MARIUM MANSOOR

PSYCHOPHARMACOLOGY

UNIVERSITY OF KARACHI

SUBMITTED TO DR.RABIA

DATE: 11-9-19

ANTIPSYCHOTICS

Antipsychotics are a group of drugs that are used to treat serious mental health conditions such
as psychosis as well as other emotional and mental conditions. In addition, they are prescribed
for the treatment of pain that can result from restlessness .
Psychosis is a condition in which a patient loses contact with reality. The condition often
includes hallucinations or delusions. When experiencing hallucinations, the patient often hears
voices that aren’t actually there, while delusions related to psychosis consist of feelings or ideas
that aren’t based on reality.

Antipsychotics help to control the symptoms of psychosis as well as less serious mental health
conditions such as bipolar and mood disorder that may develop into later psychosis.
 Antipsychotics reduce or increase the effect of neurotransmitters in the brain to regulate levels.
Neurotransmitters help transfer information throughout the brain. The neurotransmitters affected
include dopamine, noradrenaline, and serotonin. Dopamine is the primary neurotransmitter
affected by taking antipsychotics; an overactive dopamine system may be one cause of the
hallucinations and delusions commonly experienced during psychosis.

According to the Royal College of Psychiatrists, 4 out of 5 people who take antipsychotics find
they are successful in treating their symptoms...Antipsychotic medication can come as tablets, a
syrup or as an injection. The injections are called a depot.

DOPAMINE RECEPTORS:

· D1 receptor family- stimulate cAMP.  D1 is found in striatal, limbic and cortical pathways, D5
just in striatal and limbic pathways.

· D2 receptor family- inhibit cAMP.  D2 is found in striatal, limbic and cortical pathways, D3 in
the limbic and cerebellar pathways and D4 in the limbic and cortical pathways.

TYPES OF ANTIPSYCHOTICS:

There are two types of antipsychotics ,Typical or ‘first generation’, medications used since the
1950s and Atypical or ‘second generation’, medications used since the 1990s.The main
difference between these types is in their side effects. First generation antipsychotics may have
more of an effect on your movement than newer ones. Although this does not mean newer
generation antipsychotics don’t have any side effects on your movement.

First generation antipsychotics (Typical)

The following medications are typical antipsychotics

• Benperidol (Anquil)

• Chlorpromazine (Largactil)(thorazine) 150-1000 mg

• Mesoridazine (serentil) 75-300 mg

• Fluphenazine (prolaxin)2-20 mg

• Haloperidol (Haldol) 2-25 mg

• Loxapine (loxaline) 30-150 mg

1) Haloperidol:

Haloperidol is used to treat certain mental/mood such as schizophrenia, schizoaffective

disorders.It can also help prevent sucide in people who are likely to harm themselves. It also
reduces aggression and the desire to hurt others. It can decrease negative thoughts
and hallucinations.It can also be used to treat uncontrolled movements and outbursts of
words/sounds related to Tourtee's Syndrome. Haloperidol is also used for severe behavior
problems in hyperactive children when other treatments or medications have not worked.

Haloperidol works by helping to restore the balance of certain natural substances in

the brain (neurotransmitters,they block many receptors other than the primary target (dopamine
receptors), such as cholinergic or histaminergic receptors.

Side Effects:

Dizzeness,lightheadness,drowsiness,difficulturinating, sleep disturbances, headache,and anxiety 
may occur. haloperidol may increase your level of a certain chemical made by the body
prolactin.

For females,this increase in prolactin  may result in unwanted breast milk, missed/stopped

periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability,
inability to produce sperm, or enlarged breasts.
This medication may rarely cause a condition known as  tardive dyskinesia. This medication may
rarely cause a very serious condition called neuroleptic malignant syndrome (NMS).

Fever, muscle stiffness/pain/tenderness,severe tiredness, severe confusion,fast/irregular

heartbeat, dark urine, signs of kidney problems can also occurs.

2) Loxapine

Loxapine is also used to treat Schizophrenia ,It is a dopamine antagonist, and also a serotonin 5-
HT2 blocker. The exact mode of action of Loxapine has not been established, however changes
in the level of excitability of subcortical inhibitory areas have been observed in several animal
species in association with such manifestations of tranquilization as calming effects and
suppression of aggressive behavior.

Side Effects:

Drowsiness,dizziness ,lightheadedness(can increase the risk of falling),constipation,dry

mouth,weight gainand blurred vision are included. 

This drug may cause muscle/ nervous system problems (extrapyramidal symptoms- EPS) such as
stiff muscles, severe muscles spasms /cramping (such as twisting neck, arching back, eyes rolling
up), restlessness/constant need to move, shaking (tremor), slow/shuffling walk, drooling/trouble
swallowing, mask-like expression of the face.

 Other side effects includes easy bruising/bleeding fainting,depression,sucidal thoughts, , difficulty

urinating, signs of infection (such as fever, seizures severe stomatch pain, 

This medication may cause tardive dyskinesia,such as involuntary/repetitive muscle movements,lip

smacking/puckering, tongue thrusting, chewing, or finger/toe movements
3) Chlorpromazine:

Chlorpromazine is a psychiatric medication that belongs to the class of drugs called phenothiazine
antipsychotics used to treat disorders(such as psychotic disorders, manic phase of bipolar disorder ,
severe behavioral problems in children).Chlorpromazine is also used to control
nausea,vomiting ,relieve restlessness before surgery, and help treat tetanus. It helps us to think more
clearly, feel less nervous, and take part in everyday life. It can reduce aggressive behavior and the
desire to hurt yourself/others.

Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on

dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties
ejaculation difficulties), on histaminergic-receptors on productive and unproductive symptoms),
on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive
properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight
gain, fall in blood pressure

Adverse Reactions:

Tardive dyskinesia, drowsiness, jaundice, blood dyscrasias, hypotension, retinopathy, may mask
emetic signs of disease, lowered seizure threshold, rash, skin pigmentation, anticholinergic
effects, insomnia, extrapyramidal reactions, neuroleptic malignant syndrome.

4) Fluphenazine:

Fluphenazine belongs to a class of medication called phenothiazines and is also referred to as a

neuroleptic. It reduced episodes of hallucinations and delusions or bizarre behaviors that occur in
patients with schizophrenia.This medication is not recommended for use in children under 12 years
of age.

Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain;

depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the
reticular activating system thus affecting basal metabolism, body temperature, wakefulness,
vasomotor tone, and emesis.

One should not have proxlin if one have liver diseases, brain damage, bone marrow , a blood cell
disorderHigh doses or long-term use of fluphenazine can cause a serious movement disorder that
may not be reversible. Symptoms of this disorder include uncontrollable muscle movements of
your lips, tongue, eyes, face, arms, or legs. The longer you take Prolixin, the more likely you are
to develop a serious movement disorder. The risk of this side effect is higher in women and older
adults.

5) Mesoridazine:

Used in the treatment of schizophrenia, organic brain disorders, alcoholism and

psychoneuroses.Based upon animal studies, mesoridazine, as with other phenothiazines, acts
indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced
without affecting its intrinsic ability to activate the cerebral cortex. In addition, the
phenothiazines exhibit at least part of their activities through depression of hypothalamic centers.
Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic
blocking action.

Side Effects:

1.Central nervous system side effects including drowsiness, Parkinson's syndrome, weakness,

tremor, restlessness,ataxia,rigidity, slurring, akathisia, and motoric reactions (opisthotonos) have
been reported.

2.Autonomic nervous system effects including dry mouth, , fainting, stuffy nose, photophobia
and blurred vision have also been reported.

3.Genitourinary side effects including inhibition of ejaculation,incontinence have been reported.

4.Dermatologic side effects including itching, rash, hypertrophic papillae of the tonguehave been
reported.

Second generation antipsychotics (Atypical)

Following are the atypicals

• Amisulpride (Solian)

• Aripiprazole (Abilify, Abilify Maintena) 10-30 mg

• Clozapine (Clozaril, Denzapine, Zaponex) 100-900 mg

• Risperidone (Risperdal & Risperdal Consta) 1.0-6.5 mg

• Olanzapine (Zyprexa) 10-35 mg

• Quetiapine (Seroquel) 150-900 mg

• Paliperidone (Invega, Xeplion)

1) Clozapine:

 Clozapine is generally more effective than the other drugs in handling the symptoms of
psychosis along with reducing suicidal thoughts among schizophrenics. It has little effect on the
movement-controlling dopamine systems, reducing the shakiness and stiffness side effects
experienced with other drugs. It also does not generally result in tardive dyskinesia. It can make
patients who use it drowsy, and it causes an increase in the production of saliva. Clozapine also
reduces the white blood cell count in most users, increasing the chances of infection. This means
that a patient taking clozapine will have to undergo regular blood tests, and the drug will need to
be discontinued occasionally so that the bone marrow can produce the white blood cells that the
patient’s body needs.
Clozapine's antipsychotic action is likely mediated through a combination of antogistic effects at
D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2
antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.

Side Effects:

Drowsiness, dizziness, lightheadedness, headache,vision problems,weight gain,constipation , shaking

(tremor) may occur. Many of these effects (especially drowsiness) lessen as your body gets used to
the medication.Other severe effects included mental/mood changes, difficulty breathing
pain/redness/swelling of the arms/legs, persistent  nausea vomiting, stomatch pain and yellowing of
eyes and skin.

2) Aripiprazole:

Aripiprazole is an atypical antipsychotic orally indicated for treatment of schizophrenia, bipolar

I, major depressive disorder, irritability associated with autism. It is also indicated as an injection
for agitation associated with schizophrenia or bipolar mania

The antipsychotic action of aripiprazole is likely due to the agonism of D2 and 5-HT1A
receptors .Some adverse effects may be due to action on other receptors For example, orthostatic
hypotension may be explained by antagonism of the adrenergic alpha1 receptors

Side Effects:

Common side effects of Abilify includes dizziness, excess saliva ,blurred vision headache,
anxiety,drowsiness, sleep problems (insomnia),constipation,Suicidal thoughts are may occur in
some patients, especially children, teens, and young adults.Other serious side effects of Abilify
include:Tardive dyskinesia ,Neuroleptic malignant syndrome shaking mental/mood changes
(such as increased anxiety, depression, suicidal thoughts)trouble swallowing restlessness
(especially in the legs)mask-like expression of the face seizures signs of infection (such as
fever)Women who are breastfeeding should not take Abilify.
Olanzapine:

Olanzapine is a thienobenzodiazepine classified as an atypical or second-generation

antipsychotic agent.It quickly widespread due to the presumed higher efficacy, less
extrapyramidal side effects and fewer drug-drug interactions.

Olanzapine was initially used orally and intramuscularly for the chronic treatment of
schizophrenia in patients over 13 years old and other psychiatric disorders such as bipolar I
disorder including mixed or manic episodes.Olanzapine is also indicated, in combination with
lithium or valproate for the short-term treatment of acute manic or mixed episodes associated
with bipolar I disorder in adults.It is also indicated, in combination with fluoxetine for the
treatment of episodes of depression associated with bipolar disorder type 1 and treatment-
resistant depression in patients over 10 years old.

The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors

including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors
5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1
and multiple muscarinic receptors.

Side Effects:

Agitation, dysarthria, tachycardia, extrapyramidal symptoms, and reduced consciousness. One

case of overdosage-driven death was reported after ingestion of 450 mg of olanzapine.

The toxicity symptoms of olanzapine are known to includes blurred vision, respiratory
depression, hypotension, extrapyramidal symptoms and anticholinergic effects. The overdosage
effects in children are generally associated with more significant side effects.

4) Quetiapine:
Quetiapine is a second-generation atypical antipsychotic used in schizophrenia, major
depression, and bipolar disorder as a monotherapy or combined with other drugs. It is also used
in the management of post-traumatic stress disorder (PTSD), generalized anxiety disorder, and
psychosis associated with Parkinson's disease. It demonstrates a high level of therapeutic
efficacy and low risk of adverse effects during long-term treatment. It is well-tolerated and a
suitable option for some patients with high sensitivity to other drugs, such as Clozapine and
Olanzapine. 

In schizophrenia, its actions could occur from the antagonism of dopamine type 2 (D2) and
serotonin 2A (5HT2A) receptors. In bipolar depression and major depression, quetiapine's
actions may be attributed to the binding of this drug or its metabolite to the norepinephrine
transporter.

Side Effects:

Side effects may include restlessness/constant need to move, shaking (tremor), mental/mood changes
(such as increased  anxiety, depression thoughts of sucide , difficulty swallowing, constipation with
persistent abdominal pain ,persistent nausea/vomiting , loss of appetite, yellowing eyes/skin ,
interrupted breathing during sleep and trouble urinating.

Quetiapine can cause suicidal thinking or behavior in children and adolescents and should not be
given to children under 10 years of age. It is important to monitor for suicidality if this drug is
given to younger patients. In addition, this drug is not indicated for the treatment of psychosis
related to dementia due to an increased death rate in elderly patients taking this drug.

5) Risperidone:

Risperidone is used to treat schizophrenia,bipolar disorder ,irritability associated with autistic

disorder). Schizophrenia and various mood disorders are thought to be caused by an excess of
dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central
mesolimbic pathways and mesocortical pathways, respectively. Risperidone is thought to reduce
this overactivity through inhibition of dopaminergic D2 receptors and serotonergic 5-HT2A
receptors in the brain.