Antipsychotic drugs

Referance book ….Essential of pharmacology by Shah Nawaz

 Objectives Group members
• What is psychosis

• Antipsychotic drugs classification • Laiba shah

• Pharmacokinetics • Khadija tul kubra

•
• Mechanism of action • Hira hafeez

• Pharmacological action • Areej zeb

• Clinical uses • Aqleema khan

• Adverse reactions
 Psychosis :
Mental illness

Psychosis Neurosis

Major psychotic Mood disorders

illness

Schizophrenia Aggression Depress bipolar disorder

Hallucination delusion illusions

Main reason of psychosis :

Dopamine disturbance :

Psychosis if dopamine no increases Parkinson if dopamine no decreases

• Childhood trauma
• Previous drug use
• Pregnancy or birth complications
• Structural changes in the brain
 CLASSIFICATION OF DRUGS :

1. Phenothiazine

Aliphatics Piperidines Piperazines 6. Indlolones

2. Thioxanthenes 7. Dibenzoxazepines

3. Butyrophenones 8. Dibenzodiazepines

4. Benzisoxazoles 9. Benzamides

5. Thienobenzodiazepines 10. Miscellaneous Drugs

 Pharmacokinetics

➢ Orally …….Bioavailability less

➢ Through IV

➢ Drugs ….highly lipid soluble………..deposition on adipose tissues ………….prolonged effect

➢ Highly bound to plasma protein .

➢ Plasa half life……8 to 25 hour

 Mechanism of action :

Dopamine…........inhibitory neurotransmitter

hypothalamus , substania nigra ,venral tegmented area of brain

Dopamine receptors :

➢ D1
➢ D2
➢ D3
➢ D4
➢ D5

Antipsychotics mainly produce their beneficial antipsychotic effects by

blocking the D2 receptors.
 Sites of D2 receptors :

D2 receptors located in the mesolimbic-mesocortical system.

Mesocortical pathway :

one of the main dopamine pathways of the brain, the

mesocortical pathway runs from the ventral tegmental area
to the cerebral cortex
Mesolimbic pathway:

The mesolimbic pathway, is a dopaminergic pathway in the

brain. The pathway connects the ventral tegmental area in the
midbrain to the ventral striatum of the basal ganglia in the
forebrain.

The ventral striatum includes the nucleus accumbens and the

olfactory tubercle, caudate ,putamen .
 Drug :

Typical APSD Atypical APSD

1 generation or conventional drugs 2 generation drugs

Clozapine
olanzapine, significant block activity on
quetiapine, 5-HT receptors
ziprasidone,
High potency low potency risperidon
aripiprazole
Chlorpromazine
• Haloperidol
• muscarinic,
• Remoxipride
• alpha adrenoceptors and
• Pimozide
• histamine
Aripiprazole has partial agonist activity on D2, and 5-HT.1A receptors

5-hydroxytryptamine (5-HT)

In addition to these, new research is focused on the role of

GABA, glutamate a acetylcholine in schizophrenia.

gamma-Aminobutyric acid
Pharmacological
actions
 CNS

Normal person psychotic patient

Sleepiness increase psychomotor activity

restlessness. Thinking

mental activity Typing

 CVS

cause hypotension ……………………chloropromazine and Thioridazine

postural hypotension…. …………….. Thioridazine and chloropromazine

cardiac arrhythmias………………………. . Thioridazine and mesoridazine

cause increase in QT interval ………….. Sertindole

Endocrine Secretions:
Normally, dopamine inhibits the secretion of prolactin from the
anterior pituitary gland.
Antipsychotics may increase the secretion of prolactin .

Effect :

In female

It cause amenorrhoea, galactorrhoea, infertility, false positive

pregnancy test, and increased libido in the female.

In male :

In the male, prolactin may produce gynaecomastia, and

decreased libido.
Antiemetic Effect:

Except for thioridazine and mesoridazine, most older

antipsychotics may produce antiemetic effect by inhibiting the
chemoreceptor trigger zone.

An antiemetic is a drug that is effective against

vomiting and nausea .

Other Effects:
Some of them such as

chlorpromazine and thioridazine produce significant

antimuscarinic, antihistaminic, and a adrenoceptor
blocking effects.
Clinical uses
 Clinical Uses

Schizophrenia :

Positive symptoms of the disease

➢ such as Agitation (irritable behaviour),

➢ Delusions (false beliefs, patient may believe as if secret police is after him, while actually his
belief is far from truth),

➢ Hallucinations (perception of sensations without stimuli, such as seeing objects that are not
actually present) etc., show more improvement with antipsychotics.

negative symptoms,
such as social withdrawal, apathy (loss of emotional response) etc., show less improvement.
 Affective Disorders:

They are related to the mood or inner feelings of the patients.

For example:

Depression is an affective disorder in which the mood of the patient is sad.

While in mania the patient shows an abnormally happy mood.

Treatment :

Depression can be treated with antidepressant drugs, while mild mania can be
treated with lithium and carbamazepine, but severe cases of mania require
treatment with antipsychotics.
Other Psychotic Diseases:

These drugs can also be used in cases of psychosis occurring due to other
causes. For example,

Delerium :

delerium is a psychosis in which the patient shows abnormal mental

behaviour due to high fever or intoxication etc.
Treatment :

Delerium can be treated with antipsychotic drugs. Psychosis that occurs

along with depression can also be treated with antipsychotics.
Reduced awareness of the environment

This may result in:

•An inability to stay focused on a topic or to switch topics

•Getting stuck on an idea rather than responding to questions or conversation

•Being easily distracted by unimportant things

•Being withdrawn, with little or no activity or little response to the environment

Agitation and Excitement:
These can be treated with antipsychotics, even if they occur in nonpsychiatric cases.

For example,

1. Agitation (angry behaviour with slight provocation) and

2. Excitement in a person who is otherwise normal may be be controlled with these drugs.

Guiles de la Tourette Syndrome:

In this condition, patient suffers from tics of repeated utterances of some words, usually of
unsociable type such as abuses and use of filthy language. Antipsychotics may be helpful in
such patients.
Alzheimer's Disease:
Antipsychotics can be used in patients with a type of dementia known as presenile dementia or
alzheimer's dementia.

Nausea and Vomiting:

Except for thioridazine, most other older antipsychotics are effective in the treatment and
prevention of nausea and vomiting.

Pruritis:
Some antipsychotics have significant H, receptor blocking effects for example, promethazine
that may be used for the relief of pruritis or itching.
Neuroleptanalgesia and Neuroleptanesthesia:

Droperidol is an antipsychotic that is, when used along with fentanyl (an opioid),
produces an analgesic effect known as neuroleptanalgesia. If nitrous oxide is also used
along with them, then it is known as neuroleptanesthesia.

Anxiety :
Ziprasidone

Antisocial sexual behaviour

benperidol
 SELECTION OF A SUITABLE DRUG
1. If a patient has shown a good response to an antipsychotic drug in the past, then the same drug should be used again
for a subsequent attack.

2. Potent antipsychotics are now more commonly used, such as haloperidol, fluphenazine, and thiothixene.

3. If a patient does not show response with commonly used antipsychotics, then clozapine can be tried. This drug is
found to be effective in 30-40% of patients not responding to the older drugs, but agranulocytosis and seizures can
occur with clozapine,

4. If one antipsychotic is not effective or shows intolerable adverse effects, then other antipsychotics should be tried.

5. A small number of patients with schizophrenia show a prolonged remission after an attack of disease. In such
patients drug treatment can be stopped for the period of remission.
 Adverse reactions :
1.

CNS:
In normal persons and in patient suffering from less degree of psycho antipsychotics can
cause weakness, and drowsiness. Convulsions to occur with chlorpromazine and
clozapine but are rare with haloperidol and other potency antipsychotics.

2.

Neurological Effects: extrapyramidal adverse effects

They occur due to the blocked of dopamine receptors in the nigrostria system that
consists of axons of neurone located in the substantia nigra. These axons then end on
neurons in the corpus striatum (putamen and caudate nucleus).

Two types of neurological adverse effects can occur with the use of antipsychotics:
 Early Effects:

Dystonia Akathesia
(an abnormal spasm of a group of skeletal (restlessness, with marked motor activity,
muscle, usually involving the muscles of head, such as walking rapidly in the room or
face, and neck ) showing other repeated motor activities),
 Late Effects:
tardive Dyskinesia
abnormal movements of the head, face, and limbs.

Chorea Athetosis .

Chorea occurs in the form of dancing Athetosis are slow worm-like

Involuntary motor movements. movements of the various parts of
the body.
3.

Effects on ANS:
Antimuscarinic effects con occur especially with thioridazine and mesoridazine. Blockade of a,
adrenoceptor with chlorpromazine and thioridazine can cause postural hypotension and
inhibition of ejaculation. Tolerance occurs to these effects when antipsychotics are used
continuously.

4.

Endocrine Effects:

Antipsychotics increase the secretion of prolactin by preventing the inhibitory effect of dopamine on its
secretion. . Blockade of dopamine receptors in this system causes increased secretion of prolactin,
because normally dopamine inhibits the secretion of prolactin by acting on tuberoinfundibular System.
5.

Hepatobiliary System:
Cholestatic jaundice con occur, especially with the use of chloropromozaine .

Cholestatic jaundice

Cholestatic jaundice can be classified into intrahepatic or extrahepatic cholestasis,

depending upon the level of obstruction to bile flow. Clinically, cholestasis leads to
retention of the constituents of bile in blood.
6.
Blood:
Agranulocytosis can occur, especially with clozapine. Thus, weekly count of
white blood cells should be done during its use.

7.
Eye:
Thioridazine can be deposited in the retina to cause browning of vision
(the objects appear brown in colour). Chlorpromazine can be deposited in
the lens and cornea of the eye.

8.
Heart:
prolongation of QT interval, changes in T- wave, and ventricular
arrhythmias. Thus, these drugs should be used carefully in patients
suffering from heart disease or those taking quinidine or other
antiarrhythmics with quinidine-like effects
9.
Pregnancy:
Relatively safer during pregnancy, but a small incidence of teratogenic effects can occur

Teratogenic effects :

Teratogens are drugs, chemicals, or even infections that can cause abnormal
fetal development. There are billions of potential teratogens, but only a few
agents are proven to have teratogenic effects. These effects can result in a baby
being born with a birth defect.
10.
Malignant Hyperpyrexia:
This is manifested in the form of generalised muscle contraction, fever, leukocytosis, and labile
blood pressure. This syndrome appears to result from blockade of dopamine postsynaptic
receptors. It can be treated with antiparkinsonian drugs, diazepam, dantrolene, and
bromocriptine.
11.

Poisoning with Antipsychotics:

Miosis, como, convulsions, hypothermia, and hypotension can occur due to poisoning with
antipsychotics .

thioridazine and mesoridazine

ventricular arrhythmias

Treatment :
➢ Lavage

➢ Use activated charcoal and then remove by laxatives

➢ Blood pressure should be maintained with the help of infusion of fluids and
drugs (such as dopamine)

➢ Temperature should be controlled with cold sponging.

➢ Convulsions can be treated with diazepam or phenytoin sodium.

➢ Antiarrythmics should be used for the management of thioridazine or

mesoridazine induced cardiac arrhythmias. Lignocaine, propranolol, and
phenytoin sodium can be given for this purpose, but quinidine and
procainamide should not be used

➢ Sodium bicarbonate can be given intravenously for the treatment of

acidosis and cardiac conduction block.

➢ Potassium chloride can be given for hypokalcemia.

Thank you