Antipsychotics

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Questions and Answers

What is the role of GABA-ergic inhibition in healthy individuals?

It leads to a complete inhibition of cortical activity.

It enhances the excitatory output of cortical pyramidal cells.

It reduces the excitatory output, generating gamma oscillations. (correct)

It increases the density of dendritic spines on pyramidal cells.

Which alteration is characteristic of cortical circuits in schizophrenia?

Enhanced inhibition of pyramidal cells.

Loss of pyramidal cell dendritic spines. (correct)

Stable gamma activity due to balanced output.

Increased excitation of GABAergic interneurons.

How do psychosocial stressors affect the dopamine system in schizophrenia?

They decrease dopamine sensitivity and inhibit psychotic symptoms.

They lead to uniform dopamine release throughout the brain.

They sensitize the subcortical dopamine system, heightening responses to triggers. (correct)

They completely block the dopamine release in response to stimuli.

What is the proposed consequence of reduced inhibitory signaling to pyramidal cells in schizophrenia?

Aberrant gamma activity and cognitive impairment. Signup and view all the answers

What leads to inappropriate striatal dopamine release in individuals with schizophrenia?

Impaired regulatory control due to cortical deficits. Signup and view all the answers

What is the primary mechanism of action (MoA) of Haloperidol?

Blocks post-synaptic D2 receptors Signup and view all the answers

Which of the following is a significant adverse effect (AE) associated with Chlorpromazine?

QT prolongation Signup and view all the answers

Which drug is primarily indicated for treatment-resistant schizophrenia?

Clozapine Signup and view all the answers

Risperidone is primarily effective by decreasing activity in which pathways?

Dopaminergic and serotonergic pathways Signup and view all the answers

What is a common adverse effect associated with Quetiapine?

Erectile dysfunction Signup and view all the answers

What kind of reactions can Haloperidol cause in terms of neuromuscular effects?

Bradykinesia and akinesia Signup and view all the answers

Which receptor types do Clozapine antagonize significantly?

Serotonin 5-HT2 and dopamine D2 Signup and view all the answers

Which statement about Lithium's mechanism of action is true?

It acts as an uncompetitive inhibitor of inositol monophosphatase. Signup and view all the answers

What is a common cardiovascular adverse effect of Chlorpromazine?

Hypotension Signup and view all the answers

Which antipsychotic is recommended as first-line therapy for bipolar disorder?

Olanzapine Signup and view all the answers

What adverse effect is linked to prolonged use of Haloperidol?

Neuroleptic malignant syndrome Signup and view all the answers

What is a critical consideration when prescribing Lithium?

Routine monitoring is required to prevent toxicity. Signup and view all the answers

What is an effect of dopamine receptor blockade by Chlorpromazine?

Reduction of hallucinations Signup and view all the answers

Which of the following side effects is associated with prolonged use of Lithium?

Thyroid dysfunction Signup and view all the answers

What should be done prior to initiating treatment with Clozapine?

Ensure no history of substance misuse. Signup and view all the answers

Which of the following is NOT an antipsychotic drug mentioned?

Fluoxetine Signup and view all the answers

Which side effect is typically NOT associated with SSRIs used for depression?

Sedation Signup and view all the answers

What is a potential outcome of using Quetiapine for maintenance treatment?

Increased risk of relapses Signup and view all the answers

What adverse effect might occur if Lithium levels exceed 1.2 mM?

Nausea and diarrhea Signup and view all the answers

What is important to consider regarding the timing of Lithium administration in pregnant women?

It should be stopped 2 to 3 days before delivery. Signup and view all the answers

Study Notes

Schizophrenia Physiopathology

Healthy brains exhibit a balance between excitatory and inhibitory neuronal activity. Cortical pyramidal cells' excitatory output is controlled by GABAergic interneurons. This interplay creates gamma oscillations, crucial for slow, functional brain network fluctuations.
Schizophrenia involves altered cortical circuits. Reduced pyramidal cell dendritic spines decrease excitatory activity. Diminished excitatory input to GABAergic interneurons reduces inhibition of pyramidal cells. Reduced interneuron inhibition of pyramidal cells further hampers brain function leading to aberrant gamma activity, impacting functional networks, and contributing to schizophrenia's cognitive and negative symptoms.

Stress, Dopamine, and Psychosis

Psychosocial stressors heighten the subcortical dopamine system's response to further triggers. Cortical deficits lead to impaired regulatory control. Subsequent triggers (like stress) cause inappropriate striatal dopamine release. This, in turn, leads to incorrectly determining stimuli's importance and the development of psychotic symptoms. Psychosis itself is stressful, potentially further dysregulating the system.

First-Generation Antipsychotics

Chlorpromazine: A phenothiazine antipsychotic, its action likely involves long-term brain adaptation to dopamine receptor blocking. Used as an antiemetic and for intractable hiccups.
- Mechanism of Action (MoA): Dopamine receptor (D1-D4), serotonin (5-HT1, 5-HT2), histamine (H1), muscarinic (M1/M3), dopamine reuptake inhibition. Has anxiolytic, anti-depressive and anti-aggressive properties.
- Adverse Effects (AE): weight gain, cardiovascular (hypotension, syncope, QT changes), genitourinary (breast engorgement, ejaculatory disorders, priapism), corneal deposits, visual impairment, drowsiness, dystonia, extrapyramidal reaction, neuroleptic malignant syndrome, dermatitis, photosensitivity, skin pigmentation.
Haloperidol: A phenyl-piperidinyl-butyrophenone, primarily for schizophrenia and other psychoses. Also used for delusional disorders, ballism, and Tourette syndrome. Powerful antiemetic.
- MoA: inhibits dopamine effects by tightly binding to dopamine D2 receptors, blocking dopamine neurotransmission.
- AE: CNS (extrapyramidal reactions, parkinsonism, dystonia, drowsiness, akathisia), GI (constipation, abdominal pain, sialorrhea), neuromuscular (hyperkinetic activity, tremor, bradykinesia), diaphoresis, hyperglycemia, hyponatremia, genitourinary (breast engorgement), cardiovascular (sudden death, QT-prolongation, Torsades de Pointes), cataracts, retinopathy, visual disturbances, and neuroleptic malignant syndrome. Liver and skin issues are also possible.

Second-Generation Antipsychotics (SGAs)

Clozapine: A tricyclic dibenzodiazepine, used for treatment-resistant schizophrenia.
- MoA: Selective monoaminergic antagonist, high affinity for 5HT2, D2, alpha 1/2 adrenergic, and H1 receptors.
- AE: Tachycardia, hypertension/hypotension, drowsiness, sedation, dizziness, insomnia, weight gain, constipation, nausea, vomiting, dyspepsia, fever, increased transaminases (liver), agranulocytosis, leukopenia, toxic delirium, grand mal seizures.
Risperidone: A pyridopyrimidine; Paliperidone is a primary active metabolite.
- MoA: Decreases dopaminergic and serotonergic pathway activity; high affinity for 5-HT2A receptors compared to D2 receptors.
- AE: Hyperprolactinemia, galactorrhea, gynecomastia, weight gain, increased appetite, constipation, abdominal pain, sedation, extrapyramidal symptoms, akathisia, infections (nasopharyngitis, cough).
Quetiapine: A treatment for schizophrenia, and acute manic episodes.
- MoA: Dopamine (D1/D2), alpha 1/2 adrenergic, and serotonin (5-HT1A/5-HT2) receptors.
- AE: Increased blood pressure, peripheral edema, hypertension/hypotension, syncope, drowsiness, headache, agitation, dizziness, extrapyramidal symptoms, skin rash, acne, hyperprolactinemia, nausea, abdominal pain.
Lithium: A mood stabilizer for bipolar disorder, often considered first-line therapy.
- MoA: Myoinositol pathway, IP3 pathway, GSK-3, GABA modulation, cAMP and BDNF regulation.
- AE: Nausea, vomiting, loss of appetite, diarrhea, low thyroid, heart problems, electrolyte imbalances, nephrotoxicity, tremor.
- Drug interactions: Thiazides, ACE inhibitors, NSAIDs, and lithium toxicity.
- Pregnancy/Breastfeeding considerations: Use carefully, stop 2-3 days before delivery; breastfeeding not recommended
Important Considerations for all medications: Adverse effects, treatment duration, maintenance treatment, treatment resistance, and potential for relapses. Clozapine is often the treatment of choice in treatment-resistant cases, following a trial of other medications.

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Description

This quiz delves into the physiopathology of schizophrenia, focusing on the balance between excitatory and inhibitory neuronal activity. It explores how altered cortical circuits contribute to cognitive and negative symptoms, along with the role of stress and dopamine in psychosis. Test your understanding of these complex interactions and their implications for brain function.