AntiPsychotics Flashcards
Dopamine pathways
Mesolimbic pathway
Mesocortical pathway
Nigrostriatal pathway
Tuberoinfundibular pathway
Mesolimbic pathway
which is thought to be hyperactive in schizophrenia and to mediate positive symptoms of psychosis such as delusions and hallucinations, from Vta to Nac
Mesocortical pathway
which is thought to be underactive in schizophrenia and thus mediate negative psychotic symptoms such as loss of motivation and social withdrawal, from Vta to PFC.
Nigrostriatal pathway
Which is part of the extrapyramidal nervous system and controls motor functions and movements. Deficiency of dopamine in this pathway can lead to dystonia and parkinsonism disease symptoms, while excess of dopamine can lead to hyperkinetic movements such as tics and dyskinesias, From substantia nigra to basal ganglia.
Tuberoinfundibular pathway
Which controls prolactin secretion specifically dopamine in this pathway inhibits prolactin release and as a reminder prolactin is a hormone that enables milk production and is also involved in the control of sexual desire and regulation of the immune symptom. From hypothalamus arcuate nucleus to the hypothalamus median eminence.
Forms of psychosis
- Simple
- Catatonic
- Hebephrenic 4. Paranoid
- Residual
1st. generation typical antipsychotics: (classical neuroleptics)
EXAMPLES
Chlorpromazine Fluphenazine Thioridazine Thiothixene Haloperidol
1st. generation typical antipsychotics: (classical neuroleptics)
EXAMPLES
Chlorpromazine Fluphenazine Thioridazine Thiothixene Haloperidol PROCHLORPERAZINE TRIFLUOPERAZINE
1st. generation typical antipsychotics: (classical neuroleptics)
MOA
● competitive blockade of dopamine D2 receptors on postsynaptic neurons. also blocks alpha receptors, cholinergic receptors and histamine receptors
● First-generation antipsychotics are more likely to be associated with movement disorders
– > known as extrapyramidal symptoms (EPS)
● EPS = Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia
● Less likely to have any metabolic abnormalities.
● not selective for any of the four dopamine pathways
1st. generation typical antipsychotics: (classical neuroleptics)
SIDE EFFECTS
EPS symptoms Hyperprolactinemia sedation weight gain ABCDs hypotension
1st. generation typical antipsychotics: (classical neuroleptics)
CONTRAINDICATIONS
Hypersensitivity
Parkinsons
Dementia w/ Lewy bodies
Drinking
2nd generation atypical antipsychotics (atypical neuroleptics)
EXAMPLES
CLOZAPINE
OLANZAPINE
QUETIAPINE
RISPERIDONE
2nd generation atypical antipsychotics (atypical neuroleptics)
USE
Schizo pos. symptoms and neg.
symptoms (Mesocortical)
2nd generation atypical antipsychotics (atypical neuroleptics)
MOA
blocks D2 activity and 5HT-2a on postsynaptic neurons. also blocks alpha receptors, cholinergic receptors and histamine receptors
2nd generation atypical antipsychotics (atypical neuroleptics)
SIDE EFFECTS
EPS prolactin levels increased weight gain sedation hyperglycemia hypotension Agranulocytosis
2nd generation atypical antipsychotics (atypical neuroleptics)
CONTRAINDCATION
Hypersensitivity Myeloproliferative disorders
Epilepsy
BUPROPION
MOA
Inhibits DA and NE reuptake. SE: Tachycardia and insomnia.
MIRTAZAPINE
α2 antagonist, increased NE & serotonin release. H1 antagonist. SE: Sedation, increased appetite and increased weight.
TRAZODONE
Blocks serotonin receptors, α1, H1 and Serotonin reuptake. SE: Sedation, priapism.
VARENICLINE
Nicotinic partial agonist, used for smoking cessation.
VILAZODONE
inhibits serotonin reuptake and serotonin partial agonist.
1st. generation typical antipsychotics: (classical neuroleptics)
USES
● Schizophrenia
● Bipolar disorder (manic phase)
● Antiemesis
● Preop sedation
Phenothiazines
EXAMPLES
Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene
Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene
MOA
● Blocks D2 receptor
● Also blocks alpha, muscarinic, and H1 receptors
Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene
USE
● Schizophrenia
● Bipolar disorder (manic phase)
● Antiemesis
● Preop sedation
Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene
ADVERSE EFFECTS
● Extensions of alpha and muscarinic receptor blocking action.
● Extrapyramidal dysfunctions ( Dystonia, Akathisia, pseudoparkinsonism, tardive
dyskinesia)
● Hyperprolactinemia
What type of drug is haloperidol
Butyrophenone
Haloperidol
MOA
● Blocks D2 receptors
● Blocks few alpha receptors compared to phenothiazines
● Blocks few muscarinic receptors compared to phenothiazines
● Less sedation compared to phenothiazines
Haloperidol
USE
● Schizophrenia
● Bipolar disorder (manic phase)
● Huntington’s chorea
● Tourette syndrome
Haloperidol
SIDE EFFECT
● Extrapyramidal dysfunction (Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia)
list the atypical neuroleptics
Aripiprazole Brexpiprazole Clozapine ( note most important side effect - agranulocytosis ) Olanzapine Quetiapine Risperidone Ziprasidone
Aripiprazole
MOA
● partial agonists at D2 and 5-HT1A receptors, as well as antagonists of 5-HT2A receptors.
● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.
Brexpiprazole: MOA
● Newer 2nd gen drugs
● partial agonists at D2 and 5-HT1A receptors, as well as antagonists of 5-HT2A
receptors
● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.
MOST IMPORTANT SIDE EFFECT OF CLOZAPINE
agranulocytosis
Clozapine
MOA
● high affinity for D1, D4, 5-HT2, muscarinic, and α-adrenergic
● Weak D2 receptor antagonist
● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.
Olanzapine
MOA
● blocks 5-HT2A receptors to a greater extent than it does D2 receptors
● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.
Quetiapine MOA & SEs
relatively weak at blockade of D2 and 5-HT2A receptors
● low risk for EPS
Side effects: ● dizziness, feeling unsteady, or having trouble keeping your balance. ● pain in the joints, back, neck, or ears. ● weakness. ● dry mouth. ● vomiting. ● indigestion. ● constipation.
Risperidone MOA
blocks 5-HT2A receptors to a greater extent than it does D2 receptors
Clinical applications of atypical neuroleptics (1)
Actions:
● The clinical effects of antipsychotic drugs reflect a blockade at dopamine and/or serotonin receptors
● They also block cholinergic, adrenergic, and histaminergic receptors
1. Antipsychotic effects:
● reduce hallucinations and delusions associated with schizophrenia (known as “positive”
symptoms) by blocking D2 receptors in the mesolimbic system of the brain
● Many second-generation agents, such as clozapine, can reduce the negative symptoms
to some extent.
2. Extrapyramidal effects:
● Dystonias, Parkinson-like symptoms, akathisia, and tardive dyskinesia can occur with
both acute and chronic treatment
● The second-generation antipsychotics exhibit a lower incidence of EPS.
Clinical applications of atypical neuroleptics (2)
- Antiemetic effects:
● The antipsychotic drugs have antiemetic effects that are mediated by blocking D2
receptors of the chemoreceptor trigger zone of the medulla - Anticholinergic effects:
● Some of the antipsychotics, particularly thioridazine, chlorpromazine, clozapine, and
olanzapine, produce anticholinergic effects.
● The anticholinergic effects may actually assist in reducing the risk of EPS with these
agents. - Other effects:
● Blockade of α-adrenergic receptors causes orthostatic hypotension and
light-headedness.
● alter temperature-regulating mechanisms and can produce poikilothermia
● In the pituitary, antipsychotics that block D2 receptors may cause an increase in prolactin
release.
● Sedation
● Sexual dysfunction
USE of atypical neuroleptics
● Schizophrenia (positive and negative symptoms)
● Bipolar disorder
● Major depression
● Agitation (seen in alzheimers and parkinsons)
● Prevention of nausea and vomiting
● treat intractable hiccups
● treatment of the motor and phonic tics of Tourette disorder
● tic disorder
● management of disruptive behavior and irritability secondary to autism.
Side effects of atypical neuroleptics
● Urinary retention ● Weight gain (clozapine, olanzapine) ● Seizure ● Sedation ● Extrapyramidal symptoms ● Postural hypotension ● Sexual dysfunction ● Arrhythmias ● Sudden cardiac death ● Dry mouth ● Agranulocytosis (clozapine) ● Diabetes (clozapine, olanzapine) ● Hyperprolactinemia (risperidone) ● Qt prolongation (ziprasidone) ● Tardive dyskinesia ● Neuroleptic malignant syndrome
