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Questions and Answers
Which neurotransmitter is primarily targeted by selective serotonin reuptake inhibitors (SSRIs)?
What is a common side effect associated with the use of antidepressant drugs?
Which class of antidepressants is typically the most commonly prescribed in Australia?
Which of the following neurotransmitters is NOT typically associated with the action of antidepressants?
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What mechanism of action do most antidepressants primarily utilize?
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What mechanism is primarily responsible for the efficacy of anti-psychotics in the nucleus accumbens?
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Which typical anti-psychotic is known for its pure D2 receptor antagonism?
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What is the primary reason atypical anti-psychotics are considered more effective for treating negative symptoms?
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What adverse effects are most commonly associated with typical anti-psychotics like chlorpromazine?
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How do anti-cholinergic effects help manage extra-pyramidal symptoms in patients taking anti-psychotics?
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Which of the following statements accurately describes the effect of dopamine neurons on cholinergic neurons in the striatum?
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Which characteristic differentiates typical anti-psychotics from atypical anti-psychotics?
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Why does haloperidol have minimal sedating effects compared to other anti-psychotics?
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Which class of antidepressants is known to have the fewest side effects and is generally well tolerated?
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What is one of the primary reasons tricyclic antidepressants (TCAs) are less commonly prescribed today?
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Noradrenaline reuptake inhibitors (NARIs) are known to cause which of the following side effects less frequently?
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Which type of antidepressant works specifically by inhibiting serotonin reuptake?
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What is the duration for which mood improvements are typically expected after starting antidepressant treatment, despite rapid increases in neurotransmitter levels?
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Which type of antidepressant is primarily used for treating anxiety rather than depression?
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What major side effect risk is associated with combining SSRIs and monoamine oxidase inhibitors (MAOIs)?
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Which neurotransmitters are indicated as deficient in the monoamine hypothesis of depression?
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What is a common adverse effect associated with the initial use of SSRIs?
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Which of the following antidepressants is classified as an atypical antidepressant?
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What common side effect is associated with the use of mirtazapine, a Noradrenaline serotonin specific antidepressant (NaSSA)?
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What is a characteristic of serotonin and noradrenaline reuptake inhibitors (SNRIs)?
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What mechanism do tricyclic antidepressants primarily use to increase neurotransmitter levels in the synapse?
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What is one example of a reversible monoamine oxidase inhibitor (RIMA)?
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Which side effect is associated with the use of monoamine oxidase inhibitors due to tyramine intake?
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Which receptor antagonism is primarily responsible for the sedation caused by tricyclic antidepressants?
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What process is suggested by the monoamine receptor hypothesis as contributing to depression?
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What is the mechanism of action of lithium in bipolar disorder?
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Which of the following is a symptom of manic episodes in bipolar disorder?
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What distinguishes atypical antipsychotics from typical antipsychotics?
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What is a common side effect experienced with typical antipsychotics due to inhibition of the nigrostriatal pathway?
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What is the function of MAOa in neurotransmitter metabolism?
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Which neurotransmitter pathway is primarily inhibited by antipsychotic drugs to manage psychosis symptoms?
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What is a potential risk when using lithium in patients?
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Which of the following drugs is an example of a typical antipsychotic?
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Why are typical antipsychotics effective for positive symptoms of schizophrenia?
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Which of the following describes SARAIs?
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What is the term used to describe the upwards and downwards mood swings in bipolar disorder?
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What role do atypical antipsychotics play in relation to dopamine activity in the prefrontal cortex?
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How do 5HT2A receptors affect dopamine release from dopaminergic neurons?
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Which of the following is a proposed treatment duration after a first episode of psychosis?
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What is a possible consequence of smoking while on antipsychotic medication?
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What unique side effect is associated with antipsychotic therapy due to D2 receptor antagonism?
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What is the main action of MAO inhibitors in the treatment of depression?
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Which of the following is a common side effect of tricyclic antidepressants?
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What condition may be exacerbated by the use of non-selective irreversible MAOIs?
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What initial effect might someone experience when beginning treatment with SSRIs?
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What is a potential risk of taking St John’s Wort alongside conventional antidepressants?
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Which receptor types do atypical antipsychotics antagonize to reduce negative symptoms?
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What is a common effect that occurs with the use of tricyclic antidepressants due to their receptor blocking profile?
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What is one of the first-line monitoring strategies when using antipsychotics?
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What is a characteristic of focal seizures?
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Which anti-epileptic agent is known for having a lower risk of respiratory depression and is commonly used in children?
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What defines epilepsy according to diagnostic criteria?
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How do generalized seizures differ from focal seizures?
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What type of seizure is characterized by brief episodes of staring and lack of recall, often mistaken for daydreaming?
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Which of the following is a potential initiating factor for seizures?
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How do seizures typically manifest in terms of brain activity as observed in an EEG?
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What is a common misconception about seizures in relation to epilepsy?
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What is the significance of minimum alveolar anaesthetic concentration (MAC) in evaluating general anaesthetics?
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Which of the following anaesthetics has the highest potency based on its MAC value?
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Which mechanism primarily explains the action of general anaesthetics at the neuronal level?
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How does high lipid solubility influence the anesthetic action in relation to the nervous system?
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What is a primary reason for the slower onset of action of highly soluble anaesthetics like methoxyflurane?
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What characteristic of nitrous oxide contributes to its rapid induction as an anaesthetic?
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Which adverse effect is associated with the use of isoflurane, desflurane, and sevoflurane?
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Why is metabolism not a significant route of elimination for general anaesthetics?
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Which of the following is a notable characteristic of intravenous anaesthetics?
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What is the primary effect of clozapine on dopamine and serotonin levels?
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Which receptor blockade is primarily responsible for extrapyramidal symptoms (EPS) in patients taking antipsychotics?
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What potential issue can arise from smoking while being treated with clozapine?
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What is a significant side effect of antidepressants that may lead to an emergency situation?
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Which of the following antipsychotics is likely to cause more extrapyramidal symptoms?
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Levodopa primarily functions by restoring which neurotransmitter in Parkinson’s disease treatment?
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What is the main reason that the effects of levodopa can be unpredictable in advanced Parkinson's disease?
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What specific type of receptors does clozapine antagonize to help with schizophrenia symptoms?
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How does chlorpromazine contribute to a lower incidence of EPS compared to haloperidol?
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What is a potential consequence of using high doses of levodopa over time?
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Which of the following is NOT a possible side effect of clozapine use?
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What is a common treatment approach for improving effects in Parkinson's disease related to dopamine?
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What mechanism is primarily responsible for the positive symptoms of schizophrenia in relation to dopamine?
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What is a key advantage of dopamine receptor agonists compared to levodopa?
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Which adverse effect is commonly associated with dopaminergic agonists?
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How do MAO-B inhibitors function in relation to dopamine?
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Which drug example selectively works in the periphery only and is used to preserve levodopa levels?
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What condition is primarily treated with muscarinic receptor antagonists like Benztropine?
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What is a significant concern regarding the side effects of dopaminergic agonists?
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Which statement regarding Huntington's disease is correct?
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What kind of drug is tetrabenazine and its primary action?
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What is a primary function of COMT inhibitors in managing Parkinson’s disease?
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In the context of sedation, which of the following is NOT a therapeutic purpose?
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Which of the following neurotransmitters exhibits an increased activity leading to movement issues in Parkinson’s disease?
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What is a common effect of anti-cholinergic medications like Benztropine?
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Why is polypharmacy frequently needed in the treatment of Parkinson’s disease?
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Which of the following statements regarding levodopa is accurate?
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Which of the following is a sign of generalized anxiety disorder?
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What is a characteristic of social anxiety disorder?
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In panic disorder, what is a common aftereffect of experiencing a panic attack?
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What is a known side effect of benzodiazepines?
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Which treatment method is commonly used as an adjunct therapy in generalized anxiety disorder?
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What is a significant characteristic of specific phobia?
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Which of the following is considered a non-pharmacological therapy for anxiety?
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How long must symptoms occur to be classified as generalized anxiety disorder?
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What is the role of pregabalin in treating anxiety disorders?
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What does the 'cup/bucket theory' suggest about stress?
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What is a common sign of separation anxiety?
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How long does it typically take for SSRIs to show effectiveness?
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What does cognitive behavioral therapy primarily focus on?
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Why is patient-centered care important in anxiety treatment?
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What is the primary function of HVA calcium channels in relation to seizures?
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Which anti-epileptic drug is particularly effective for absence seizures due to its action on T type calcium channels?
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Which anti-epileptic drug is often the first-line treatment for generalized seizures?
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What risk is particularly associated with the use of valproate in women of child-bearing age?
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What common side effect can occur with all anti-epileptic drugs?
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What is a notable characteristic of phenytoin's pharmacokinetics?
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Which calcium channel type is primarily linked to the regulation of neuronal electrical activity and is analogous to the sinoatrial node?
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How do contraceptives interact with anti-epileptic drugs?
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What should be a consideration when managing a patient on anti-epileptic drugs who becomes pregnant?
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What adverse effect is unique to phenytoin when compared to other anti-epileptic drugs?
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What is a typical consequence of sudden withdrawal from anti-epileptic drugs?
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Which of the following is true regarding the metabolism of anti-epileptic drugs?
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What can be a side effect of valproate, aside from sedation?
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Which drug is used as adjunct therapy but is not typically effective when used alone for seizure control?
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What is the primary goal of increasing GABA neurotransmission in the brain?
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Which drug is classified as a GABA transaminase inhibitor?
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What physiological process occurs when GABA binds to its receptor?
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What characterizes status epilepticus?
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What is the action of sodium channel blockers in the context of epilepsy treatment?
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What is a potential issue associated with the use of benzodiazepines for treating seizures?
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Which of the following best describes the use dependence concept regarding anti-epileptic ion channel inhibitors?
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What is the result of blocking GAT1 transporters?
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What happens during the depolarization phase of an action potential?
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Which drug is a GABA receptor modulator?
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What is the primary role of calcium channels in neurotransmission?
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What happens to sodium channels during frequent neuronal firing in epilepsy?
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What is the primary effect of elevating GABA levels within the presynaptic nerve?
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Study Notes
Antidepressants
- Antidepressants are used to treat various conditions, including depression and anxiety.
- They influence mood by affecting neurotransmitters like serotonin, noradrenaline, dopamine, and melatonin.
- Common side effects include nausea, dizziness, weight gain, and sexual problems.
Selective Serotonin Reuptake Inhibitors (SSRIs)
- The most widely prescribed antidepressants in Australia.
- Generally well tolerated, with fewer side effects.
- Examples: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.
Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)
- Have a lower likelihood of side effects compared to SSRIs.
- May be used for more severe depression.
- Examples: duloxetine, venlafaxine, and desvenlafaxine.
Noradrenaline Reuptake Inhibitors (NARIs)
- Less likely to cause drowsiness than other classes.
- Example: reboxetine.
Tricyclic Antidepressants (TCAs)
- Less commonly prescribed due to potential for adverse effects.
- Examples: amitriptyline, nortriptyline, clomipramine, dothiepin, doxepin, imipramine, and trimipramine.
Reversible Inhibitors of Monoamine Oxidase A (RIMAs)
- More commonly used to treat anxiety than depression.
- Example: moclobemide.
Noradrenaline Serotonin Specific Antidepressants (NaSSAs)
- Newer class, fewer sexual side effects.
- Can cause weight gain.
- Example: mirtazapine.
MAOIs (Monoamine Oxidase Inhibitors)
- Rarely prescribed due to the risk of side effects.
- Examples: phenelzine and tranylcypromine.
Atypical Antidepressants
- Examples: agomelatine and vortioxetine.
- Agomelatine stimulates melatonin receptors to affect mood.
- Vortioxetine acts on serotonin receptors differently than SSRIs and SNRIs.
The Monoamine Hypothesis - Biologic Basis of Depression
- Depression is believed to be linked to a deficiency in monoamines (noradrenaline, serotonin, and dopamine).
- Antidepressant treatment aims to restore these neurotransmitter levels.
- A lag period of 2-4 weeks is typically observed between increased neurotransmitter levels and mood improvement.
Monoamine Receptor Hypothesis
- Proposes that depression involves an upregulation of monoamine receptors, leading to increased sensitivity.
- Antidepressants may also work by downregulating these elevated receptor levels.
Targeting Reuptake
- TCAs block the reuptake of noradrenaline and serotonin, increasing their levels within the synapse.
- Their effects are influenced by their blocking of other receptors, leading to side effects like dry mouth, constipation, postural hypotension, sedation, and cardiac toxicity.
Selective Serotonin Reuptake Inhibitors (SSRIs)
- Selectively block serotonin reuptake.
- Preferred to TCAs due to fewer side effects.
- Example: fluoxetine (Prozac).
- Initial increase in anxiety is common due to elevated serotonin levels before receptor downregulation occurs.
Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)
- Block reuptake of both noradrenaline and serotonin.
- Generally well tolerated.
- Example: venlafaxine.
Noradrenaline Reuptake Inhibitors (NRIs)
- Block reuptake of noradrenaline.
- Can lead to predictable sympathomimetic side effects due to increased noradrenaline levels.
- Example: reboxetine.
Targeting Metabolism to Treat Depression
- Monoamine oxidase (MAO) is the enzyme responsible for metabolizing neurotransmitters like noradrenaline and serotonin.
- MAO inhibitors increase neurotransmitter levels by preventing their breakdown.
Irreversible Monoamine Oxidase Inhibitors
- Non-selective MAOa/b inhibitors, leading to an increase in noradrenaline, serotonin, and dopamine.
- Effects persist until new enzyme is synthesized.
- Example: tranylcypromine.
Precautions for MAOIs
- Dietary restrictions are crucial to avoid tyramine-rich foods, which can lead to a hypertensive crisis.
Reversible Monoamine Oxidase Inhibitors
- Selectively and reversibly inhibit MAOa, only affecting noradrenaline and serotonin.
- No risk of the "cheese reaction.”
- Example: meclobemide.
Targeting Receptors to Treat Depression
- SARIs (Serotonin Antagonists and Reuptake Inhibitors) block serotonin reuptake and antagonize serotonin 2A receptors.
- They may reduce the initial anxiety associated with SSRIs.
- Example: trazadone.
Alpha 2 Receptor Antagonists (Tetracyclic Antidepressants)
- Block alpha 2 receptors, increasing the release of noradrenaline and serotonin.
- Example: mianserin.
Bipolar Disorder
- Characterized by cyclical mood swings, including episodes of depression and mania.
- Bipolar 1 is more severe than bipolar 2.
Signs and Symptoms of Bipolar Disorder
- Manic episodes: Disinhibition, risky behaviors, overconfidence, poor concentration, grandiosity, rapid speech.
- Depressive episodes: Low mood, loss of pleasure, feelings of guilt and dissatisfaction.
Aims of Bipolar Disorder Drug Therapy
- Manage acute manic and depressive phases.
- Prevent recurrence of mood cycles to promote stability.
Lithium - Main Bipolar Treatment
- Used for both acute mania and long-term prevention of manic and depressive episodes.
- Mechanism of action is still unclear:
- May lodge in voltage-dependent sodium channels and inhibit dopamine and serotonin release.
- May disrupt cell signaling by altering levels of secondary messengers.
Risks and Side Effects of Lithium
- Narrow therapeutic window.
- Nephrotoxic.
- May induce diabetes insipidus.
- Can be associated with the development of hypothyroidism.
Other Drugs for Acute Mania
- Lithium combined with olanzapine (antipsychotic) and valproate (anti-epileptic).
Antipsychotics
- Used to treat psychosis, a condition characterized by difficulty distinguishing reality from non-reality.
- Symptoms include confusion, delusions, paranoia, and hallucinations.
- Antipsychotics primarily affect dopamine receptors in the brain.
Typical vs. Atypical Antipsychotics
- Typical antipsychotics (first generation): Older drugs used for decades. (Examples: chlorpromazine and haloperidol)
- Atypical antipsychotics (second generation): Newer drugs generally considered more effective. (Examples: risperidone, olanzapine, and quetiapine)
Drug Targets in Schizophrenia
- Schizophrenia is linked to elevated levels of dopamine and its metabolites, specifically in certain brain regions.
- Dopamine pathways involved:
- Mesocortical and mesolimbic: Regulate behavior and mood.
- Nigrostriatal: Fine motor control and movement coordination.
- Tuberohypophyseal: Connects the hypothalamus and pituitary.
Aims of Schizophrenia Drug Treatment
- Effective antipsychotics are dopamine (D2) receptor antagonists.
- Goal is to inhibit dopamine actions in the mesolimbic pathway, quieting emotions, slowing psychomotor activity, and reducing agitation.
- Unwanted effects can result from dopamine inhibition in other pathways.
Unwanted Effects of Schizophrenia Drug Treatment
- Inhibiting the nigrostriatal pathway: Extrapyramidal symptoms (EPS), resembling Parkinson's disease (rigidity, stiffness, bradykinesia).
- Inhibiting the tuberohypophyseal pathway: Increased prolactin production and release, leading to gynaecomastia and amenorrhea.
Typical vs Atypical Antipsychotics – A Comparison
- Typical antipsychotics: Effective for positive symptoms (hallucinations, delusions) but less so for negative and cognitive symptoms.
- Atypical antipsychotics: Comparable to typical agents for positive symptoms but more effective for negative and cognitive symptoms.
Why Atypical Antipsychotics Are Better for Negative Symptoms
- They have a weaker affinity for D2 receptors, leading to less EPS and enhanced cognitive function.
- Atypical antipsychotics may influence other neurotransmitters like serotonin, modulating brain activity beyond dopamine.
Receptor Blocking Profiles of Typical Antipsychotics
- Haloperidol: Primarily a D2 receptor antagonist with a limited affinity for other receptors. Strongly associated with EPS due to its D2 selectivity.
- Other typical antipsychotics: Block D2 receptors, but also have varying affinity for other receptors, contributing to side effects such as postural hypotension, sedation, anticholinergic effects, and weight gain.
Basis of Extrapyramidal Symptoms (EPS)
- Due to the disruption of the balance between dopamine and acetylcholine in the striatum.
- Blocking D2 receptors removes the tonic inhibitory influence of dopamine on cholinergic neurons, leading to increased acetylcholine signaling and Parkinsonian effects.
- Muscarinic receptor antagonism can help minimize EPS by restoring this balance.
Dopamine and Atypical Antipsychotics
- Atypical antipsychotics promote dopamine activity in the prefrontal cortex to alleviate negative symptoms of schizophrenia.
- 5HT2A receptors negatively regulate dopamine release in the prefrontal cortex, causing dopamine deficiency in this region.
- Atypical antipsychotics antagonize 5-HT2A receptors, reducing inhibition of dopamine release and increasing dopamine levels in the prefrontal cortex.
- Atypical antipsychotics are effective D2 receptor antagonists, similar to chlorpromazine.
- Antagonism of 5-HT2A and 5-HT2C receptors contributes to the efficacy of atypical antipsychotics against negative symptoms.
Monitoring Antipsychotic Use
- Atypical antipsychotics are typically the first-line treatment for psychosis.
- Treatment duration can vary, with recommendations for 1 year following a first episode, 2 years following a relapse, and longer durations for subsequent relapses.
- Antipsychotics, like olanzepine, are also used to manage the manic phase of bipolar disorder.
Managing Adherence to Antipsychotic Treatment
- Antipsychotic medication is typically administered orally, allowing for convenient and easy adherence.
- Plasma drug concentrations can be monitored to assess adherence.
- Long-acting injectable preparations are available for patients with poor adherence to oral therapy, requiring regular physician visits for administration.
Monitoring for Adverse Effects
- Antipsychotics can cause weight gain, ECG issues (prolonged QT interval), altered triglyceride levels, and neutropenia.
- Smoking can increase antipsychotic drug plasma concentrations, leading to potential toxicity.
- Regular monitoring of blood pressure, heart rate, ECG, blood glucose and lipid levels, weight, waist circumference, BMI, full blood count, and smoking status is crucial.
Neuroleptic Malignant Syndrome
- A rare and serious adverse effect of antipsychotics.
- Direct consequence of D2 receptor antagonism.
- Symptoms include severe muscle rigidity and hyperthermia.
- Occurs shortly after starting antipsychotic therapy or during dose increases.
- Requires immediate emergency treatment.
MAO Inhibitors
- Non-selective MAO inhibitors prevent MAO from degrading all three neurotransmitters, allowing increased release.
- They are irreversible inhibitors, taking two weeks to reach full inhibition.
- MAO also metabolizes tyramine, leading to the "cheese reaction" with high tyramine food intake.
- Tyramine increases noradrenaline levels, potentially causing hypertension if concentrations are too high.
Selective Serotonin Reuptake Inhibitors (SSRIs)
- Inhibit serotonin reuptake by the presynaptic neuron.
- This increases serotonin levels in the synaptic cleft, enhancing serotonin signaling.
- Initial increased serotonin signaling can lead to anxiety due to increased receptor expression.
- Receptor levels eventually normalize after reinternalization.
Tricyclic Antidepressants
- Block muscarinic receptors, H1 receptors, and alpha/beta receptors.
- Cause cardiotoxicity due to the block of these receptors.
- Block of muscarinic receptors increases acetylcholine concentrations, contributing to effects like postural hypotension.
- Increase in sympathetic activity and decrease in parasympathetic activity.
Predictable Side Effects of Tricyclic Antidepressants
- Cardiotoxicity
- Dry eyes and mouth
- Constipation
- Orthostatic hypotension
- Drowsiness
Non-selective Irreversible MAOIs
- "Cheese reaction" and potential hypertensive crisis.
- Increased noradrenaline leads to increased tyramine and vasoconstriction.
- Cause dry mouth and constipation.
Predictable Side Effects of SSRIs
- Initial anxiety due to increased serotonin receptor expression.
- Serotonin syndrome: increased shivering, seizures, muscle rigidity, occurring with increased serotonin levels.
- Decreased sex drive
- Diarrhoea
Case Study: SSRI and St. John's Wort
- SSRIs increase serotonin levels in the synaptic cleft, causing initial anxiety due to increased receptor expression.
- St. John's Wort also affects serotonin levels, potentially increasing the risk of serotonin syndrome.
- Serotonin syndrome can cause fever, muscle spasms, confusion, agitation, diarrhea, and shivering.
Antipsychotics: Typical vs. Atypical
- Typical antipsychotics like haloperidol and chlorpromazine block dopamine receptors, reducing dopamine levels in the mesocortical and mesolimbic pathways.
- Atypical antipsychotics like clozapine and risperidone block dopamine receptors and also increase dopamine levels in the prefrontal cortex to reduce negative symptoms.
Receptor Blockade Effects of Antipsychotics
- Dopamine D2 receptor blockade: Extrapyramidal symptoms (EPS), Parkinsonian symptoms, dystonia, increased prolactin release, and gynaecomastia.
- Alpha 1 receptor blockade: Orthostatic hypotension.
- Histamine H1 receptor blockade: Sedation and drowsiness.
- Muscarinic M receptor blockade: Dry mouth, dry eyes, and constipation.
- Serotonin 5-HT2 receptor blockade: Weight gain.
Case Study: Clozapine Treatment
- Clozapine is effective against both positive and negative symptoms of schizophrenia.
- It may still have an effect on movement, but can potentially worsen movement problems.
- Antagonizes 5-HT2A receptors in the prefrontal cortex, increasing dopamine levels.
Monitoring with Clozapine
- Weight gain
- ECG abnormalities, exacerbating pre-existing hypertension.
- Smoking can decrease clozapine levels, potentially requiring adjustments.
- Risk of neutropenia.
- Elevated lipid levels.
Chlorpromazine and EPS
- Chlorpromazine causes less extrapyramidal symptoms (EPS) compared to haloperidol due to antagonism of muscarinic receptors in the nigrostriatum and weaker binding to dopamine receptors.
Parkinson's Disease
- Parkinson's disease is characterized by a deficiency in dopaminergic signaling in the nigrostriatal pathway, responsible for fine motor control.
- The disease is linked to the death of dopaminergic cell bodies in the substantia nigra, leading to reduced dopamine release in the striatum.
- Treatment aims to restore dopaminergic signaling and increase dopamine concentrations.
Dopamine Synthesis
- Dopamine is synthesized from tyrosine, which is converted to dopa and then dopamine.
- Dopamine is stored in vesicles and released through exocytosis.
Levodopa (Dopamine Precursor)
- Levodopa has a short half-life (2 hours) and requires multiple daily doses.
- Dopa decarboxylase (DDC) metabolizes levodopa, both in the periphery and CNS.
- Peripheral dopamine effects can cause nausea and hypotension.
- Central dopamine elevation, particularly in the mesolimbic pathway, can lead to hallucinations.
- As Parkinson's progresses, dopaminergic neurons die off, making levodopa effects unpredictable.
Levodopa "On-Off" Effects
- The short half-life of levodopa leads to fluctuating effects.
- Patients experience periods of improved mobility ("on" phase) followed by periods of reduced mobility ("off" phase).
Dopamine Receptor Agonists
- Pramipexole and rotigotine bypass the need for enzymatic conversion to dopamine.
- They have less dyskinesia compared to levodopa and a longer half-life.
- Available in immediate-release and extended-release formulations.
- Similar adverse effects as levodopa, including nausea, hypotension, hallucinations, and impulse control disorders.
MAO Inhibitors: Selegiline
- MAO, particularly MAOB, metabolizes dopamine.
- MAOB inhibitors increase dopamine levels by preventing metabolism.
- Selegiline is a selective MAOB inhibitor with no dietary restrictions.
Catechol-O-Methyl-Transferase (COMT) Inhibitors
- COMT metabolizes levodopa and dopamine in both the periphery and CNS.
- Entacapone is peripherally active only.
- Tolcapone is both peripherally and centrally active.
Cholinergic Modulation
- Cholinergic neurons in the nigrostriatal pathway are tonically inhibited by dopaminergic neurons.
- Loss of dopaminergic neurons in Parkinson's leads to increased cholinergic activity, contributing to motor issues.
- Muscarinic receptor antagonists, like benztropine, restore the balance by blocking acetylcholine receptors.
Polypharmacy in Parkinson's Disease
- As Parkinson's progresses, patients may require multiple medications to manage symptoms, including non-pharmacological interventions.
Huntington's Disease
- An autosomal dominant hereditary disorder.
- Causes the production of abnormal huntingtin protein (Htt) and the selective loss of GABA neurons in the striatum.
- Loss of GABA neurons leads to dopamine hyperactivity in the striatum.
- Drug treatments are symptomatic and aim to suppress dopamine signaling or enhance GABA.
Drug Treatments for Huntington's Disease
- D2 receptor antagonists: Antipsychotics like chlorpromazine.
- GABAb receptor agonists: Baclofen, promoting inhibition of spinal cord motor neurons.
- VMAT inhibitors: Tetrabenazine, inhibiting dopamine transport into vesicles.
Anxiety
- A complex condition with variable presentation and no single, clear biological mechanism.
- Generalized anxiety disorder characterized by excessive anxiety and worry, muscle soreness, impaired concentration, fatigue, irritability, restlessness, and sleep difficulties.
- Panic disorder occurs when anxiety symptoms disrupt daily activities repeatedly.
Sedatives, Hypnotics, and Anesthetics
- These drugs suppress sensation and consciousness, used for therapeutic and procedural purposes.
- They are crucial for treating anxiety, insomnia, and facilitating safe surgical procedures.
Anxiety
- Various types of anxiety exist, including generalized anxiety disorder, social anxiety disorder, separation anxiety, specific phobia, and panic disorder.
- Generalized anxiety disorder is characterized by excessive and pervasive worry, present most days for at least 6 months.
- Social anxiety disorder involves irrational fears related to social situations, often stemming from concerns about judgment or humiliation.
- Separation anxiety manifests as significant distress when apart from loved ones.
- Specific phobia is marked by an intense, often irrational fear of a specific object or situation.
- Panic disorder involves sudden and recurring panic attacks, followed by excessive worry about future attacks.
- Anxiety can be influenced by cultural factors and location.
- The cup/bucket theory is a useful model to conceptualize anxiety.
- Short-term stressors can accumulate, eventually leading to an "overflow" of anxiety.
- Individuals have varying "bucket" capacities, and coping mechanisms impact the rate of "emptying."
- Effective coping strategies reduce anxiety levels in the long term.
Pharmacological Treatments for Anxiety
- Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for anxiety disorders.
- SSRIs can take 2-6 weeks to achieve their full effect, potentially due to biological mechanisms or improved coping strategies.
- Benzodiazepines were previously the first-line treatment for anxiety but are now mostly used in combination therapy.
- They work by enhancing GABA neurotransmission, reducing neuronal excitability.
- Benzodiazepines have a short-term therapeutic effect, as tolerance and dependence can develop with prolonged use.
- Pregabalin, a GABA analogue, is well tolerated for generalized anxiety disorder as a monotherapy or adjunct to antidepressants.
Non-Pharmacological Therapies for Epilepsy
- Cognitive behavioral therapy (CBT) is a well-supported approach that targets unhelpful thoughts and reframes stressful situations.
- Symptomatic medications, like beta-blockers, can be used to address acute anxiety symptoms.
- Lifestyle modifications, including regular exercise and a healthy diet, can also benefit individuals with anxiety.
General Anaesthetics
- General anesthetics revolutionized surgery, rendering patients unconscious and insensitive to pain.
- They relax muscles, sedate, and have a wide safety margin, enabling rapid induction.
- Their high lipid solubility facilitates rapid entry into the brain.
- General anesthetics are thought to work by opening potassium and chloride channels, leading to neuronal hyperpolarization.
- The precise mechanisms of general anesthetics are still not fully understood, but they likely involve opening TREK1 potassium channels.
- The minimum alveolar anesthetic concentration (MAC) is a key measure of anesthetic potency.
- High MAC values indicate lower potency, while low MAC values reflect high potency.
- Nitrous oxide has a high MAC, indicating low potency, but it acts quickly.
- Methoxyflurane is an anesthetic with high potency but a slower onset of action due to its high lipid solubility.
- Recovery from anesthetics is also related to MAC, with lower potency drugs leading to faster recovery.
Epilepsy
- Epilepsy is a neurological disorder affecting 0.5-1% of the population.
- It is characterized by recurrent seizures, which result from excessive neuronal activity.
- Seizures can be focal (limited to specific brain areas) or generalized (affecting multiple areas).
- Focal seizures can be aware (consciousness intact) or involve impaired awareness.
- Generalized seizures always involve loss of consciousness and can be motor (muscle stiffness and spasms) or non-motor (absence seizures with minimal motor disturbance).
- The primary goal of epilepsy treatment is to prevent seizures or manage them acutely.
- This is achieved by enhancing GABA neurotransmission and disrupting neuronal membrane excitability.
Anti-epileptic Agents
- GABA is the major inhibitory neurotransmitter in the brain.
- Various anti-epileptic drugs target the GABA system.
- GABA transaminase inhibitors (valproate, vigabatrin) increase GABA levels by preventing its breakdown.
- GAT-1 inhibitors (tiagabine) block GABA reuptake, enhancing its availability in the synapse.
- GABAa receptor modulators (benzodiazepines like midazolam) enhance GABA action by binding to the benzodiazepine receptor site, increasing chloride influx.
- Benzodiazepines are effective in acute settings but are not suitable for long-term use due to their addictive potential.
Status Epilepticus
- Status epilepticus is a medical emergency characterized by continuous or repeated seizures with no recovery of consciousness between them。
- It requires immediate treatment with anti-epileptic medications to prevent prolonged seizure activity and its potential complications, such as respiratory arrest.
- Anti-epileptic drugs also target ion channels to regulate neuronal excitability.
- Sodium channel blockers (carbamazepine, lamotrigine, phenytoin) preferentially block sodium channels in frequently firing neurons, reducing their excitability.
- Calcium channel blockers are also used in epilepsy treatment.
- High-voltage activated (HVA) calcium channel blockers (gabapentin) are adjunctive therapies for partial seizures.
- T-type calcium channel blockers (ethosuximide) are specifically effective against absence seizures, as they target the thalamic neurons involved in pacing cortical activity.
Choosing Anti-epileptic Medications
- The choice of anti-epileptic medications considers factors such as seizure type, patient response, and drug safety.
- First-line treatment for generalized seizures often involves valproate, a broad-spectrum anti-epileptic.
- Carbamazepine is typically the first-line treatment for focal seizures.
- Medications may be started at the therapeutic dose or titrated up depending on the drug and individual patient needs.
- If a drug proves ineffective, a second drug may be introduced.
- Multiple drugs are often needed to achieve effective seizure control.
Pregnancy and Anti-Epileptic Drugs (AEDs)
- All AEDs pose a risk to a developing baby, with valproate carrying the most significant teratogenic risks.
- Valproate can cause a wide range of birth defects.
- Female patients of childbearing age should use contraception while on AEDs.
- Contraception can impact serum drug levels, potentially inhibiting or inducing liver enzymes that metabolize AEDs.
- Similarly, AEDs can also affect contraceptive efficacy.
- Discuss contraception planning with a healthcare professional.
- Weigh the risk to the fetus against the risk of uncontrolled seizures.
- If AED therapy continues during pregnancy, maintain the lowest effective dose.
- No AED is considered the "drug of choice" during pregnancy due to their inherent risks.
- Monitor drug levels during pregnancy, as metabolism can change.
- Note that phenytoin may be more likely to be toxic when combined with contraceptives.
Pharmacokinetic Drug Interactions
- AEDs are lipophilic to penetrate the brain.
- AEDs rely on liver metabolism via cytochrome P450 enzymes, making them susceptible to drug interactions.
- Other medications, both related and unrelated to AEDs, can affect serum drug levels, patient safety, and seizure control by inducing or inhibiting enzyme activity.
- Serum drug level monitoring might become necessary if drug interactions are suspected.
Elimination
- Phenytoin is known for its unique pharmacokinetic properties.
- It exhibits zero-order elimination, where its elimination is independent of plasma drug concentration.
- In contrast, first-order elimination involves elimination proportional to the drug concentration in the plasma.
- Phenytoin has a narrow therapeutic range, meaning small changes in concentration can lead to toxicity.
Phenytoin-Specific Side Effects
- Phenytoin can cause gum hyperplasia and acne.
Common Side Effects of AEDs
- Sedation: A common side effect across all AEDs.
- Weight Gain: Especially prevalent with valproate.
-
Cosmetic Changes:
- Phenytoin: hirsutism (unwanted hair growth), gum hyperplasia, acne.
- Valproate: hair loss (alopecia).
- Skin Rashes: Can vary in severity from temporary to allergic or hypersensitivity reactions.
- Monitoring: Patients require monitoring for these side effects.
- Compliance: These effects can negatively affect compliance, highlighting the need for serum drug level monitoring.
General Precautions
- Combining AEDs with CNS depressants like alcohol, opioids, or benzodiazepines can lead to excessive CNS inhibition.
- Sudden withdrawal of AED therapy can trigger status epilepticus. Gradual withdrawal is crucial, especially if a patient has been seizure-free for an extended period.
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Test your knowledge on antidepressants and their effects on neurotransmitters. This quiz covers neurotransmitter mechanisms, common side effects, and the most prescribed antidepressant classes. Perfect for psychology students and those interested in mental health.