AntiDepressants & Stimulants Flashcards
biogenic or monoamines
serotonin & norepinephrine
Monoamine hypothesis of depression
-In depressed patients: decreased levels of the NE metabolice, MHPG, & others
-altered expression of adrenergic receptors (less NE, up regulate receptors)
CSF has reduced serotonin (elevated serotonin receptors)
-neuronal loss in prefrontal cortex and hippocampus
drugs that ____ brain amine stores may _____________
deplete, cause or worsen depression. ex: reserpine
Tricyclic Antidepressants MOA
- nonspecific blockers of monoamine uptake by blocking NET and SERT (usually SERT > NET)
- therapeutic effect requires 2 weeks
- highly lipid soluble, penetrates CNS
- long 1/2 life (10-40 hours)
- high binding to plasma PRO (90-95%)
TCA side effects
1) antimuscarinic effects: blurred vision, dry mouth, constipation, urinary retention, aggravation of glaucoma and epilepsy
2) CV: tachycardia, slowing of the AV conductance
3) orthostatic hypotension (blockade of alpha 1 adrenergic receptors)
4) sedation (blockage of histamine receptors)
5) metabolic-endocrine: weight gain (antihistamine), sexual dysfunction
6) seizures
7) delirium in the elderly (antimuscarinic), aggravation of psychosis, induction of mania in patients with bipolar disorder
SSRI MOA
-block SERT (some block NET v. mildly)
-therapeutic effect requires > 2 weeks
highly lipid soluble, readily penetrates CNS
long half life (1-3 days)
(fluoxetine demethylated to active metabolite norfluoxetine 1/2 30 days)
high binding to plasma PRO (70-90%)
high 2st pass metabolism (CYP)
Blocks several CYPs
SSRI drug interactions
Blocks CYP2D6, CYP1A2, CYP3A4
TCAs, neuroleptic drugs (haloperidol), some antiarrhythmics, some B adrenergics
SSRI SE
early: nausea, anxiety, insomnia
late: anorexia, sexual dysfunction, mania
SNRI MOA
-used to rx patients refractory to SSRI
-inhibit NET and SERT, structurally unrelated to TCA
-orally active
-therapeutic effect requires > 2 weeks
-lipid soluble, readily penetrates CNS
-shorter 1/2 life : 11-12 hours
duloxetine exhibits high binding to plasma PRO (90-95%) whereas venlafaxine has low binding (27%)
metabolized by CYPs
eliminated by kidneys
TCA names
amitriptyline
nortriptyline
imipramine
amoxapine
SSRI names
fluoxetine
citaopram
escitalopram
sertaline
SNRI names
velafaxine
duloxetine
SNRI SE
nausea, anxiety, insomnia, sexual dysfunction, increased BP and HR (SE level b/t SSRI and TCA)
mirtazapine MOA
blocks alpha 2 receptors (increases NE release), enters synapse and causes NE release
buproprion MOA
inhibits dopamine transporter
nefazodone
inhibits SERT and receptor, which may relate to gluamate release in pre-frontal cortex
atypical antidepressants SE
h/a, nausea, tinnitis, insomnia, nervousness
-safer than TCA
phenelzine/tranlcypromine MOA
-inhibit (permanently) MAO A on NE synapse
-inhibit (perm) MAO A/B on Dopa synapse
-inhib (perm) MAO A on serotonin synapse
orally active
-therapeutic effect requires > 2 weeks
selegiline MOA
- inhib (perm) MAO A/B on dopa synapse
- inhib (perm) MAO A on serotonin synapse
- therapeutic effect requires > 2 weeks
- transdermal patch
MAOI SE
severe and unpredictable
-CNS (restlessness, agitation, psychoses)
CV: orthostatic hypotension and tachycardia
serotonin syndrome
cheese effect
MAOI cheese effect
tyramine (found in cheese, liver, ETOH) is naturally occuring monoamine, metabolized by MAO
in the presence of MAOI, elevated tyramine causes release of large amounts of catecholamines (h/a, tachycardia, HTN, seizures, stroke)
lithium salts MOA
unclear
-blocks hydrolysis of inositol phosphate to free inositol, prevents formation of phosphatidylinositol required for many signaling p-ways
blocks GSK-3B kinase, increases b-catenin translocation to the nucleus/gene transcription and glycogen synthesis
inhibits 5-HT1A and 1B receptors, dampens serotonin signals
-enhances glutamate uptake
therapuetic effect: 3-4 weeks
-rapidly absorbed in GI tract
-soluble ion (no plasma PRO binding)
-peak plasma level by 2-4 hours, 1/2 life 20-40 hr
eliminated by kidneys (toxic levels lead to reduced kidney function)
Li salts often combined with _____ in rx of bipolar d/o
antidepressants (fluoxetine and olanzapine) , neuroleptics (risperidone, olanzapine, quetapine) , and anticonvulsants (valproic acid, carbamazepine, lamotrigine)
LI salt SE
Low TI therapeutic 0.5-1.4 mEq/L; toxic: 1.6-2 mEq/L
-CNS: tremors, mental confusion, convulsions, and coma (Li can sub for Na+)
-CV: arrhythmias
-Thyroid: decreased function
-renal: polydipsia, polyuria, increased DI
teratogenic effects
drug interactions: thiazide diuretics and NSAIDS
amphetamines MOA
- MAO inhibitor
- enters via transporter and increases vesicular and non-vesicular release of NE and dopa
- absorbed by GI tract
- psychomotor stimulants
- metabolized in liver by de-esterification
amphetamines names
amphetamine
dextroamphetamine
methylphenidate
amphetamines SE
CNS: euphoria, anxiety, vertigo, insomnia, confusion, paranoia, psychoses, suicidal/homicidal impulses
CV: arrhythmia, HTN
GI: N/D
potential for addition
