psychopharmacology - lecture

which symptoms for depression/anxiety stem from the prefrontal cortex? (6)

- concentration

- psychomotor fatigue (mental)

- guilt

- suicidality

- worthlessness

- mood

which symptoms for depression/anxiety stem from the striatum? (2)

- psychomotor fatigue (physical)

- pleasure/interests

which symptoms for depression/anxiety stem from the hypothalamus?

- sleep

- appetite

which symptoms for depression/anxiety stem from the amygdala? (4)

- guilt

- suicidality

- worthlessness

- mood

which symptoms for depression/anxiety stem from the cerebellum?

pschyomotor symptoms

which symptoms for depression/anxiety stem from the spinal cord?

fatigue (physical)

what are the main types of antidepressants?

- SSRIs

- SNRIs

- mirtazapine

- trazadone

- tricyclics

- MAOIs

what are SSRIs?

selective serotonin reuptake inhibitors

what is the moa of SSRIs?

- block serotonin reuptake transporter (SERT) on presynaptic neurone to increase synaptic availability of serotonin

- allows more serotonin to bind to 5-HT2 receptors on postsynaptic neurone = excitation

what can SSRIs also bind to?

5-HT1 autoreceptors which decreases neurone firing (may explain very low mood when first taking SSRIs)

which part of the body contains more serotonin than the brain?

GI

which cells release serotonin in the gut?

enterochromaffin cells

what does serotonin do in the gut?

regulates intestinal motility

where else are serotonin transporters (SERT) found?

platelet membranes

what does serotonin do to platelets normally?

mediates platelet aggregation

what happens when SSRIs block SERT on platelets?

less platelet aggregation = easier bruising

what are the side effects of SSRIs? (5)

- insomnia

- GI disturbance

- sexual dysfunction

- decreased platelet aggregation

- increase suicidal ideation in under 25s

which SSRI is used most frequently?

sertraline (and escitalopram)

what are other examples of SSRIs?

- fluoxetine

- paroxetine

- escitalopram

which SSRI is most associated with QT prolongation?

escitalopram

which SSRI has the shortest half-life?

paroxetine

what are the clinical effects of having a short half life?

discontinuation syndrome

what are SNRIs?

serotonin and noradrenaline reuptake inhibitors

why is sertraline preferred?

least cardiotoxic and best tolerated

when are SNRIs useful?

in patient with comorbid pain

what is the moa of SNRIs?

- inhibits serotonin reuptake transporters (SERT) and noradrenaline reuptake transportsers

- increases serotonin and noradrenaline availability in synaptic cleft

what are two commonly used SNRIs?

- venlafaxine (desvenlafaxin = active metabolite)

- duloxetine

what are the side effects of SNRIs?

- similar to SSRIs

- more activating (tremors)

- bad discontinuation with venlafaxine due to short half life

what is mirtazapine?

α2-autoreceptor antagonist

what is the moa of mirtazapine

- blocks presynaptic α2 autoreceptors

- decreases inhibitory effect of α2 autoreceptors

- excitation of 5-HT neurones in the cortex

what else does mirtazapine inhibit?

H1 (histamine receptors)

what are the side effects of mirtazapine due to?

inhibition of histamine (H1) receptors

what are the side effects of mirtazapine? (2)

- sedation

- weight gain

what is trazodone?

serotonin reuptake transporter inhibitor at high doses

what is the moa of trazodone as an antidepressant?

- inhibits SERT

- decreased reuptake of serotonin into presynaptic neurone

- more serotonin available in synaptic cleft

what other receptors does trazodone inhibit?

histamine (H1)

what are the side effects fo trazodone caused by?

inhibition of H1 receptors

what are the side effects of trazodone?

- sedation

- weight gain

what is the moa of tricyclic antidepressants?

block serotonin reuptake transporters (SERT) and noradrenaline reuptake transporters to increase the concentration of these in the synaptic cleft

what do tricyclic antidepressants also block?

- H1

- Na+ channels

- NET (noradrenaline transporters)

- M1

- α1

what are the side effects of tricyclic antidepressants according to what they block?

H1 - sedation and weight gain

M1 - dry mouth, constipation, blurred vision, urinary retention, cognitive impairment

α1 adrenoreceptors - orthostatic hypotension, dizziness

voltage sensitive sodium channles (VSSCs) in heart - cardiac arrhythmias and cardiac arrest

VSCCs in brain - coma and seizures in overdose

what are tricyclic antidepressants examples?

amitriptyline, nortriptyline

are tricyclics used often?

not anymore due to cardiotoxic side effects

when are MAOIs used?

used in depressions that are resistant to other medications

what is the moa of MAOIs?

irreversible non-competitvely inhibits MAO-A, so reduces breakdown of NA and 5-HT

what is the cheese reaction?

- when on MAOIs, cannot have foods containing tyramine

- if on MAOIs, MAO cannot break down tyramine and it begins to act like noradrenaline

- causes a hypertensive reaction

what foods cause the cheese reaction?

cheese and marmite

how long do you need to wait to use another drug after stopping MAOIs and why?

2 weeks as they have lots of drug interactions

what are the symptoms of serotonin syndrome?

- clonus

- agitation

- diaphoresis (sweating)

- tremor

- hyperreflexia

what are anxiolytics?

anti-anxiety drugs

what are some different types of anxiolytic drugs? (6)

- barbiturates

- benzodiazepines

- buspirone

- beta blockers

- antidepressants (high doses)

- pregabalin

what is the moa of benzodiazepines?

GABA-A agonists

what does GABA-A normally do?

- binds to channels that allow Cl- influx into cell

- causes hyperpolarisation

- INHIBITORY as less likely to be depolarised

when can benzodiazepines function?

only when GABA is already bound to Cl- channels

what is pregabalin?

a structural analogue of GABA

what is the moa of pregabalin?

- binds to α2δ ligand on voltage-sensitive calcium channels (VSCCs)

- this opens calcium channels to reduce calcium influx

- therefore blocks overactive VSCCs in amygdala and CSTC loops