Lecture 15 (CNS Pharmacology IV- Antidepressant drugs) Flashcards
What are the two disorders associated with depression? (2)
-Unipolar depression
-Bipolar depression
What is unipolar depression?
And what are the two types of it and what do they mean? (4)
Mood swings in negative direction
Reactive – caused by real life effects (75%)
Endogenous – without underlying cause (25%)
What is bipolar depression?
Bipolar depression - mood swings, alternate between negative mood swings, and mania – self confidence impatience, aggression
What are typical symptoms of depression? (7)
-Low mood (anhedonia), negative thoughts, misery, pessimism, irritability
-apathy: loss of interest in daily activities
-Severe loss or gain in weight/appetite
-Low self-esteem, feelings of worthlessness or guilt
-Sleep disturbance: insomnia or excessive sleeping
-Loss of appetite & libido
-Diminished ability to think/concentrate
When is a patient diagnosed with clinical depression?
Subjective-qualitative: patients exhibit depressed behaviour for over 2 weeks and symptoms disrupt normal social and occupational function
Describe the neural pathways which shows the effect of anti-depressants? (3)
-Nucleus accumbens (NAc) has an antidepressant effect on individuals who have treatment-resistant depression
-Stimulation of NAc means increased production of brain-derived neurotrophic factor (BDNF)
-Increased BDNF means decreased CREB (Cyclic AMP response element), associated with high levels of cortisol (stress and anxiety)
What part of the brain shows fear?
What part of the brain do hormones effect?
produces dopamine?
-Amygdalla
-Hypothalamus
-Ventral tegmental area (VTA)
Which two hormones guide appetite? (2)
-Ghrelin
-Leptin
What is postnatal depression?
Babies brain waves can become altered if the
mother is depressed (usually for 2-8 weeks)
What are the animal models for testing depression? (4)
-Water bath - how much they struggle in water
-Measuring social interaction - decreases in depression
-Learned-helplessness test - measures the development of passive responses to inescapable foot shock
-Intracranial self-stimulation - measures effort that an animal expends to stimulate brain reward circuits electrically
What happens to animal in learned helplessness when they receive continuous electric shocks?
They stop trying to escape
(this changes with analgesic drugs)
Which neurotransmitters are involved in depression? (3)
-Na (Noradrenaline) and 5HT (Serotonin) reduced
-BDNF/TrkB reduced neurogenesis
-NMDA over-activation (causes neurogenesis)
What is the monoamine hypothesis of depression?
The cause of depression is a depletion in the levels of serotonin, norepinephrine, and/or dopamine in CNS
What are the four types of anti-depressants? (4)
-Monoamine oxidase inhibitors (MAOIs eg. Phenylzine, moclobemide)
-Classical Tricyclic antidepressants (TCAs eg. imipramine) - blocks MOA uptake
-Selective serotonin(5-HT) reuptake inhibitors (SSRIs eg. fluoxetine) - changes levels of diff MOAs
-Monoamine Receptor Antagonists
What do MAOIs (Monoamine Oxidase Inhibitors) do in type A and B? (2)
What is their side-effect?
What happens when combined with tyramine?
-MAOIs, inhibition of MAO type A produces anti-depressant effect, better at breakdown of noradrenaline and serotonin (type B inhibitors useful in Parkinson’s)
-Noradrenaline (NA) depletion in sympathetic terminals, causes postural hypertension
-Hypertension (cheese effect)
What do TCA anti-depressants do?
What side-effects does it have?
What happens in overdose?
-TCAs inhibit neuronal reuptake of 5-HT and NA
-(mACh, dry mouth, blurred vision, constipation), adrenergic (a2 block, postural hypotension) and histaminergic (H1 block, sedation) effects
-Dangerous in overdose: confusion & mania, cardiac dysrhythmias
What do SSRI anti-depressants do?
SSRIs specifically inhibit 5-HT re-uptake
less side effects & toxicity
(high degree of selectivity, less side-effects)
What are functions of NA in CNS?
Functions –> arousal/attention, mood, blood pressure regulation, pain
(deficiency of NA pathways in brain leads to depression) - TCAs and MOAIs increase NA
What are the functions of 5HT (serotonin) in CNS?
Functions –> Hallucinations, sleep and wakefulness, mood and emotion, feeding behaviour, sensory pathways and nociception, body temperature, vomiting
Anhedonia-the inability to gain pleasure from normally pleasurable experiences - 5-HT has role in regulating limbic processes so if not working causes this
What type of processing do these have a role in?
-NA
-5HT
NA - sensory processing
5HT - limic processing
How many subfamilies for 5HT are there?
which one is a target for antidepressants?
-7 subfamilies
-5HT1
How does chronic treatment with anti-depressants affect BDNF (brain deprived neutrophil factor)?
What does BDNF do in regards to synaptic connections?
-Increases BDNF
-BDNF stabilizes synaptic connections
What is the evidence in support of the monoamine hypothesis of depression? (3)
-Iproniazid, the first specific antidepressant, is an MAO Inhibitor
-Reserpine, which produces depression and parkinsonism, depletes stores of monoamine transmitters.
-Tricyclic ADs (originally synthesised in attempt to develop new antipsychotics) inhibit re-uptake of 5-HT and/or NA.
What part go the brain do these come from? (3)
Dopamine -
Serotonin -
Noradrenaline -
Dopamine - Ventral Tegmental Area (VTA)
Serotonin - Dorsal Raphe
Noradrenaline - Locus Coureleus (LC)
Which antidepressant is preferred TCAs or MAOs?
TCAs
Why do antidepressants with 5-HT make you feel worse at first?
-Depression gets worse at first, we end up losing inhibitory receptors so we get increased neuronal activity and increase in neurotransmitter release, increased neural pathway function
Why is there a slow action mechanism of SSRIs?
Need to desensitize somatodendritic 5HT1A receptors
What does BDNF (brain deprived neutrophic factor) do?
Stabilises synaptic connections
(depression linked to lack of BDNF but knock out mutant of BDNF show no signs of depression) - shows how complex it is, multiple combinations
What are the 3 main types of antidepressants? (3)
-TCAs
-MAOIs
-SSRIs
