Antidepressants Flashcards
(54 cards)
Symptoms of Depression
Depressed mood Loss of interest/pleasure Weight/appetite issues insomnia/hypersomnia psychomotor probs fatigue worthlessness/guilt poor concentration Thoughts of death/suicide
Monoamine Hypothesis: Depression is related to a loss of function or amount of monoamine neurotransmitters: ___, ___, ____
norepinephrine, dopamine and serotonin.
inadequate theory
All of the currently used antidepressant drugs involve….
elevating monoamine levels or modulation of monoamine receptors.
Neurotropic Hypothesis:
This theory states that depression is associated with a loss of ____, especially ____.
trophic factors
brain-derived neurotrophic factor (BNDF).
Neurotropic Hypothesis: The reduction or loss of trophic factors causes ____ in regions of the brain involved in affective behavior
A decrease in the number of synapses
Hormone/neurohormone theory: Depression is associated with several abnormalities in ____, especially _____
hormonal regulation
especially hormones in the hypothalamus-pituitary axis
Catecholamines
Dopamine, NE, Epi
____ is the primary mechanism of elimination for the catecholamines. There are two transporters for the catecholamines. One transports ____ and the other ___.
Reuptake
dopamine (DAT)
norepinephrine and epinephrine (NET).
Monoamine Oxidase metabolizes ___ and indolamines that are not protected by storage in synaptic vesicles.
intracellular catecholamines
There are two isoenzymes of MAO: ___ and ___
MAO-A and MAO-B
MAO-A is found in ____
MAO-B is found in ____
MAO-A is found in brain areas containing catecholamines and in the liver
MAO-B is found in brain areas containing serotonin neurons, platelets, lymphocytes and liver.
Catechol-O-methyltransferase (COMT): can metabolize ___.
COMT located in the liver is the major site for metabolizing ___
extracellular catecholamines.
catecholamines released by the adrenal gland.
Serotonin: Reuptake into neurons – The ____ is the major pathway for elimination from synaptic cleft.
The presynaptic serotonin transporter (SERT)
Serotonin Receptors
14 different serotonin receptors: 5-HT1 - 5-HT7
All are ___ except ….
All are G-protein coupled receptors except 5-HT3 (ligand-gated channel)
Serotonin Autoreceptors: Activation of ____ inhibits the firing of the serotonin neuron.
Activation of the 5-HT1B and 5-HT1D receptors (presynaptc nerve terminals) inhibits ____ from the nerve terminal.
5-HT1A receptors
serotonin release
SSRIs do not have ___ and are the _____
significant side effects of the older classes
most commonly used antidepressants.
The SSRIs bind to an allosteric site on the ____ and inhibit the reuptake of serotonin into the _____
synaptic serotonin transporter (SERT)
presynaptic nerve terminal.
SSRIs: At therapeutic doses approximately 60-80% of ____ is inhibited.
The inhibition of reuptake occurs ____, but full therapeutic effects do not appear ____.
Antidepressant effects are probably not directly due to ___
5-HT Reuptake
immediately, 3-8 weeks later
the elevation of synaptic serotonin levels.
SSRIs have low affinity for the NET and DAT and little to no affinity for the H1, alpha1-adrenergic, muscarinic receptors, and cardiac Na channels and thus do not produce:
sedation, orthostatic hypotension, anticholinergic or arrhythmic side effects.
SSRI Side Effects 1. 2. 3. 4. 5. 6.
- Sexual (50% of patients of both sexes) d/t stimulation of 5-HT2 receptors
- GI probs early on that resolve
- Drowsiness, weight gain
- Discontinuation Syndrome
- Paroxetine and CV malformations (teratogenic)
- Serotonin Syndrome
Serotonin Syndrome
may occur when administered with ____. Symptoms of the Serotonin syndrome include:
MAOIs.
hyperthermia, muscle rigidity, myoclonus, tremors, autonomic instability, confusion, irritability and agitation.
Fluoxetine (Prozac)
SSRI
long duration of action (t1/2= 53 hr)
SERT Inhibitor
active metabolite (norfluoxtine).
1/week formulation is available.
Paroxetine (Paxil)
SSRI
SERT Inhibitor
warning about suicidal potential in teens,
t1/2 = 17 hr.
may cause weight gain.
Teratogenic
Sertraline (Zoloft)
SSRI
t1/2 = 23 hr
SERT Inhibitor
active metabolites
