Drugs Used in the Treatment of Depression Flashcards
What is the monoamine theory?
A theory of depression to try and treat it.
deficit of monoamine NTs (5HT and noradrenaline) in areas of brain
however takes weeks to show improvement so secondary effects probably what improves mood
How do SERT and NET work
Symporters that cotransport sodium as a driving source for transporting NTs across membrane
Dependant on extracellular Cl-
Discuss SERT structure
12 Transmembrane domains. Intracellular N and C termini
Glycosylated EC loop between TM3 AND 4
Substrate binding site accessible to either external or internal medium at once
How do reuptake inhibitors work for depression
Prevent reuptake of serotonin or NA into the neuones
Enhanses synaptic level of serotoin or NA
ss- selective serotonin
SN- seroonin and NA
Give some SSRIs
Fluoxetine, paroxetine, sertraline, citalopram
SNRIs
Buproprion, reboxetine, atomoxetine
Non selective RIs
Venlafaxine, duloxetine
Tricyclic antidepressants
Imipramine, amitriptyline
what could justify the slow onset of action for SSRIs?
5-HT acts on 5-HT1a on dendrites to inhibit 5-HT release and cancels out effects of SSRIs
Chronic administration, high 5-HT levels induce desensitisation of 5-HT1a receptors and decreases inhibitory effects of 5-HT
How can NA control 5-HT levels
NA can act on excitatory alpha1 receptors in enhance release
alpha2 receptors are downregulated by antidepressants (presynaptic)
alpha2 receptor antagonists could enhance 5-HT release more (mirtazapine)
Monoamine Oxidase - explain forms etc
MAO A - preference for 5-HT and NA
MAO B - preference for dopamine
Inhibitors increase tissue levels
Examples of MAO inhibitors
moclobemide
phenelzine
side effects of MAOi
Hypotension
tremours/ imsomnia
increased appetite
cheese reaction- tyramine in foods which is broken down by MAO and is therefore absorbed and causes HT and headaches.
Nmae some theories of depression
MonoAmine theory
Neuoendocrine mechanisms
inflammatory mechanisms
structural changes
neuroplasticity and neurogenesis
How does the neuroendocrine mechanism cause depression
High cortisol in depression causing impaired glucocorticoid induced feedback control
How does inflammatory mechanisms cause depression
Behavioural chances can mimic depressive like behaviour
cytokines cause this
IL2 IFN-Y
How can structural changes cause depression
decrease of grey matter volume
enlargement of ventricles in brain
loss in GABAergic neurones
How can neuroplasticity and neurogenesis cause depression?
nerogenesis- forming new neurones from stem cells
Neuroplasticity- adapt to changing environment
Neurogenesis caused by BNDF
Antidepressents can restore BDNF levels in spinal fluid and form new neurones
