Term
Theraputic effects are delayed due to: |
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Definition
the time required for 5HT1A autoreceptors to downregulate/desensitize. |
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Term
Side Effects Appear When: |
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Definition
As soon as postsynaptic receptors (especially 5HT2) are activated by the increase in 5HT caused by antagonism of transporter Dissipate when postsynaptic receptors have downregulated or desensitized |
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Term
Acute/excessive activation 5-HT2A/2C in amygdala, VMPFC |
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Definition
can lead to mental agitation, anxiety, panic |
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Term
Acute/excessive activation 5HT2A in basal ganglia |
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Definition
leads to decreased DA and akathisia, psychomotor retardation, mild parkinsonism, dystonia |
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Term
Acute/excessive activation 5HT2C in mesolimbic pathway |
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Definition
lead to decreased DA and apathy, anhedonia, and decreased libido |
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Term
Acute/excessive activation 5HT2C/2A in VTA & locus coeruleus |
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Definition
lead to decreased DA & NE, respectively, in prefrontal cortex and deficits in attention, cognition |
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Term
Acute/excessive activation 5HT2A in brainstem sleep areas |
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Definition
lead to nocturnal myoclonus (perhaps by disinhibition of cholinergic neurons), disruption of slow-wave sleep, awakenings |
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Term
Acute/excessive activation 5HT3 in hypothalamus, area postrema |
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Definition
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Term
Acute/excessive activation 5HT2A/2C in lower spinal cord |
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Definition
lead to delayed organism, anorgasmia |
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Term
Acute/excessive activation 5HT3/4 in GI |
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Definition
lead to motility (cramps, diarrhea) |
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Term
Increased activation of 5-HT1A receptors |
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Definition
lead to decreased negative affect (dysphoria, rumination, guilt/disgust, worthlessness, loneliness, fear/anxiety, irritability, hostility, suicidality) |
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Term
Noradrenergic ascending system |
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Definition
soma of neurons located in locus coeruleus & projecting widely to cortex, cerebellum |
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Term
From locus coeruleus to Prefrontal cortex |
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Definition
regulates mood, attention |
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Term
From locus coeruleus to Limbic cortex |
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Definition
regulates emotions as well as energy, fatigue, psychomotor agitation/retardation |
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Term
From locus coeruleus to Cerebellum |
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Definition
Inhibits pain regulates motor movements, especially tremor |
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Term
From NE neurons in lower brainstem to spinal cord |
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Definition
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Term
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Definition
binds NE on NE neuron On dendrites/soma, inhibits firing leads to decreased release of NE On terminal, inhibits release of NE |
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Term
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Definition
binds NE on 5-HT terminal Inhibits release of 5-HT |
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Term
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Definition
binds NE on soma/dendrites of 5-HT neuron (in raphe nuclei) Facilitates firing leading to increased release of 5-HT |
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Term
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Definition
decrease in “positive affect” and increase in “negative affect” |
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Term
Antagonizing NE re-uptake |
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Definition
increase positive affect and decreasing negative affect |
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Term
serotonin norepinephrine reuptake inhibitors |
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Definition
Somewhat more activating because of NE May be more likely to induce mania in bipolar pts If NE is increased, activation is not usually excessive due to blunting by 5-HT. -also increases DA in prefrontal cortex. -Good for very severe depression or highly recurrent depression, which don’t respond well to SSRI’s |
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Term
Why does NRI also increases DA in prefrontal cortex |
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Definition
DA in PFC normally taken up by NE reuptake mechanisms |
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Term
norepinephrine dopamine reuptake inhibitor |
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Definition
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Term
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Definition
Used when increased activation/stimulation is advantageous to treat “reduced positive affect” Switch to or augment w/ buproprion when SSRI or SNRI fails to treat these sx’s or causes them |
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Term
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Definition
restlessness, anxiety, tremor, insomnia, psychosis, generalized seizures (very rare w/ extended-release forms), panic in susceptible pts, switch to mania. |
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Term
Drugs that have Alpha 2 antagonism properties |
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Definition
antidepressant, anxiolytic effects. |
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Term
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Definition
decreases dopamine (reward center) and thus SSRI's decrease libido, and Martazapine corrects because it antagonizes this receptor |
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Term
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Definition
Effective for decreasing anxiety Often used for insomnia Sleep induction (at doses lower than 15 mg due to H1 antagonism) Restorative sleep due to 5HT2A antagonism Wt gain is common. Such wt gain may be beneficial for elderly, pts w/ wasting diseases or pts w/ anorexia. |
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Term
SARIs (serotonin 2A antagonist/reuptake inhibitors |
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Definition
Know this line: Used mainly for sleep (at low dose) Very sedating (blocks H1, 1 receptors) Hypnosis is main use due to small antidepressant effect at tolerable doses. Used as adjunct to antidepressants by blocking some SEs associated w/ stimulation of 5HT2A receptors (anxiety, agitation, insomnia, sexual dysfunction) Orthostasis and dizziness are common; priapism may rarely occur. trazodone and nefazodone |
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Term
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Definition
Inhibit reuptake of 5HT & NE to varying degrees, depending on exact drug Currently used to augment newer AD’s or for pain Demonstrated efficacy in adults but not in youth No abuse potential (no effect on DA) Antagonism of voltage-gated Na+ channels leading to seizures, coma, arrhythmia, death in overdose. Antagonism of numerous receptors (M1, H1, alpha1) causes many side effects (SEs). |
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Term
Tricyclics (TCA) half-lives |
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Definition
Long, 22-95 hours, Especially critical for elderly (cognitive impairment, falls, constipation, urinary retention) |
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Term
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Definition
metabolizes 5-HT, DA, NE, EP |
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Term
MAOI’s (monoamine oxidase inhibitors) |
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Definition
Considered “gold standard” of drugs for MDD Can decrease “negative affect” and increase “positive affect” Can cause hypertensive crisis & fatal strokes (the “cheese effect”) if taken with foods that contain tyramine Tyramine potently releases NE. |
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Term
MAO inhibitors are used when |
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Definition
Other ADs or combinations have failed Atypical depression, depression in the elderly, dysthymia, panic disorder, phobia, anorexia nervosa, bulimia, or hypochondriasis |
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Term
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Definition
With a drug that can cause serotonin syndrome If pt has cardiovascular or cerebrovascular disease, pheochromocytoma, frequent or severe headaches, or will have elective surgery requiring general anesthesia |
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Term
When switching to of from a MAOI |
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Definition
Must wait for 5 weeks after D/C of a serotonergic drug before initiating MAOI. Must wait for 2 weeks after D/C of MAOI before initiating another antidepressant. |
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Term
SPAs (5-HT1A partial agonists) |
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Definition
property have antidepressant & anxiolytic effects. Ex: buspirone (BuSpar)and vilazodone (Viibryd®) |
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Term
SEs of TCAs and antidepressants in general: |
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Definition
Vary w/ drug, patient, DDI’s Most usually occur early (within 2 wks) and then dissipate to various degrees. |
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Term
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Definition
Nausea Anxiety/activation Sleep disturbance Akathisia (restlessness) Sexual dysfunction Least likely w/ bupropion (Wellbutrin®) |
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Term
Catecholaminergic (DA, NE) |
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Definition
Activation Sympathomimetic (jacked up Sympathetic nervous system) |
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Term
One of the general ADs SEs: behavioral activation (irritability, hypomanic sx’s) |
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Definition
Primarily due to 5-HT2 (Increased Glu activity) May occur within hrs of starting or increasing dose; usually gone in 10 days. May signal switching to mania in bipolar Usually during first 2-3 wks, but as late as 2 months later Can increase suicidality/suicide risk |
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Term
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Definition
Risk of increased suicidality in pts < 24 yrs of age on ADs: All AD’s have black box warning. Sometimes, vegetative sxs (appetite, sleep, energy) improve before mood sxs. Highest risk for completed suicides with increased energy but still depressed One study indicated highest risk in first 9 days |
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Term
Greatest risk of suicidality |
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Definition
First 9 days (Pt's getting more energy and motivation to actually follow through with ideation) |
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Term
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Definition
Worsening of depression Gradual cognitive & affect blunting Occurs w/ most AD’s Seizure risk (all AD’s lower seizure threshold) Hypertension Most seen w/ Effexor Allergies Most common sx’s are hives/rash Orthostasis (blocking alpha1 receptor) Rare w/ newer generation AD’s Mainly w/ trazodone |
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Term
Hypertensive crisis when MAOI’s added to |
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Definition
Drugs that stimulate alpha1 postsynaptic vascular receptors, such as the decongestants (phenylephrine & pseudoephedrine) Stimulants (amphetamines, methylphenidate) |
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Term
MAO’s added to: ADD’s with NRI NRI’s SNRI’s NDRI’s TCA’s |
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Definition
DDI’s more common & can be more lethal than MAOI’s-tyramine |
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Term
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Definition
Confusion, psychosis, fever, sweating, diarrhea, restlessness, agitation, hyper-reflexia, tremor/myoclonus, migraines, seizures, brain damage, coma, death |
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Term
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Definition
60% of pts; within several days, persisting 3-4 wks “FINISH” sxs |
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Term
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Definition
Flulike sxs (lethargy, myalgias, chills, headache) Insomnia (including vivid dreams) Nausea (nausea, vomiting, diarrhea) Imbalance (dizziness, vertigo, ataxia) Sensory sxs (paresthesia sensation of electric shocks in limbs or head) Hyperarousal (anxiety, agitation) Hyperactivity, depersonalization, dysphoria, cognitive dysfunction may occur. |
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Term
Antihistaminic (blocking H1 receptor) |
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Definition
Sedation Especially w/ Luvox, Remeron (at doses lower than 15 mg), trazodone (at lower doses of 25-50 mg) Weight gain Especially w/ Remeron Wellbutrin is only one that does not. |
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Term
All SSRI’s except citalopram (Celexa®) and escitalopram (Lexapro®) |
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Definition
inhibit all 4 major families of isoenzymes. |
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Term
Choosing an Antidepressant (KNOW) |
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Definition
diagnose properly and go beyond dxs and treat sxs & problems of that unique person |
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Term
Most common reason for lack of response |
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Definition
-Inadequate standard treatment -Other reeasons: permanent neurologic impairment, naddressed psychological issues, and toxic living environment |
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Term
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Definition
Improve adherence if necessary Psychotherapy can be invaluable Check DDIs, including drug abuse Increase Dose Increase Time |
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Term
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Definition
2nd antidepressant from a different class Add NDRI or 5-HT1A partial agonist to SSRI T3 (Cytomel) or T4 (e.g., Synthroid) lithium Other agents as sxs require Psychotherapy may: Increase or prolong therapeutic effects Decrease probability of relapse or recurrence If no remission, try Remeron + Effexor = “California rocket fuel” or MAOI |
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