MDD Pharmacology_EO Flashcards
Side effects of 5-HT (2&3) activation?
especially initial activation for insomnia (5HT2A) and anorexia (5HT2C). Sexual dysfunction and anxiety 5HT2.
5HT3: nausea & Diarrhea
EPS - stiffness if 5HT2 decreases dopaminergic firing in the nigrostriatal pathway
Trazodone targets which receptors?
At low-dose (25-150mg): alpha1 and 5HT2A-antagonism
At higher dose: SERT antagonism, 5-HT2C- antagonism, alpha1 and 5HT2A-antagonism
What are the side effects of Trazodone?
Rare priapism, sedation, orthostatic hypotension, rare arrythmias.
Note: less sexual dysfonction and less weight gain
What metabolizes trazodone?
CYP4A4
Which receptors are targeted by mirtazapine?
alpha2 antagonist, H1 antagonist
5-HT3 antagonist
5-HT2A antagonist
5-HT2C antagonist
What happens when alpha2 receptors are blocked?
It increases the release of serotonine and NE.
By blocking presynaptic alpha2 receptors, the feedback inhibition exerted on the release of NE is removed. Thus, the net effect is to increase NE secretion
Which psychotropics have the property of bloking alpha2? (6)
Risperidone, paliperidone, mirtazapine, asenapine,quetiapine and clozapine
What happens when 5HT2C is blocked?
Increased NE and DA in PFC which may improve motivation and concentration
What happens when 5HT3 is blocked?
Increase in DA and ACh, anti-nausea effect
What are the side effects of mirtazapine?
Weight gain, sedation, rare blood dyscrasia and rare hepatotoxicity
Note: rere sexual side-effects
On which receptors does quetiapine work?
Low dose: H1, alpha1
Depression dose: H1, alspha1, alpha2, norepinephrine-reuptake-inhibitor, 5HT2A, 5HT2C
More than 300mg: D2, 5HT1A agonist, M1, H1, alpha1, alpha2, norepinephrine-reuptake-inhibitor, 5HT2A, 5HT2C
What metabolizes quetiapine?
CYP 3A4
Which receptors are targeted by wellbutrin?
Mechanism of action not well understood. Increases DA, NE and increases firing of 5HT neurons.
Antagonist of nicotinic cholinergic receptor
What are the side effects of wellbutrin
Dry mouth, nausea, headache, insomnia, constipation, irritability
Decreases seizure threshold
Note: minimal weight gain and sexual side effects.
What metabolizes wellbutrin
Substat of CYP 2B6
Inhibits 2D6
On which receptores does vortioxetine (trintellix) work?
Inhibits SERT, 5HT3 and 5HT7
5HT1A agonist
Which receptor causes weight gain?
H1
As well as sedation
Whats the side effect of receptors targeting alpha1?
HTO and sedation
Most SERT inhibition among TCA?
Clomipramine
Good for OCD
TCA metabolism?
Tertiary amines converted in secondary amines.
Amytriptiline in nortriptyline
Imipramine in desipramine
Most TCA are metabolizedby 2D6
2D6 inhibitors?
Fluoxetine and paroxetine: 4x dose
Bupropion, duloxetin and high dose sertralinr: 2x dose
Receptors targetted by TCA?
SERT NET 5-HT2 H1 Alpha1 MAch Na-channeld
TCA overdose sx?
Cardiotoxic (ventricular arrhythmias, wideQRS, QTc prolongation, 1 degree AV block) and seizure from blockage of Na channels
Side effects of moclobemide
Insomnia, GI, irritability
Rareweight gain, uncommon sexual side effectd, activating
Switching from SSRI to MAOI, how long the pause in between?
5x half life of ssri
Switching MAOI to SSRI, hoe long the pause in between?
2weeks
What is the mechanism under tyramine hypertensice crisis?
Tyramine increases NE. Irréversible MAOI strops destruction of NE. Increase in NE leads to elevation of BP
Tyramine hypertensive crisis sx?
Diastolic superior 120; occipital headache, palpitations, neck stiffness, No, Vo, mydriase, sweat
Do not treat (nifedipine) without evidence of tyramine ingestion or end organ damage
Foods that contain tyramine to avoid when taking MAOI
Draft beer
Old cheese
Fermented veggies and old meat
Soy
Mechanism of serotonin syndrome
5-HT post synaptic receptors over stimulated by SERT blocked and MAO stopped
Usually within 6-8 hours of starting or increasing drug
Sx of serotonin toxicity
Clonus-tremor
Hyperreflexia
Autonomic instability:
Tachypnea
Tachycardia
Agitation
Hyperthermia
Diaphorese
Tx of serotonin syndrome
Cyproheptadine 12mg, then 2mg q2hrs
If cannot take PO, chlorpromazine 50-100mg IM
Rx to avoid with IMAO?
Ssri, snri, vilazodone, clomipramine, tramadol, methadone, fentanyl, ziprasidonr, dextromethorphan, Rx that can cause HTN
What are the theoritical benefits of blocking NET?
Beneficial for symptoms of loss of interest, loss of energy and psychomotor retardation
What are the theoritical benefits of blocking SERT
Most beneficial for negative affect sx such as guilt, irritability, dysphoria, SI and obsessions
