SECOND

GENERATION
ANTIPSYCHOTICS

By Idongesit Ekpo
Introduction
• Second generation antipsychotics are also
known as neuroleptics or atypical
antipsychotics.
• They are called atypical because it has ability to
produce antipsychotic effect without causing
extrapyramidal effects
(dystonia,akathisia,parkinsonism characteristics
like rigidity, bradykinesia,tremor and tardive
dyskinesia.) and they have improved efficacy.
The main therapeutic uses of
antipsychotic drugs are to reduce
hallucinations, delusions, agitation, and
psychomotor excitement in schizophrenia,
mania, or psychosis secondary to a
medical condition.

The drugs are also used prophylactically

to prevent relapses of schizophrenia and
other psychoses.
Advantages of atypical drugs
• 1 atypicals are serotonin- Dopamine receptor antagonist.
• 2.They improve two classes of disabilities
• (a) Positive symptoms -hallucination, delusion, thought
disorders, agitation.
• (b)Negative symptoms -social withdrawal, flat affect,
anhedonia, poverty of speech-alogia, catatonia, cognitive
impairment.
• 3.They have greater effect against negative symptoms of
psychosis. They are less likely to cause EPSE
• 4. A very low risk of hyperprolactinemia
• 5. Low risk of Tardive dyskinesia.
Classes of Second generation
antipsychotic drugs
• Benzamides e.g Amisulpride, Sulpride,
Remoxipride, Sultopride ,Neomonapride
• Benzisoxazoles e.g Risperidone,
iloperidone,Ocaperidone .
• Benzisothiazol e.g Lurasidone
• Dibenzodiazepine e.g Clozapine
• Thienobenzodiazepine e.g Olanzepine
• Dibenzothiazepine e.g Quetiapine.
• Dibenzo-oxepinopyrrole e.g Asenapine
 Amisulpride
• Mechanism of action (MOA)
• It is a selective D2 receptor antagonist.They also
lack sedative and anticholinergic properties.
• Amisulpride works by blocking the dopamine D2
and D3 receptors in the brain.Additionally,
amisulpride also has some effects on other
neurotransmitters, such as serotonin and
norepinephrine, which may contribute to its
effectiveness in treating depression and anxiety
disorders.
Pharmacokinetics of amisulpride
• Amisulpride is well absorbed after oral
administration and reaches peak plasma
concentrations within 1-3 hours.
• The drug is metabolized in the liver and its
metabolites are excreted mainly in the urine.
• The elimination half-life of amisulpride is around 12
hours.
• The drug is not significantly bound to plasma
proteins and does not undergo significant first-pass
metabolism.
Indications for amisulpride
• Amisulpride is indicated in schizophrenia and other
psychotic disorders.
• Amisulpride is generally reserved for patients who
have not responded adequately to other
antipsychotic medications or who have experienced
intolerable side effects with other treatments.
• The drug is typically prescribed by a psychiatrist and
requires careful monitoring and dose adjustment to
ensure optimal therapeutic outcomes and minimize
the risk of adverse effects.
Side effects of amisulpride
• - Extrapyramidal symptoms (EPS), such as tremors,
muscle stiffness, and involuntary movements
• - Weight gain, Drowsiness or sedation, Dry mouth,
Constipation, Headache, Anxiety, Insomnia,
Increased prolactin levels.
• Less common but potentially serious side effects of
amisulpride:
• - Blood disorders, such as leukopenia or
agranulocytosis (a decrease in white blood cells
• - Liver dysfunction
 Contraindications for amisulpride
• Amisulpride is contraindicated in patients with:
• - Known hypersensitivity to amisulpride
• Pheochromocytoma
• Severe renal impairment (creatinine clearance less than 30 mL/min)
• Severe hepatic impairment
• Parkinson's disease or other conditions that cause extrapyramidal
symptoms, unless the benefits outweigh the risks and appropriate
precautions are taken.
• History of neuroleptic malignant syndrome (NMS)
• Amisulpride should also be used with caution in patients with a
history of seizures, cardiovascular disease, or diabetes, as it may
worsen these conditions. It should not be used in children or
adolescents under the age of 18.
 Risperidone
• MOA
• Risperidone is a potent antagonist at both 5-
HT2 receptors and dopamine D2 receptors. It
also possesses α1-adrenoceptor blocking
properties, which can cause mild sedation
and hypotension.
• Paliperidone is an active metabolite of
risperidone.
Pharmacokinetics of Risperidone
• Risperidone is absorbed after oral administration,
with peak plasma concentrations occurring within
1-2 hours. It undergoes first-pass metabolism in the
liver.
• The elimination half-life of risperidone is
approximately 20 hours, while that of its metabolite
is 23 hours. Risperidone is primarily eliminated via
renal excretion and faeces.
Indication for Risperidone
• Risperidone is indicated for the treatment of
schizophrenia,
• bipolar disorder,
• autistic disorder in children and adolescents.
Side effects of Risperidone
• Drowsiness
• Nausea
• Restlessness
• Vomiting
• Diarrhea
• Constipation
• Heartburn
• Dry mouth
• Sexual dysfunction
• Weight gain
• Hypotension
Contraindications for Risperidone

• It is also contraindicated in patients with dementia-

related psychosis due to an increased risk of
mortality.
• it should not be used in patients with a history of
QT prolongation, arrhythmias, or other cardiac
conditions.
• Risperidone should be used with caution in patients
with hepatic impairment, or renal impairment.
• It is not recommended for use during pregnancy or
breastfeeding.
Drug interactions of Risperidone

• Carbamazepine and other enzyme inducers may

reduce plasma levels of risperidone.
• If a person is taking both carbamazepine and
risperidone, the dose of risperidone will likely need
to be increased.
• risperidone can cause hypotension, its use should
be monitored closely when a patient is also taking
antihypertensive medicines to avoid severe low
blood pressure.
LURASIDONE
• MOA
• Lurasidone is a potent 5-HT2 and D2 receptor
antagonist.
• It binds only weakly to histamine H1 receptors,
which makes it less likely to cause weight gain and
sedation than olanzapine or quetiapine.
Pharmacokinetics of Lurasidone
• Lurasidone is administered orally .
• Has peak plasma concentrations occurring within
1-3 hours after dosing.
• It is extensively metabolized in the liver by
cytochrome P450 enzymes, primarily CYP3A4 and
to a lesser extent CYP2D6.
• The major metabolites of lurasidone are inactive
and are eliminated primarily in the feces.
Lurasidone has a half-life of approximately 18
hours.
Indications for Lurasidone
• Lurasidone is indicated for the treatment of
schizophrenia in adults
• for the treatment of depressive episodes associated
with bipolar I disorder (bipolar depression) in adults
as monotherapy or as adjunctive therapy with
lithium or valproate.
Side effects of Lurasidone
• Somnolence,
• Akathisia
• Parkinsonism
• Nausea
• Insomnia
Contraindications for Lurasidone
• Not indicated for dementia-related psychosis
• Pregnancy and lactation
• Renal impairment
• Hepatic impairment
• Cardiovascular conditions
CLOZAPINE
• MOA
• Clozapine is a weak dopamine D2-receptor
antagonist but has a high affinity for 5-HT2
receptors.
• It also binds to a variety of other neurotransmitter
receptors, including histamine H1, α1-adrenergic
and muscarinic cholinergic receptors.
Pharmacokinetics of clozapine
• Clozapine is given oral, with peak plasma concentrations
occurring within 1-4 hours. It undergoes first-pass
metabolism in the liver.
• norclozapine, which is its active metabolite and has a
longer half-life than clozapine itself.
• Clozapine is primarily eliminated by metabolism in the
liver, with less than 1% of the dose excreted unchanged
in urine or feces.
• It has a narrow therapeutic index and requires careful
monitoring of plasma concentrations to ensure efficacy
and minimize the risk of adverse effects.
Indications for clozapine
• Clozapine is indicated for the treatment of
schizophrenia in patients who have failed to
respond adequately to other antipsychotic
medications.
• It may also be used to reduce the risk of recurrent
suicidal behavior in patients with schizophrenia or
schizoaffective disorder.
Side effects of clozapine
• most common side effects of clozapine include dizziness,
drowsiness, constipation, dry mouth, weight gain, and
increased appetite.
• Other possible side effects include:Agranulocytosis ,Low
blood pressure, Rapid heartbeats, Fainting, Seizures,
Fever, Sore throat, Difficulty breathing,Chest pain,Swelling
of the face, lips, tongue, or throat, thrombocytopenia,
jaundice,Muscle stiffness or spasms, Restlessness,
agranulocytosis, dysphagia, pulmonary embolism.
• Note: increase in seizure frequency occurs above
600mg/day.
Drug interactions in clozapine
• Lithium can increase the risk of developing seizures,
confusion,dyskinesia.
• Smoking decreases plasma conc. by increasing
clearance while caffeine increase it .
Contraindications for Clozapine

• Hypersensitivity reactions
• Myeloproliferative disorders
• Paralytic ileus
• Severe CNS depression.
• Clozapine should not be given with any
agent that is likely to potentiate its
depressant effect on white cell count,
such as carbamazepine, co-trimoxazole
and penicillamine.
OLANZEPINE
MOA
It's binds to dopamine D2 receptors and
serotonin 5-HT2 receptors, which
reduces the activity of these
neurotransmitters in certain areas of the
brain.
Pharmacokinetics of Olanzepine
It is administered orally and is rapidly absorbed from
the GIT.
The peak plasma concentration is achieved within 5-
8 hours after oral administration. Food does not
affect the absorption of olanzapine.
It is metabolized in the liver by the cytochrome P450
enzyme.
Pharmacokinetics of olanzepine
• Elimination: Olanzapine has a half-life of
approximately 30 hours, which means it takes
about 30 hours for half of the drug to be eliminated
from the body.
• The drug is eliminated primarily through hepatic
metabolism and subsequent renal excretion of
metabolites. Only a small amount of unchanged
olanzapine is excreted in urine and feces.
Indications for Olanzepine
• Olanzapine is indicated for the treatment of
schizophrenia, bipolar disorder, and as an
adjunctive therapy for major depressive disorder.
• It may also be used for other psychiatric conditions
such as anxiety disorders, obsessive-compulsive
disorder, and post-traumatic stress disorder.
Side effects of Olanzepine
• Common side effects of olanzapine :
• weight gain, drowsiness, dizziness,
constipation, dry mouth, increased appetite,
and blurred vision. Other potential side
effects include increased blood sugar levels,
high cholesterol, extrapyramidal symptoms
and orthostatic hypotension (low blood
pressure when standing up).
• agranulocytosis
Contraindications for Olanzepine
• Contraindicated in patients with a known
hypersensitivity to the product.
• May exacerbate, possibly precipitate, diabetes
mellitus, low white blood cell count or liver
dysfunction.
• Caution in galactosemia and phenylketonuria due
to excipients.
Quetiapine
• MOA
• Quetiapine is also a histamine H1-receptor
antagonist; it has modest 5HT2-receptor
antagonist effects, and rather weaker D2-
receptor antagonist properties.
• It has a low propensity to cause movement
disorders and, like olanzapine, is highly
sedating.
Pharmacokinetics of Quetiapine
• Absorption: Quetiapine is administered orally in
tablet or extended-release (XR) tablet form.
• After oral administration, it undergoes extensive
first-pass metabolism in the liver.
• Food can delay the absorption of quetiapine.

• quetiapine has a half-life of about 3 hours.

Pharmacokinetic of Quetiapine
• Metabolism: Quetiapine undergoes
extensive hepatic metabolism, primarily
via the cytochrome P450 enzyme
system in the liver.
• The main metabolite formed is
norquetiapine, which also has
pharmacological activity.
 Pharmacokinetics of Quetiapine
• Elimination: Quetiapine and its
metabolites are eliminated primarily
through hepatic metabolism and
subsequent renal excretion.
Indication of Quetiapine
• Schizophrenia
• Bipolar disorders
• Depressive disorder
• Generalised Anxiety disorders.
Side effects of Quetiapine
• Dizziness
• Fatigue
• Increased diastolic blood pressure
• Increased triglycerides
• Increased total cholesterol
• Increased appetite
• Constipation
• Dry mouth
• Headache
• Somnolence
• QTc prolongation
Contraindications of Quetiapine
• Hypersensitivity.
• In dementia-related ppsychosis
• Use with caution in cardiovascular and
cerebrovascular disease
• May worsen hypotensive conditions
• Use with caution in breast cancer and history of
seizure.
Asenapine
• MOA
• Asenapine binds potently to 5-HT2 receptors.
It also binds significantly to D2 receptors, as
well as to a range of other 5-HT receptors
and the alpha-2-adrenoreceptor.
Pharmacokinetics of Asenapine

Absorption: Asenapine is available in

sublingual form, which means it is placed
under the tongue where it rapidly
dissolves and is absorbed through the
oral mucosa. This sublingual route allows
for direct systemic absorption, bypassing
first-pass metabolism by the liver.
Pharmacokinetics of Asenapine
• Elimination: The elimination half-life of
asenapine ranges from approximately 17 to
24 hours. The majority (about 95%) of the
administered dose is eliminated via hepatic
metabolism, primarily through the feces,
while a small portion is eliminated in urine.
Indication for Asenapine
• Schizophrenia
• Bipolar disorder
Side effects of Asenapine
• akathisia
• drowsiness,
• extrapyramidal reaction,
• headache.
Contraindications of Asenapine

• It should not be used in patients with severe

hepatic impairment or severe renal impairment.
• It may cause orthostatic hypotension and should be
used with caution in patients with a history of
cardiovascular disease, cerebrovascular disease, or
conditions that predispose to hypotension.
• Asenapine is not recommended for use in elderly
patients with dementia.
• It is contraindicated in breastfeeding women.
 Aripiprazole

• They are still grouped under atypical drugs. second

Generation/ third generation antipsychotic drug.
• MOA: It is a dopamine D2 receptor partial agonist.
Partial agonist activity at serotonin 5HT1A receptors.
Antagonist activity at 5HT2A receptors. It has alpha
blocking activity.
• It appears to show predominantly antagonist activity
on postsynaptic D2 receptors and partial agonist
activity on presynaptic D2 receptors, D3 and partially
D4 and is a partial activator of serotonin (5-HT1A,5-
HT2A)
Indication for aripiprazole

• It is primarily used in the treatment of

schizophrenia, obsessive compulsive disorder
(OCD), and bipolar disorder;
• other uses include as an add-on treatment in major
depressive disorder, tic disorders, and irritability
associated with autism
Pharmacokinetics of aripiprazole
Plasma Half- life: Parent Drug, 75 hr
Plasma Peak Time: 3-5 hours.
Protein Bound: 99%.
Absorption: Oral (3-5 hr.); IM (1-3 hr.).
Metabolism: Aripiprazole is metabolized largely by
liver.
Excretion: Feces (55%) and Urine. (25%)
Dosage Form: Oral or IM.
Side effects of aripiprazole
• Side Effects :
• Weight Gain.
• GIT effects like nausea and constipation
• Postural Hypotension
• Extrapyramidal Symptoms
• Tardive dyskinesia on long-term administration
• Lightheadedness and drowsiness
• Hyperglycemia and sometimes diabetes.
• Increased risk of hyperlipidemia.
Contraindications of aripiprazole
• In Hepatic Impairment because Aripiprazole is metabolized
by hepatic enzymes.
• Elderly patients with dementia related psychosis.
• Pregnancy.
• Patients with cardiovascular Disease.
• Patients predisposed to hypotension.
• AVOID in patients with hypersensitivity.
• Operating Heavy Machinery and work that requires skill (eg.
driving) probably because Aripiprazole causes sedation.
• In breast-feeding. Aripiprazole is secreted in breast milk.
DRUG TRADE NAME DOSAGE(mg/day) ROUTES OF
ADMINISTRATION

CLOZAPINE sizopin, clozaril, 50-450 Oral

lozapin

RISPERIDONE Sizodon, sizomax 2-10 Oral, IM

OLANZEPINE Zyprexa, Oleanz 10-20 Oral, IM

QUETIAPINE Seroquel, qutan 150-750 Oral

ZIPRASIDONE Zeldox, zisper 20-80 Oral, IM

ARIPIPRAZOLE Abilify, Aristada 5-30 Oral IM,

Thank you