13- Antidepressants/Stimulants Flashcards
duloxetine (Cymbalta)
SNRI
- inhibit NET and SERT but structurally diff. from TCAs
- fewer off target s/fx (nausea, anxiety, insomnia; inc. BP, HR)
- may be used to treat patients refractory to SSRIs
- orally active but therapeutic effect required >2 weeks
- readily penetrate CNS (half-life 11-12 hrs)
- HIGH binding to plasma proteins (90-95%)
- metabolized by CYPs and eliminated in kidneys
venlafaxine (Effexor)
SNRI
- inhibit NET and SERT but structurally diff. from TCAs
- fewer off target s/fx (nausea, anxiety, insomnia; inc. BP, HR)
- may be used to treat patients refractory to SSRIs
- orally active but therapeutic effect required >2 weeks
- readily penetrate CNS (half-life 11-12 hrs)
- LOW binding to plasma proteins (27%)
- metabolized by CYPs and eliminated in kidneys
bupropion (Wellbutrin)
atypical antidepressant
- inhibits DAT thus preventing dopamine reuptake and inc. its levels in synapse
- efficacy similar to TCAs and SSRIs
- often used in combo with TCAs for ppl that don’t respond to single agent
- s/fx: headache, nausea, tinnitus, insomnia (safer then TCAs)
mirtazapine (Remeron)
atypical antidepressant
- inhibits a2 receptors thus inc. the release of serotonin and NE (eliminates feedback inhibition)
- efficacy similar to TCAs and SSRIs
- often used in combo with TCAs for ppl that don’t respond to single agent
- s/fx: headache, nausea, tinnitus, insomnia (safer then TCAs)
nefazodone (Serzone)
atypical antidepressant
- inhibits SERT thus preventing serotonin reuptake and blocks post-synaptic serotonin receptor sites
- efficacy similar to TCAs and SSRIs
- often used in combo with TCAs for ppl that don’t respond to single agent
- s/fx: headache, nausea, tinnitus, insomnia (safer then TCAs)
phenelzine (Nardil)
MAOI
-blocks MAOa on noradrenergic neurons, MAOa/b on dopaminergic neurons, and MAOa on serotonergic neurons
-orally active but therapeutic effect requires >2 weeks
-block MAO irreversibly (takes weeks to replace)
-most dangerous catagory of antidepressants d/t broad effects and severe/unpredictable s/fx
S/Fx: restless, agitation, psychosis, ortho, hypotension, tachycardia, serotonin syndrome, cheese effect (tyramine)
selegiline (Emsam)
MAOI
-blocks MAOa/b on dopaminergic neurons, and MAOa on serotonergic neurons
-orally active but therapeutic effect requires >2 weeks
-block MAO irreversibly (takes weeks to replace)
-most dangerous catagory of antidepressants d/t broad effects and severe/unpredictable s/fx
S/Fx: restless, agitation, psychosis, ortho, hypotension, tachycardia, serotonin syndrome, cheese effect (tyramine)
tranylcypromine (Parnate)
MAOI
-blocks MAOa on noradrenergic neurons, MAOa/b on dopaminergic neurons, and MAOa on serotonergic neurons
-orally active but therapeutic effect requires >2 weeks
-block MAO irreversibly (takes weeks to replace)
-most dangerous catagory of antidepressants d/t broad effects and severe/unpredictable s/fx
S/Fx: restless, agitation, psychosis, ortho, hypotension, tachycardia, serotonin syndrome, cheese effect (tyramine)
Monoamine Hypothesis
Depression caused by a deficiency in monamines, particularly serotonin and norepinephrine
Cheese Effect
In the presence of MAOIs elevated tyramine causes release of large amounts of catecholamines
- Patients taking MAOIs have a restricted diet
Brain Derived Neurotrophic Factor (BDNF)
-signaling factor that promotes formation of new neurons in the hippocampus
Psychomotor Stimulants
- drugs that increase vesicular and non-vesicular release of NE and DA
amitriptyline
TCA: NON-specific blockers of monoamine uptake
-therapeutic effect requires >2 weeks
-highly lipid soluble
-long 1/2 life
-high plasma protein binding
-metabolized by CYPs
side effects: Anti-muscarinic, othrostatic hypotension, SEDATION, weight gain, sexual dysfunction, seizures, and psychiatric
amoxapine
TCA: NON-specific blockers of monoamine uptake
-therapeutic effect requires >2 weeks
-highly lipid soluble
-long 1/2 life
-high plasma protein binding
-metabolized by CYPs
side effects: Anti-muscarinic, othrostatic hypotension, SEDATION, weight gain, sexual dysfunction, seizures, and psychiatric
imipramine
TCA: NON-specific blockers of monoamine uptake
-therapeutic effect requires >2 weeks
-highly lipid soluble
-long 1/2 life
-high plasma protein binding
-metabolized by CYPs
side effects: Anti-muscarinic, othrostatic hypotension, SEDATION, weight gain, sexual dysfunction, seizures, and psychiatric
nortriptyline
TCA: NON-specific blockers of monoamine uptake
-therapeutic effect requires >2 weeks
-highly lipid soluble
-long 1/2 life
-high plasma protein binding
-metabolized by CYPs
side effects: Anti-muscarinic, othrostatic hypotension, SEDATION, weight gain, sexual dysfunction, seizures, and psychiatric
citalopram
SSRI- Selective Serotonin Reuptake Inhibitor
-therapeutic effect requires > 2 weeks
-highly lipid soluble and plasma protein binding
- long 1/2 life
-high 1st pass metabolism (CYP)
-BLOCK several CYPs (drug interactions)
side effects: INSOMNIA, nausea, anxiety
late onset side effects- anorexia, sexual dysfunction, mania-bipolar
escitalopram
SSRI- Selective Serotonin Reuptake Inhibitor
-therapeutic effect requires > 2 weeks
-highly lipid soluble and plasma protein binding
- long 1/2 life
-high 1st pass metabolism (CYP)
-BLOCK several CYPs (drug interactions)
side effects: INSOMNIA, nausea, anxiety
late onset side effects- anorexia, sexual dysfunction, mania-bipolar
fluoxetine
SSRI-Selective Serotonin Reuptake Inhibitor
-therapeutic effect requires >2 weeks
-highly lipid soluble and plasma protein binding
-demethylated to active metabolite norfluxetine (1/2 life up to 30 days)
-block several CYPs (drug interactions)
early onset side effects- INSOMNIA, nausea, anxiety
late onset- anorexia, sexual dysfunction, mania-bipolar
sertraline
SSRI- Selective Serotonin Reuptake Inhibitor
-therapeutic effect requires > 2 weeks
-highly lipid soluble and plasma protein binding
- long 1/2 life
-high 1st pass metabolism (CYP)
-BLOCK several CYPs (drug interactions)
side effects: INSOMNIA, nausea, anxiety
late onset side effects- anorexia, sexual dysfunction, mania-bipolar
Lithium
Lithium Salt
-Tx ofBP D/O
-MOA unclear
-therapeutic effects take 3-4wks
-soluble ion; does not bind to Plasma proteins
-Ther level 0.6-1.4 mEq/L; toxic= 1.6-2 mEq/L
-S/E:
+CNS: tremors, confusion, convulsion, coma
+CV: arrhythmias; Thyroid: decrease function
+Renal: polydipsia, polyphagia, induced DI
+Drug interactions: NSAID and thiazides
amphetamine (Adderall)
Amphetamine, Psychostimulant
- Tx of ADHD and narcolepsy
- increased vesicular and non-vesicular monoamine release (NE and DA).
- inhibit NE and DA reuptake and reverse transports them back into synapse.
- metabolized in liver via de-esterification.
- S/E: euphoria, insomnia, vertigo, arrhythmias, HTN, NV, habit forming.
atomoxetine (Strattera)
Non-psychostimulant
- NE re-uptake inhibitor
- Tx of ADHD
- not habit forming
dextro-amphetamine (Dexedrine)
Amphetamine, Psychostimulant
- Tx of ADHD and narcolepsy
- increased vesicular and non-vesicular monoamine release (NE and DA).
- inhibit NE and DA reuptake and reverse transports them back into synapse.
- metabolized in liver via de-esterification.
- S/E: euphoria, insomnia, vertigo, arrhythmias, HTN, NV, habit forming.
methylphenidate (Ritalin)
Amphetamine, Psychostimulant
- Tx of ADHD and narcolepsy
- increased vesicular and non-vesicular monoamine release (NE and DA).
- inhibit NE and DA reuptake and reverse transports them back into synapse.
- metabolized in liver via de-esterification.
- S/E: euphoria, insomnia, vertigo, arrhythmias, HTN, NV, habit forming.
modafinil (Provigil)
- used to treat narcolepsy
- MOA not completely understood (likely involves NE and DA).
- fewer psychoactive and euphoric effects.
- fewer effects on mood and thinking.