Antidepressants Flashcards
Describe the monoamine theory and its limitations.
Deficits in monoamine neurotransmitters (NA and 5-HT) cause depression.
Limitations:
- hypothesis originally formulated for NA, but emphasis later shifted to 5-HT
- studies of monoamine markers in depressed pts yielded inconsistent results
- MA hypothesis alone is inadequate to explain all the pharmacological actions in depression
Describe unipolar depression.
Mood swings always in same direction.
- Reactive depression (75%): non-familial, associated with life events
- Endogenous depression (25%): familial, not directly related to external stress
Describe bipolar depression.
Depression alternates with mania.
- periodicity of oscillations in mood usually occur over several weeks
- strongly familial
- usually appears in early adulthood
What are the symptoms of depression?
Emotional Smx:
- Misery, apathy and pessimism
- Low self-esteem
- Indecisiveness, loss of motivation
Others:
- Retardation of thoughts and actions
- Loss of libido
- Sleep disturbances and loss of appetite
Which form of MAO breaks down 5-HT, NA and dopamine?
5-HT mainly by MAO-A, but also MAO-B.
NA and dopamine by both forms.
How do MAOIs work?
Inhibit breakdown of MA to increase MA availability in the synapse
List examples of MAOIs.
Phenelzine: non-selective, irreversible
Moclobemide: MAO-A selective, reversible
Major adverse effects of MAOIs?
- Postural hypotension - accumulation of dopamine in cervical ganglia, where it inhibits NA production
- Restlessness and insomnia - CNS stimulation
- (When combined with other drugs enhancing serotonergic function) Hyperexcitability, increased muscular tone, myoclonus (jerking, involuntary movements), loss of consciousness
Describe the “Cheese Reaction” (drug-food interaction between MAOIs and cheese/concentrated yeast products)
Acute hypertension, giving severe throbbing headache and occasionally, intracranial haemorrhage.
MAOIs inhibit breakdown of tyramine, tyramine accumulates and causes sympathomimetic effect. Tyramine competes with NA for reuptake + storage in vesicles ➝ more NA released into synapses.
List some common TCAs.
Non-selective for SERT/NET: imipramine, amitriptyline, nortriptyline
Selective for NET: desipramine
Why is nortriptyline preferred to imipramine or amitriptyline?
Second gen TCA, milder side effects and improved compliance
Major adverse effects of TCAs
- Postural hypotension - blocks alpha adrenergic receptors
- Sedation - due to H1 histamine receptor antagonism. Tolerance to sedation can develop in 1-2 weeks
- Dry mouth, blurred vision, constipation - muscarinic receptor antagonism
- DDIs - plasma protein bound; hepatically metabolised
What are the advantages of SSRIs over TCAs?
Overall, safer in overdose + better compliance.
- Lack of effect at histamine receptors - reduced sedation. (*citalopram can still cause some sedation)
- Low affinity for alpha-adrenoceptors - lack of cardiovascular effects, safer in overdose
- Low affinity for muscarinic receptors - minimal anticholinergic side effects e.g. dry mouth, constipation
Adverse effects of SSRIs
- Nausea and insomnia (between doses)
- Sexual dysfunction due to increased stimulation of 5HT2 receptors (can prevent with cyproheptadine or other 5HT2 blockers)
What are the effects of serotonin syndrome?
- Tremor
- Hyperthermia
- Cardiovascular collapse