Antidepressant Drugs Flashcards
1
Q
- What is the Monoamine Theory of Depression?
- What is this theory based on?
A
- Monoamine theory depression results from functionally deficient monoamine (NE and/or 5-HT) transmission in the CNS
- Based on pharmacological evidence of the ability of known antidepressant drugs (TCAs and MAO inhibitors) to facilitate monaminergic transmission of drugs, such as reserpine, that depletes amines to cause depression
2
Q
Describe neurotransmitter localization in the brain:
- Locus coeruleus:
- Raphe nuclei:
- Substantia nigra & Ventral tegmental area of the midbrain:
- Basal Forebrain Complex:
A
- **Locus coeruleus: **
- Neurons contain: norepinephrine
- Innervate nearly every part of the CNS
-
Raphe nuclei:
- Neurons contain: serotonin
- Projection: most of the brain
-
Substantia nigra & Ventral tegmental area of the midbrain:
- Neurons contain: dopamine
- Projection:
- striatum ⇒ substantia nigra
- Ventral tegmental area of the midbrain ⇒ prefrontal cortex and parts of the limbic system
- **Basal Forebrain Complex: **
- Septal nuclei and nucleus basalis
- Neurons contain: ACh
- Projection: hippocampus, neocortex
3
Q
What is the mechanism of action of TCAs?
A
Increases NE and 5-HT in the synapse (block reuptake)
4
Q
What is the mechanism of action for SSRIs?
A
Inhibits serotonin-specific reuptake
5
Q
What is the mechanism of action for drugs like phenelzine?
A
Nonselectively inhibits MAO, which increases levels of amine neurotransmitters
6
Q
SSRIs:
- Drugs
- Clinical Use
- Side Effects
- Toxicity
A
-
Drugs
- Fluoxetine, paroxetine, sertraline, citalopram
-
Clinical Use
- Depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social phobias, PTSD
-
Side Effects
- nausea, insomnia, sexual dysfunction
-
Toxicity
- Serotonin Syndrome, no food reactions
*FDA warning: Neuroleptic malignant syndrome
7
Q
When do symptoms of SSRI withdrawal manifest?
A
Symtoms begin 1 - 7 days following SSRI stoppage
8
Q
List the symptoms of SSRI withdrawal (15):
A
- dizziness,
- light-headedness
- vertigo or feeling faint
- shock-like sensations
- paresthesia
- anxiety
- diarrhea
- fatigue
- gait instability
- headache
- insomnia
- irritability
- nausea or vomiting
- tremor
- visual disturbances
9
Q
SSRI approved uses:
A
- Major Depression
- Obsessive-Compulsive disorder
- Panic disorder
- Social Anxiety Disorder
- PTSD
- Generalized Anxiety disorder
- PMS –Now PDD (Premenstrual Dysphoric Disorder)
- Hot flashes associated with menopause
10
Q
What are the commonly prescribed SSRIs and their clinical use?
A
-
Fluoxetine (Prozac®)
- Effects on drug metabolism
- Long half-life active metabolite - 7 days or more
- Sustained release product - PMS
-
Sertraline (Zoloft®)
- Similar in action to fluoxetine with less effects on drug metabolism
- Shorter half-life
- OCD, PTSD, Panic attacks
-
Paroxetine (Paxil®)
- also approved for hot flashes associated with menopause
-
Fluvoxamine (Luvox®)
- approved for OCD
- Citalopram (Celexa®) and Escitalopram (Lexapro®)
11
Q
- What is the mechanism of action of SNRIs?
- How does the side effect profile compare to SSRIs?
A
- Drugs block both 5-HT and NE reuptake
- Side effect profile is more SSRI-like than TCA-Like
12
Q
What are the commonly prescribed SNRIs and their clincial use?
A
-
Duloxetine (Cymbalta®)
- Major Depressive Disorder and anxiety
- Also approved for neuropathic pain syndromes, fibromyalgia, back pain and osteoarthritis pain
- Use with caution in patients with liver disease
-
Venlafaxine (Effexor®)
- Major Depressive Disorder and anxiety
-
Milnacipran (Savella®)
- approved for fibromyalgia
- also levomilnacipran (Fetzima®) which is approved for major depressive disorder
13
Q
What is the definition of an atypical antidepressant?
A
- Drugs without typical tricyclic structure or SSRI or SNRI action
- May or may not block catecholamine uptake
14
Q
List the Atypical Antidepressants (5):
A
- Bupropion (Wellbutrin® and Zyban®)
- Mirtazapine (Remeron®)
- Trazodone (Oleptro®)
- Vilazodone (Viibryd®)
- Vortioxetine (Brintellix®)
15
Q
What are the differences between the atypical antidepressants?
A
-
Bupropion (Wellbutrin® and Zyban®)
- Weakly blocks NE and dopamine uptake
- also approved for nicotine withdrawal and seasonal affective disorder
- No weight gain or sexual dysfunction
-
Mirtazapine (Remeron®)
- Blocks presynaptic α2 receptors in brain
- Increases appetite
- Used for AIDS patients
-
Trazodone (Oleptro®)
- Weak SSRI-like effect
- Sedating (used for insomnia)
- Low incidence of cardiovascular side effects
- Can cause priapism
-
Vilazodone (Viibryd®)
- serotonin uptake inhibitor and also a partial agonist of the 5-HT1A receptor
- recently approved antidepressant
-
Vortioxetine (Brintellix®)
- newest drug approved to treat MDD
- Has a SSRI-like action in addition to 5-HT1A agonist and 5-HT3 antagonist activity
16
Q
TCAs:
Pharmacologic Properties and Side Effects
A
22
Q
How do MAOIs affect the metabolism of tyramine?
A
- Due to MAO inhibtion in the liver, tyramine metabolism is also inhibited
- Leads to increased levels of tyramine
