Antidepressants [5] Flashcards
Name as many affective disorders as possible
Major depressive disorder (MDD)
Unipolar / bipolar depression
Attention deficit hyperactivity disorder (ADHD)
Obsessive compulsive disorder (OCD)
Panic disorder
Post traumatic stress disorder (PTSD)
Seasonal affective disorder (SAD)
Emotional symptoms of depression
Misery
Apathy
Hopelessness
Low self esteem
Guilt
Inadequacy
Biological symptoms of depression
Retardation of thought
Loss of libido
Sleep disturbance
Loss of appetite
Difference between unipolar and bipolar depression
Unipolar - only negative moods & no evidence for genetic cause
Bipolar - depression + mania & evidence for genetic cause
What are the two types of unipolar depression
Reactive and endogenous
What is reactive depression
Response to distress
3-10% population
Women > men
What is endogenous depression
Biochemical cause
1% population
Women = men
What is the monoamine theory of depression and mania
Depression - deficient monoaminergic transmission
Mania - excessive NA & 5-HT transmission
What is 5-HT and what does it control
Serotonin
Mood , sleep , sexual behaviour , appetite , sensory perception
What are the noradrenaline receptors
Alpha and beta adrenergic receptors
What locus does NA bind
Locus coeruleus
Malfunctions cause depression / anxiety
How is dopamine made
From the precursor DOPA by DOPA decarboxylase
What does dopamine control
Motivation, reward, reinforcement
What dopamine receptors increase cAMP
D1 and D5
What dopamine receptors decrease cAMP
D2, D3 and D4
How are Parkinson’s disease and dopamine linked
Caused by death of dopamine
How are schizophrenia and dopamine linked
Caused by overactivity of dopamine levels in certain brain regions
How does cocaine affect dopamine
It inhibits uptake
Increased conc of dopamine in synapse
Prolonges it’s action
What is the pharmacological evidence for the monoamine theory
Reserpine (inhibits brain storage of NA and 5-HT) causes depression
What is the pharmacological evidence against the monoamine theory
Amphetamine (release do NA & blocks reuptake) has no effect in depressed patients
Cocaine (inhibits NA reuptake) has no effect on depressed patients
Biochemical evidence for the monoamine theory
Urinary & CSF conc of MOPEG (a NA metabolite) is reduced by 25% in depressed patients
CSF conc of 5-H1AA (5-HT metabolite) is reduced in some depressed patients
Biochemical evidence against the monoamine theory
Urinary excretion of 5-H1AA does not change in depression
CSF conc of 5-1AA is not reduced in all patients
What are the reuptake inhibitor antidepressant drugs
Serotonin reuptake inhibitors (SRI)
NA reuptake inhibitors (NRI)
Selective SRI (SSRI)
Selective NRI (SNRI)
What are tricyclic antidepressants (TCA) structurally closely related to
Neuroleptics
TCA has extra atom in central ring
Mechanism of TCAs
Blocks reuptake of amines by nerve terminals
Mainly effective on NA and 5-HT with little selectivity
Why do TCAs cause side effects
They also bind to Muscarinic receptors
Cause dry mouth, blurred vision, constipation and urinary retention
How are TCAs metabolised
By N-demethylation and ring hydroxylation (3° -> 2° amines)
2 forms of MAO
MAO-A and MAO-B
MAO-A has substrate preference for …
5-HT
MAO-B has substrate preference for …
Phenylethylamine
MAOIs have preference for …
MAO-A
Monoamine oxidase regulates what
Concentrations of NA & dopamine
Side effects of MAOIs
Hypotension
Excessive central stimulation
Weight gain
Hepatotoxicity
Explain the cheese reactions
Caused by MAOIs
Tyramine found in mature cheese and marmite
Usually metabolised by MAO in gut wall
MAOIs cause tyramine to be absorbed and it’s sympathomimetic effect enhances
- acute hypertension
- severe headache
- intracranial bleeding
Examples of SSRIs
Fluoxetine, sertraline, citalopram
Do SSRIs or TCAs have fewer side effects
SSRI
Theory behind the 2-3 weeks therapeutic effect of SSRI
Quick increase in serotonin inhibits serotonin firing
Desensitisation of autoreceptors after prolonged SSRI exposure
Feedback regulation requires chronic administration to sustain serotonin levels
Need to alter delta and beta adrenergic receptor expression
4 advantages of SSRIs over TCAs & MAOI
Lack of anticholinergic & cardiovascular side effects
No weight gain
Low acute toxicity (low risk of overdose)
No food reaction
Disadvantages of SSRIs
Nausea, anorexia, insomnia
Reported increase in aggression
What happens when SSRIs is combined with MAOI
Serotonin syndrome
Example of NRI
Reboxetine - most effective for social functioning
Example of dopamine agonist
Bupropion - blocks reuptake of NA and dopamine
