Download Antipsychotic drugs

Psychopharmacology
Ms.Viji Prasad.C
Asst.Professor
Department of Psychiatric Nursing
• Antipsychotics ( typical and atypical)
• Antidepressants (cyclic, SSRIs, MAOIs)
• Mood stabilizers/ antimanic
• antianxiety (hypnotics , sedatives )
• Antiepileptics
• Antiparkinsonean agents
• Drugs for alcoholism and drug dependence
Contd…
• Miscellaneous ( Ca channel blockers , drugs used in
sleeping disorder, eating disorders , addiction and
vitamins
Antipsychotic drugs
Tyrosine
Tyrosine
L-DOPA
DA
Dopamine Synapse
Introduction
• Antipsychotic drugs = “major tranquilizers”,
“neuroleptic”.
• Anti-schizophrenic drugs
• Dopamine receptor antagonists
• There are two broad categories of
antipsychotic drugs:
a. 1st generation or traditional
(phenothiazines & butyrophenomes)
b. 2nd generation or atypical (dual action
drugs)
•
Drugs currently used in the prevention of
psychosis.
•
They have also been termed neuroleptics, because
they suppress motor activity and emotionality.
** These drugs are not a cure **
Pharmacokinetics
• readily but incompletely absorbed
• first pass metabolism
• highly lipid soluble protein bound
• completely metabolized
• little excreted unchanged
• t ½ is 10 -24 hours
Mechanism Of Action
• Dopamine receptor-blocking activity in the brain
• Serotonin receptor-blocking activity in the brain
• Block cholinergic, adrenergic & histaminergic
receptors
DOPAMINERGIC SYSTEM
• The dopamine pathways are central to psychosis, the
drug treatment of psychosis.
dopamine pathways
• Mesocortical pathway, extends from the ventral
tegmental region of the mid-brain to the frontal
cortex. One theory of schizophrenia poses that under
activity in this pathway causes an early event in the
development of schizophrenia: difficulties with
executive and other cognitive functions.
• (Behaviour )
• It is possible that under activity of this pathway may
be involved in the negative symptoms of
schizophrenia.
• The side-effect of antipsychotics known as the
“secondary” negative symptoms may arise in large
part through further disruption of transmission in this
pathway.
• Mesolimbic pathway : extends from the ventral
tegmentum to the nucleus accumbens, a limbic
system structure.
• Impulses then pass on to other components of the
limbic system and temporal lobe structures (including
the auditory cortex).
Contd….
•
In schizophrenia , when cognitive tasks are
performed less efficiently, there is a compensatory
increased activity in the mesolimbic pathway, and
this produces the positive symptoms of hallucinations
and delusions.
• As the limbic system is also involved in pleasurable
sensations, this pathway may also be involved in
negative symptoms.
• Nigrostriatal pathway: extends from the substantia
nigra of the midbrain to the basal ganglia. (The basal
ganglia are predominantly involved with movement,
but some structures, such as the ventral striatum, also
have limbic system functions.)….. VOLUNTARY
MOVEMENT
• Tuberoinfundibular pathway :extends from the
hypothalamus to the portal system which serves the
anterior pituitary.
• In the healthy individual, tonic release of dopamine
into this system inhibits the release of prolactin.
• Unintentional disruption of this system leads to
elevation of serum prolactin and the side-effects of
gynecomastia, galactorrhea and sexual dysfunction.
Dopamine pathways
1. Mesocortical pathway
• Difficulties with executive and other cognitive
functions.
• Disturbnce in behaviour and negative symptoms
2.Mesolimbic pathway• Positive symptoms of hallucinations and delusions,
and negative symptoms.
3. Nigrostriatal pathway- disturbance in
voluntary movement
4. Tuberoinfundibular pathway-
• Elevation of serum prolactin
• Side-effects of gynecomastia, galactorrhea
and sexual dysfunction.
Mechanism of action
• Exact mechanism is unknown
• Antidopaminergic activity
• Block D2 receptors which are mainly present in meso
cortical- mesolimbic system (mesolimbic- emotional
reactions), nigro-striatal system and tuberoinfundibular system)
Antipsychotic Medications Block Dopamine
Dopamine
Speaking
Brain Cell
Listening
Brain Cell
Antipsychotic Medication
Blocks Receptor Site
Indications
• Organic psychiatric disorders
 Delirium (haloperidol, risperidone)
 Dementia
 Delirium tremens
 Drug induced psychosis (amphetamine induced
psychosis)- haloperidol
 Organic hallucinosis, organic delusional disorders
Non organic psychiatric disorders
• Schizophremia
• Schizoaffective disorders
• Manic episodes in bipolar disorders
• Tourette syndrome
• Senile dementia
• Major depression
• Delusional disorders
Neurotic and other psychiatric disorders
• Severe , intractable and disabling anxiety
• Refractory obsessive compulsory disorder
• Anorexia nervosa
Medical disorders
• Huntington’s chorea (haloperidol)
• Intractable cough (chlorpromazine)
• Nausea and vomiting
• Tic disorders ( haloperidol, risperidone )
Contd..
Non psychiatric indications
• Anti-emetic effect (prochlor perazine)
• Anti-pruritic effect (phenothiazines)
• Preoperative anesthesia.(Promethazine)
• Neuroleptic anesthesia.(Droperidol)
A. Classification
1. Typical (conventional) antipsychotic drugs:
– Often sub classified according to their oral potency
(high potency or low potency).
a. High-potency drugs
– piperazine phenothiazines, e.g., fluphenazine
– butyrophenones e.g., haloperidol
– more likely to produce extra pyramidal
reactions.
a. Low-potency drugs
• aliphatic phenothiazines, e.g.,triflupromazine
• piperidine phenothiazines, e.g., thioridazine
– are less likely to produce acute extrapyramidal
reactions
– more likely to produce sedation and postural
hypotension.
2. Atypical antipsychotic drugs
- example: Clozapine, risperidone, olanzapine,
quetiapine, aripiprazole.
–
have generally replaced the conventional drugs
for initial treatment of first-episode patients.
–
Clozapine is reserved for treatment-resistant
patients.
3. Other typical heterocyclic antipsychotic drugs
–
e.g., loxapine and molindone
–
intermediate potency
–
have no clear advantage over other conventional
drugs.
E.
•
Adverse effects and contraindications
The adverse effects of antipsychotic agents are due
to their antagonist actions at receptors
 in the CNS
– dopamine D2-receptors , histamine H1-receptors
(and possibly serotonin receptors)
 in the periphery
– muscarinic cholinoceptors and α-adrenoceptors
1. Central nervous system
A. Extra pyramidal syndromes
1. These adverse effects are related to a dopaminereceptor blockade in the basal ganglia that leads
to an imbalance in dopamine and acetylcholine
actions in the nigro striatal pathway.
2. These effects are a major cause of
noncompliance.
Extra pyramidal effects are:
• most likely to occur with high-potency
conventional antipsychotic drugs that have a
high affinity for post junctional dopamine D2-
receptors in the basal ganglia.
• occur with few atypical drugs like risperidone.
- These effects can sometimes spontaneously
remit.
Extra pyramidal syndromes include the following:
1.
Acute dystonia : sustained muscle contractions
cause twisting and repetitive movements or
abnormal postures
–
This condition is often elicited during the first
week of therapy.
Acute dystonia
Contd…
2.
Akathisia is the irresistible compulsion to be in
motion.
Walkies and talkies ( urge to move about)
–
This condition can develop as early as the first 2
weeks of treatment or as late as 60 days into
therapy.
Contd…
3.
Parkinsonian-like syndrome
•
Parkinsonian-like syndrome is characterized by
tremors, bradykinesia, rigidity, and other
signs of parkinsonism.
•
This syndrome can develop from 5 days to
weeks into treatment.
4. Periodic Tremor Rabbit Syndrome
Peri-oral tremors after months or years of
treatment
B. Tardive dyskinesia (10—20%)
•
CNS disorder characterized by:
• twitching of the face and tongue
• involuntary motor movements of the trunk and
limbs
•
More likely with conventional antipsychotic agents.
The only effective treatment for tardive dyskinesia is
the discontinuation of treatment.
Orofacial
movements
Dystonic posture
• Tardive dyskinesia generally occurs after months to
years of drug exposure; it may be exacerbated or
precipitated by the discontinuation of therapy.
• Tardive dyskinesia is often irreversible.
• More likely to occur in the elderly or in
institutionalized patients who receive long-term,
high-dose therapy.
c.
•
Neuroleptic malignant syndrome
Due to excessively rapid blockade of
postsynaptic dopamine receptors.
•
This syndrome is characterized by:
– altered blood pressure and heart rate.
– muscle rigidity
Contd…
– diaphoresis
– profound hyperthermia
•
This condition occurs, often explosively, in 1% of
patients; it is associated with a 20% mortality rate.
NMS
• This condition is treated by:
1.Discontinuing drug therapy
2.Initiating supportive measures, including the use of
bromocriptine to overcome the dopamine
receptor blockade
3.Muscle relaxants such as dantrolene and
diazepam to reduce muscle rigidity.
d.
•
Sedation
More likely with low-potency antipsychotic
agents and with the atypical agents, are due to a
central histamine H1-receptor blockade.
•
These effects may be mild to severe.
•
The elderly are particularly at risk.
•
May be temporary
e. Confusional state with memory impairment.
- This effect is likely with antipsychotic agents with
pronounced antimuscarinic activity.
f. Seizures: Seizures are especially common with
chlorpromazine and clozapine.
- This effect is due to a lowering of the seizure
threshold; antipsychotic drugs may precipitate or
unmask epilepsy.
2. Autonomic Nervous system
1.
α-Adrenoceptor blockade
 More likely to occur with:
– conventional low-potency
– atypical antipsychotic agents.
•
Postural hypotension- phenothiazines
when a person moves to a more vertical position: from
sitting to standing or from lying down to sitting or
standing.
CONTD..
•
Orthostatic hypotension – (atypical drugs)
symptoms: dizziness, faintness or lightheadedness
which appear only on standing, and which are
caused by low blood pressure.
•
Failure to ejaculate –(phenothiazines)
contd..
2. Muscarinic cholinoceptor blockade
• More common with:
conventional low-potency antipsychotic agents
atypical agent like clozapine.
symptoms : (dry mouth, constipation, urinary
retention, and visual problems)
• Elderly patients are more at risk
3. Endocrine and metabolic disturbances
• Most likely with
– most conventional antipsychotic agents
– atypical agent risperidone
• Due to dopamine (D2)-receptor antagonist activity in
the pituitary, resulting in hyperprolactinemia.
Contd..
 In women, these disturbances include:
 galactorrhea
 loss of libido
 delayed ovulation and menstruation or amenorrhea.
 In men;
 gynecomastia
 impotence.
Contd..
 Weight gain, which is likely with:
 most conventional
 atypical antipsychotic agents, except
aripiprazole and ziprasidone, may be due in
part to histamine H1-receptor antagonist activity.
4. Other adverse effects
a.
Withdrawal-like syndrome
1. Symptoms: nausea, vomiting, insomnia, and
headache
•
in 30% of patients, especially those receiving lowpotency antipsychotic drugs.
2. Symptoms may persist for up to 2 weeks.
3. Symptoms can be minimized with a tapered reduction
of drug dosage.
b. Cardiac arrhythmias
•
More likely with thioridazine and ziprasidone,
which can prolong the Q-T interval and lead to
conduction block and sudden death.
c. Blood dyscrasias
– rare, except in the case of clozapine, which may
induce agranulocytosis (severe neutropenia) in
up to 3% of patients and, therefore, is used only
when other drug groups prove ineffective.
c.
Cholestatic jaundice, which is caused primarily by
chlorpromazine
d. Photosensitivity
1. The effect is specific to chlorpromazine
–
it includes dermatitis (5%), rash, sunburn, and
pigmentation, and it may be irreversible.
2. Chlorpromazine and high-dose thioridazine also
produce retinitis pigmentosa