Antidepressants Flashcards
Depression types
Unipolar
Bipolar
Unipolar depression can be divided into
Reactive depression (~75%) Endogenous depression (~25%)
What are the factors of reactive depression ?
Associated with circumstance (e.g. stress)
Non-familial
What are the factors of endogenous depression?
Unrelated to external pressure
Familial
Biological symptoms of depression.
Cognitive deficits
Loss of sex drive
Sleep disturbance
Loss of appetite
Depression can be treatable through surge affecting which pathways?
Serotonergic and noradrenergic
Where is 5-HT released from?
Dorsal rapid
What are the main 5-HT receptors?
5-HT1A
5-HT2A
5-HT2c
5-HT3
Location and function of 5-HT1A receptor
Presynaltic Gi/o
Decrease 5-HT release
Other location of 5-HT1A and function receptors?
Postsynaptic Gi/o
Decrease depression & decrease anxiety
Location and function of 5-HTA2A receptor
Gq
Increase anxiety
Location and function of 5-HTA2c receptor
Gq
Increase depression, anxiety, stress & appetite
Location and function of 5-HTA3 receptor
Ligand-gated cation channel
Increase nausea
How long does it take for antidepressants to generate a therapeutic effect?
~ 2 weeks
Antidepressant classes
Selective serotonin reuptake inhibitors (SSRIs)
Tricyclic antidepressants (TCAs)
Serotonin / Noradrenaline reuptake inhibitors (SNRIs)
Monoamine receptor antagonists
Monoamine oxidase inhibitors
Function of SSRIs
Increase amount on serotonin in synaptic cleft
Increase activity through post synaptic receptors
All SSSRIs have a half life of?
Long- 18 hours
Administration of SSRIs
Oral tablets once daily
Side effects of SSRIs on CNS
Sleep disturbance, weight gain, sexual dysfunction, agitation / anxiety
SSRIs side effects on GI
diarrhoea & nausea
SSRIs side effect on CVS
Bleeding disorders
What happens when SSRIs is taking in overdose
Serotonin syndrome
Fluoxetine
Specific SSRI
“Prozac”
Long duration (t 1/2 up to 96h)
Citalopram
Specific SSRI
Milder side effects (anti cholinergic)
Escitalopram
Specific SSRI
Racemic form of citalopram
No anti cholinergic
Paroxetine
Specific SSRI
“Seroxat”
Withdrawal symptoms
Anti cholinergic effect
SSRIs with anti cholinergic effect
Citalopram
Paroxetine
MOA of TCA & SNRIs
Serotonin cleared from synapse by 5-HT & Noradrenaline re-uptake transporters
Subsequent breakdown by intracellular monoamine oxidase A (5-HT & NA) and catechol-O-methyltransferase (NA only)
Venlafaxine
SNRI inhibitor (Serotonin & Noradrenaline Reuptake Inhibitors )
Weak, non selective
Weak receptor blocking
Side effects of SNRIs
Similar to SSRIs + Dry mouth Dizziness Arrhythmia Seizure Overdose risk of serotonin syndrome
Most famous tricyclic antidepressant (TCA)
Amitryptline
Use of TCA
neuropathic pain with lower dose
antagonists at α1, mACh, Histamine H1 (similar side effects to antipsychotics)
Side effects of TCA
Anticholinergic effects
Sedation
Postural hypotension
Impotence
Cautions with TCA
Significant overdose risk
Drug interactions with other CNS depressant and hepatic metabolism
CV disorders
Most common noradrenaline selective reuptake inhibitor
Bupropion
Bupropion
NA- selective reuptake inhibitor
antidepressant & anxiolytic. Also inhibits DA uptake, some 5-HT uptake. Mostly used for smoking cessation
Side effects of bupropion (or any NA-selective reuptake inhibitor)
General sympathomimetic & CNS stimulant side effects (e.g. dry mouth, insomnia, dizziness, tachycardia, constipation)
Most common monoamine receptor antagonist(MOA)
Mirtazepine
Mirtazepine
MOA antagonist
Antagonist adrenergic a2
5-HT2A,C & 5-HT3
No serious drug interactions. Faster onset
MOA inhibitors mechanism of action
- Monoamines cleared from synapse by 5-HT & NA re-uptake transporters
- Subsequent breakdown by intracellular monoamine oxidase A, and catechol-O-methyltransferase (NA only)
- Some MAOIs nonselective; also inhibit MAO-B
Side effects for MAO
Serious; SSRI side effects plus “cheese reaction” (tyramine), anticholinergic side effects, arrhythmias
MAOIs must not be given concurrently with other antidepressants at least?
2 week gap between medication changed
All antidepressant classes have similar effectiveness; usually side effects determine preference. In which order?
SSRIs > SNRIs > TCAs
How do we treat bipolar disorder?
Generally stabilise mania, less so depression
Conventional antidepressants controversial for bipolar disorder; usually given with additional anti-mania drug
What is used as anti-mania drug?
Lithium
moa of lithium to as anti-mania
Enters cells selectively via certain Na+ channels (e.g. brain, kidneys)
Accumulation: not pumped out by Na+/K+ exchanger.
Other bipolar disorder drugs are?
Anticonvulsants
Atypical antipsychotics
(May be prescribed in conjunction with antidepressants, usually SSRI (e.g. fluoxetine)
