Podcast
Questions and Answers
Which of the following antipsychotics exhibits a higher affinity for blocking 5HT2A receptors compared to D2 receptors?
Which of the following antipsychotics exhibits a higher affinity for blocking 5HT2A receptors compared to D2 receptors?
- Risperidone (correct)
- Fluphenazine
- Haloperidol
- Chlorpromazine
Which of the following is a common side effect associated with drugs that have high affinity for D2 receptors, such as haloperidol?
Which of the following is a common side effect associated with drugs that have high affinity for D2 receptors, such as haloperidol?
- Extrapyramidal symptoms (EPS) (correct)
- Significant weight gain
- Profound sedation
- Severe hypotension
Which mood stabilizer is thought to exert its therapeutic effects by suppressing inositol signaling?
Which mood stabilizer is thought to exert its therapeutic effects by suppressing inositol signaling?
- Carbamazepine
- Lamotrigine
- Valproic acid
- Lithium (correct)
A patient taking which of the following antipsychotics would be MOST likely to experience significant anticholinergic side effects?
A patient taking which of the following antipsychotics would be MOST likely to experience significant anticholinergic side effects?
Which of the following first-generation antipsychotics is characterized by a high risk of orthostatic hypotension and a high degree of sedation?
Which of the following first-generation antipsychotics is characterized by a high risk of orthostatic hypotension and a high degree of sedation?
Which of the following second-generation antipsychotics would be LEAST likely to cause extrapyramidal symptoms (EPS) at typical doses?
Which of the following second-generation antipsychotics would be LEAST likely to cause extrapyramidal symptoms (EPS) at typical doses?
Based on their receptor binding profiles, which pair of antipsychotics would MOST likely be effective in treating both positive and negative symptoms of schizophrenia, while also minimizing the risk of EPS and tardive dyskinesia?
Based on their receptor binding profiles, which pair of antipsychotics would MOST likely be effective in treating both positive and negative symptoms of schizophrenia, while also minimizing the risk of EPS and tardive dyskinesia?
Considering the established therapeutic mechanisms of mood stabilizers, which of the following best explains how lithium, valproic acid, and lamotrigine collectively contribute to mood stabilization in bipolar disorder?
Considering the established therapeutic mechanisms of mood stabilizers, which of the following best explains how lithium, valproic acid, and lamotrigine collectively contribute to mood stabilization in bipolar disorder?
Which characteristic distinguishes a neuroleptic from other types of antipsychotic drugs?
Which characteristic distinguishes a neuroleptic from other types of antipsychotic drugs?
According to the dopamine hypothesis of schizophrenia, what is a key factor contributing to psychosis?
According to the dopamine hypothesis of schizophrenia, what is a key factor contributing to psychosis?
Which neurotransmitter receptor is primarily targeted by atypical antipsychotics to reduce hallucinogenic effects?
Which neurotransmitter receptor is primarily targeted by atypical antipsychotics to reduce hallucinogenic effects?
What effect does diminished GABA activity have on glutamate receptors, according to the glutamate hypothesis of schizophrenia?
What effect does diminished GABA activity have on glutamate receptors, according to the glutamate hypothesis of schizophrenia?
Which of the following best describes the action of an inverse agonist at a receptor?
Which of the following best describes the action of an inverse agonist at a receptor?
Which of the following antipsychotics is considered a prototype atypical antipsychotic?
Which of the following antipsychotics is considered a prototype atypical antipsychotic?
Which of the following enzymes plays a role in the biotransformation of antipsychotic medications?
Which of the following enzymes plays a role in the biotransformation of antipsychotic medications?
A patient is prescribed an antipsychotic medication. Considering the typical pharmacokinetics of these drugs, what is a likely consequence regarding bioavailability?
A patient is prescribed an antipsychotic medication. Considering the typical pharmacokinetics of these drugs, what is a likely consequence regarding bioavailability?
A researcher discovers a novel compound that shows promise as an antipsychotic but has no direct effect on D2 receptors in vitro. Based on current understanding, what is the most plausible mechanism by which this compound could still exert antipsychotic effects?
A researcher discovers a novel compound that shows promise as an antipsychotic but has no direct effect on D2 receptors in vitro. Based on current understanding, what is the most plausible mechanism by which this compound could still exert antipsychotic effects?
An experimental drug demonstrates high affinity for both 5HT2A and D2 receptors, acting as an agonist at 5HT2A and an antagonist at D2. If this drug were administered to a patient with schizophrenia, what paradoxical effect might be observed, considering the known pharmacology of antipsychotics?
An experimental drug demonstrates high affinity for both 5HT2A and D2 receptors, acting as an agonist at 5HT2A and an antagonist at D2. If this drug were administered to a patient with schizophrenia, what paradoxical effect might be observed, considering the known pharmacology of antipsychotics?
Antagonism at which receptor type is generally required for antipsychotic action, though exceptions may exist?
Antagonism at which receptor type is generally required for antipsychotic action, though exceptions may exist?
Which of the following adverse reactions is LEAST likely to be associated with antipsychotic drug use?
Which of the following adverse reactions is LEAST likely to be associated with antipsychotic drug use?
A patient on clozapine requires regular blood monitoring due to the risk of which severe adverse effect?
A patient on clozapine requires regular blood monitoring due to the risk of which severe adverse effect?
What is a key diagnostic feature of neuroleptic malignant syndrome (NMS)?
What is a key diagnostic feature of neuroleptic malignant syndrome (NMS)?
Which of the following is NOT a typical symptom during the manic phase of bipolar disorder?
Which of the following is NOT a typical symptom during the manic phase of bipolar disorder?
What property of lithium is most relevant to its distribution within the body?
What property of lithium is most relevant to its distribution within the body?
Lithium's therapeutic effect on mood stabilization is thought to be primarily mediated through its action on which of the following?
Lithium's therapeutic effect on mood stabilization is thought to be primarily mediated through its action on which of the following?
Which common adverse effect is associated with Lithium use?
Which common adverse effect is associated with Lithium use?
A patient presents with polyuria and excessive thirst while taking lithium. Which of the following adverse effects is the MOST likely cause?
A patient presents with polyuria and excessive thirst while taking lithium. Which of the following adverse effects is the MOST likely cause?
A researcher is investigating the effects of a novel antipsychotic drug. They observe that the drug binds strongly to D2 receptors but does not elicit a decrease in cAMP levels, inhibit calcium ($Ca^{2+}$) channels, or open potassium ($K^+$) channels. Based on this information, where is the most probable location of the receptors?
A researcher is investigating the effects of a novel antipsychotic drug. They observe that the drug binds strongly to D2 receptors but does not elicit a decrease in cAMP levels, inhibit calcium ($Ca^{2+}$) channels, or open potassium ($K^+$) channels. Based on this information, where is the most probable location of the receptors?
What are the 'positive' symptoms of Schizophrenia? (Select all that apply)
What are the 'positive' symptoms of Schizophrenia? (Select all that apply)
What are the “negative” symptoms of Schizophrenia?
What are the “negative” symptoms of Schizophrenia?
What is the mechanism of action of haloperidol?
What is the mechanism of action of haloperidol?
Is haloperidol a typical or atypical antipsychotic?
Is haloperidol a typical or atypical antipsychotic?
What are extrapyramidal side effects (EPSs) of antipsychotic drugs?
What are extrapyramidal side effects (EPSs) of antipsychotic drugs?
Which autonomic nervous system receptors are antagonized by antipsychotic drugs?
Which autonomic nervous system receptors are antagonized by antipsychotic drugs?
Flashcards
Neuroleptic
Neuroleptic
Antipsychotic drug type causing extrapyramidal side effects (EPS).
Psychosis
Psychosis
A mental disorder with delusions, hallucinations and disorganized thinking.
Schizophrenia
Schizophrenia
Thinking disturbance with a clear sensorium.
Inverse Agonist
Inverse Agonist
Blocks the constitutive activity of a receptor.
Signup and view all the flashcards
Dopamine Hypothesis
Dopamine Hypothesis
Excessive dopamine (DA) activity plays a role in psychosis.
Signup and view all the flashcards
PCP and Ketamine
PCP and Ketamine
Inhibitors of NMDA receptors, causing diminished GABA activity.
Signup and view all the flashcards
Phenothiazine Derivatives
Phenothiazine Derivatives
A class of antipsychotics including chlorpromazine, producing sedation and weight gain.
Signup and view all the flashcards
Clozapine
Clozapine
Prototype atypical antipsychotic.
Signup and view all the flashcards
CYP 2D6, 1A2, 3A4
CYP 2D6, 1A2, 3A4
Enzymes responsible for the biotransformation of antipsychotics.
Signup and view all the flashcards
Dopamine Systems
Dopamine Systems
Dopamine pathways are involved in voluntary movement and eating behavior.
Signup and view all the flashcards
D2 Receptor Affinity
D2 Receptor Affinity
Efficacy of antipsychotics often correlates with their binding strength to D2 receptors.
Signup and view all the flashcards
D2 Receptor Effects
D2 Receptor Effects
D2 receptor stimulation decreases cAMP, inhibits Ca2+ channels, and opens K+ channels.
Signup and view all the flashcards
Extrapyramidal Reactions
Extrapyramidal Reactions
Can occur as Parkinsonism, Akathisia and acute dystonia.
Signup and view all the flashcards
Tardive Dyskinesia
Tardive Dyskinesia
Late-onset syndrome causing abnormal, involuntary movements, often after long-term antipsychotic use.
Signup and view all the flashcards
Neuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome
Life-threatening reaction to antipsychotics involving muscle rigidity, fever, and elevated creatinine kinase.
Signup and view all the flashcards
Mania Symptoms
Mania Symptoms
Excitement, hyperactivity, impulsivity, aggression, and diminished need for sleep.
Signup and view all the flashcards
Depression Symptoms
Depression Symptoms
Depressed mood, sleep disturbance, anxiety and high risk of suicide.
Signup and view all the flashcards
Lithium
Lithium
Small monovalent cation, similar to sodium, used to stabilize mood in bipolar disorder.
Signup and view all the flashcards
Lithium's Mechanism
Lithium's Mechanism
Inhibits inositol phosphate signaling, affecting alpha-adrenergic and muscarinic neurotransmission.
Signup and view all the flashcards
Lithium's ADRs
Lithium's ADRs
Tremor, decreased thyroid function, nephrogenic diabetes insipidus, and edema.
Signup and view all the flashcards
Atypical Antipsychotics
Atypical Antipsychotics
Drugs that block 5HT2A receptors more strongly than D2 receptors (5HT2A > D2).
Signup and view all the flashcards
Butyrophenone
Butyrophenone
Drug that blocks D2 receptors more strongly than 5HT2A receptors (D2 >> 5HT2A).
Signup and view all the flashcards
Mood Stabilizers
Mood Stabilizers
Drugs used to stabilize mood, often by influencing intracellular signaling pathways.
Signup and view all the flashcards
First Generation Antipsychotics
First Generation Antipsychotics
First Generation Antipsychotics block D2 receptors more strongly than 5HT receptors (D2 >> 5HT).
Signup and view all the flashcards
Second Generation Antipsychotics
Second Generation Antipsychotics
Second Generation Antipsychotics block 5HT receptors more strongly than D2 receptors (5HT > D2).
Signup and view all the flashcards
Neurotransmitter Imbalance in Psychosis
Neurotransmitter Imbalance in Psychosis
Elevated levels of norepinephrine, serotonin, and dopamine in the central nervous system.
Signup and view all the flashcardsStudy Notes
- Neuroleptic drugs are antipsychotics producing extrapyramidal side effects (EPS).
- Psychosis involves mental disorders, delusions, hallucinations, and disorganized thinking.
- Schizophrenia features a clear sensorium with marked thinking disturbance and has high heritability.
History of Antipsychotics
- Reserpine, which depletes biogenic amine levels, was the first drug used to treat psychotic symptoms.
- Chlorpromazine is an antipsychotic that induces EPS by blocking dopamine (DA) receptors.
- Clozapine is an atypical antipsychotic drug and does not produce EPS.
Serotonin Hypothesis of Schizophrenia
- LSD and mescaline (from psychedelic mushrooms) are serotonin (5HT) agonists.
- Hallucinogenic properties of these drugs are due to their binding to 5HT2A receptors.
- Atypical antipsychotics act as inverse agonists at 5HT2A receptors, examples include clozapine and quetiapine.
- Inverse agonists block the constitutive activity of receptors.
- 5HT2A receptors modulate dopamine (DA) release in the cortex, limbic region, and striatum.
Dopamine Hypothesis of Schizophrenia
- Excessive dopamine (DA) activity contributes to psychosis.
- Many antipsychotic drugs function by blocking D2 receptors.
- Drugs, such as amphetamines, levodopa, and apomorphine, that increase dopamine (DA) activity can induce psychosis.
- Schizophrenics who have never been treated show increased dopamine (DA) receptor density.
- Postmortem studies in schizophrenics show increased dopamine (DA) levels and D2 receptor density.
- Imaging studies reveal increased amphetamine and dopamine (DA) release.
- Effective antipsychotics may have little effect on D2 receptors in some cases.
Glutamate Hypothesis of Schizophrenia
- Glutamate is the major excitatory neurotransmitter in the brain.
- Phencyclidine (PCP, angel dust) and ketamine inhibit NMDA receptors.
- Hypofunction of NMDA receptors on GABA interneurons can reduce inhibitory influences on neuronal function.
- Diminished GABA activity leads to overactivity of glutamate receptors.
Basic Pharmacology of Antipsychotic Agents: Chemical Types
- Phenothiazine derivatives include aliphatic derivatives like chlorpromazine and piperidine derivatives like thioridazine and perphenazine, both types causing sedation and weight gain.
- Thioxanthene derivatives include thiothixene.
- Butyrophenone derivatives include haloperidol, the most widely used in this group.
- Miscellaneous structures include typical antipsychotics such as pimozide and molindone.
- Atypical antipsychotics are prototyped by clozapine.
Pharmacokinetics
- Antipsychotics undergo a first-pass effect.
- Bioavailability averages 25-35%, except for haloperidol at 65%.
- Biotransformation occurs via CYP 2D6, 1A2, and 3A4 enzymes.
Pharmacodynamics: Dopamine Systems
- Dopamine (DA) is used in various brain pathways.
- These pathways are involved in voluntary movement, inhibition of prolactin secretion, and eating behavior.
Dopamine Receptors
- Efficacy correlates with affinity for D2 receptors.
- Receptor activation decreases cAMP levels, inhibits Ca channels, and opens K channels.
- Receptors are found pre- and post-synaptically.
- Antagonism at D2 receptors is required for antipsychotic action, but there can be exceptions.
Clinical Pharmacology: Adverse Reactions (ADRs)
- Extrapyramidal reactions include Parkinson's Syndrome, akathisia (uncontrolled restlessness), and acute dystonic reaction (spastic retrocollis or torticollis).
- Tardive dyskinesia is a late-onset syndrome of abnormal choreoathetoid movements.
- Antimuscarinic effects include urinary retention.
- Weight gain, loss of libido, impotence, and infertility can occur.
- Agranulocytosis (1-2% of patients) is mainly caused by clozapine; patients must have CBC every week for the first 6 months and every 3 weeks after that.
- Neuroleptic malignant syndrome is life-threatening, caused by extrapyramidal effects of antipsychotics, with symptoms like muscle rigidity, high fever (sweating impaired), and high creatinine kinase (CK) levels, reflecting muscle damage, it is caused by rapid blocking of dopamine receptors and is treated with diazepam (muscle relaxant) and antiparkinsonism drugs.
Lithium, Mood-Stabilizing Drugs, and Other Treatment for Bipolar Disorder
- Bipolar disorder, previously called manic-depressive illness, is on a continuum from schizophrenia.
- It occurs in 1-3% of the adult population and is often diagnosed in the third or fourth decade of life.
- Manic phase symptoms include excitement, hyperactivity, impulsivity, disinhibition, aggression, diminished need for sleep, and cognitive impairment.
- Depressive phase symptoms include depressed mood, sleep disturbance, anxiety, and high risk of suicide.
Lithium
- Lithium is a small, monovalent cation that distributes mostly into body water (Vd = 0.5 L/Kg) and undergoes no biotransformation.
- It is cleared by the kidneys with a half-life of approximately 20 hours and target Cp levels of 0.6 – 1.4 mEq/L.
- It is closely related to sodium in its properties.
- The best-defined effect of lithium is on inositol phosphates.
- Lithium impacts inositol trisphosphate and diacylglycerol second messengers in alpha-adrenergic and muscarinic transmission.
- Lithium inhibits these messengers' production and down-regulates pathways that use them.
Bipolar Affective Disorder
- Lithium was once the drug of choice but has been replaced by others.
- Numerous ADRs include tremor (Common), decreased thyroid function, nephrogenic diabetes insipidus, and edema.
Other Drugs Used in Place of Lithium
- Valproic Acid, carbamazepine, lamotrigine all covered in previous chapters.
Chapter 29 Antipsychotics
- Drugs Required in Bold Including all those in the previous text.
PHENOTHIAZINE DERIVATIVES
- Block of D2 >> 5HT2A receptors
- Includes chlorpromazine, fluphenazine, thioridazine, trifluoperazine, thiothixene
ATYPICAL ANTIPSYCHOTICS
- Block of 5HT2A > block of D2 receptors
- Includes aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone
BUTYROPHENONE
- Block of D2 >> 5HT2A receptors
- includes haloperidol
MOOD STABILIZERS
- Suppress inositol signaling
- Includes lithium, carbamazepine, lamotrigine, valproic acid
Comparison of antipsychotics
| Drug | Sedation | Orthostatic Hypotension | EPS | ACh Effects |
|---|---|---|---|---|
| aripiprazole | low | low | +/0 | + |
| clozapine | high | high | 0 | +++++ |
| haloperidol | low | low | +++++ | + |
| risperidone | low | mild | + | + |
- EPS = Parkinson dystonias, dystonias, akathisia.
- ACh Effects = anticholinergic side effects
Brief Summary
- The theory for the cause of schizophrenia, bipolar disorder, and psychosis associated with dementia is that certain CNS neurotransmitters (NT) are elevated in the CNS
- Reducing the activity of these NTs, including NE, 5HT, and DA is a goal in drug therapy in psychotic conditions.
- Drugs act by attaching to and blocking a specific receptor for one or more NTs.
- First Generation Antipsychotics D2 >>5HT (stronger block of dopamine receptors compared to 5HT (serotonin) receptors)
- Includes chlorpromazine, fluphenazine, thioridazine, thiothixene, haloperidol
- Second Generation Antipsychotics 5HT > D2 (stronger block of 5HT receptors compared to dopamine receptors)
- Includes aripiprazole, brexpiprazole, cariprazine, clozapine, lurasidone, ziprasidone, olanzapine, quetiapine, risperidone
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
