CHAPTER 10: ANTIDEPRESSANTS- SSRIs & SNRIs

Question 1

what is depression? 2 types of symptoms

Answer 1

emotional symptoms: intense sadness, hopelessness, despair, low self esteem, indecisiveness, loss energy, guilt

biological symptoms: retardation of thought and action, loss libido, change in sleep pattern/appetite

Question 2

mania

Answer 2

enthusiasm, rapid thought and speech patterns, extreme self confidence, impaired judgement

Question 3

biogenic amine theory of depression

Answer 3

depression results from deficiency of biogenic amines (NE, DA, 5-HT)
- in key areas of brain that regulate arousal, alertness, attention, moods, sensory

Question 4

3 known reasons of developing biogenic amine depression

Answer 4

• MAO break the neurotransmitters down to be recycled/restored
• rapid fire of neurons lead to their depletion (less neurotransmitters inside=biosynth can’t catch up)
• # or sensitivity of postsynaptic receptors may increase, depleting neuro levels

Question 5

serotonin neurotransmission

Question 6

SSRIs: Selective Serotonin Reuptake Inhibitors
- MOA
- drugs

Answer 6

• block reuptake of 5HT by SERT, no effect on NE
• selective action, little adverse effects

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

Question 7

SSRIs: actions

Answer 7

inhibit CNS reuptake serotonin
- little effect on NE, little affinity for cholinergic, histaminic, alpha adrenergic sites

Question 8

SSRIs: Indications

Answer 8

• Depression
• OCD
• panic attacks
• bulimia
• PMDD
• PTSD
• social phobias
• social anxiety

Question 9

SSRIs: how long to see effect

Answer 9

take at least 2 weeks to see improvement in mood
- max benefit= 12 weeks or more

• accumulate in lipid drafts, may take longer to see effect

Question 10

SSRIs: pharmacokinetics

Answer 10

• absorbed from GI
• half life 16-26 hrs
• fluoxetine 50 hrs
• metabolize in liver
• FLUOXETINE and PAROXETINE are potent inhibitors of CYP450 isoenzyme
• inhibit enzymes degrading them, less metab of these drugs=longer half life

Question 11

SSRIs: contraindications

Answer 11

known allergy, pregnancy, lactations, impaired renal/hepatic function, suicidal patients

Question 12

SSRIs: adverse effects

Answer 12

Sleep disturbances
- paroxetine & fluvoxamine for sedating
-fluoxetine or sertraline for PTs who are fatigued

sexual dysfunctions
- bupropion or mirtazapine (atypical)

Question 13

SSRIs: adverse effects contd.

Answer 13

in children/teens
- 1/50 become suicidal

discontinuation syndrome
- headache, malaise, flu-like symp, agitation, irritability, nervousness, change in sleep
-short half life/inactive metabolite drugs cause this

Question 14

SSRIs: drug to drug interactions

Answer 14

• serotonin syndrome w MAOIs: act on diff pathways, inhibiting reuptake AND metabolism is too much opposite effects
• TCAs inc of therapeutic and toxic effect
• serotonin syndrome in SSRI taken w/ drugs that inc 5-HT levels
• inc risk of bleeding taken w NSAIDS and anticoagulants

Question 15

SNRIs: Serotonin Norepinephrine Reuptake Inhibitors
- drugs
- effect

Answer 15

-venlafaxine, desvenlafaxine, levomilnacipran, duloxetine
- treat depression and neuropathic pain when SSRI is ineffective
-littleactivity at alpha adrenerg, muscarinic, or histaminic
- less side effect that TCA, more than SSRIs

Question 16

SNRIs: venlafaxine vs duloxetine

Answer 16

-ven potent inhibitor of 5-HT, inhibits NE at HIGH doses but dulox works at all doses
- ven has minimal CYP450 inhibition, dulox is extensively metabolized
- ven half life is 11hrs, dulox 12 hrs and food delays absorption

Question 17

SNRIs: venlafaxine vs duloxetine ADVERSE EFFECTS

Answer 17

ven: nausea, dizzy, insomnia, sedation, constipation
HIGH dose= inc BP and HR

dulox: nausea, dry mouth, constipation, insomnia, dizzy, somnolence/drowsiness, sweating, sexual dysfunc

Question 18

SNRIs: drug to drug interactions

Answer 18

DULOXETINE
- moderate inhib of CYP2D6 izosymes
- may inc conc of drug metabolized by this pathway such as antipsychotics