabis,tetrahydrocannabinol, in that cannabidiol lacks the typical mind altering

and recreational effects. One study has suggested that cannabidiol may be as effective as

atypical antipsychotics in treating schizophrenia. Some further research has supported these

results, and found fewer side effects with cannabidiol than with amisulpride.

Tetrabenazine is similar in function to antipsychotic drugs, though is not, in general, considered

an antipsychotic itself. Its main usefulness is the treatment of hyperkinetic movement

disorders such as Huntington's disease and Tourette syndrome, rather than for conditions such as

schizophrenia. Also, rather than having the potential to cause tardive dyskinesia, which mostantipsychotics have, tetrabenazine can be an effective treatment for the condition.

Metabotropic glutamate receptor 2 agonism has been seen as a promising strategy in the

development of novel antipsychotics. When tested in patients, the research

substance LY2140023 yielded promising results and had few side effects. The

active metabolite of this prodrug targets the brain glutamate receptors mGluR2/3 rather

than dopamine receptors.

Glycine transporter 1 inhibition. RG1678 has been shown in phase 2 clinical trials to be selectively

effective for the negative symptoms of schizophrenia.

A placebo-controlled trial has suggested that adding L-theanine, an amino acid found in green tea

and available as supplement, to ongoing antipsychotic medication may be helpful in reducing

some symptoms of schizophrenia.

anti psychotic pharma

Documents