Pharmacology Flashcards
what are the two systems in the brain broadly and what neurochemical is involved in them
approach (appetitive) system = dopamine
aversive (defensive) system = seratonin
what is involved in the approach system
ventral striatum
dorsal striatum (movement)
amygdala (conditioning/ learning)
anterior cingulate (attention/ conflict/response selection)
orbitofrontal cortex (relative reward preference/ rule learning)
what is involved in the aversive system
NA / CRF / peptide transmitters
central nucleus of amygdala
hippocampus
ventroanterior and medial hypothalamus
periaqueductal gray matter
how do MAO inhibitors work
prevent the breakdown of dopamine, norepinephrine and serotonin
how do TCAs work
block the re-uptake of serotonin and norepinephrine
how do SSRIs work
block the re-uptake of serotonin
what are SSRIs and examples of them
Selective Serotonin Re-uptake Inhibitors
e.g. fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine
how long does it take for SSRIs to work
2-3 weeks
MOA of SSRIs
1 - at baseline, 5-HT re-uptake is unaffected and the firing rate is normal
2 - with AD re-uptake of 5-HT is inhibited
3 - increased extracellular conc of 5-HT stimulated the 5-HT1a auto receptors to inhibit firing
4 - Chronic occupancy of the 5-HT1A receptor causes it to desensitize. This leads to a return of normal firing.
5 - facilitates serotonergic transmission in the presence of reuptake blockade.
S.E. of SSRIs
GI dysfunction (nausea, dyspepsia, constipation, diarrhoea, abdo pain) Short-term anxiety, agitation Insomnia Headache Dizziness Sexual dysfunction
In young patients, there is an increased risk of self harm in first few weeks
when should the use of SSRIs be avoided
in patients using NSAIDs, aspirin or warfarin
why do patients using TCAs at a high dose need an ECG
side effects include arrhythmias, heart block, tachycardia, syncope
what are the common side effects of TCAs
Constipation
Dry mouth
Blurred vision
Postural hypotension
what is the MOA of MAOIs
inhibit monoamine oxidase A and B
Increased storage and availability for release of 5-HT and NA
examples of MAOIs
phenelzine, isocarboxazid, tranylcypromine
when are MAOIs commonly used
3rd line or 4th line
S.E. of MAOI
Tyramine is normally inactivated in the gut by MAO
Hypertensive crises can occur with tyramine-containing foods and some drugs
Sx = flushing, headache, increased BP
Tx = alpha blockade
what S.E. do all anti-depressant drugs have
hypotension
drowsiness
increased appetite
weight gain
Acetylcholine receptor (muscarinic) Sx = dry mouth, constipation, blurred vision and difficulty initiating micturition
why do you sometimes get extra-pyramidal side effects in anti-depressant treatment
antagonism of dopamine [DA] receptors (primarily D2 receptors)
what is the main inhibitory neurotransmitter and what does it do
GABA
allows flow of either Cl- ions into the cell or K+ ions out of the cell
» causing hyperpolatisation
what are Sx of withdrawal of benzodiazepine
confusion
toxic psychosis
convulsions
insomnia anxiety loss of appetite/wt tremor perspiration tinnitus
what does chronic benzodiazepine do to the brain
chronic treatment causes ↓ response to GABA.
Withdrawal results in anxiety/convulsions possibly due to ↓ density of BZ receptors
what is the correct way to withdraw benzodiazepines
1 . Transfer patient to equivalent daily dose of diazepam/chlordiazepoxide (longer acting) preferably taken at night
- Reduce dose every 2–3 weeks in steps of 2 or 2.5mg; if withdrawal symptoms occur, maintain this dose until symptoms improve
- Reduce dose further, if necessary in smaller steps; it is better to reduce too slowly rather than too quickly
- Stop completely; time needed for withdrawal can vary from about 4 weeks to a year or more
how do SSRIs help in anxiety
increase extracellular 5-HT and have anxiogenic properties
what do patients being treated with SSRI need to be informed about
they will feel worse initially
cover this period with benzo
