CNS - Drugs for antidepressants Flashcards
what do SSRIs stand for?
Selective Seretonin Reuptake Inhibitors
What are the SSRIs?
Fluo|xetine
Paro|xetine
Ser|tara|line
Cita|lopram
ES|citalopram
what is the MoA of SSRIs?
normal: serotonin undergoes reuptake by serotonin transporters
SSRIs: block serotnon transporters
= block serotonin reabsorption into presynaptic nerve ending
= increase [serotonin] in synaptic cleft
= increase serotonin activity at the post synaptic receptor sites
= make person feel happier
what are the adverse effects of SSRIs + explain them
excess serotonin
= act on different serotonin receptors which would otherwise not be acted on
= overactivation of 5-HT3 receptors in the gut
= GI symptoms
= nausea, diarrhoea
excessive serotonin
= act on 5-HT2A receptors in the limbic system
= decrease dopamine release
= loss of libido, sexual dysfunction
(dopamine: short term happiness, serotonin: long term joy)
headache, anxiety, weight loss/ gain
**no fatility in OD (as it just increases serotonin, and nothing to do with NE)
what does SNRIs stand for
serotonin norepinephrine reuptake inhibitors
what are the SNRI drugs?
vena|flaxine
tra|zodone
nefa|zodone
what are the TCA drugs?
amitriptyline
imi|pramine
what are the side effects of the TCAs and SNRIs?
CNS - sedation, fatigue
CVS - tachycardia, arrhythmia, postural hypotension
anticholinergic effects -
definition of anticholinergic
block acetylcholine
= cannot have parasympathetic NS
what is the MoA of TCAs and SNRIs
and from this, conclude the side effects
inhibit serotnin and NE transporter (is 2 seprate transporters)
= increase synapse [serotonin + NE]
= increase mood
side effects:
more NE in the system
= ‘less chill’ –> sympathetic activation
1. tachycardia
2. arrhythmias
3. urinary retention + constipation
4. glaucoma
which class of drugs to give for mild vs severe depression?
mild: SSRIs = no OD risk
severe: TCAs + SNRIs = risk of OD
characteristics of depression
low mood etc
SYMPTOMS MUST PERSIST FOR >2 weeks
what does NaSSAs stand for
Noradrenergic and Specific Serotinergic Antidepressants
what is the MoA of NaSSAs?
FIRST METHOD:
ground rules: alpha-2 receptors prevent NE and 5-HT NTs from entering (happy chemicals)
alpha-2 AUTOreceptors: norAdrenaline neurone
alpha-2 HETROreceptors: serotonergic neurons
NaSSAs block alpha-2 hertroreceptors and autoreceptors
= more NE and 5-HT allowed into the synaptic cleft
SECOND METHOD:
5-HT1 is the mood regulation, and has strong antidepressant effects when activated
5-HT2&3 cause sexual dysfunction, nausea etc
NaSSAs block 5-HT2&3 receptors on post synaptic membrane
= increase 5HT-1 neurotransmission
= decrease side effects from 5-HT2&3, while causing more antidepressant effects from 5-HT1
what is the monoamine hypothesis?
and what are the extra hypothesises that researchers have come up with
depression is caused by low levels of 5-HT, NE, and dopamine in the brain
- neuroplasticity hypothesis
- overactivation of HPA axis
= excess cortisol
= damaged neurons in hippocampus
why does it take a few weeks for anti-depressants to work?
brain needs time to adapt by…
1. upregulate receptors (to use the increasee in NT efficiently)
2. decrease cortisol
3. increase neuroplasticity = increase growth of new synaptic connections
what are some examples of NaSSAs?
mir|taza|pine
mia|ns|erin
why does increase reuptake at post synaptic cleft = happy
but
increase reuptake at pre synaptic cleft = sad?
GROUND RULES:
presynaptic receptors (eg. 5-HT autoreceptors)
= brakes which regulate how much seritoin is released
how does serotonin follow a release, bind, and reuptake cycle?
serotonin transmission occurs in one synapse at a time
presynaptic neuron contains serotonin stored in vesicles
= action potential arrives
= stored serotonin is released into synaptic cleft
= serotonin binds to post synaptic receptors
= excess serotonin is reabsorbed by the presynaptic neuron via serotonin transporter
**each neuron has to synthesise their own serotonin when there is an action potential
