Antidepressants 1 Flashcards
What is the hypothesis of mood?
Major depressive disorders result from a functional deficiency of NE, 5-HT, and dopamine at synapses in the CNS
What 3 neurotransmitter defiiencies is thought to cause major depressive disorders?
NE
5-HT
Dopamine
T/F: All classes of antidepressants appear to enhance the synaptic availability of 5-HT, norepinephrine, or dopamine
TRUE
T/F: Attempts to develop antidepressants that work on other neurotransmitter systems have been effective to date.
FALSE
Attempts to develop antidepressants that work on other neurotransmitter systems have NOT been effective to date.
Changes in what 2 components appear to play a major role in the development of major depression?
BDNF
hormones
What is considered successful tx of depression?
a change in BDNF and hormones
NTs carry ______ between cells.
messages
These bind to a specific receptor, and this coupling initiates a cascade of events.
NTs
These are reabsorbed back ininto nerve cells by reuptake pumps (transporter molecules) at which point they may be recycled for later use or broken down by enzymes
NTs
MOA for which drugs?
inhibit the transporter molecules and allow more NT to remain in the synapse
antidepressants
Which dz?
associated with changes in serotonin or norepinephrine signaling in the brain (or both) with significant downstream effects (lesser-dopamine)
Depression
Most antidepressants cause changes in _____ signaling.
Most antidepressants cause changes in amine signaling.
What neuroendocrine factors are associated with more severe forms of depression?
Abnormal HPA axis
Elevated cortisol levels
Thyroid dysregulation
Estrogen/testosterone deficiency
Trytophan deficient diet
How do elevated cortisol levels contribute to major depression?
lead to dysregulation of the stress hormone axis
Why would a tryptophan deficient diet cause major depression?
tryptophan is a precursor of serotonin synthesis
What are the 3 phases of tx in MDD?
acute phase
continuation phase
maintenance phase
lasts 6 to 12 wks in which the goal is remission (absence of symptoms)
Which phase of MDD tx?
acute
lasts 4 to 9 mos after remission is achieved, in which the goal is to eliminate residual symptoms or prevent relapse (ie, return of symptoms within 6 months of remission)
Which phase of MDD is this?
Continuation Phase
lasts at least 12 to 36 mos in which the goal is to prevent recurrence (a separate episode of depression)
Which phase of MDD is this?
Maintenance Phase
Which acne tx is associated with drug-induced depressive sx?
isotretinoin
Which anticonvulsants are associated with drug-incuced depressive sx?
Levetiracetam
Topiramate
Vigabatrin
“Leave it To Viagara”
Which antimigraine tx is associated with drug-induced depressive sx?
triptans
Which CV tx are associated with drug-induced depressive sx?
Beta blocker
Clonidine
Methyldopa
reserpine
“The beta fish cloni takes meth with the serpent”
Which hormonal therapies are associated with drug-induced depressive sx?
Gonadotropin-releasing hormone
Oral contraceptives
Steroids (prednisone)
Tamoxifen
Which immunologic agents are associated with drug-induced depressive sx?
Interferons
Which smoking cessation drug is associated with drug-induced depressive sx?
Varenicline
What are the 6 antidepressant pharmacotherapy options?
Tricyclic antidepressants
MAO inhibitors
SSRIs
SNRIs (5-HT-NE)
5-HT₂
Heterocyclic antidepressants
The hypothesis that major depressive disorders result from a functional deficiency of norepinephrine or serotonin at synapses in the CNS
Which hypothesis?
Amine hypothesis of mood
Structurally related drugs that block reuptake transporters of both norepinephrine (NE) and serotonin (5-HT)
Which drug?
tricyclic
Drugs that selectively inhibit serotonin (5-HT) transporters with only modest effects on other neurotransmitters
Which drug?
SSRIs
Heterocyclic drugs that block NE and 5-HT transporters, but lack the alpha blocking, anticholinergic and antihistaminic actions of TCAs
Which drug?
SNRIs
Structurally related drugs that block this subgroup of serotonin receptors with only minor effects on amine transporters
5-HT2 receptor antagonists
Term used for antidepressants of varying chemical structures, the characteristics of which do not strictly conform to any specific designations
Heterocyclics
What are the 4 PK of antidepressants?
Fairly rapid oral absorption
Achieve peak plasma levels within 2-3 hours
Tightly bound to plasma proteins
Undergoes hepatic metabolism
Renally cleared
What are the 5 main antidepressant indications?
Major depressive disorder (MDD)
Panic disorder
Generalized anxiety disorder (GAD)
Post traumatic stress disorder (PTSD)
Obsessive-compulsive disorder (OCD)
Other A-depressant indications
Neuropathic pain
Pain associated with fibromyalgia
Premenstrual dysphoric disorder (PMDD)
Mitigates vasomotor symptoms of menopause
Stress incontinence
What 6 conditions would you use TCAs for?
MDD (backup)
chronic pain
OCD
Pain conditions
Enuresis (urinary inconintence)
insomnia
What are the names of the 4 tricyclic antidepressants?
imipramine
desipramine
doxepin
nortriptyline
What TCA would you use for OCD?
clomipramine
Toxicities of which drug?
α block
Muscarinic block
sedation, weight gain
Overdose: arrhythmias, seizures
TCAs
Drug interaction if you take TCAs with ethanol or sedative hypnotics?
increased CNS depression
Drugs inhibiting monoamine oxidases that metabolize norepinephrine and serotonin (MAO type A) and dopamine (MAO type B)
Which drug?
MAOI
What are the 4 indications for MAOI?
MDD unresponsive to other agents
Anxiety
panic disorder
Selegiline-Parkinson’s disease: Amphetamine-like metabolites
What are the 3 MAOIs we should know?
Phenelzine
Tranylcypromine
Selegiline
Which MAOI is more active against MAO-B?
selegiline
What is the clinical application for MAOIs?
Major depression unresponsive to other drugs
PK & drug interactions of which drug?
HTN with tyramine and sympathomimetics
Serotonin syndrome with SSRIs
Very long half-lives
MAOI
What are the toxicities of MAOIs?
Hypotension
insomnia
What foods should pts taking MAOIs avoid?
anything with tyramine content:
dairy products
alcohol
canned meats
yeast products
chocolate
coffee
