ADIGRAT UNIVERSITY

college of medicine and health

since
department of psychiatry
 Antipsychotic Medication
• Also called conventional antipsychotics
• Drugs used to treat psychotic disorder
• sometimes also called classical antipsychotics
• or typical antipsychotics
• or first-generation antipsychotics
chlorpromazine
• the first antipsychotic drugs with
antihistamine Properties
• Low potency
 D2 receptor antagonism
• also called first-generation antipsychotics
• or typical antipsychotics
• Old antipsychotics
• block dopamine D2 receptors specifically in
the mesolimbic dopamine pathway
• reducing the hyperactivity in the pathway that
cause the positive symptoms of psychosis
• the nucleus accumbens is widely considered
to be the “pleasure center” of the brain
• Antipsychotics also block D2 receptors in the
mesocortical DA pathwa
• This can cause or worsen negative and
cognitive symptoms
• even though there is only a low density of D2
receptors in the cortex.
 Extrapyramidal symptoms and tardive
dyskinesia
• When a of D2 receptors are blocked in the
nigrostriatal DA pathway
• Produce various disorders of movement
• much like those in Parkinson’s disease
• Since the nigrostriatal pathway is part of the
extrapyramidal nervous system
• if these D2 receptors in the nigrostriatal DA
pathway are blocked chronically
• hyperkinetic movement disorder known
as tardive dyskinesia
• Tardive dyskinesia is caused by long term
administration of antipsychotics
• sometimes irreversible in the D2 receptors of
the nigrostriatal DA pathway
 Prolactin elevation
• When D2 receptors in the tuberoinfundibular
DA pathway are blocked
• causes plasma prolactin concentrations to rise
• The condition called hyperprolactinemia
• This is associated with conditions called
galactorrhea (i.e breast secretions) and and
amenorrhea (i.e irregular or lack of menstrual
periods)
 Hyperprolactinemia problem

• galactorrhea (i.e., breast secretions)

• amenorrhea (i.e., irregular or lack of menstrual
periods)
• interfere with fertility in women
• rapid demineralization of bones, especially in
postmenopausal
• sexual dysfunction
• weight gain
 Muscarinic cholinergic blocking
properties of antipsychotics
• When Muscarinic M1-cholinergic receptor are
blocked
• This cause undesirable side effects such as
 dry mouth
 blurred vision,
 constipation, and
 cognitive blunting
• How does muscarinic cholinergic receptor
blockade reduce the EPS caused by dopamine D2
receptor blockade in the nigrostriatal pathway?
• The reason is
 dopamine and
 acetylcholine
have a reciprocal relationship with each other in
the nigrostriatal pathway
 Side effects of muscarinic cholinergic
receptor blockade
• constipation,
• blurred vision
• dry mouth and
• drowsiness.
 Reciprocal relationship of dopamine and
acetylcholine
 in the nigrostriatal dopamine pathway
Dopamine neurons
 make postsynaptic connections with
cholinergic
 inhibits acetylcholine release from
postsynaptic nigrostriatal cholinergic neurons
 thus suppressing acetylcholine activity
 Atypical antipsychotics
• equal positive symptom antipsychotic actions
• but low extra pyramidal symptoms and
• less hyperprolactinemia compared to typical
antipsychotics
• also called second-generation antipsychotics
• serotonin–dopamine antagonists
• Serotonin 5HT2A receptor antagonism
• low EPS and less hyperprolactinemia
• More weight gain
 Pharmacologic properties of individual
antipsychotics
the pines, the dones ,two pips and a rip
 The pines (peens
Clozapine
• 5HT2A– D2 antagonist
• or serotonin–dopamine antagonist (SDA)
• “prototypical" atypical antipsychotic
• the first antipsychotic to be recognized as
“atypical”
• cause few extra pyramidal side effects
• but not cause
 tardive dyskinesia and
 elevate prolactin
 effective when other antipsychotic agents
have failed
 the “gold standard” for efficacy in
schizophrenia.
 reduce the risk of suicide in schizophrenia
 reduce tardive dyskinesia severity
 associated with
 greatest risk of develop agranulocytosis
 Olanzapine
• is more potent than clozapine
• Lacks
 EPS
 sedating properties
 does not often raise prolactin levels
• associated with weight gain because of its
antihistaminic and 5HT2C antagonist
properties
• greatest known cardio metabolic risks
 Dopamine Pathways
 Mesolimbic
 Mesocortical
 Tuberoinfundibular (hypothalamic)
 Nigrostriatal