Antidepressants and Antipsychotics Flashcards
Five (out of seven) of these must be present for a diagnosis of depression, and be present for 2 weeks.
Depressed mood Loss of interest/pleasure Appetite changes; weight loss or gain Feelings of worthlessness or guilt Fatigue Problems with thinking and concentration/indecisiveness Sleep problems - insomnia or hypersomnia
4% have had X in the last month; 43% of them have Y.
Depressive episode; severe disability.
Depression recurs in 40% or 99% of people?
40%.
Main feature of bipolar?
Distinct manic and depressive episodes.
Some bipolar patients have only manic episodes. How many?
10%
Which are the monoamine transmitters?
5HT (Seratonin) and NAd (Noradrenaline) and DA (dopamine).
5HT and NAd are the main drug targets though.
Which molecules are in that big Rang and Dale slide?
5-HT, NAd, BDNF (brain-derived neurotrophic factor) and glutamate. Those second two aren’t monoamines.
Sort into good/bad guys for neurogenesis and protection from neuroapoptosis:
BDNF, NAd, Cortisol, Seratonin, Glutamate
BDNF, NAd 5HT are good.
Glutamate and cortisol are bad.
Think glutamate, think…
excitotoxic effects on hippocampal glutamatergic neurons, with poorly understood influence by antidepressants.
Skipping the detrimental transcription and going straight for the neuroapoptotis in the hippocampus.
Think hypothalamus-pituitary-adrenal cortex axis, think…
cortisol enhancing transcription of detrimental (pro-apoptotic or anti-protective) genes in the hippocampus and/or prefrontal cortex.
NAd, 5HT and BDNF counteract this transcription.
Cortisol release by the adrenal glands is stimulated by X from the Y, which is stimulated by B release by the A, stimulated by stress.
adrenocorticotrophic hormone (ACTH); pituitary; corticotrophin releasing hormone (CTH); hypothalamus
-pramines and -triptylines are all what?
TCAs.
TCAs all end in either…
-pramine or -triptyline
Two things to remember about TCAs - one relates to a neurotransmitter it may or may not influence greatly, the other relates to onset of something.
A bonus third is about their effectiveness.
- little to no effect on DA uptake.
- Takes 2-3 weeks for mood elevation to kick in.
- They are equieffective; choice of TCA relates to differing unwanted sedative and anticholinergic effects.
Three uses of TCAs.
- against depression symptoms (70% success rate)
- bipolar depression
- 2nd line for anxiety
What adverse effects of TCAs tend to develop tolerance?
hypotension and anticholinergic effects.
What are “anticholinergic effects”?
AKA “atropine-like” effects?
(i.e. pro-sympathetic or pro-parasympathetic?)
Block parasympathetic signalling -> leads to sympathetic effects. Blocks acetylcholine transmission.
Also called atropine-like effects.
Also called muscarinic blockade.
Also called antimuscarinic effects.
Bonus details: pupil dilation, far vision, dry mouth, inhibited digestion, blood goes to muscles, vasodilation, higher heart rate, bronchodilation.
What are common anticholinergic side effects of a drug?
Dry-mouth, constipation, blurry vision.
Also called atropine-like effects.
Also called muscarinic blockade.
Also called antimuscarinic effects.
Name the big four side effect headings of TCAs.
- alpha blockade (makes you fat, dizzy and bad in bed - not very alpha. Alpha is muscular, a beast in the sack and can change positions without fainting).
- histamine blockade (H is a monoamine)
- antimuscarinic effects
- Misc (overdose/change in dose)
Think alpha blockade (side effect), think…
TCA side effect. Fat, dizzy, bad in bed.
Think histamine blockade, think…
TCA side effect - causes sleepiness. Remember Ken’s advice about plane travel.
Do TCAs have a low therapeutic index?
Yes
TCA dose changes risk two problems. What are they and what who do you have to watch out for?
SEIZURES and HEART PROBLEMS.
Increasing dose can lower the seizure threshold and cause arrhythmias. Cardiotoxicity can kill the human.
Watch out for epileptics and people with heart conduction problems.
TCAs can kill the human in two main situations. What are they?
Overdose/dose change - cardiotoxicity.
In combination with MOAIs.
Name six SSRIs.
PROMPT: Fluo, fluvo, Sir. Trampoline, parrot, sitting metallic baby, e-sittingmetallicbaby
fluoxetine, fluvoxamine, paroxetine, citalopram, escitalipram, sertraline
Name six SSRIs (no prompts)
fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram
Pro of SSRIs compared to TCAs
Less anticholinergic effects
Pro of SSRIs compared to MOAIs
No “cheese reactions”
Con of SSRIs compared to TCAs
Not as good at treating severe depression.
Equieffective for moderate
What are three irreversible MOAIs?
PROMPT: fish herb magazine, Noz in Cyprus being mean, isolated cardboard box with a pimple.
tranylcypromine, phenelzine, isocarboxazid
What is the reversible MOAI?
PROMPT: mock bam bam
Moclobemide
MOAb is good for oxidising DA. What’s MOAa good for and in what order?
5HT > NAd > DA
Three side effects of MAOIs unrelated to cheese
Insomnia, weight gain, peripheral oedema.
Lotta foods contain tyramine. MOAIs block tyramine metabolism in the gut wall. What’s the problem here?
Massive andrenergic stimulation - hypertensive crisis. Because tyramine enhances sympathetic catelcholamine release into adrenal medulla.
Why does moclobemide have less of a tyramine reaction?
Because moclobemide is selective for MOAa (hence 5HT > NAd > DA), and tyramine can be metabolised by MOAb.
Apart from no tyramine reaction, why is moclobemide better than phenelzine, tranylcypromide or isocarboxazid?
Few CV effects,
much harder to overdose on.
What are two reasons SSRIs are better than TCAs for people with CV problems?
Less H1 antagonism means no sedation.
Less atropine-like symptoms
So out of TCAs, SSRIs, irreversible MOAIs and reversible MOAIs, which two are hard to overdose on?
SSRIs and reversible MOAIs.
BUT SSRIs can cause seratonin syndrome in combination.
What two headings are big for SSRI unwanted effects?
Other than seratonin syndrome, which is an adverse effect
Like teenage Snake from the Simpsons, 1. aggression and 2. suicidal thoughts among children and adolescents.
What does seratonin syndrome look like? List four symptoms.
- Febrility (temp and shivering), 2. me-in-iso mentally, 3. sweating, 4. clonus (flailing), 5. hyperreflexia
Different antidepressant classes are similar in X but different in Y.
X: efficacy
Y: side effects
How long should an effective antidepressant regimen go for?
Two years or more.
Human is mildly depressed. Give human drugs?
No - only from moderate depression and up.
How effective are antidepressants as mood stabilisers?
NOT AT ALL never do it, this will fuck up the human.
-results include mood elevation, cycle acceleration and mixed episodes.
Lithium is more selective for the A and the B because sodium channels are more active there.
Brain and kidney.
Lithium has neuroprotective effects (antiapoptotic and anti-oxidative).
What does IP3-related signal inhibition got to do with it?
Inhibits Glu activation
Inhibits DA activation (mania)
Facilitates GABA.
Does lithium have a narrow or a wide therapeutic index?
Narrow. Blood levels must be monitored.
