Psychopharmacology Quiz
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Questions and Answers

Which neurotransmitter is primarily targeted by selective serotonin reuptake inhibitors (SSRIs)?

  • Serotonin (correct)
  • Dopamine
  • Melatonin
  • Noradrenaline

    • What is a common side effect associated with the use of antidepressants?

  • Increased energy levels
  • Enhanced appetite suppression
  • Improved sleep quality
  • Weight gain (correct)

    • Which class of antidepressants is most commonly prescribed in Australia?

  • Monoamine oxidase inhibitors (MAOIs)
  • Noradrenergic reuptake inhibitors
  • Tricyclic antidepressants
  • Selective serotonin reuptake inhibitors (SSRIs) (correct)

    • What influences mood through neurotransmitters in the brain and is treated with antidepressants?

    <p>Depression/anxiety</p> Signup and view all the answers

    Which of the following neurotransmitters is NOT commonly associated with the mechanism of action of most antidepressants?

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

    What is the primary mechanism by which haloperidol exerts its efficacy?

    <p>It antagonizes D2 receptors in the nucleus accumbens.</p> Signup and view all the answers

    Which extra-pyramidal symptom (EPS) is most commonly associated with the use of typical antipsychotics?

    <p>Parkinsonian effects</p> Signup and view all the answers

    What effect does the anti-cholinergic action of some typical antipsychotics have on the likelihood of EPS?

    <p>It minimizes the likelihood of EPS.</p> Signup and view all the answers

    Why are atypical antipsychotics considered more effective for managing negative symptoms compared to typical agents?

    <p>They also affect serotonin receptors and have a broader mechanism.</p> Signup and view all the answers

    Who is most likely to experience postural hypotension when using typical antipsychotics?

    <p>Patients using pharmacological agents that block H1 receptors.</p> Signup and view all the answers

    What is the expected outcome when D2 receptors are blocked in the context of cholinergic signaling?

    <p>Unopposed acetylcholine signaling.</p> Signup and view all the answers

    Which of these antipsychotics is noted for its 'pure' D2 receptor antagonism?

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

    What common effect is seen with most other typical antipsychotics when compared to haloperidol?

    <p>Higher incidence of sedation and weight gain.</p> Signup and view all the answers

    Which statement best describes the mechanism of action of serotonin and noradrenaline reuptake inhibitors (SNRIs)?

    <p>They block the reuptake of both noradrenaline and serotonin.</p> Signup and view all the answers

    What is a major risk associated with irreversible monoamine oxidase inhibitors?

    <p>They may lead to hypertensive crisis if tyramine is consumed.</p> Signup and view all the answers

    Which conditions are characterized primarily by cycling mood in bipolar disorder?

    <p>Bipolar 1 and 2 disorders</p> Signup and view all the answers

    What specific action do alpha 2 receptor antagonists perform?

    <p>They promote the release of noradrenaline and serotonin.</p> Signup and view all the answers

    Which drug is characterized as a reversible monoamine oxidase inhibitor and considered to have no risk of the 'cheese reaction'?

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

    How does lithium act in the treatment of bipolar disorder?

    <p>By accumulating in cells and inhibiting neurotransmitter release.</p> Signup and view all the answers

    What are typical antipsychotics primarily used to target in schizophrenia?

    <p>Positive symptoms such as delusions and hallucinations.</p> Signup and view all the answers

    Which neurotransmitter system is primarily targeted by antipsychotic drugs?

    <p>Dopamine (D2) receptor system.</p> Signup and view all the answers

    Which drug is an example of a typical antipsychotic?

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

    What effect can inhibiting dopamine in the nigrostriatal pathway lead to?

    <p>Extrapyramidal symptoms resembling Parkinson’s disease.</p> Signup and view all the answers

    Which of the following is a major side effect of atypical antipsychotics compared to typical ones?

    <p>Weight gain and metabolic syndrome.</p> Signup and view all the answers

    Which characteristic distinguishes bipolar 1 from bipolar 2 disorder?

    <p>Presence of severe manic episodes.</p> Signup and view all the answers

    Which aspect of mood is primarily affected in unipolar depression?

    <p>Consistent low mood without fluctuations.</p> Signup and view all the answers

    Which patient population should avoid the use of lithium?

    <p>Patients with renal dysfunction.</p> Signup and view all the answers

    Which class of antidepressants is known for having less harmful side effects compared to tricyclic antidepressants?

    <p>Selective serotonin reuptake inhibitors (SSRIs)</p> Signup and view all the answers

    Which antidepressant class is associated with anticholinergic effects such as dry mouth and constipation?

    <p>Tricyclic antidepressants (TCAs)</p> Signup and view all the answers

    What is a potential initial side effect of starting selective serotonin reuptake inhibitors (SSRIs)?

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

    Which of the following antidepressants is most likely to cause weight gain as a side effect?

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

    What is the main mechanism of action for tricyclic antidepressants (TCAs)?

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

    Which type of antidepressant is known for its risk of precipitating serotonin syndrome when combined with other serotonin-affecting drugs?

    <p>Selective serotonin reuptake inhibitors (SSRIs)</p> Signup and view all the answers

    What do serotonin levels rapidly increase after starting an SSRI treatment but take longer for mood improvement?

    <p>Receptor downregulation takes time</p> Signup and view all the answers

    Which class of antidepressants includes drugs like phenelzine and tranylcypromine?

    <p>Monoamine oxidase inhibitors (MAOIs)</p> Signup and view all the answers

    What is the purpose of downregulating monoamine receptors in the treatment of depression?

    <p>To mitigate receptor overactivity related to depression</p> Signup and view all the answers

    Which antidepressant class has fewer side effects but is usually well tolerated?

    <p>Selective serotonin reuptake inhibitors (SSRIs)</p> Signup and view all the answers

    Which drug class includes medications that can potentially cause cardiac toxicity?

    <p>Tricyclic antidepressants (TCAs)</p> Signup and view all the answers

    What class of antidepressants can be used for treating anxiety disorders, in addition to depression?

    <p>Serotonin and noradrenaline reuptake inhibitors (SNRIs)</p> Signup and view all the answers

    Which neurotransmitters are typically deficient in individuals suffering from depression, according to the monoamine hypothesis?

    <p>Noradrenaline, dopamine, serotonin</p> Signup and view all the answers

    Which of the following antidepressants is commonly tolerated but can lead to weight gain and sedation?

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

    What is the role of atypical antipsychotics in the treatment of negative symptoms?

    <p>They antagonize the 5-HT2A receptors to increase dopamine levels in the prefrontal cortex.</p> Signup and view all the answers

    Which receptor antagonism is primarily responsible for the efficacy of atypical antipsychotics against negative symptoms?

    <p>5-HT2A receptor antagonism</p> Signup and view all the answers

    What is a common adverse effect of many antipsychotics that requires monitoring?

    <p>Weight gain and altered triglyceride levels</p> Signup and view all the answers

    Why might some patients require long-acting injectable forms of antipsychotic medication?

    <p>To improve adherence among patients who struggle with oral medications.</p> Signup and view all the answers

    Which of the following is a significant side effect from the use of tricyclic antidepressants?

    <p>Dry mouth and constipation</p> Signup and view all the answers

    What physiological reaction can occur if a patient consumes high levels of tyramine while on non-selective MAO inhibitors?

    <p>Hypertensive crisis</p> Signup and view all the answers

    What is the mechanism behind the initial increase in anxiety observed in patients beginning SSRIs?

    <p>Upregulation of serotonin receptors leading to heightened signaling.</p> Signup and view all the answers

    What is a rare but serious side effect associated with D2 receptor antagonism in antipsychotic therapy?

    <p>Neuroleptic malignant syndrome</p> Signup and view all the answers

    How can smoking affect the efficacy of antipsychotic medication?

    <p>By increasing plasma concentrations of the medication.</p> Signup and view all the answers

    What effect does the blockade of 5-HT2A receptors have on dopamine levels?

    <p>Increases dopamine levels by removing inhibition.</p> Signup and view all the answers

    What class of antidepressants primarily blocks the reuptake of serotonin?

    <p>Selective serotonin reuptake inhibitors (SSRIs)</p> Signup and view all the answers

    What outcome results from the initial increase in serotonin receptor expression in patients taking SSRIs?

    <p>Initial anxiety before mood improvement.</p> Signup and view all the answers

    What type of preparation allows for easier adherence to antipsychotic treatment for non-compliant patients?

    <p>Long acting injectable formulations</p> Signup and view all the answers

    What is a key side effect that leads to drug monitoring in patients taking antipsychotics?

    <p>Weight gain and metabolic issues</p> Signup and view all the answers

    What is a primary benefit of dopamine receptor agonists compared to levodopa?

    <p>Longer half-life</p> Signup and view all the answers

    What adverse effect is commonly associated with dopamine receptor agonists?

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

    Which drug class can help enhance GABA effects in Huntington's disease?

    <p>GABAb receptor agonists</p> Signup and view all the answers

    Which of the following is a side effect of muscarinic receptor antagonists?

    <p>Dry mouth</p> Signup and view all the answers

    What is the mechanism of action for MAOb inhibitors?

    <p>Prevent metabolism of dopamine</p> Signup and view all the answers

    In treating Parkinson's disease, what role does COMT play?

    <p>Metabolizes levodopa and dopamine</p> Signup and view all the answers

    What type of receptor antagonists may be co-administered with some dopaminergic agonists?

    <p>Peripherally selective dopamine receptor antagonists</p> Signup and view all the answers

    What is the genetic inheritance pattern of Huntington's disease?

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

    Which drug can act both in the periphery and the CNS for Parkinson's treatment?

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

    What condition may develop in patients due to increased dopamine signaling associated with drug treatments?

    <p>Impulse control disorders</p> Signup and view all the answers

    What is a common effect of polypharmacy in Parkinson's disease?

    <p>Increased severity of off periods</p> Signup and view all the answers

    What is a significant consequence of the loss of GABAergic neurons in Huntington's disease?

    <p>Dopamine hyperactivity</p> Signup and view all the answers

    Which of the following statements regarding sedation and anaesthesia is TRUE?

    <p>Sedation can be used for anxiety and insomnia treatment.</p> Signup and view all the answers

    What primary effect does clozapine have on dopamine levels in the prefrontal cortex?

    <p>Increases dopamine levels to alleviate negative symptoms</p> Signup and view all the answers

    Which of the following symptoms is primarily associated with the use of antipsychotics blocking D2 receptors?

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

    What potential risk is heightened in a patient being treated with clozapine who is also a heavy smoker?

    <p>Decreased efficacy of the drug</p> Signup and view all the answers

    Which mechanism primarily contributes to the effectiveness of levodopa in treating Parkinson's disease?

    <p>Increases dopamine release in the nigrostriatal pathway</p> Signup and view all the answers

    What is a key characteristic of typical antipsychotics such as chlorpromazine?

    <p>They reduce dopamine levels in various pathways</p> Signup and view all the answers

    Which side effect is least likely to be caused by chlorpromazine?

    <p>Severe muscle spasms</p> Signup and view all the answers

    What best describes the role of the nigrostriatal pathway in motor control?

    <p>Facilitates fine motor control and movement execution</p> Signup and view all the answers

    What is a common side effect mechanism of atypical antipsychotics compared to typical ones?

    <p>Less sedation due to serotonin receptor modulation</p> Signup and view all the answers

    What is true regarding the effectiveness of clozapine on schizophrenia symptoms?

    <p>Affects both positive and negative symptoms</p> Signup and view all the answers

    What complication can occur due to the use of levodopa in Parkinson's disease patients?

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

    What characteristic is common to both Parkinson's and Huntington's Disease in relation to their treatment?

    <p>Both conditions involve a deficit in dopamine signaling</p> Signup and view all the answers

    How does smoking impact the efficacy of clozapine treatment?

    <p>It decreases clozapine concentration by inducing metabolic enzymes</p> Signup and view all the answers

    What type of receptor blocking is primarily associated with chlorpromazine and contributes to weight gain?

    <p>Serotonin 5-HT2 receptor</p> Signup and view all the answers

    What does increased Dopamine Decarboxylase (DDC) activity in the periphery potentially lead to when administering levodopa?

    <p>Peripheral dopamine side effects</p> Signup and view all the answers

    What is the relationship between MAC and the potency of a general anaesthetic?

    <p>A lower MAC indicates a higher potency.</p> Signup and view all the answers

    Which of the following best describes the effect of a lipophilic anaesthetic on neuronal function?

    <p>It can lead to hyperpolarization of the neuron.</p> Signup and view all the answers

    Why does nitrous oxide have a higher MAC compared to methoxyflurane?

    <p>Nitrous oxide is less soluble in lipids.</p> Signup and view all the answers

    What is a significant safety consideration regarding the use of general anaesthetics for theatre staff?

    <p>There are concerns about toxic metabolites.</p> Signup and view all the answers

    How do intravenous anaesthetics achieve a very short duration of action?

    <p>They are rapidly redistributed to other compartments.</p> Signup and view all the answers

    Which of the following anaesthetics is known for providing analgesic effects at sub-anaesthetic doses?

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

    What factor affects the transfer of anaesthetics from the lungs to the blood?

    <p>Lipid solubility</p> Signup and view all the answers

    What common phenomenon occurs during the induction phase of general anaesthesia?

    <p>Breathing may be impeded.</p> Signup and view all the answers

    What is the proposed mechanism of how general anaesthetics induce their effects?

    <p>By hyperpolarizing the membrane potential.</p> Signup and view all the answers

    Which anaesthetic is most commonly used to maintain general anaesthesia?

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

    What characterizes focal seizures?

    <p>They originate in one part of the brain and can spread.</p> Signup and view all the answers

    Which type of seizure is often mistaken for daydreaming, particularly in children?

    <p>Absence seizures</p> Signup and view all the answers

    What is required for a diagnosis of epilepsy?

    <p>At least two unprovoked seizures occurring more than 24 hours apart.</p> Signup and view all the answers

    What is a significant challenge in diagnosing seizures?

    <p>Electroencephalogram (EEG) results can show abnormalities even after a seizure has occurred.</p> Signup and view all the answers

    Which of the following is a common feature of generalized seizures?

    <p>They involve loss of consciousness.</p> Signup and view all the answers

    What is one risk associated with the use of propofol and thiopental as anti-epileptic agents?

    <p>Significant adverse effects.</p> Signup and view all the answers

    What type of information is crucial for diagnosing a seizure if the patient does not recall the event?

    <p>Accounts from witnesses of the seizure</p> Signup and view all the answers

    What distinguishes a tonic-clonic seizure from other seizure types?

    <p>They are characterized by muscle stiffness and alternating spasms.</p> Signup and view all the answers

    What is a defining criterion for generalized anxiety disorder?

    <p>Excessive anxiety that persists for most days of the week for at least 6 months</p> Signup and view all the answers

    Which of the following symptoms is NOT commonly associated with generalized anxiety disorder?

    <p>Elevated heart rate</p> Signup and view all the answers

    What psychological treatment is commonly used for anxiety disorders?

    <p>Cognitive behavioral therapy</p> Signup and view all the answers

    How do benzodiazepines primarily reduce anxiety?

    <p>By enhancing the effect of GABA at its receptor</p> Signup and view all the answers

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

    <p>Development of tolerance and dependence</p> Signup and view all the answers

    Which symptom is primarily associated with panic disorder?

    <p>Sudden panic attacks and recurring worry about them</p> Signup and view all the answers

    What is likely to increase the severity of anxiety symptoms according to the cup/bucket theory?

    <p>Accumulation of smaller stressors</p> Signup and view all the answers

    Which of the following is a symptom of separation anxiety?

    <p>Unfounded fears of harm to loved ones</p> Signup and view all the answers

    Pregabalin is primarily used for which condition?

    <p>Managing symptoms of generalized anxiety disorder</p> Signup and view all the answers

    What is a common side effect of pregabalin at higher doses?

    <p>Dizziness and headaches</p> Signup and view all the answers

    Social anxiety disorder is characterized by which of the following fears?

    <p>Fear of social humiliation or judgment</p> Signup and view all the answers

    Why might lifestyle changes be beneficial for those with anxiety disorders?

    <p>They can improve overall well-being and coping mechanisms</p> Signup and view all the answers

    Which of the following statements about anxiety treatments is true?

    <p>Pharmacological and non-pharmacological therapies can be combined for better outcomes</p> Signup and view all the answers

    What is a key feature of panic attacks?

    <p>Intense, sudden fear with physiological symptoms</p> Signup and view all the answers

    What type of calcium channels does gabapentin primarily target?

    <p>High voltage activated calcium channels</p> Signup and view all the answers

    Which anti-epileptic drug is considered first-line therapy for generalized seizures?

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

    What is a common side effect associated with the use of valproate?

    <p>Hair loss</p> Signup and view all the answers

    Which type of seizures are T type calcium channels particularly associated with?

    <p>Absence seizures</p> Signup and view all the answers

    What major risk do all anti-epileptic drugs (AEDs) pose to pregnant individuals?

    <p>Teratogenic effects</p> Signup and view all the answers

    What should be monitored when a patient is on anti-epileptic drugs and contraceptives?

    <p>Serum drug levels</p> Signup and view all the answers

    Which adjective best describes the elimination kinetics of phenytoin?

    <p>Zero-order elimination</p> Signup and view all the answers

    What common adverse effect is associated with most anti-epileptic drugs?

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

    Which drug is often used as adjunct therapy due to its calcium channel blocking properties?

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

    Which of the following can lead to excessive CNS inhibition when combined with anti-epileptic drugs?

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

    What is one reason why the choice of anti-epileptic drug may require a trial-and-error approach?

    <p>Individual variability in response</p> Signup and view all the answers

    Which common cosmetic change is associated with phenytoin usage?

    <p>Gum hyperplasia</p> Signup and view all the answers

    What can happen if anti-epileptic therapy is abruptly withdrawn?

    <p>Status epilepticus</p> Signup and view all the answers

    What pharmacokinetic property is crucial for drugs to effectively enter the brain?

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

    What is the primary goal in preventing seizures?

    <p>Modulating enzyme activity to increase GABA levels</p> Signup and view all the answers

    Which medication is an example of a GABA transaminase inhibitor?

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

    What characterizes the action of benzodiazepines like midazolam?

    <p>They enhance the action of GABA already bound to receptors.</p> Signup and view all the answers

    What defines status epilepticus?

    <p>Continuous seizure activity for over 30 minutes</p> Signup and view all the answers

    Which of the following would enhance GABA neurotransmission?

    <p>Inhibiting GABA transaminase</p> Signup and view all the answers

    What is the effect of blocking sodium channels in seizure control?

    <p>It prevents depolarization in excitatory neurons.</p> Signup and view all the answers

    Which of the following is a characteristic of use dependence with sodium channel blockers?

    <p>The intensity of block increases with channel frequency.</p> Signup and view all the answers

    What causes hyperpolarization in postsynaptic neurons upon GABA receptor activation?

    <p>Influx of chloride ions</p> Signup and view all the answers

    Which drug is known for being a sodium channel blocker?

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

    What is a primary feature of GAT1 inhibitors like tiagabine?

    <p>They block the reuptake of GABA.</p> Signup and view all the answers

    How do sodium channel blockers achieve selectivity during seizure treatment?

    <p>By preferentially blocking frequently firing neurons.</p> Signup and view all the answers

    What is a common treatment approach for status epilepticus?

    <p>Acutely administered benzodiazepines.</p> Signup and view all the answers

    Which ion channel is crucial for the depolarization phase of action potentials?

    <p>Sodium channels</p> Signup and view all the answers

    Which neurotransmitter is primarily inhibitory in the CNS?

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

    Study Notes

    Antidepressants

    • Antidepressants work on neurotransmitters in the brain to influence mood.
    • Common side effects include nausea, dizziness, weight gain, and sexual problems.
    • Neurotransmitters involved include serotonin, noradrenaline, dopamine, and melatonin.

    Types of Antidepressants

    • Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. Examples include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.
    • Serotonin and noradrenaline reuptake inhibitors (SNRIs) have fewer side effects than SSRIs and may be used for more severe depression. Examples include duloxetine, venlafaxine, and desvenlafaxine.
    • Noradrenaline reuptake inhibitors (NARIs) work on noradrenaline and are less likely to cause drowsiness. Reboxetine is an example.
    • Tricyclic antidepressants are less commonly prescribed due to harmful side effects. Examples include amitriptyline, nortriptyline, clomipramine, dothiepin, doxepin, imipramine, and trimipramine.
    • Reversible inhibitors of monoamine oxidase A (RIMAs) are more commonly used for anxiety than depression. Moclobemide is an example.
    • Noradrenaline serotonin specific antidepressants (NaSSAs) are a new class with fewer sexual side effects but can cause weight gain. Mirtazapine is an example.
    • MAOIs (monoamine oxidase inhibitors) are rarely prescribed due to their risk of side effects. Examples include phenelzine and tranylcypromine.
    • Atypical antidepressants include agomelatine and vortioxetine.
      • Agomelatine stimulates melatonin receptors to affect mood. -Vortioxetine works on serotonin receptors differently from SSRIs and SNRIs.

    The Monoamine Hypothesis

    • Depression is associated with a deficiency in the neurotransmitters noradrenaline, serotonin, and dopamine.
    • Antidepressants work by raising the levels of these neurotransmitters back to their normal levels.
    • There is a lag between the increase in neurotransmitter levels and improvement in mood, taking 2-4 weeks.
    • The monoamine receptor hypothesis suggests that depression is also associated with an upregulation of monoamine receptors.

    Targeting Reuptake

    • Tricyclic antidepressants (TCAs) block the reuptake of noradrenaline and serotonin, increasing their levels in the synapse.
    • Disadvantages of TCAs include anticholinergic effects, postural hypotension, sedation, and cardiac toxicity.
    • Selective serotonin reuptake inhibitors (SSRIs) inhibit the reuptake of serotonin on the presynaptic neuron.
    • SSRIs are preferred to TCAs due to fewer side effects. Fluoxetine (Prozac) is a well-known example.
    • SSRIs are used to treat anxiety disorders.
    • Adverse effects of SSRIs include sleep disturbance, decreased sex drive, nausea, diarrhea, and increased anxiety.

    Serotonin Syndrome:

    • This occurs when SSRIs are used in conjunction with other serotonin affecting drugs, like MAOIs, triptans, and St. John’s Wort.
    • Symptoms include agitation, confusion, fever, muscle spasms, and diarrhoea.
    • Must be treated as a medical emergency.

    Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)

    • Block the reuptake of both noradrenaline and serotonin.
    • Do not have receptor antagonist effects like TCAs.
    • Well tolerated and an example is venlafaxine.

    Targeting Metabolism

    • Monoamine oxidase (MAO) isoforms are enzymes responsible for metabolising noradrenaline, serotonin, and dopamine.
    • There are two isoforms: MAOa and MAOb.
    • Inhibitors of MAO can be reversible or irreversible.
    • Irreversible MAO inhibitors (e.g., tranylcypromine) are non-selective and increase the levels of noradrenaline, serotonin, and dopamine.
    • Precautions include avoiding foods high in tyramine, which can lead to a hypertensive crisis (the "cheese reaction").
    • Reversible MAO inhibitors (e.g., meclobamide) are selective for MAOa and have a reduced risk of cheese reaction.

    Targeting Receptors

    • Serotonin antagonist and reuptake inhibitors (SARIs) (e.g., trazadone) block serotonin reuptake and antagonise serotonin 2A receptors.
    • Alpha 2 receptor antagonists (e.g., mianserin) are also known as tetracyclic antidepressants. They increase the release of noradrenaline and serotonin by blocking alpha 2 receptors.

    Bipolar Disorder

    • Bipolar disorder is characterized by cycling moods between depression and mania.
    • Bipolar 1 is more severe than Bipolar 2.
    • Drug therapy aims to manage acute mania and depression episodes, as well as prevent their recurrence.

    Lithium

    • Lithium is a main treatment for bipolar disorder.
    • It is used chronically to prevent manic and depressive episodes and for acute mania.
    • Mechanism of action is unclear, but it is believed to accumulate in excitable tissue, inhibiting dopamine and serotonin release and disrupting cell signaling.
    • Risks and side effects include a narrow therapeutic window, nephrotoxicity, diabetes insipidus, and hypothyroidism.

    Antipsychotics

    • Antipsychotics treat psychosis, a mental health condition characterized by confusion, delusions, paranoia, and hallucinations.
    • Typical antipsychotics are first-generation drugs like chlorpromazine and haloperidol.
    • Atypical antipsychotics are newer drugs like risperidone, olanzapine, and quetiapine.

    Drug Targets in Schizophrenia

    • Schizophrenia is associated with elevated levels of dopamine and its metabolites in certain brain regions. This suggests an excess of dopamine in the brain.
    • Dopamine pathways in the brain include the mesocortical, mesolimbic, nigrostriatal, and tuberohypophyseal pathways.

    Aims of Schizophrenia Drug Treatment

    • All effective antipsychotic drugs are dopamine (D2) receptor antagonists.
    • They aim to inhibit dopamine in the mesolimbic pathway, resulting in emotional quieting, psychomotor slowing, and decreased agitation.
    • Unwanted effects arise from dopamine inhibition in the nigrostriatal and tuberohypophyseal pathways.

    Unwanted Effects of Schizophrenia Drug Treatment

    • Extrapyramidal symptoms (EPS), resembling Parkinson’s disease, result from inhibiting dopamine in the nigrostriatal pathway.
    • Increased prolactin production results from inhibiting dopamine in the tuberohypophyseal pathway.
    • Gynaecomastia (breast swelling) and amenorrhea (lack of menstruation) can occur.

    Typical Antipsychotics

    • Typical antipsychotics (e.g., haloperidol, chlorpromazine) are less effective in treating negative and cognitive symptoms of schizophrenia.
    • They are effective in managing positive symptoms, especially delusions and auditory hallucinations.
    • Haloperidol is a potent D2 receptor antagonist but has a higher risk of EPS.
    • Other typical antipsychotics resemble the actions of chlorpromazine, causing side effects like postural hypotension, sedation, anticholinergic effects, and weight gain.

    Basis of Extrapyramidal Symptoms

    • Dopamine normally inhibits cholinergic neurons in the striatum.
    • Blocking dopamine with antipsychotics disinhibits acetylcholine, which is associated with EPS.
    • Anticholinergic effects can minimize EPS by restoring the balance between dopamine and acetylcholine.

    Atypical Antipsychotics

    • Atypical antipsychotics (e.g., risperidone, clozapine, quetiapine) are as effective as typical drugs for managing positive symptoms.
    • They are more effective in managing negative and cognitive symptoms.
    • They are better at treating negative symptoms due to their greater affinity for serotonin receptors, which is thought to modulate dopamine activity in a more balanced way.

    Prefrontal Cortex Activity

    • Dopamine deficiency in the prefrontal cortex is linked to negative symptoms of schizophrenia. This deficiency is caused by increased dopamine in the mesolimbic and mesocortical pathways, which lead to positive symptoms.
    • Atypical antipsychotics promote dopamine activity in the prefrontal cortex to alleviate negative symptoms.

    Basis of Negative Symptoms

    • Dopamine neurons have 5HT2A receptors, and dopamine interacts with many receptor types.
    • 5HT2A receptors negatively regulate dopamine release from dopaminergic neurons, leading to dopamine deficiency in the prefrontal cortex.
    • Atypical antipsychotics antagonize 5HT2A receptors to increase dopamine levels in the prefrontal cortex.

    Receptor Blocking Profile of Atypical Antipsychotics

    • Atypical antipsychotics resemble chlorpromazine's receptor blocking profile.
    • They are effective D2 receptor antagonists.
    • Their efficacy against negative symptoms is attributed to their antagonism of 5HT2A and 5HT2C receptors.

    Monitoring Antipsychotic Use in Practice

    • Atypical antipsychotics are generally the first choice of treatment for psychosis.
    • Treatment doesn't need to be indefinite; recommendations suggest treatment for one year following a first episode of psychosis, two years following a relapse, and longer durations after subsequent relapses.
    • Antipsychotics like olanzapine are also used to manage the manic phase of bipolar disorder.

    Managing Adherence to Treatment

    • Antipsychotic medications are typically administered orally for convenience.
    • Adherence can be monitored through plasma drug concentrations.
    • Long-acting injectable preparations are available for patients who struggle with oral medication adherence. These require regular physician visits, ensuring patient monitoring.

    Monitoring for Adverse Effects

    • Several antipsychotics can cause weight gain, ECG issues (prolonged QT interval), altered triglyceride levels, and neutropenia.
    • Smoking can increase antipsychotic drug plasma concentrations, potentially leading to toxicity.
    • Regular monitoring is necessary for blood pressure, heart rate, ECG, blood glucose and lipid levels, weight, waist circumference, BMI, full blood count, and smoking status.

    Neuroleptic Malignant Syndrome (NMS)

    • NMS is a rare and serious side effect of antipsychotic medications, directly linked to D2 receptor antagonism.
    • Symptoms include severe muscle rigidity and hyperthermia.
    • It can occur shortly after starting antipsychotic therapy or during dose increases.
    • NMS requires immediate medical attention as it is a life-threatening condition.

    Antidepressant and Antipsychotic Drugs

    MAO Inhibitors

    • Non-selective MAO inhibitors prevent MAO from degrading all three neurotransmitters (dopamine, noradrenaline, and serotonin), allowing for their re-release.
    • These are irreversible inhibitors, taking approximately two weeks to achieve full inhibition.
    • MAO also metabolizes tyramine, a stimulatory neurotransmitter. Excessive tyramine intake can lead to a "cheese reaction" characterized by hypertension.
    • Tyramine increases noradrenaline levels, potentially causing hypertension if concentrations are too high.

    Selective Serotonin Reuptake Inhibitors (SSRIs)

    • SSRIs inhibit the reuptake of serotonin by the presynaptic neuron, increasing serotonin signalling in the synaptic cleft.
    • Initially, increased serotonin signalling might occur due to increased receptor expression, but receptors are eventually reinternalized, leading to normal serotonin receptor levels.

    Tricyclic Antidepressants

    • Tricyclic antidepressants block muscarinic, H1, and alpha/beta receptors.
    • These blocks can lead to cardiotoxicity due to increased acetylcholine concentrations. Blocking muscarinic receptors also causes increased sympathetic activity and decreased parasympathetic activity, resulting in orthostatic hypotension.

    Predictable Side Effects

    Tricyclic Antidepressants
    • Cardiotoxicity
    • Dry eye/mouth
    • Constipation
    • Orthostatic hypotension
    • Drowsiness
    Non-selective Irreversible MAOIs
    • "Cheese reaction" and subsequent hypertensive crisis due to increased noradrenaline and tyramine levels, leading to vasoconstriction.
    • Dry mouth and constipation.
    Selective Serotonin Reuptake Inhibitors (SSRIs)
    • Initial anxiety caused by increased serotonin receptor expression.
    • Serotonin syndrome, characterized by increased shivering, seizures, and muscle rigidity, can occur in situations of high existing serotonin levels.
    • Decreased sex drive and diarrhoea.

    Case Study: SSRI and St. John's Wort

    • SSRIs can initially increase anxiety due to increased serotonin receptor expression before mood improvement.
    • St. John's Wort, a natural remedy often used for mood support, can also affect serotonin levels. Co-administration with SSRIs could lead to serotonin syndrome due to increased serotonin levels.

    Antipsychotics

    • Haloperidol blocks D2 receptors.
    • Chlorpromazine blocks D2, a1, H1, M, and 5-HT2 receptors.
    • Both haloperidol and chlorpromazine are considered typical antipsychotics as they reduce dopamine levels in the mesocortical and mesolimbic pathways.

    Receptor Block Effects

    • Extrapyramidal Symptoms (EPS) (D2): Parkinsonian symptoms, dystonia, increased prolactin release, and gynecomastia (due to dopamine's role in the tuberohypophyseal pathway).

    • Orthostatic hypotension

    • Sedation/drowsiness

    • Dry mouth, dry eyes, constipation

    • Weight gain (5-HT2)

    • These effects primarily reduce positive symptoms (delusions and hallucinations).

    • Clozapine and risperidone are atypical antipsychotics because they block the same receptors as chlorpromazine but also increase dopamine in the prefrontal cortex, reducing negative symptoms alongside positive symptoms.

    Case Study: Clozapine

    • Clozapine is effective against both positive and negative symptoms.
    • It can still affect movement due to D2 antagonism.
    • It antagonizes 5HT2A receptors in the prefrontal cortex, increasing dopamine levels.

    Precautions for Clozapine Use

    • Given the patient's BMI of 31 and heavy smoking status, potential weight gain and ECG abnormalities (exacerbated hypertension) should be closely monitored.
    • Clozapine levels may be significantly increased if the patient discontinues smoking due to smoking's induction of enzymes that metabolize clozapine.
    • Close monitoring for neutropenia and lipid metabolism issues is also necessary, as Clozapine can affect lipid levels.

    Chlorpromazine vs. Haloperidol

    • Chlorpromazine causes less EPS than haloperidol due to muscarinic receptor antagonism in the nigrostriatum and weaker binding to dopamine receptors.

    Drugs for Parkinson's Disease

    Neurochemical Deficits and Pathology

    • Multiple dopamine signalling pathways exist in the brain.
    • The nigrostriatal pathway (striatum + substantia nigra) is responsible for fine motor control.
    • Death of dopaminergic cell bodies in the substantia nigra leads to a decrease in signalling between this region and the striatum, reducing dopamine release in the striatum.

    Treating Parkinson's Disease: Restoring Dopamine Signalling

    • The aim is to restore synaptic concentrations of dopamine.

    Dopamine Synthesis

    • Dopamine synthesis starts with tyrosine, which is then converted to dopa and finally to dopamine.
    • Dopamine is packaged into vesicles and released through exocytosis.
    • Levodopa, a dopamine precursor, can be administered to boost dopamine release.

    Levodopa

    • Levodopa has a short plasma half-life (around 2 hours), requiring multiple daily doses.
    • It gets metabolized by dopa decarboxylase (DDC) in both the periphery and the central nervous system. Excessive peripheral metabolism can cause nausea and hypotension.
    • Levodopa's effectiveness can be unpredictable as Parkinson's progresses, leading to a decline in the number of dopaminergic neurons (source of DDC) and potentially diminishing effects.
    • Increased CNS dopamine, especially in the mesolimbic pathway, can lead to hallucinations.

    Levodopa On-Off Effects

    • Levodopa's short half-life means that its effects peak shortly after administration and then fade, causing periods of difficulty initiating movement("off") and periods of good movement ("on").

    Dopamine Receptor Agonists

    • These drugs (e.g., pramipexole, rotigotine) bypass the need for enzymatic conversion to dopamine.
    • They have longer half-lives and potentially cause fewer dyskinesias than levodopa.
    • Extended-release formulations are available for convenient administration.

    Adverse Effects of Dopamine Agonists

    • Similar to levodopa, these drugs can cause nausea, hypotension, and hallucinations.
    • Some dopamine receptor agonists can cause severe nausea and may require co-administration of peripherally acting dopamine receptor antagonists.
    • Impulse control disorders can occur, as dopamine is involved in the reward pathway, potentially leading to addictive behaviors and compulsions.

    MAOB Inhibitors

    • MAOB preferentially metabolizes dopamine, while MAOA also exists in the brain.
    • MAOB inhibitors selectively inhibit MAOB, allowing for increased recycling of dopamine in the presynaptic neuron with no dietary restrictions (no "cheese reaction").
    • Selegiline is an example of a MAOB inhibitor.

    COMT Inhibitors

    • Catechol-O-methyl-transferase (COMT) is present in both the periphery and the CNS.
    • COMT inhibitors can preserve both levodopa and dopamine levels.
    • Entacapone is active only in the periphery.
    • Tolcapone is active in both the periphery and the CNS.

    Modulating Other Neurotransmitter Pathways

    • Acetylcholine can also be targeted in Parkinson's treatment.
    • In the nigrostriatal pathway, dopaminergic neurons typically inhibit cholinergic neurons.
    • Loss of dopaminergic neurons leads to increased cholinergic activity, contributing to movement issues associated with Parkinson's.

    Muscarinic Receptor Antagonists

    • Muscarinic receptor antagonists (e.g., benztropine) restore balance in the nigrostriatal pathway by reducing cholinergic activity.
    • These drugs are centrally active and can cross the blood-brain barrier.
    • They are associated with predictable anticholinergic side effects like dry mouth, dry eyes, and constipation.

    Polypharmacy in Parkinson's Disease

    • Polypharmacy is common as Parkinson's progresses, requiring additional treatments to manage increasingly severe symptoms and "off time".
    • Non-pharmacological treatments may also be needed to manage the disease in advanced stages.

    Huntington's Disease

    • Huntington's disease is a hereditary disorder with an autosomal dominant pattern.
    • Affected individuals have a 50% chance of passing the condition to their offspring.
    • Symptoms often manifest in middle age.

    Neurochemical Changes

    • Huntington's disease is caused by the production of an abnormal huntingtin protein (Htt) that disrupts neuronal survival and metabolism.
    • Selective loss of GABA neurons in the striatum leads to dopamine hyperactivity.

    Drug Treatments

    • Drug treatments are symptomatic and only effective short-term.
    • They focus on suppressing dopamine signalling or enhancing GABA activity.
    • D2 receptor antagonists (e.g., antipsychotics like chlorpromazine) are used to manage symptoms.
    • GABA receptor agonists (e.g., baclofen) are used to treat muscle spasticity. Baclofen acts centrally in the spinal cord to inhibit motor neurons.
    • VMAT inhibitors (e.g., tetrabenazine) inhibit the transport of dopamine from the cytoplasm into vesicles for release. This reduces dopamine availability.

    Sedatives, Hypnotics, and Anesthetics

    Suppression of Sensation and Consciousness

    • Suppression of sensation and consciousness is essential for both therapeutic and procedural purposes, including treating anxiety or insomnia and enabling safe surgery.

    Anxiety

    • Anxiety is a complex condition with variable presentations and experiences.
    • There's no single clear biological mechanism associated with anxiety.
    • Generalised Anxiety Disorder (GAD) is characterized by excessive anxiety and worry, increased muscle aches and soreness, impaired concentration, fatigue, irritability, restlessness, and difficulty sleeping.

    Panic Disorder

    • Panic disorder is a more severe form of anxiety characterized by frequent and intense panic attacks.

    Anxiety

    • Psychological screening tools exist to detect anxiety
    • There are different types of anxiety
      • Generalised anxiety disorder is characterized by excessive and pervasive worries occurring most days for at least 6 months.
      • Social anxiety disorder involves irrational fears related to social situations, such as fear of judgment, humiliation, or unintentionally offending others.
      • Separation anxiety involves distress when separated from loved ones, often with unfounded fears of harm to them.
      • Specific phobia involves an intense and often irrational fear of a specific trigger.
      • Panic disorder features sudden and recurrent panic attacks followed by excessive worry about future attacks.
    • Anxiety is often culturally and location dependent.
    • It is generally considered a pattern of intrusive thoughts combined with physical sensations like increased heart rate, unease, and sweating, but presentation varies.
    • The cup/bucket theory can be applied to anxiety, with stressors gradually filling the cup until it overflows.
      • Different individuals have different cup sizes and emptying mechanisms.
      • Poor coping strategies may temporarily reduce stress but worsen it over time.
      • The biological mechanism of this theory is still unknown.

    Anxiety Treatments

    • Pharmacological treatments are often used for anxiety disorders, with a strong overlap between anxiety and depression treatments.
      • SSRIs are the first-line treatment for anxiety disorders, but can take 2-6 weeks to work.
      • Benzodiazepines were once the first-line treatment but are now often used in combination therapy with SSRIs. They work by increasing GABA activity, reducing neuronal excitability, and can have side effects such as drowsiness, decreased alertness, and lack of coordination.
      • Pregabalin, a GABA analogue, is commonly used in generalized anxiety disorder as a monotherapy or adjunct to antidepressants. It has side effects like dizziness, headaches, and diarrhea, usually appearing at higher doses.
    • Non-pharmacological therapies are an important part of anxiety management.
      • Cognitive behavioral therapy (CBT) is well-supported in helping reframe stressful situations and challenging unhelpful thoughts.
      • Symptomatic therapies may involve beta-blockers to manage unsettling symptoms like rapid heart rate and chest pain.
      • Lifestyle changes, such as regular exercise and a healthy diet, can also help reduce anxiety.
      • Alternative therapies, like acupuncture, herbs and medicines, and meditation, may be beneficial for some individuals.

    General Anaesthetics

    • General anesthetics revolutionized surgery by rendering patients unconscious and insensitive to pain.
    • They are highly lipophilic, allowing easy passage into the brains.
    • Their mechanism of action is still not fully understood, but they are thought to:
      • Hyperpolarize neurons.
      • Open potassium and chloride channels.
      • Disrupt neuronal membrane structure, leading to channel openings.
    • TREK1 potassium channel is thought to be involved in the maintenance of the resting membrane potential and potentially impacted by anesthetic action.
    • Minimum Alveolar Anaesthetic Concentration (MAC) is the concentration required to immobilise 50% of patients.
      • MAC is directly correlated to the compound's lipid solubility, with higher solubility meaning a lower MAC and higher potency.
    • Lipid solubility can also influence how quickly a drug takes effect due to how it partitions itself in tissues.
    • Blood gas coefficient plays a role in the speed of induction.
      • Highly soluble compounds may bind to plasma proteins, delaying diffusion into the brain.
    • Recovery from anaesthetics is also related to MAC. The lower the MAC, the faster the recovery.
    • There is some evidence suggesting toxic metabolites can form with anesthetic breakdown.
    • Common general anaesthetics include:
      • Isoflurane, desflurane, and sevoflurane for maintaining general anesthesia.
      • Nitrous oxide for maintaining general anesthesia, though less commonly.
      • Methoxyflurane for providing analgesia at sub-anaesthetic doses, though less commonly used for general anesthesia.

    Epilepsy

    • Seizures are characterized by excessive and unsynchronized firing of cortical neurons, which can be focal or generalized depending on their origin.

    • Epilepsy is diagnosed if someone experiences at least two unprovoked seizures occurring over 24 hours apart.

    • Anti-epileptic agents aim to manage or prevent seizures by enhancing GABA neurotransmission or disrupting neuronal membrane excitability.

    • Enhancing GABA neurotransmission involves increasing GABAergic activity through several mechanisms:

      • GABA transaminase inhibitors like valproate and vigabatrin block the breakdown of GABA, increasing its availability.
      • GAT1 inhibitors like tiagabine block the reuptake of GABA, prolonging its action.
      • GABAa receptor modulators like benzodiazepines potentiate GABA action at the GABAa receptor, enhancing GABA's inhibitory effects and are useful for acute treatment of status epilepticus, a life-threatening condition characterized by prolonged seizure activity.

    • Regulating neuronal excitability by targeting ion channels involves:

      • Sodium channel blockers like carbamazepine, lamotrigine, and phenytoin reduce neuronal firing by blocking sodium channels. They are said to exhibit use dependence, meaning their blocking effect is stronger on frequently-firing neurons.
      • Calcium channel blockers like gabapentin and ethosuximide are used to target specific types of calcium channels.
        • High-voltage activated (HVA) calcium channels are associated with partial seizures and are often used as adjunct therapy with other drugs.
        • T-type calcium channels are located in thalamic neurons and are responsible for regulating oscillatory activity, making ethosuximide effective for absence seizures.

    • Choosing an anti-epileptic involves several factors:

      • Identifying the type of seizure, whether focal or generalized.
      • Considering the individual patient's response to different medications.
      • Determining the appropriate dosage and titration regimen.
      • Recognizing that anti-epileptic treatment often involves a trial-and-error approach.### Anti-Epileptic Drugs and Pregnancy

    • All anti-epileptic drugs (AEDs) pose a risk to a developing fetus, especially valproate.

    • Valproate can cause various birth defects.

    • Female patients of childbearing age need to use contraception while on AEDs.

    • Contraceptives can alter AED serum levels due to their effect on liver enzymes involved in drug metabolism.

    • AEDs can also affect contraceptive efficacy, necessitating discussion with a physician regarding contraception planning.

    • The risk of uncontrolled seizures must be weighed against the risk to the fetus.

    • If AED therapy continues during pregnancy, the dosage should be minimized to the lowest effective dose.

    • All AEDs carry a high risk to the developing fetus, with no single "drug of choice."

    • Drug metabolism can change during pregnancy. Monitoring is crucial to ensure therapeutic drug levels and prevent toxicity.

    • Phenytoin is more likely to be toxic when a contraceptive is used.

    Pharmacokinetic Drug Interactions

    • AEDs are lipophilic to allow penetration into the brain.
    • They undergo liver metabolism via cytochrome P450 enzymes, making them susceptible to pharmacokinetic interactions.
    • Other medications, including AEDs and non-AEDs, can affect AED serum levels, patient safety, and seizure control.
    • Enzyme activity can be induced or inhibited, potentially requiring serum drug level monitoring.

    Elimination: Example of Phenytoin

    • Phenytoin exhibits complex pharmacokinetics.
    • It undergoes zero-order elimination, meaning its elimination rate is independent of plasma drug concentration.
    • This contrasts with first-order elimination, where elimination is proportional to drug concentration.
    • Phenytoin has a narrow therapeutic range, making small increases in concentration potentially toxic and compromising patient safety.

    Phenytoin Adverse Effects

    • Gum hyperplasia (overgrowth of gum tissue) and acne are commonly associated with phenytoin.

    Anti-Epileptic Drug Unwanted Effects

    • Common to all AEDs due to their action on ion channels:
      • Sedation
      • Weight gain, especially with valproate.
    • Cosmetic changes:
      • Phenytoin: hirsuitism (excessive hair growth), gum hyperplasia, acne.
      • Valproate: alopecia (hair loss).
    • Skin rashes:
      • Variable severity, some resolving with drug initiation.
      • Others may indicate allergy or hypersensitivity.
    • Monitoring and patient communication are essential to manage these effects and ensure compliance.

    General Precautions

    • Combined use with CNS depressants like alcohol, opioids, and benzodiazepines can lead to excessive CNS inhibition.
    • Abrupt withdrawal of AED therapy may precipitate status epilepticus.
    • Even if a patient has been seizure-free for years, AEDs should be gradually withdrawn.

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    Test your knowledge on psychopharmacology with this quiz covering neurotransmitters, antidepressants, and antipsychotics. Explore the mechanisms of action and side effects associated with various classes of medication used to treat mental health disorders. Perfect for students and professionals in psychology and medicine.

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