Antidepressants Flashcards
What is the monoamine theory?
Deficits in monoamine neurotransmitters (NA and serotonin) cause depression.
What observation was made about Reserpine?
It inhibits noradrenaline and serotonin storage -> NA and serotonin get into cytoplasm and cannot be released into synapse in coordinated way -> depression
What is a later finding for the monoamine theory?
Most likely monoamines are important, but there are complex interactions with other neurotransmitter systems as well.
What is monoamine oxidase? What are the different forms of MAO?
Enzyme that oxidizes and breaks down monoamines.
MAO-A mainly breaks down serotonin.
MAO-B breaks down NA and dopamine.
What MAO inhibitor is used in Parkinson’s Disease?
There is lack of dopamine in Parkinson’s disease. So preserve dopamine by using MAO-B selective inhibitor.
What is the MOA of MAOI?
MAOI inhibit breakdown of monoamines -> increase biological availability of monoamines.
What is phenelzine?
It is a MAOI, non selective between MAOA and MAOB. Irreversible MAOI.
Adverse effects of MAOIs?
What should MAOIs not be combined with?
- postural hypotension (due to sympathetic block produced by accumulation of dopamine in the cervical neck ganglia -> acts as inhibitory transmitter)
- restlessness and insomnia due to CNS stimulation (MAOI block breakdown of NA -> fight or flight)
- should NOT be combined with other drugs enhancing serotoninergic function, e.g. pethidine (bc too much serotonin -> hyperexcitability, increased muscular tone, jerking movements, etc.)
What is the cheese reaction?
- a drug food interaction between cheese and MAOI
- less likely to occur with reversible, MAOA selective inhibitors like moclobemide; more likely to occur with irreversible, non-selective MAOI.
- MAOI can lead to accumulation of tyramine (in cheese) -> compete with NA for vesicular compartment -> increase release of NA into synpase -> sympathomimetic effect -> can cause acute hypertension
What is the MOA for Tricyclic Antidepressants (TCA)?
Inhibits serotonin transporter or NA transporter -> neurotransmitter stays longer in in synapse -> increase in monoamine
Which TCAs are non selective and which are selective?
Non-selective for SERT/NET:
Imipramine, Amitriptyline, nortriptyline
Selective for NET:
Desipramine
What is nortriptyline?
- second generation TCA
- milder side effects than amitriptyline and imipramine -> better compliance
What are the adverse effects of TCAs?
- sedation due to H1 histamine receptor antagonism -> tolerance to sedation can develop in 1-2 weeks
- Postural hypotension (due to alpha adrenoceptor sympathetic block)
- dry mouth, blurred vision and constipation due to muscarinic receptor antagonism
TCAs metabolized by the liver
What are the three TCAs?
1st gen - imipramine
2nd gen - amitriptyline and nortriptyline
What is the most widely prescribed antidepressant today?
Fluoxetine
Examples of SSRI (selective serotonin reuptake inhibitors)?
Fluoxetine and citalopram
Advantages of SSRI?
It has fewer adverse effects than TCAs.
Low affinity for alpha adrenoceptors -> less postural hypotension, lack of cardiovascular effects and safer in overdose
Lack of effect at histamine receptors -> reduced sedation
Low affinity for muscarinic cholinergic receptors -> minimal anticholinergic effects like dry mouth and constipation
Overall SSRI is safer in overdose and less side effects lead to better compliance. Improved side effect orofile also allows for prescription of more adequate doses.
Adverse effects of SSRI?
Nausea, insomina (when plasma level of drug falls betwen doses. usually only when you first start taking the drug)
Sexual dysfunction (cyproheptadine or other 5HT2 blockers can be given ro prevent SSRI induced sexual dysfunction)
Citalopram has some histamine receptor antagonism leading to sedation
Serotonin syndrome can occur if SSRI taken with other drugs increasing serotoninergic activity like MAOI. Effects include tremors, hyperthermia (feel v hot) and cardiovascular collapse)
What are NARI?
Noraderenaline Reuptake Inhibitors.
- greater selectivity for NA than serotonin
- example: reboxetine
- fewer adverse effects than TCAs and SSRI.
What is maprotiline?
An earlier NARI, has TCA like adverse effects due to alpha adrenoceptor and histamine receptor effects and occasionally caused seizures.
Adverse effects of reboxetine (NARI)?
- dry mouth, constipation due to anticholinergic effects
- insomnia due to increased noradrenergic activity in the CNS
- tachycardia due to increased availability of NA at sympathetic fff synapses
What are SNRIs?
- serotonin and noradrenaline reuptake inhibitors
- similar dual serotonin and NA reuptake inhibition profiles as non selective TCAs
- examples include Venlafaxine, desvenlafaxine and duloxetine.
Advantages of Venlafaxine?
- fewer adverse effects than TCAs
Adverse effects or SNRIs?
- serotoninergic adverse effects similar to SSRI like nausea, insomnia and sexual dysfunction
- serotonin syndrome when combined with other serotoninergic drugs and MAOI
- withdrawal effectsmay be more common and stronger than for SSRI and TCA
