week 7- Mental Health and Affective Disorders Sway Flashcards

Question

how do MAO inhibitors work?

Answer 1

• Increase cytoplasmic stores of noradrenaline and 5-HT in nerve terminals • Irreversible non-competitive inhibitors – e.g. phenelzine, iproniazid • Most are non-selective for different forms of MAO • Reversible MAO-A selective inhibitors – moclobemide • Can be increase in spontaneous release of neurotransmitter and increase in release by sympathomimetic amines (e.g.tyramine)

Answer 2

- Hypotension – common side effect - Central stimulation – tremors, excitement, insomnia - Increased appetite causing weight gain - Drug & food interaction – the cheese reaction • Ingestion of tyramine in foods such as ripe cheese and marmite • Typically degraded in gut by MAO • With MAOI – tyramine absorbed into circulation and has sympathomimetic effect • Acute hypertension and severe headaches

Answer 3

-stimulation of the hypothalmus causes the release of CRF -CRF which then acts on on the piturity gland which then releases ACTH which then acts on the adrenal cortex which releases gluccorticosteriod • Increased plasma cortisol levels in severe depression • Impaired glucocorticoid induced feedback control • Injection of CRH (CRF) into brain can mimic aspects of depression • Cushing’s syndrome – often causes depression • No current clinical intervention

Answer 4

-they regulate the brain

Answer 5

-comes from sickness behaviour • Behavioural changes experienced with infections can mimic depressive-like behaviour • Cytokines cause these changes • Infusion of particular cytokines induces depression in humans and rodents • IL-2 and IFN-γ • People with autoimmune disease more likely to have depression • Post-mortem evidence of microglial activation in patients with depression

Answer 6

• Regional specific neuronal cell loss, changes in synaptic activity causing the imbalances in neurotransmitters • Functional imaging studies show a decrease in gray matter volume in pre-frontal cortex and hippocampus • Smaller volume of important brain structures • Post-mortem studies conform a loss in GABAergic neurons, astrocytes and oligodendrocytes in the pre-frontal cortex

Answer 7

• Neurogenesis – formation of new neurons from pluripotent stem cells • Neuroplasticity – growth and adaptability of neurons • Neurogenesis is controlled by trophic factors such as BDNF • Humans – reduced BDNF in CSF of patients • Antidepressants can raise BDNF levels • In animal models reducing neurogenesis can prevent the action of antidepressants • injection of BDNF has an antidepressant effect

Answer 8

``` • Ketamine derivative • No delay in the anti-depressant effect of esketamine • NMDA receptor non-competitive channel blocker • Approved by EMA for treatmentresistant depression in 2019 • Proposed mechanism: blocking NMDA receptors on GABA interneurons prevents tonic activity – causes a glutamate surge which increases BDNF signalling ```

Answer 9

• Do not work in everybody • Side effects for SSRIs include nausea, insomnia, sexual dysfunction, paroxetine linked to increased suicidality, risk of drug interactions CYP • Tricyclics can have a sedating effect, anticholinergic effects, confusion, motor incoordination effect, higher risks with overdose • SNRIs side effects include sedation, dizziness, nausea and some can have withdrawal effect • Monoamine oxidase inhibitors (MAOI) side effects include CNS stimulation, weight gain, insomnia, postural hypotension • Major problem with MAOI is the cheese reaction – tyraminecontaining foods – increased tyramine causes sympathomimetic effect (acute hypertension, headache)

Answer 10

• Bipolar I (episodes of mania) and bipolar II (episodes of | hypomania and depression)

Answer 11

• Pathophysiology involves dendritic spine loss, altered cellular connectivity and neural plasticity

Answer 12

• Stabilisation of mood is the overall goal • Lithium - taken orally as lithium carbonate • Used in prophylaxis and treatment of mania • Carbamazepine, valproate and lamotrigine anti-epileptic drugs can be used• Quetiapine, olanzepine and other anti-psychotic drugs can be used • Benzodiazepines can be used for calming effect • Use of anti-depressants is not recommended – can lead to switching to manic phase

Answer 13

``` • Lithium is a monovalent cation • Lithium is thought to accumulate inside cells, cause inhibition of inositol phosphate pathway and inhibition of GSK3 affecting cellular responses -accumulates as it isnt pumped out the cells through sodium potassium symporter ```

Answer 14

• Carbamazepine, valproate and lamotrigine – affect NaV channels • Blocking action on NaV channels prevents action potential generation • These drugs show use dependence therefore more activity is seen with higher firing rates (e.g. in epilepsy) • Lamotrigine has a broader mechanism of action – also affects neurotransmitter release and may have activity on CaV channels • Mechanism of action in bipolar disorder – due to reduction in neuronal excitation• Better side effect profile than lithium

Answer 15

* Olanzepine, quetiapine, risperidone, aripiprazole – act as antagonists at D2 and 5-HT2A receptors * Also may have activity at several other receptors including α1, H1, 5-HT1Aand mAChR * Second generation antipsychotics * Effective against treatment of mania

Answer 16

``` • Chronic disorder • Depression is often co-morbid with anxiety • Clinical recognised anxiety states include: - Generalised anxiety disorder (GAD) - Social anxiety disorder - Phobias - Panic disorder - PTSD - OCD ```

Answer 17

• Anxiety arises from an abnormal regulation of fear response • Fear – subjective response to threatening stimulus • Anxiety is longer lasting and can persist due to lack of signs of safety • Disorders are distinguished based on • symptoms • precipitating factors • Genetic component – run in families • Amygdala is activated by induction of fear – neuroimaging suggests patients have heightened activity in amygdala circuits

Answer 18

• Psychological approaches are used as well as medication • Main drugs used: 1. Antidepressants (SSRIs, SNRIs) – increase 5HT and NA levels • E.g. Escitalopram and paroxetine, venlafaxine, duloxetine 2. Benzodiazepines – enhance action of GABA on GABAA receptors containing α2 subunit e.g. lorazepam, diazepam, flurazepam Benzodiazepine side effects are sedation, confusion, tolerance and dependence 3. Buspirone (5HT1A receptor agonist) – can be used to treat generalised anxiety disorder • 5HT1A receptors can act as inhibitory autoreceptors on serotonergic neurons, postsynaptic 5HT1A receptors are involved in emotional behaviour 4. Gabapentin, pregabalin, valproate – affect NaV and CaV channels – anxiolytic properties 5. Atypical antipsychotics – olanzepine, quetiapine – can be effective in GAD and PTSD 6. Propranolol - a β-blocker which can be used for relief of situational anxiety, GAD 7. Non-pharmacological treatments: Counselling Cognitive therapy Dietary and lifestyle changes

week 7- Mental Health and Affective Disorders Sway Flashcards

(42 cards)