Depression Flashcards
Suicide is the _ leading cause of death in US?
10
What is the criteria for depression?
5 or more symptoms (including 1 of the first 2) in 2 week period
1. Depressed mood
2. Loss of interest/pleasure
3. Changes in sleep
4. Changes in appetite
5. Changes in activity
6. Guilt
7. Death/suicide
8. Fatigue
9. Decreased focus/concentration
What is reserpine?
VMAT Inhibitor- inhibits vesicular monamine transport
Used for psychosis/hypertension
Associated with depression
What monoamines did reserpine block? How did that lead to the discovery of new medicine?
Reserpine was an antipsychotic that blocks ALL monoamine vesicles.
Decreases Dopamine= lowers psychosis
Decrease norepi= Decreases BP (Hypertension)
Decrease in serotonin= Increases DEPRESSION
What is the primary mechanism of action of most antidepressant drugs?
Increase monoamine neurotransmission
What are MAO?
Monoamine oxidase is an enzyme that degrades dopamine, norepinephrine and epinephrine
Blocking MAO does what?
increases monoamine levels, effective antidepressant
How many types of MAO are there?
MAO A and MAO B
Which monamines are associated with MAO-A and MAO-B
NE and DA
Which monoamine is associated with MAO-A? Where are they located?
5-HT (serotonin), GI and liver
Name the MAOIs
-Rasagiline (Azilect)
-Selegiline (Eldepryl, Zelapar)
-Isocarboxazid (Marplan)
-Phenelzine (Nardil)
-Tranylcypromine (Parnate)
What is an important adverse effect associated with MAOIs?
Cheese reaction, tyramine increases without MOA to degrade it and converts into norepinephrine leading to hypertensive crisis
What are normal side effects of MAO?
-Orthostatic hypotension
-Decreased sexual function
-Sleep disturbances
-Weight gain
What and when was the first TCA ever found?
Impiramine was a derivative of chlorpromazine, discovered in 1950’s
What is chlopromazine? What’s the historical story surrounding it?
Chlopromazine is an antipsychotic that was give to bipolar patients and induced mania BUT helped depression… led to discovery of TCA imipramine
What are TCA’s?
Non-selective monoamine reuptake transporter inhibitors
Name TCAs in the market?
-Amitriptyine
-Desipramine (Norpramin)
-Doxepin (Sinequan)
-Imipramine (Tofranil)
-Nortriptyline
-Protriptyline
-Trimipramine
What receptors do TCAs antagonize?
(DA, NE, 5-HT)
But also, A1, A2, D2, H1, mACH
TCA side effects of MI receptor antagonism
Anticholinergic effects including dry mouth, blurred vision, constipation, urinary retention and impotence
TCA side effects H1 receptor antagonism?
Sedation and weight gain
TCA side effects of adrenergic a receptor antagonism?
Postural hypotension
Why do TCAs have so many side effects?
NON-SELECTIVE
What was the first rationally designed class of psychotropic meds?
SSRIs
What is the most commonly prescribed class of drug for depression?
SSRI
What are the SSRI meds?
-Fluoxetine
-Sertraline
-Paroxetine
-Escitalopram
-Nefazodone
-Venlafaxine
5HT2 receptor activation from SSRIs results in?
Decreased libido and sexual dysfunction associated with SSRI
5HT3 receptor activation from SSRIs leads to GI side effects?
Nausea but may include diarrhea and emesis
What is the black box warning for SSRIs?
Suicide in children and adolescents?
When do you prescribe SSRis to adolescents?
When the scale outweighs the risk of not being on the antidepressants
First few months are at risk
Important to monitor
How long does it take SSRI’s to work?
6 weeks for maximum response
Name atypical antidepressants:
-Bupropion
-Trazodone
-Brexanolone
-Ketamine
How does burpropion (wellbutrin) work?
Blocks NE and Dopamine reuptake (minimally dopamine) (NDRI)
What is an important side effect that might be important for patients in regards to SSRI vs Bupropion?
Sexual dysfunction is not a problem in burpropion
What is the negative side effect of burpropion (wellbutrin)
Seizure- rare but serious
What are they/ what do Trazodone and Nefazdone do?
SARI: Serotonin antagonist and reuptake inhibitor
Block the reuptake transporter to increase the amount of serotonin in the cleft.
They block 5HT2A and 5HT2C receptors that are known to cause sexual dysfunction, insomnia and anxiety.
This leaves 5HTIA open to receive serotonin- and work as an antidepressant.
What medication is used for postpartum depression?
Brexanolone (Zulresso)
What is the mechanism of action for Brexanolone?
A GABAA receptor positive allosteric modulator indicated for treatment of PPD. It targets extrasynaptic GABA receptors to enhance GABA’s inhibitory effects.
How long does it take a single sub-anesthetic infusion of ketamine to produce effects?
40 minutes- it is a rapid antidepressant
What are negative side effects of ketamine?
Psychological: hallucinations, out of body experiences
Abuse is high
Which part of the brain plays a role in depression and antidepressant efficiency?
Hippocampus
Explain the optogenic research method:
-Blue light turned off hippocampus but still had ketamine
-It showed that without the hippocampus, the effects of ketamine did not work. Therefore, hippocampus was necessary for antidepressive effects.
-Yellow light turned on hippocampus without ketamine
-Produces the same amount of antidepressive response
What is a receptor only found in the hippocampus?
alpha5-GABAa Receptor
What was the name of the drug that could target alpha5-GABAa receptor in the hippocampus?
L655,708
What was the IV administration to the rats from the antidepressant experiment supposed to show?
Whether or now L655,708 could be used to get high essentially.
They presented the rats with two levels, active and inactive lever. If ketamine, which causes hallucinations/abuse, was in the active lever the rats would hit it millions of times to get high. But when L655,708 was added, they stopped using it. So much so, that it was equivalent to the inactive lever with a placebo.
What was the summary of antidepressant rat experiment?
GABAa modulators may be novel antidepressants.
