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MNI Lecture 5 - Antipsychotics
Terms in this set (58)
Schizophrenia is defined as a _______________ characterized by _____________, __________, ___________, and ___________
What are the 3 types of symptoms present in schizophrenia?
Chronic psychotic disorder
Disturbed behavior, thinking, emotions and perceptions
1. Positive symptoms
2. Negative symptoms
3. Cognitive symptoms
Positive symptoms of schizophrenia reflect ___________________
What are the 5 things included in this category?
An excess of normal functions
1. Hallucinations & delusions
2. Thought disorder
3. Perceptual disturbances
4. Incongruous mood
5. Increased motor function
Negative symptoms of schizophrenia reflect ___________________
What are the 4 things included in this category?
Diminution or loss of normal functions
1. Blunted affect
2. Poverty of speech
3. Diminished motivation
4. Social withdrawal
Cognitive symptoms of schizophrenia reflect ___________________
Deficits in memory and cognitive control of behavior
Positive symptoms of schizophrenia are believed to be linked to __________________
OVERACTIVITY of the mesolimbic pathway
-Excess of normal function
Negative and cognitive symptoms may be due to ________________________
HYPOACTIVITY of the mesocortical pathway
-Diminution or loss of normal function
What are the 4 well-defined dopamine pathways in the brain?
1. Mesolimbic pathway (responsible for positive symptoms)
2. Mesocortical pathway (responsible for negative symptoms)
3. Nigrostriatal pathway
4. Tuberoinfundibular pathway
The mesolimbic pathway projects from _____________ to ____________
It plays an important role in ______________
Hyperactivity may cause _____________ psychotic symptoms, while blockade of D2 receptors causes a _______________ psychotic symptoms
Midbrain to limbic system
Decrease in positive
The mesocortical pathway projects from _____________ to ____________
Reduced activity may cause _________ and ___________, while blockade of D2 receptors may ____________________
Midbrain to prefrontal cortex
Cognitive and negative symptoms
Cause or worse negative and cognitive symptoms
The tuberoinfundibular pathway projects from _____________ to ____________
Dopamine released from these neurons ______________ (does what?), therefore, blockade of these receptors will ______________, which may cause ____________
Hypothalamus to anterior pituitary
Inhibits prolactin secretion
Increase prolactin levels
The nigrostriatal pathway projects from _____________ to ____________, and it controls _______________
Blockade of D2 receptors may lead to __________ because this pathway is part of the _____________ nervous system
Substantia nigra to basal ganglia
Disorders of movement
Motor adverse effects associated with _____________ are called _____________
Blockade of dopamine receptors
Extrapyramidal reactions (EPR)
In the nigrostriatal pathway, _________ and __________ synapse on the ______________
Dopaminergic and cholinergic neurons
-GABA's primary directive is to fine-tune movement
Hallucinogens like _______ and ________ are ________________
Stimulation of _______________ cause hallucinations
LSD and mescaline
5-HT2 receptor subtypes
-Blockade of these receptors is a key factor in the MOA of atypical antipsychotics
Atypical antipsychotics are ______________ of ___________ receptors
-Modulate the release of dopamine, norepinephrine, glutamate, GABA and acetylcholine
What are the 2 types of antipsychotics?
How are they alike and how are they different?
1. Classical -> Also known as first generation or typical
2. Atypical -> Also known as second generation
Alike: ALL antipsychotics block D2 receptors in the CNS
Different: Second generation antipsychotics have decreased extrapyramidal symptoms (as opposed to first generation drugs)
What are the 4 classical antipsychotics discussed?
What are the 5 atypical antipsychotics discussed?
Most antipsychotic drugs are _____________ metabolized, mainly by ________, _________ and _________
What is important to note about antipsychotic drugs?
CYP2D6, CYP1A2 and CYP3A4
DO NOT interfere with the metabolism of other drugs
What are the 2 classical antipsychotics that have high potency?
What are the 2 that have low potency?
In terms of classical antipsychotics, high potency drugs such as ___________ and ___________, are more likely to produce ______________
Fluphenazine and Haloperidol
EPRs (extrapyramidal reactions)
In terms of classical antipsychotics, low potency drugs such as ___________ and ___________, are less likely to produce ______________, and are more likely to produce _________ and _________
Chlorpromazine and Thioridazine
EPRs (extrapyramidal reactions)
Sedation and postural hypotension
The efficacy of classical antipsychotics correlates closely with their ability to _______________ in the _____________
Block D2 receptors
Atypical antipsychotic drugs have ___________ affinities for ____________ compared to the _____________
What are the 5 receptors that clozapine has a high affinity for?
This drug is a ____________
Clozapine is the prototype of atypical agents
Risperidone blocks ____________ to a greater extent than it does __________
Atypical antipsychotics have ___________ antagonism at __________ and/or _________ receptors. Part of their action is due to _______________
They are less likely to cause ___________ than classical agents, ___________, or _______________
5-HT2 and/or D2
5HT receptor blockade
EPRs (extrapyramidal reactions)
Increases in prolactin
Atypical antipsychotics are most effective at treating _______________, and they are effective in ____________ populations
Atypical antipsychotics are known to be less likely to cause EPRs. What is the drug in this category that is an exception to that?
What are the 2 agents that are least likely to cause EPRs?
RISPERIDONE -> this drug causes EPRs (rare at therapeutic doses)
Aripiprazole (atypical agent) is a _________ at _______ and ________ receptors and an ____________ at ___________ receptors
D2 and 5HT1A
What are the 4 actions of antipsychotic drugs?
What is the onset of action of these drugs?
1. Reduce hallucinations & agitation
2. Have a calming effect
3. Do not depress intellectual function
4. Motor incoordination is minimal
< or = 24 hours
With the exception of ___________ and ____________, most neuroleptics have antiemetic effects
This antiemetic effect is mediated by ______________ of the ____________________
Aripiprazole (atypical) and Thioridazine (typical)
Blockade of D2 receptors
Chemoreceptor trigger zone of the medulla
What are the 7 AE of antipsychotics discussed?
1. Weight gain
3. Insulin resistance
4. Diabetes (metabolic effects)
6. QTc / T-wave changes (cardiac toxicity)
7. EPRs (extra pyramidal reactions)
9. Neuroleptic malignant syndrome
10. Anticholinergic effects
11. Orthostatic hypotension and impaired ejaculation
12. Increased prolactin secretion
13. Ocular changes
Extrapyramidal reactions are associated with ________________, and are most likely to occur with ___________ antipsychotics, such as _____________ and __________, which have a ______________
These reactions are less likely with ____________ antipsychotic drugs, such as ___________ or ___________, which have _____________ activity
Haloperidol and Fluphenazine
High affinity for D2-receptors
Chlorpromazine and Thioridazine
Strong anticholinergic activity
Note: Atypical antipsychotic drugs have a low potential for causing EPRs
Extrapyramidal reactions (EPRs) include what 4 things?
4. Tardive diskynesia
Parkinsonism can be treated with _____________ drugs like _____________ or _____________, with ______________, or with _______________
___________ should NEVER be used in these patients
Benztropine or trihexyphenidyl
LEVODOPA (never used in these patients)
Dystonia can be controlled with _____________, ______________ or _____________
Benztropine, trihexyphenidyl or diphenhydramine
Management of akathisia requires ______________ or ______________
The drugs most commonly used to manage this are ______________ or ______________
Reduction of dosage
A change of the antipsychotic drug
Clonazepam (benzodiazepine) or propranolol (beta blocker)
Tardive dyskinesia is a ____________ syndrome of ________________
This effect is potentially ____________ and may be due to _____________________
Abnormal choreoathetoid movements
-Most important unwanted effect of antipsychotics
Dopamine receptor up-regulation
To manage tardive dyskinesia, we must ______________ or _____________
MUST eliminate ALL drugs with ____________________
Discontinue antipsychotic drug or reduce dose
Central anticholinergic action
The ______________, ______________ or _____________ can be used to treat tardive dyskinesia
Administration of a _____________ may help!
____________ is recommended for patients with tardive dyskinesia who require antipsychotics
Tetrabenazine or Valbenazine
EPR Risk of Antipsychotic Agents - Summary!
Sedation is more likely with ____________ antipsychotics and with ______________ agents
This is due to _________________
Blockade of central H1 receptors
Neuroleptic malignant syndrome is a rare and life threatening disorder characterized by what 5 things?
___________ or __________ may be helpful!
1. Rigidity, tremor, hyperthermia
2. Altered mental status
3. Autonomic instability
4. Elevated WBC, elevated CK
5. Myoglobinemia, with potential nephrotoxicity
Dantrolene or Bromocriptine
Some antipsychotics block ___________ receptors, producing ______________ effects
__________ effects are beneficial in relation to EPRs
Blockade of Alpha 1 receptors causes _____________ and ____________
Orthostatic hypotension and impaired ejaculation
Clozapine causes _____________ in 1-2% of patients, therefore, ________________ are mandatory
Regular blood cell counts
Thioridazine causes a high incidence of _________ and _________ changes, and may rarely produce __________ and ___________
QTc- and T-wave
Ventricular arrhythmias and sudden death
Blockade of D2 receptors in the pituitary leads to _________________
What is the effect that this has on women?
What is the effect that this has on men?
_____________ antipsychotics are less likely to produce _____________
Increase in prolactin secretion
-Because dopamine normally inhibits prolactin secretion, so if you block dopamine receptors, you're essentially inhibiting the inhibition of prolactin secretion
Women: Amenorrhea-galactorrhea syndrome and infertility
Men: Loss of libido, infertility and impotence
Chlorpromazine causes deposits in the ___________ and ____________
Thioridazine causes _____________ deposits
Cornea and lens
Second generation antipsychotics (atypical) have a more favorable ___________ side effect profile when compared to first generation drugs (typical)
However, ____________ and other __________ effects are the most common side effects of second generation antipsychotics (atypical)
-Routine monitoring of metabolic parameters is recommended for ALL antipsychotics despite the difference in risk between the two generations!
What are the 3 AE of weight gain, seen with second generation antipsychotics (atypical)?
1. Type 2 DM
Metabolic AE - Summary!
Other AE - Summary!
What are the 7 psychiatric indications for antipsychotic usage?
2. Bipolar disorder
3. Suppression of tics in Tourette's disorder
4. Control of disturbed behavior in Alzheimer's disease
5. Adjuncts to antidepressants in treatment-resistant major depression
6. In combination with antidepressants in psychotic depression
7. Irritability associated with autistic disorder
What are the 3 non-psychiatric indications for antipsychotic usage?
3. Used in combination with FENTANYL in neurolept-anesthesia
What are the 3 reasons why atypical drugs are usually preferred?
1. Benefit for negative symptoms & cognition
2. Diminished risk of EPRs & tardive dyskinesia
3. Lesser increases in prolactin levels
____________ is currently the most prescribed antipsychotic in the US
Clozapine, because of its potential for _______________ is reserved for ___________ patients
Antipsychotic drugs are considered category __________, only ____________ is category _________
The risks of __________ and __________, which may be problematic in pregnancy, is greater when using ___________ antipsychotics
Weight gain and hyperglycemia
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