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Flashcards

Monoamine pharmacology -Antidepressant drugs - Dr. Emma Robinson

Anna mph Neuropharmacology Degree English 83 cards

Cards in this deck (83)

  1. 1What are the emotional symptoms of depression? (2)1) Mood
    2) Thought disorder
  2. 2What are the biological symptoms of depression? (2)1) Anhedonia (no reward feeling)
    2) Motivational impairments
  3. 3What are the cognitive symptoms of depression? (2)1) Difficulty in decision making
    2) Poor concentration
  4. 4Which mood disorder is bipolar?Manic depression
  5. 5What are the four main characteristics of mania?1) Less sleep required
    2) Excessive exuberance, enthusiasm and confidence etc
    3) Behaviours inappropriate to circumstance
    4) Disorders of thought (psychosis)
  6. 6What are the two main possible causes of depression?1) Monoamine theory
    2) Neuroplasticity/degeneration
  7. 7What monoamines are thought to be affected in the monoamine theory?Functional deficit of 5-HT and NA (possibly DA)
  8. 8What evidence is there in support of the monoamine theory? (5)1) Current anti-depressants target MA system
    2) Good link between MA and mood
    3) Measurements in some patients show MA deficit
    4) Depleting 5-HT can induce a relapse into depression
    5) Genetic evidence for 5-HT depletion
  9. 9What evidence is there against the monoamine theory?1) Amphetamine and cocaine lack efficacy
    2) Some patients are resistant to treatment
    3) Improvements are delayed (3-4weeks)
    4) Non-pharmacological treatments have efficacy
  10. 10Why does a varying response to treatment not necessarily undermine the monamine theory?Depression is a heterogenous disorder with a complex pathology - i.e. low mood is common symptom but cause may vary
  11. 11What is neuroplasticity/neurodegeneration in depression caused by?1) Genes - 40% genetic vulnerability
    2) Environmental stress
  12. 12How can stress lead to neurodegeneration? (3)1) Increase detrimental transcription via cortisol release
    2) Increase detrimental transcription via inhibiting NA, 5-HT and BDNF
    3) Increase neural apoptosis via glutamate release
  13. 13How does stress lead to the release of cortisol?CRF (Corticotropin releasing factor) released from the hypothalamus
    ACTH (adrenocorticotropic hormone) released from pituitary
    Cortisol released from adrenal cortex
  14. 14How does glutamate release lead to cell death?Over activation of NMDA receptors leads to excitotoxicity
  15. 15How does detrimental gene transcription lead to depressive symptoms? (2)1) Increased neural apoptosis
    2) Decreased neurogenesis
  16. 16Which area of the brain can neuro-degeneration be seen in depressed patients?Hippocampus
  17. 17What are the three ways of increasing monoamine function in the CNS?1) Enzyme inhibitors
    2) Uptake blocker
    3) Block pre-synaptic autoreceptors
  18. 18What is moclobemide?Inhibitor of MAO
  19. 19What is fluoxetine (prozac)Uptake inhibitor
  20. 20What is Mitrazapine?Receptor blocker
  21. 21What are the four types of typical anti-depressants?1) MAO
    2) Tricyclic Antidepressants (TCA)
    3) SSRI
    4) NARI (Selective Noradrenaline Re-uptake Inhibitors)
  22. 22What is the mechanism of MAOI?Prevents breakdown of monoamine
  23. 23Which monoamine(s) does MAOa prefer?5-HT
  24. 24Which monamine(s) does MAOb prefer?DA and NA
  25. 25At which other receptors can MAOI act and cause side effects?M1
    a1
    H1
    5-HT2
  26. 26What is the CHEESE reaction?If MAO gets too low tyramine enters blood and displaces NA causing a hypertensive crisis
  27. 27Why are reversible MAOI better than irreversible MAOI?Reversible MAOI can be displaced in places where substrate is high (eg in the gut) but still act where substrate is low (eg in brain for depression). Less likely to cause side effects/cheese reaction.
  28. 28What is the therapeutic index for MAOI like?Moderate
  29. 29Give an example of a irreversible and a reversible MAOI?1) Iproniazid
    2) Moclobemide (MAOaI)
  30. 30What is the mechanism for TCAs?Block re-uptake of 5-HT and/or NA
  31. 31Which adrenoreceptor do TCAs also effect? What side effects does this lead to?a2-adrenoreceptor - dry mouth, sympathetic effects
  32. 32Which other receptors can TCAs target? What does this effect?Histamine (drowsiness)
    Muscarinic actions
    a1-adrenergic
    5-HT2 - weight gain (antagonism) effects sleep wake cycle
  33. 33What is the therapeutic index of TCAs like?What can this lead to?Low TI - leads to cardiotoxicity - tachycardia, arrythmias and hypotension
  34. 34What is the only way of preventing death once an overdose has been taken?Prevent TCAs from being absorbed from the gut.
  35. 35Which opioid agonist reacts badly with TCAs?Tramidol
  36. 36On which MA does clomipramine act?5-HT, not and SSRI as it have many sites of action despite being fairly selective
  37. 37On which MA does amitriptyline act?NA/5-HT
  38. 38Which MA does desipramine act on?NA
  39. 39Why do SSRIs show less side effects?Doesn't bind to or act at any other receptors
  40. 40What are the 5 benefits of SSRIs?1) No cholinergic side effects
    2) No interaction with food
    3) Less weight gain
    4) Reduced drug interactions
    5) Low toxicity in overdose
  41. 41Which 5-HT receptor is responsible for mediating weight gain?5-HT2C (anatgonism causes weight gain)
  42. 42What are the 5-HT side effects caused by SSRIs?1) Nausea
    2) Anorexia
    3) Insomnia
    4) Sexual dysfunction
    5) 5-HT syndrome (similar to ecstasy overdose)
  43. 43Through which 5-HT receptor is nausea mediated?5-HT3
  44. 44Through which 5-HT receptor is Anorexia mediated?5-HT2
  45. 45Through which 5-HT receptors is weight loss mediated?5-HT2
  46. 46Through which 5-HT receptors is sexual dysfunction mediated?5-HT2
  47. 47What are the 5 atypical types of anti-depressants?1) SNRI
    2) 5-HT2 antagonist + SSRI
    3) 5-HT2 antagonist +SNRI/SSRI
    4) a2-adrenoreceptor antagonist + 5-HT antagonist
    5) Agomelatine
  48. 48What is.... (4) Who ... it used for? What does ... increase? VENLAFAXINESNRI
    Severely depressed, hypersomnic, weight gaining atypical depressives
    Increases NA
  49. 49TRAZEDONESSRI + 5-HT2 antagonist
    Treats anxiety, improves slow wave sleep, causes sedation and can reduce sexual function
    Reduces 5-HT2 activity
  50. 50MITRAZAPINEa2 adrenoreceptor (Gi/o) and 5-HT antagonist
    Via a2 >> Increases NA and 5-HT by blockade of presynaptic inhibition.
    5-HT >> 5-HT3 = Nausea
    5-HT2 = sexual dysfunction, reduced anxiety and sleep enhancement
  51. 51What is agomelatine?Melatonin agonist, 5-HT2 antagonist
  52. 52Explain how mirtrazapine works and why the effects of elevated 5-HT works mainly through 5-HT1 receptors?a2 - adrenoreceptor antagonist component blocks autoreceptors on NA cells. This leads to increased release of NA which acts on 5-HT system (and NA system) increasing activity. 5-HT2 and 5-HT3 postsynaptic (to 5-HT neuron) are blocked by mitrazapine so 5-HT1 mediates effect of increased 5-HT.
  53. 53How is electroconvulsive therapy performed?1) Patient anaesthetised, electrodes inserted, seizure induced
  54. 54What are the changes that come about from ECT? (2)1) Increase in MA conc.
    2) Changes in MA receptor function a2-adreno. and 5-HT2 downregulated.
  55. 55What are the three theories as to why onset of antidepressants are delayed?1) Neurochemical and neuroadaptive
    2) Neuroplasticity and neurogenesis
    3) Cognitive
  56. 56Describe the two parts of the Neurochemical and neuroadaptive theory (receptor activation)1) Activation of somatodendritic autoreceptors (5-HT1a and a-2 adreno) leads to decreased neuronal firing.
    2) Activation of pre-synaptic autoreceptors (5-HTb/d, a-2 adreno) leads to decreased neurotransmitter release.
  57. 57Explain the neuroplasticity/neurogenesis theory.Chronic activation of receptors leads to down regulation - only at that point is there a real increase in the concentration of the MA at the synapse.
  58. 58Explain the cognition theory (2)1) Hippocampal neurogenesis - delayed onset as neurons take a while to grow
    2) Post synaptic receptor adaptation takes a while
  59. 59With a placebo what percentage of patients see a response in 8 weeks?30%-60%
  60. 60How do you treat mild/moderate depression?Cognitive Therapy
  61. 61How do you treat severe depression?Drugs
  62. 62What is the first line of drugs?SSRI
  63. 63What is usually the second line?MAO-I
  64. 64How longs should you take ADs following remission?6-12 months
  65. 65With which type of drugs are you most likely to see 'discontinuation syndrome'SSRIs
  66. 66In how many patients does discontinuation syndrome occur in?1 in 3
  67. 67What are the symptoms of discontinuation syndrome? (5)Dizziness, anxiety, mood disturbance, GI disturbance and 'flu-like symptoms'
  68. 68Is discontinuation syndrome more common with paroxetine or fluoxetine?Paroxetine
  69. 69Over what time scale do concentration of paroxetine and fluoxetine need to be reduced?6-8 weeks
  70. 70What is Lithium CarbonateA mood stabilising drug
  71. 71What is lithium carbonate most effective and controlling but why does the patient need careful monitoring?Mania - potential toxicity
  72. 72How does Lithium carbonate work? (3)1) Effects G-protein signalling - prevents transduction of signalling
    2) Interacts with inositol monophosphates and reduces IP3 pathway signalling
    3) Inhibits glycogen synthase kinase 3 - GSK3 - reduces phosphorylation of key enzymes
  73. 73What is valproic acid and how can it be used to reduce mania?1) Anti-epileptic
    2) Weak GABA-T inihbitor - increases inhibitory neurotransmission with some effect on Na+ channels with acute use
  74. 74What is Carbamazepine and how does it help treat mania?1) Derived from TCAs
    2) Use dependent block of Na+ channels
  75. 75What is olanzapineAtypical antipsychotic
    mixed D2 and 5-HT2 antagonist
  76. 76BIPOLAR DISORDER What are the first and second line treatments for.. ACUTE MANIC EPISODES1) Lithium/Carbamazepine
    2) Valproate
  77. 77PROPHYLAXIS1) Lithium/olanzapine
    2) Carbamazepine
  78. 78What are combination treatments for bipolar disorder?antidepressant SSRI + antiepileptic/antipsychotic
  79. 79With prophylactic treatment: What are the relapse percentages after 1) With treatment after 1 year? 2) With treatment after 5 years? 3) Without treatment after 1 year?1) 40%
    2)90%
    3) 80%
  80. 80What else can SSRIs be used to treat? (5)1) OCD
    2) Panic disorder
    3) Social phobia
    4) Anxiety disorders
    5) Eating disorders (bulimia/binge-eating)
  81. 81What can TCAs (name one specifically) be used to treat other than depression?1) Analgesic agent
    2) Migraine phrophylaxis drug
    Amytryptyline (NA/5-HT)
  82. 82What can 5-HT/NA reuptake inhibitors be used for other than depression (eg Duloxetine)Chronic pain management eg due to chemotherapy or damaged nerve endings
  83. 83What is a drug that could be used to treat depression with a rapid onset?Ketamin

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Degree Neuropharmacology Flashcards on Monoamine pharmacology -Antidepressant drugs - Dr. Emma Robinson, created by Anna mph on 17/12/2015.
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