Understanding Anxiety and Fear Responses
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What is a common cognitive symptom of schizophrenia?

  • Delusions
  • Impaired Executive Function (correct)
  • Hallucinations
  • Agitation

    • Which symptom is NOT typically associated with the positive symptoms of schizophrenia?

  • Incoherent speech
  • Hallucinations
  • Poor self-care (correct)
  • Paranoia

    • Which of the following is a characteristic of negative symptoms in schizophrenia?

  • Delusions
  • Social withdrawal (correct)
  • Agitation
  • Exaggeration of normal function

    • What type of drug classification includes Chlorpromazine and Haloperidol?

    <p>First-generation antipsychotics</p> Signup and view all the answers

    Which of the following is an example of a second-generation antipsychotic?

    <p>Clozapine</p> Signup and view all the answers

    In schizophrenia, which of the following is characterized by a poverty or simplicity of speech?

    <p>Negative symptoms</p> Signup and view all the answers

    Which symptom indicates a distortion of reality in psychosis?

    <p>Hallucinations</p> Signup and view all the answers

    How do first-generation antipsychotics primarily function?

    <p>By blocking dopamine receptors</p> Signup and view all the answers

    What is a significant consequence of the long half-life of nordazepam?

    <p>Increased risk of dependency</p> Signup and view all the answers

    Which adverse effect is commonly associated with the use of benzodiazepines?

    <p>Cognitive impairment</p> Signup and view all the answers

    What action do benzodiazepines primarily perform on GABAA receptors?

    <p>Enhance GABA activity</p> Signup and view all the answers

    What is a major clinical use of short-acting benzodiazepines?

    <p>Pre-operative sedation</p> Signup and view all the answers

    Which benzodiazepine is classified as long-acting?

    <p>Diazepam</p> Signup and view all the answers

    What is the primary action of SNRIs?

    <p>Inhibit reuptake of serotonin and norepinephrine</p> Signup and view all the answers

    What effect does the substance flumazenil have on benzodiazepines?

    <p>Acts as a competitive antagonist</p> Signup and view all the answers

    Which of the following drugs primarily treats insomnia and acts on GABAA receptors?

    <p>Zaleplon</p> Signup and view all the answers

    Which neurotransmitter systems do SSRIs minimally interact with?

    <p>Noradrenergic, adrenergic and cholinergic</p> Signup and view all the answers

    What key feature contributes to the popularity of SSRIs?

    <p>Ease of use and safety in overdose</p> Signup and view all the answers

    What is a risk associated with long-term use of benzodiazepines?

    <p>Increased tolerance</p> Signup and view all the answers

    Which of the following is an example of an SSRI?

    <p>Sertraline</p> Signup and view all the answers

    Which subtype of benzodiazepine receptor is most associated with anxiolytic effects?

    <p>BZ2</p> Signup and view all the answers

    What is a characteristic of SSRIs in relation to their effect on serotonin?

    <p>They prolong the activation of postsynaptic receptors.</p> Signup and view all the answers

    What is a common issue that can occur with the cessation of long-term benzodiazepine use?

    <p>Rebound insomnia</p> Signup and view all the answers

    Which SSRI has been identified as 'minimally toxic in doses up to 1,500 mg'?

    <p>Fluoxetine</p> Signup and view all the answers

    What pharmacological property describes SSRIs?

    <p>Lipophilic</p> Signup and view all the answers

    What do SSRIs primarily target within the synapse?

    <p>The serotonin transporter</p> Signup and view all the answers

    What is the primary action of typical antipsychotics on dopamine receptors?

    <p>They block D2 receptor activity.</p> Signup and view all the answers

    Which of the following is NOT a symptom of pseudoparkinsonism caused by extrapyramidal syndrome?

    <p>Facial grimacing</p> Signup and view all the answers

    Which statement about high-potency antipsychotics is true?

    <p>They can result in higher rates of extrapyramidal symptoms.</p> Signup and view all the answers

    What condition can result from increased prolactin secretion due to D2 receptor antagonism?

    <p>Hyperprolactinaemia.</p> Signup and view all the answers

    Which of the following describes akathisia?

    <p>A restless feeling that prevents one from standing still.</p> Signup and view all the answers

    What symptom is characteristic of tardive dyskinesia?

    <p>Protrusion and rolling of the tongue</p> Signup and view all the answers

    Which typical antipsychotic is noted for having the lowest incidence of extrapyramidal side effects?

    <p>Chlorpromazine</p> Signup and view all the answers

    Which of the following can be a result of high levels of prolactin in females treated with typical antipsychotics?

    <p>Menstrual irregularities.</p> Signup and view all the answers

    Which of the following is a mechanism of action for typical antipsychotic drugs?

    <p>Blockade of D2 receptors</p> Signup and view all the answers

    What is a characteristic effect of atypical antipsychotic drugs compared to typical ones?

    <p>Lower risk of extrapyramidal side effects</p> Signup and view all the answers

    What side effect is commonly associated with the long-term use of typical antipsychotics?

    <p>Dystonia</p> Signup and view all the answers

    How do atypical antipsychotics primarily differ in terms of receptor action compared to typical antipsychotics?

    <p>They antagonize multiple receptors including D2 and others</p> Signup and view all the answers

    What effect does aripiprazole have on dopamine in the nigrostriatal pathway?

    <p>Increase in dopamine levels</p> Signup and view all the answers

    Which of the following is NOT a side effect linked to atypical antipsychotics?

    <p>Lower risk of weight gain</p> Signup and view all the answers

    Aripiprazole is classified as which type of antipsychotic?

    <p>Atypical antipsychotic</p> Signup and view all the answers

    What is a notable effect of the partial agonism of D2 receptors by aripiprazole?

    <p>Very minor extrapyramidal symptoms</p> Signup and view all the answers

    What is the primary purpose of mood stabilizers in bipolar disorder treatment?

    <p>To prevent manic episodes</p> Signup and view all the answers

    What beneficial effects of lithium typically take 3-4 weeks to develop?

    <p>Control of manic behavior</p> Signup and view all the answers

    What occurs if a patient stops taking lithium for bipolar disorder?

    <p>Increase in manic behavior</p> Signup and view all the answers

    Which of the following is a common side effect of lithium treatment?

    <p>Memory loss and confusion</p> Signup and view all the answers

    How often is lithium typically administered for the prevention of cycling in bipolar disorder?

    <p>Daily</p> Signup and view all the answers

    Which statement is true regarding lithium's effectiveness during an acute attack in bipolar disorder?

    <p>It primarily reduces manic symptoms.</p> Signup and view all the answers

    What is a key goal in the treatment of bipolar disorder?

    <p>To alleviate depressive symptoms</p> Signup and view all the answers

    What mood episodes can be associated with bipolar disorder?

    <p>Both manic and depressive episodes</p> Signup and view all the answers

    What is a common initial challenge when using SSRIs for anxiety disorders?

    <p>Increased anxiety during the initial weeks of treatment</p> Signup and view all the answers

    Which of the following statements accurately describes the effect of SNRIs over time?

    <p>They require receptor desensitization for longer-term effects</p> Signup and view all the answers

    Which of the following best describes a hallmark symptom of depression?

    <p>Chronic feelings of dysphoria throughout the day</p> Signup and view all the answers

    In the context of hypnosedative effects in general anesthesia, what is one key use of certain medications?

    <p>For cessation of their sedative effects post-surgery</p> Signup and view all the answers

    What is a notable psychological effect associated with the initial phase of treatment with SSRIs?

    <p>The potential for increased mental anguish during adjustment</p> Signup and view all the answers

    What effect does activation of GABAB receptors primarily have on neuronal activity?

    <p>Leads to a hyperpolarizing current</p> Signup and view all the answers

    How do benzodiazepines predominantly affect anxiety levels?

    <p>Enhance the effect of GABA, reducing anxiety</p> Signup and view all the answers

    Which sub-units make up the GABAA-benzodiazepine receptor complex?

    <p>Alpha, beta, and gamma sub-units</p> Signup and view all the answers

    Why are benzodiazepines not recommended for long-term therapy?

    <p>They quickly develop tolerance in patients.</p> Signup and view all the answers

    What is a major consequence of decreased GABA activity?

    <p>Higher levels of anxiety to panic</p> Signup and view all the answers

    Which of the following correctly describes GABAB receptor activation?

    <p>Increases K+ channel opening, causing hyperpolarization</p> Signup and view all the answers

    What side effect is commonly associated with high levels of GABA activity?

    <p>Marked sedation and sleep</p> Signup and view all the answers

    What is the primary function of benzodiazepines when co-administered with SSRIs?

    <p>To enhance anxiolytic effects during acute anxiety</p> Signup and view all the answers

    What is a notable feature of second-generation MAOIs compared to traditional MAOIs?

    <p>Selective binding to MAO-A</p> Signup and view all the answers

    What is a unique characteristic of ketamine’s effects on depressive symptoms?

    <p>It shows a rapid but short-lasting response.</p> Signup and view all the answers

    In what situation is electroconvulsive therapy (ECT) typically utilized?

    <p>After other treatment options have failed</p> Signup and view all the answers

    What is the primary mechanism of action of Transcranial Magnetic Stimulation (TMS)?

    <p>Non-invasive magnetic fields influencing brain neuronal activity</p> Signup and view all the answers

    What limitation do reversible inhibitors of MAO, like Moclobemide, have in terms of dietary restrictions?

    <p>They have no dietary restrictions imposed.</p> Signup and view all the answers

    What is a common misconception about the reputation of electroconvulsive therapy (ECT)?

    <p>It has an outdated reputation but is effective when used correctly.</p> Signup and view all the answers

    Which of the following patients is most likely to benefit from Esketamine nasal spray?

    <p>Patients with treatment-resistant depression</p> Signup and view all the answers

    What distinguishes the administration of ketamine from traditional antidepressants?

    <p>It can provide rapid relief from symptoms without the delay seen with other medications.</p> Signup and view all the answers

    What is the primary difference between anxiolytics and sedative-hypnotics?

    <p>Anxiolytics are used for chronic conditions, while sedative-hypnotics are for acute use.</p> Signup and view all the answers

    Which anxiety disorder is characterized by an intense fear response after experiencing a traumatic event?

    <p>Post-Traumatic Stress Disorder</p> Signup and view all the answers

    Which class of drugs requires an extended duration of treatment to achieve therapeutic effects?

    <p>SSRIs</p> Signup and view all the answers

    What is a common adverse effect associated with the long-term use of benzodiazepines?

    <p>Tolerance and dependence</p> Signup and view all the answers

    What type of drug is Propranolol, and how is it utilized in the treatment of anxiety disorders?

    <p>A beta-blocker often used with exposure therapy for phobias</p> Signup and view all the answers

    Which mechanism of action is primarily associated with first-generation antipsychotic agents?

    <p>Antagonizing dopamine D2 receptors</p> Signup and view all the answers

    Which symptom is NOT typically associated with anxiety disorders?

    <p>Euphoria</p> Signup and view all the answers

    Among the following options, which describes a key characteristic of cognitive symptoms in schizophrenia?

    <p>Reduced attention and memory function</p> Signup and view all the answers

    What is a distinguishing factor of atypical antipsychotic agents compared to typical antipsychotics?

    <p>Multifaceted receptor action including serotonin receptors</p> Signup and view all the answers

    In the context of treating chronic anxiety, which of the following approaches is most effective?

    <p>Employing SSRIs or SNRIs as a long-term strategy</p> Signup and view all the answers

    What is a major reason clozapine is not used as a first-line treatment for schizophrenia?

    <p>It requires regular blood monitoring due to agranulocytosis risk.</p> Signup and view all the answers

    Which antipsychotic is suggested to be effective for treating cognitive symptoms due to its D3 partial agonism?

    <p>Aripiprazole</p> Signup and view all the answers

    Why is cariprazine considered effective for negative symptoms of schizophrenia?

    <p>It has a higher affinity for D3 receptors compared to aripiprazole.</p> Signup and view all the answers

    Which of the following best describes D2 receptor antagonism's effect in patients?

    <p>It causes a higher risk for extrapyramidal symptoms.</p> Signup and view all the answers

    What cardiovascular risk factors may arise from the use of clozapine?

    <p>Hyperglycaemia and dyslipidaemia</p> Signup and view all the answers

    Which of the following properties does clozapine have concerning D2 and 5-HT receptors?

    <p>Partial agonist at D2 and high affinity full antagonist at 5-HT2A.</p> Signup and view all the answers

    What adverse cardiovascular effects are particularly noted with clozapine treatment?

    <p>Myocarditis and cardiomyopathy</p> Signup and view all the answers

    What is a major risk when using high-potency antipsychotics like haloperidol?

    <p>Higher incidence of extrapyramidal symptoms</p> Signup and view all the answers

    Which statement most accurately represents the side effect profile of cariprazine compared to other antipsychotics?

    <p>It causes only very minor extrapyramidal symptoms due to its partial agonism.</p> Signup and view all the answers

    Which of the following adverse effects is characteristic of acute dystonia?

    <p>Involuntary upward eye movement</p> Signup and view all the answers

    What effect does antipsychotic administration have on prolactin levels?

    <p>Increases prolactin secretion</p> Signup and view all the answers

    Which of the following symptoms is specifically associated with tardive dyskinesia?

    <p>Protrusion and rolling of the tongue</p> Signup and view all the answers

    What is a common side effect associated with lower-potency antipsychotics like chlorpromazine?

    <p>Greater sedation and side effects</p> Signup and view all the answers

    Which of these is an example of a symptom of pseudoparkinsonism?

    <p>Rigidity</p> Signup and view all the answers

    What is a common symptom of akathisia?

    <p>Inability to sit still</p> Signup and view all the answers

    Which type of antipsychotic is most likely linked to hyperprolactinemia?

    <p>High-potency typical antipsychotics</p> Signup and view all the answers

    Study Notes

    Anxiety

    • Fear is a complex physiological, behavioral, and cognitive response to a threatening stimulus
    • It's an adaptive response to threats and usually temporary
    • The normal fear response has several components: defensive behaviors, autonomic reflexes, arousal and alertness, corticosteroid secretion, and negative emotions
    • Anxiety is meant to increase the likelihood of survival in dangerous situations
    • Symptoms include increased arousal, hypervigilance, tachycardia, physical preparedness (sympathetic nervous system activation)
    • Anxiety is a longer-lasting response to danger
    • It can have a specific cause related to something that signals danger or be caused by anticipated adverse consequences
    • When anxiety persists beyond genuine risk or produces a response out of proportion to the possible threat, it's considered an anxiety disorder
    • Currently recognized anxiety disorders include generalized anxiety disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, simple phobias, and obsessive-compulsive disorder

    Therapeutic Strategies in Anxiety Disorders

    • GAD (Generalized Anxiety Disorder):
      • Acute state: Benzodiazepines
      • Chronic state: SSRI/SNRI
    • Phobia:
      • SSRI
      • Propranolol and exposure therapy
      • CBT (Cognitive Behavioral Therapy), biofeedback

    Slow vs. Rapid-Acting Anxiolytic Drugs

    • Benzodiazepines: rapid onset (effects within 30 minutes), useful for acute treatment, can be taken as needed
    • Antidepressants and Buspirone: slow onset (require 3+ weeks for therapeutic effect)

    Propranolol and Exposure Therapy

    • Propranolol is a beta-blocker traditionally used for hypertension and arrhythmias
    • Used in psychiatry for exposure therapy to treat phobias and PTSD
    • Blocks adrenaline effects, reducing physical anxiety symptoms
    • May influence emotional memory recall, potentially making it easier to confront fearful situations
    • Exposure therapy systematically desensitizes individuals to feared imagery and stimuli

    GABA

    • GABA is the major inhibitory neurotransmitter in the brain
    • Most inhibitory synapses use GABA as a neurotransmitter

    GABA Receptors

    • GABA interacts with two major receptor subtypes: GABAA and GABAB
    • GABAA receptors are found postsynaptically
    • GABAB receptors are found presynaptically and can inhibit synaptic release
    • GABAA receptors mediate inhibitory synaptic transmission throughout the CNS

    GABA Receptors and Chloride Ions

    • GABAA receptors are permeable to chloride ions (Cl-)
    • Upon activation, Cl- influx hyperpolarizes the membrane, inhibiting action potentials

    GABAB Receptors and Seizures

    • GABAB receptors are associated with second messenger systems rather than chloride channels
    • Second messenger systems often result in opening K+ channels, leading to hyperpolarization
    • Decreasing GABA release and drugs that activate GABAB receptors can cause seizures

    Behavioral Spectrum of GABAA Activation

    • Decreased GABA activity: seizures, high anxiety, and panic
    • Slightly decreased GABA activity: increased anxiety
    • Normal GABA activity
    • Increased GABA activity: sedation
    • Higher GABA activity: marked sedation and sleep.

    Benzodiazepines

    • Mechanism of Action: Enhance the effect of the neurotransmitter GABA, leading to central nervous system depression.
    • Examples: Diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax), and clonazepam (Klonopin).

    Behavioral Spectrum of GABAA Activation

    • Normal GABA activity
    • Slightly increased GABA activity: anti-anxiety
    • High GABA activity: sedation
    • Higher GABA activity: marked sedation and sleep

    Clinical Importance of GABAA

    • Each of the five subunits of the GABAA-benzodiazepine receptor complex is a different protein
    • These can be classified into families based on structural similarities (coded as α, β, and γ subunits)
    • GABA binds to the β subunit

    Benzodiazepines as Rapid Onset Anxiolytics

    • Used to treat acute anxiety
    • Those used to treat anxiety have long biological half-lives
    • They are no longer used in long-term therapy

    Benzodiazepines acting on GABAA receptors

    • Benzodiazepines act as positive allosteric modulators on the GABAA receptor
    • This facilitates the opening of GABA-activated chloride channels, enhancing the inhibitory response to GABA
    • Benzodiazepines bind specifically to a modulatory site separate from the GABA binding sites

    Channel Modulators - Benzodiazepines

    • Benzodiazepines work by increasing the affinity of the GABA binding site for GABA
    • This means GABA can activate the channels at a higher rate, increasing chloride transmission

    Long-acting Benzodiazepines and Nordazepam

    • Some long-acting agents (e.g., diazepam and chlordiazepoxide) are converted to a long-lasting active metabolite (nordazepam)
    • Nordazepam has a half-life of about 60 hours
    • This accounts for the tendency of many benzodiazepines to produce cumulative effects and long hangovers when given repeatedly

    Benzodiazepines Adverse Effects

    • Sedation: Dizziness and ataxia, Impaired coordination and balance, Cognitive impairment, Anterograde amnesia, Psychomotor slowing, Motor impairment
    • Dependence and Withdrawal (with long-term use): Serious withdrawal effects, Tolerance (higher doses to achieve therapeutic effects), Risk of overdose (especially with alcohol)

    Reuptake Inhibitors in Anxiety

    • SSRIs (Selective Serotonin Reuptake Inhibitors): useful for long-term management of anxiety disorders, but may worsen anxiety initially
    • SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): useful for long-term management of anxiety disorders, but may worsen anxiety initially Commonly prescribed SSRIs: Fluoxetine (Prozac), Paroxetine (Paxil, Pexeva), Citalopram (Celexa), Escitalopram (Lexapro), Sertraline (Zoloft) Commonly prescribed SNRIs: Venlafaxine XR (Effexor XR), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq)
    • First-line for anxiety: Benzodiazepines are effective immediately but are contraindicated for long-term use
    • First-line for anxiety: SSRIs and SNRIs take time to work, causing anxiety initially, but can be used long-term

    Depression

    • The central feature of depression is an unpleasant (dysphoric) mood present most of the day for a long period of time
    • Often accompanied by intense mental anguish, inability to experience pleasure, generalized loss of interest, and sometimes anger and irritability
    • Three effective treatments for major depressive disorder include antidepressant drugs, cognitive-behavioral psychotherapy, and electroconvulsive therapy

    The Monoamine Hypothesis of Major Depression

    • Suggests that depression is related to a deficiency in the amount or function of monoamines, including serotonin, noradrenaline, and dopamine.
    • These neurotransmitters are involved in various mechanisms, contributing to depressive symptoms

    Drugs which Block Reuptake of Monoamine Neurotransmitter Molecules from the Synaptic Cleft

    • Tricyclic antidepressants (TCAs)
    • Selective serotonin reuptake inhibitors (SSRIs)
    • Serotonin-noradrenaline reuptake inhibitors (SNRIs)
    • Norepinephrine-dopamine reuptake inhibitors (NDRIs)

    Neurotransmitter Reuptake

    • Specific transporter proteins remove most small-molecule neurotransmitters (or their metabolites) from the synaptic cleft, returning them to the presynaptic terminal for reuse

    Tricyclic antidepressants (TCAs)

    • Mechanism of action: block the transporter at serotonergic and noradrenergic synapses, leaving serotonin/noradrenaline in the synaptic cleft for a longer period, activating postsynaptic receptors for longer
    • Example: Imipramine (Tofranil), Amitriptyline (Elavil), Nortriptyline (Pamelor)
    • Adverse effects: antagonists at H1 receptors (drowsiness), adrenergic a1 receptors (postural hypotension), muscarinic receptors (dry mouth, confusion, and memory impairment), and blurred vision, cardiac arrhythmias in overdose, and potentiation of alcohol effects (severe respiratory depression)
    • Overdose: Second most common cause of fatal drug poisoning in developed countries (1970s and 1980s), accounting for 20-25% of fatal cases in the UK and US

    Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

    • Mechanism of action: inhibit the reuptake of both serotonin and norepinephrine, increasing the availability of neurotransmitters in the synaptic cleft
    • Examples: Venlafaxine (Effexor XR), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq)
    • Differ from TCAs: TCAs block reuptake pumps of both serotonin and norepinephrine but are not selective. SNRIs are designed to specifically block serotonin and norepinephrine reuptake.

    Selective Serotonin Reuptake Inhibitors (SSRIs)

    • Mechanism of Action: These transporters are highly specific, block the transporter, leaving serotonin in the synaptic cleft for a longer period.
    • Examples: Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil), Citalopram (Celexa)

    Selective Serotonin Reuptake Inhibitors (SSRIs)

    • SSRIs are currently among the most commonly prescribed antidepressants due to their efficacy and favorable side effect profile compared to older antidepressants, like TCAs.
    • SSRIs are highly lipophilic.
    • Their popularity stems from ease of use, safety in overdose, relative tolerability, cost, and broad spectrum of uses

    SSRI/SNRIs and Suicidality

    • Risk of suicidality and aggression in children and adolescents may double with SSRI/SNRI treatment

    First-line in Anxiety

    • Benzodiazepines are effective immediately, but have side effects and are contraindicated for long-term use
    • SSRIs and SNRIs take time to work, may initially worsen anxiety, but can be used longer term

    Ketamine

    • Single intravenous, sub-anaesthetic dose of ketamine (a non-competitive NMDA channel blocker) produces a rapid, but short-lasting decrease in depressive symptoms
    • This is without the usual delay, unlike other antidepressants

    Esketamine

    • An analogue of ketamine, available as a nasal spray
    • Has milder side effects compared to ketamine
    • Could be used with oral antidepressants to treat resistant cases
    • Administered in clinics with patients observed for 2-3 hours

    Electroconvulsive Therapy (ECT)

    • Highly effective against depression
    • Administered with modern anesthesia; relatively safe
    • Single most effective treatment option for serious major depression when other medications fail

    Transcranial Magnetic Stimulation (TMS)

    • Non-invasive neuromodulation technique using magnetic fields to stimulate specific brain areas
    • Effective for patients with major depressive disorder (MDD) who don't respond to first-line pharmacological treatments (treatment-resistant depression)

    Schizophrenia

    • Affects about 1% of the population
    • Predominantly affects young people (average onset age of 18 in men, 25 in women)
    • Characterized by psychosis (loss of contact with reality)
    • Symptoms include difficulty processing information, disorganized thoughts, distortions of reality, delusions, hallucinations, incoherence, catatonia, and aggressive/violent behavior
    • Divided into groups: Negative symptoms (decrease/loss of function and motivation), Positive symptoms (exaggeration of normal function, such as agitation, incoherent speech, hallucinations, delusions, paranoia), Cognitive symptoms (reduce ability to think clearly and perform daily tasks, such as impaired attention/concentration, working memory, executive function, reasoning/problem-solving)

    Classification of Antipsychotic Drugs

    • First-generation (typical, classical, or conventional): Chlorpromazine, Haloperidol, Fluphenazine
    • Second-generation (atypical): Risperidone, Olanzapine, Quetiapine, Aripiprazole, Clozapine

    Antipsychotic Agents Mechanisms of Action

    • Five subtypes of dopamine receptors (D1 through D5)
    • Typical antipsychotics block D2 (dopaminergic) receptors
    • Atypical antipsychotics block D2 and D4 dopamine, and 5-HT2A receptors

    Typical Antipsychotics

    • Dopamine receptor blockade: Chlorpromazine, Haloperidol These typically induce extrapyramidal side effects (EPS), such as pseudoparkinsonism, acute dystonia, akathisia, and tardive dyskinesia
    • Higher risk and duration of EPS-related side effects

    Atypical Antipsychotics

    • These typically block D2 and 5-HT2A receptors, and there's a lower risk of EPS
    • More effective in treating negative symptoms. Examples include Risperidone, Olanzapine, Quetiapine Aripiprazole, Clozapine

    Hyperprolactinaemia

    • Antipsychotic drugs binding to D2 receptors can increase prolactin secretion leading to elevated prolactin levels, causing decreased libido, impotence, and gynecomastia in males, and amenorrhea (stopping menstruation) and infertility in females.

    Typical Antipsychotic Drugs and EPS

    • High-potency agents (haloperidol and fluphenazine) have a higher incidence of EPS, especially at higher doses
    • Lower-potency agents (chlorpromazine and thioridazine) have lower EPS rates but are more likely to cause sedation

    Atypical Antipsychotics - Common Adverse Effects

    • Generally have a lower risk of EPS compared to typical antipsychotics
    • Some (olanzapine and clozapine) are associated with metabolic side effects like weight gain, diabetes, and dyslipidemia

    Why are Atypical Antipsychotics Better with EPS?

    • Typical antipsychotics block dopamine (D2) receptors in the striatum, which prevents inhibition of GABAergic neurons, leading to EPS
    • Typical antipsychotics have no activity at 5-HT2A receptors and do not promote their activation of GABA neurons
    • Atypical antipsychotics block dopamine (D2) receptors to a lesser degree, preventing excessive GABAergic neuronal activation and reducing EPS risk
    • Inhibit 5-HT2A receptors to stop the activation of GABA neurons.

    Differences between Typical and Atypical Antipsychotic Drugs

    • Typical antipsychotics block D2 receptors, causing higher risk of EPS and tardive dyskinesia, less effective treating negative symptoms. Examples: haloperidol, chlorpromazine
    • Atypical antipsychotics block multiple receptors, including D2 and 5-HT2A, causing a lower risk of EPS and being more effective for negative symptoms. Examples: risperidone, olanzapine

    Aripiprazole

    • Partial agonist at D2, D3, and 5-HT1A receptors
    • Antagonist at 5-HT2A receptors
    • Has a better side effect profile
    • Stabilizes dopamine and serotonin within the nucleus accumbens, ventral tegmental area, and frontal cortex, effectively managing positive, negative, and cognitive symptoms in schizophrenia.

    Cariprazine

    • Partial agonist at D2, D3, and 5-HT1A receptors
    • Not an antagonist at 5-HT2A receptors
    • Relatively effective for treating schizophrenia negative symptoms, with minimal EPS

    Antipsychotic Drugs Drawbacks

    • Not all schizophrenic patients respond to drug therapy (30% "treatment-resistant")
    • Clozapine is an option when other antipsychotics are ineffective, despite its severe drawbacks (agranulocytosis, myocarditis, cardiomyopathy, and metabolic syndrome).

    Bipolar Disorder

    • Usually appears in early adult life
    • Less common than major depression
    • Strong hereditary tendency (but no specific genes identified)
    • Involves swings between manic and depressive moods
    • Treatment goals: preventing manic episodes, relieving depressive symptoms, and avoiding rapid cycling

    Drugs used in Bipolar Disorder

    • Treatment Goals: Prevent manic episodes, alleviate depressive symptoms, avoid rapid cycling
    • Mood stabilizers are used to control mood swings, examples include: Lithium, Carbamazepine, Valproate, Lamotrigine
    • Lithium—first drug used to manage bipolar disorder, controls flight of ideas and hyperactivity; takes several weeks for symptom reduction; can cause serious side effects (e.g., nausea, vomiting, diarrhoea, tremor, toxicity from overdose); risks include prolonged treatment (renal toxicity, thyroid issues).

    Antiepileptic Drugs Effective In Bipolar Disorder

    • Carbamazepine, valproate, and lamotrigine have fewer side effects and are effective in preventing mood cycling between manic and depressive states
    • Also used to treat epilepsy

    Sodium Channel Inhibitors

    • Many antiepileptic drugs bind to sodium channels in the deactivated state, preventing them from returning to the resting state. This reduces the number of functional channels, which may play a role in controlling the bipolar cycle

    Carbamazepine

    • Stabilizes the inactivated state of voltage-gated sodium channels

    Atypical Antipsychotics

    • Effective for bipolar mania, not necessarily for rapid cycling between mania and depression
    • Examples of atypical antipsychotic drugs include olanzapine and risperidone.

    Use of SSRIs and Bipolar Disorder

    • SSRIs and SNRIs can precipitate mania, leading to misdiagnosis of bipolar disorder, especially in patients with unipolar depression
    • Antidepressants should be used cautiously in patients with bipolar disorder or a history of mania, and combined with mood stabilizers
    • Antidepressant monotherapy is high risk for inducing mania and should not be used alone
    • Preferred treatments pair antidepressants with mood stabilizers or antipsychotics
    • Mood stabilizers (e.g., lamotrigine) and atypical antipsychotics (e.g., aripiprazole) are preferred
    • SSRIs should be used with caution, always in combination with mood-stabilizing agents

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