Antidepressant Pharmacology Flashcards
Amitriptyline
Tricyclic antidepressant.
Inhibits reuptake of both NA and serotonin into presynaptic terminals. Can also block muscarinic, H1 and a1 receptors. Causes A/E of sedation, confusion and motor incoordination. Takes 4-6 weeks to work.
Mirtazapine
ATYPICAL ANTIDEPRESSANT
Tetracyclic (atypical) antidepressant.
Postsynaptic blockage of serotonin (5HT2 and 5HT3), alpha 2 receptors, and potent H1 blockade.
Can be considered first line.
Fluoxetine
Selective Serotonin Reuptake Inhibitor (SSRI).
Selectively inhibits the presynaptic reuptake pump for serotonin. Increases serotonin in the synapse. Takes 4-6 weeks to work. Less sedating and less anti-muscarinic effects. Metabolized by CYP450.
Venlafaxine
Serotonin and noradrenaline reuptake inhibitor (SNRI).
Inhibits serotonin, noradrenaline and dopamine uptake. At low doses will act like a SSRI, at higher doses has more effect on NA. Metabolized to active form, meaning lasts longer in system.
Reboxetine
ATYPICAL ANTIDEPRESSANT
Noradrenaline reuptake inhibitors (NRI).
Inhibits NA reuptake and weakly inhibits serotonin reuptake. Antagonists a2 receptors.
Phenelzine
Monoamine oxidase inhibitor (MAOI).
Irreversible inhibition of MAO-A and MAO-B in the CNS and periphery. Increases brain levels of serotonin, NA and dopamine. Tyrosine cheese effect.
Moclobemide
Monoamine oxidase inhibitor (MAOI).
Selective reversible inhibition of MAO-A.
Less interactions with food but more drug interaction.
St John’s Wort
Weak MAOI effect and inhibition of serotonin reuptake. Used in mild depression only, few side effects at normal doses.
What are the treatment options for depression?
Cognitive Behavioural Therapy with a psychologist, or antidepressant drugs.
- TCAs
- SSRIs
- SNRIs
- Atypical ADs
- MAOIs
- St John’s Wort
Depression can be secondary to…
Hypothyroidism, Cushing’s Syndrome, tumours, postpartum, and other medication.
What are the theories of depression?
Monoamine Deficiency Theory
Receptor Sensitivity Theory
Serotonin Only Theory
Permissive Theory
Monoamine Deficiency Theory
Linked to improper amount of amines. Drugs that increase the amount of NA and serotonin available can alleviate depression. Doesn’t explain the time delay in the clinical relief of depression.
Receptor Sensitivity Theory
Receptors for neurotransmitters is less sensitive in depression. Clinical relief comes from a normalization of receptor sensitivity.
Serotonin Only Theory
Downplays the role of NA, but does not explain why there is still a delay in clinical relief of symptoms, and does not explain the role of NA in depression.
Permissive Theory
Mood controlled by balance of NA and serotonin not overall levels. If serotonin cannot balance NA and NA falls to abnormally low then pt becomes depressed. Opposite of this is if NA cannot balance serotonin and NA becomes high, pt becomes manic.
What neurotransmitter ratio is important in depression?
Serotonin and NA - the balance between depression and anxiety.
What are atypical ADs?
Agents that do not fit into any other category of ADs because they have a unique MoA. However they still affect NA and serotonin levels, and usually dopamine levels.
What side effects are linked with depression?
Serotonergic, adrenergic, dopaminergic and anti-cholinergic.
What is serotonin syndrome?
Serotonin syndrome (serotonin toxicity) is caused when a high dose of a single drug is given, or when >1 serotinergic agents are used together. Can also occur when ADs are switched without a proper washout period. Synaptic serotonin increases, overstimulating the receptors causing hyperreflexia, clonus, terror, incoordination, mental state changes, shivering, sweating, fever and diarrhoea.
What needs to happen when switching ADs?
A washout period to prevent adverse effects due to drug interactions. ADs must be tapered slowly to avoid withdrawal.
