AntiDepressants & Stimulants

Question 1

biogenic or monoamines

Answer 1

serotonin & norepinephrine

Question 2

Monoamine hypothesis of depression

Answer 2

-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

Question 3

drugs that ____ brain amine stores may _____________

Answer 3

deplete, cause or worsen depression. ex: reserpine

Question 4

Tricyclic Antidepressants MOA

Answer 4

• 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%)

Question 5

TCA side effects

Answer 5

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

Question 6

SSRI MOA

Answer 6

-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

Question 7

SSRI drug interactions

Answer 7

Blocks CYP2D6, CYP1A2, CYP3A4

TCAs, neuroleptic drugs (haloperidol), some antiarrhythmics, some B adrenergics

Question 8

SSRI SE

Answer 8

early: nausea, anxiety, insomnia
late: anorexia, sexual dysfunction, mania

Question 9

SNRI MOA

Answer 9

-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

Question 10

TCA names

Answer 10

amitriptyline
nortriptyline
imipramine
amoxapine

Question 11

SSRI names

Answer 11

fluoxetine
citaopram
escitalopram
sertaline

Question 12

SNRI names

Answer 12

velafaxine

duloxetine

Question 13

SNRI SE

Answer 13

nausea, anxiety, insomnia, sexual dysfunction, increased BP and HR (SE level b/t SSRI and TCA)

Question 14

mirtazapine MOA

Answer 14

blocks alpha 2 receptors (increases NE release), enters synapse and causes NE release

Question 15

buproprion MOA

Answer 15

inhibits dopamine transporter

Question 16

nefazodone

Answer 16

inhibits SERT and receptor, which may relate to gluamate release in pre-frontal cortex

Question 17

atypical antidepressants SE

Answer 17

h/a, nausea, tinnitis, insomnia, nervousness

-safer than TCA

Question 18

phenelzine/tranlcypromine MOA

Answer 18

-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

Question 19

selegiline MOA

Answer 19

• inhib (perm) MAO A/B on dopa synapse
• inhib (perm) MAO A on serotonin synapse
• therapeutic effect requires > 2 weeks
• transdermal patch

Question 20

MAOI SE

Answer 20

severe and unpredictable
-CNS (restlessness, agitation, psychoses)
CV: orthostatic hypotension and tachycardia
serotonin syndrome
cheese effect

Question 21

MAOI cheese effect

Answer 21

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)

Question 22

lithium salts MOA

Answer 22

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)

Question 23

Li salts often combined with _____ in rx of bipolar d/o

Answer 23

antidepressants (fluoxetine and olanzapine) , neuroleptics (risperidone, olanzapine, quetapine) , and anticonvulsants (valproic acid, carbamazepine, lamotrigine)

Question 24

LI salt SE

Answer 24

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

Question 25

amphetamines MOA

Answer 25

• 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

Question 26

amphetamines names

Answer 26

amphetamine
dextroamphetamine
methylphenidate

Question 27

amphetamines SE

Answer 27

CNS: euphoria, anxiety, vertigo, insomnia, confusion, paranoia, psychoses, suicidal/homicidal impulses
CV: arrhythmia, HTN
GI: N/D
potential for addition