7.4: Antidepressant Agents Flashcards
True or False:
Major depressive disorder is a depressed mood most of the time for at least 2 week or loss of interest or pleasure in most activities.
True
True or False:
Other characteristics of major depressive disorder are disturbance in sleep and appetite, deficits in cognition and energy, and thoughts of guilt, worthlessness, and suicide.
True
What are the 3 pathophysiology of major depression?
- Monoamine hypothesis
- Neurotrophic hypothesis
- Neuroendocrine factors
Determine what kind pathophysiology:
- Norepineprine (NE) and serotonin (5-HT)
- Functional decrease in the activity (depression)
- Functional increase in the activity (mood elevation)
Monoamine hypothesis
Determine what kind pathophysiology:
- Regulation of neural plasticity, resilience, and neurogenesis
- Exert its influence on neuronal survival and growth effects by activating tyrosine kinase receptor B in both neurons and glia
Neurotrophic hypothesis
Brain derived neurotrophic factor (BDNF)
Determine what kind pathophysiology:
It affects
1. Hippocampus
2. Anterior cingulate gyrus
3. Medial frontal cortex
Neurotrophic hypothesis
Determine what kind pathophysiology:
Adrenocorticotropic hormone
* Nonsuppression of adrenocorticotropic hormone (ACTH) release in the dexamethasone suppression test
* Dysregulation of the stress hormone axis
Neuroendocrine factors
Determine what kind pathophysiology:
- Thyroid hormone
- Thyroid dysregulation in depressed patients
- Blunting of response of thyrotropin to thyrotropin-releasing hormone, and elevations in circulating thyroxine during depressed states
Neuroendocrine factors
Determine what kind pathophysiology:
Sex steroids
* Estrogen deficiency states, which occur in the postpartum and postmenopausal periods, are thought to play a role in the etiology of depression in some women
* Severe testosterone deficiency in men is sometimes associated with depressive symptom
Neuroendocrine factors
What is the primary action of Selective Serotonin Reuptake Inhibitors (SSRIs)?
Inhibition of serotonin transporter (SERT)
What are the 6 major approved SSRIs?
- Fluoxetine
- Sertraline
- Citalopram
- Paroxetine
- Fluvoxamine
- Escitalopram
FluSerCiPFE !!! >:(
True or False:
The MOA of SSRIs is Serotonin transporter (SERT) is a glycoprotein with 12 transmembrane regions embedded in the axon terminal and cell body membranes of serotonergic neurons.
True
What are the other indications of SSRIs?
- Generalized Anxiety Disorder (GAD)
- Post-traumatic stress disorder (PTSD)
- Obsessive Complusive Disorder (OCD)
- Panic Disorder
- Premenstrual Dysphoric Disorder (PMDD) and Bulimia
What is the half-live of SSRIs?
18-24 hours
Identify the drug interactions of SSRIs:
- Interaction between fluoxetine and a MAOI
- Life-threatening
- Reason: Fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered
Serotonin syndrome
Identify the drug interaction of SSRIs:
- Severe muscle rigidity
- Myoclonus
- Hyperthermia
- Cardiovascular instability
- CNS stimulatory effects-seizures
Serotonin syndrome
What are the drugs included in Serotonin syndrome?
- MAOIs
- TCAs
- Meperidine
- MDMA (ecstasy)
In serotonin syndrome, what is the antidepressant drug that blocks the 5-HT receptors?
Cyproheptadine
What are the 3 antidepressants of SNRIs?
- Venlafaxine and Duloxetine
- Tricyclic Antidepressants
- 5HT2A Antagonists
Identify this antidepressant of SNRIs:
- Metabolized in the liver to Desvenlafaxine
- Lowest protein binding amongst all anti-depressant (27-30%)
- Similar half lives of 11 hours (once daily dosing)
- 45% are excreted unchanged in the urine
Venlafaxine
Identify this antidepressant of SNRIs:
- Well-absorbed
- Half-life: 12 hours
- Tightly bound to protein
Duloxetine
Identify this antidepressant of SNRIs:
- NET is structurally very similar to the 5-HT transporter
- 12-transmembrane domain complex that allosterically binds norepinephrine
- NET also has a moderate affinity for dopamine
Venlafaxine
True or False:
Venlafaxine is a strong inhibitor of NET.
False
Weak dapat.
True or False:
Desvenlafaxine, duloxetine, and milnacipran are more balanced inhibitors of both SERT and NET.
True
True or False:
Nonetheless, the affinity of most SNRIs tends to be much greater for SERT than for NET.
True