Pharm: Antidepressants

Front 1

List Sx of major depressive disorder.

Back 1

Guilt, thoughts of death, loss of libido, insomnia, fatigue, wt. loss, apathy, feelings of hopelessness, worthlessness, anhedonia

Front 2

How are anti-depressants selected? 2) typical response? 3) how long until therapeutic response seen?

Back 2

1) Based on adverse effects. 2) variable individual responses. 3) Can take weeks.

Front 3

List 6 indications for antidepressants and if applicable a goto drug for them.

Back 3

1) Major unipolar depression. 2) Bipolar depression -> Lithium. 3) Anxiety disorder -> SSRI. 4) Chronic pain -> SSRI or SNRI. 5) Neuropathic pain -> SNRI. 6) Smoking cessation -> bupropion

Front 4

What gives support to the biogenic amine hypothesis of depression? What are 3 descrepancies?

Back 4

Reserpine depletes NE and 5HT -> Causes a depression. Additionally TCA, MAOI, and SSRI enhance NE & 5HT. 1) Cocaine is not antiDP. 2) no consistent change in levels of NE/5HT of depressed pts. 3) Effects of MAOI and ECT are immediate but their effect on depression is delayed for days-weeks !!!

Front 5

List 3 mechanisms of antiDP action.

Back 5

1) reduction/block of beta2 receptors, decrease in cAMP. 2) desensitization and reduction/block of prejunctional 5HT and NE (alpha2) receptors. 3) increased neural plasticity and neurogenesis (BDNF)!!

Front 6

Major therapeutic indication for TCAs? 2) name 5 TCAs. 3) 2 of which turn into 2 others how?

Back 6

1) Major depression. 2) Amitriptyline -> Nortriptyline. Imipramine -> Desipramine. Amoxapine. 3) demethylation of aliphatic side chain.

Front 7

What is unique about amoxapine?

Back 7

metabolite blocks DA receptors -> hyperprolactinemia, EPS/TD

Front 8

TCA MOA

Back 8

Blocks reuptake of catecholamines by specific transporters into prejunctional nerve

Front 9

TCA solubility? Halflife? Metabolization? Plasma levels?

Back 9

1) very lipid soluble. 2) long halflife. 3) metabolized by ring hydroxylation and glucuronide conjugation. 4) plasma levels used for compliance and toxicity.

Front 10

How are many TCA adverse effects accounted for?

Back 10

Antagonistic activity at alpha adrenergic and H1 receptors.

Front 11

6 CNS side effects of TCA?

Back 11

1) sedation from antagonist activity at H1-R. 2) confustion/memory dysfxn from anticholinergic property of TCA. 3) mania. 4) seizures -> TCA lowers threshold and tonic-clonic occurs. 5) tremor from sympathomimetic of TCA - can be managed with propranolol. 6) Movement d/o of TD/EPS

Front 12

TCA CV side effects (3):

Back 12

Sinus tachycardia, prolonged conduction time, arrhythmia

Front 13

TCA ANS side effects (3):

Back 13

1) Postural hypotension - alpha1 antagonist activity. 2) dry mouth, blurred vision, constipation, difficulty urinating from anticholinergic. 3) Can precipitate narrow-angle glaucoma, paralytic ileus, or urine retention.

Front 14

TCA grab bag of 'other' side effects 5:

Back 14

1) wt. gain - H1 antagonistic activity. 2) sex dysfxn - alpha1 antagonistic activity. 3) "switch reaction" - depression -> bipolar. 4) suicide in adolescents. 5) rebound effects

Front 15

Triad of TCA overdose? 2) what would be two drugs that would be useful?

Back 15

1) arrhythmias, seizures, respiratory depression. 2) antiarrhythmic -> phenytoin. Anticonvulsant -> phenytoin or BZ

Front 16

Drug interactions with TCA (5, don't worry about inc/dec metab):

Back 16

1) drugs that depress CNS - sedative-hypnotics. 2) drugs w/ anticholinergic activity (antihistamines). 3) TCAs block antihypertensive agents like clonidine. 4) MAOI: serotonin syndrome -> severe agitation, hyperthermia, seizures, coma

Front 17

What drugs dec TCA levels?

Back 17

Drugs that induce liver enzymes (CYP2DG) -> anticonvulsants like phenytoin, carbamazepine, chronic alcohol

Front 18

What drugs inc TCA levels?

Back 18

Drugs that interfere with microsomal enzymes -> aspirin, cimetidine, thiazide diuretics, SSRI (fluoxetine), acute ethanol, oral contraceptives

Front 19

Uses for SSRI (3)

Back 19

First choice for depression. Anxiety d/o. Chronic pain.

Front 20

SSRI MOA

Back 20

inhibits uptake of serotonin

Front 21

SSRI advantages (5)

Back 21

1) minimal sedation. 2) minimal hypotension. 3) minimal muscarinic anatagonistic activity. 4) less likely to do "switch" reaction. 5) NO cardiotoxicity or lethality w/ overdose

Front 22

Adverse effects of SSRIs (8)

Back 22

1) HA. 2) N/V heartburn GI stuff. 3) wt loss then wt. gain. 4) sexual dysfxn. 5) mild anxiety. 6) insomnia. 7) apathy. 8) rarely seizures

Front 23

SSRI drug interactions:

Back 23

Serotonin syndrome: agitation, sweating, diarrhear, fever, hyperreflexia, myoclonus, hyperpyrexia, convulsions, death (think about adding this with MAOI)

Front 24

SSRI rebound Sx:

Back 24

nausea, irritability, mood swings, flu-like Sx

Front 25

Fluoxetine: 1) halflife. 2) metabolite. 3) Other drug interaction? 4) Specificity?

Back 25

1) long half-life. 2) active metabolite, norflluoxetine. 3) inhibits liver enzymes CYP2D6. 4) least specific SSRI

Front 26

Order of halflife for Fluoxetine, Paroxetine, Sertraline? Implication?

Back 26

Paroxetine < Sertraline < Fluoxetine halflives, which means Paroxetine has the worst rebound syndrome…...

Front 27

Trazadone / Nefazodone MA? Overdose?

Back 27

Blocks 5HT-2 postjuntional receptors. Has no muscarinic activity so no anticholinergic side effects. 2) Safer than TCA in overdose

Front 28

Trazadone / Nefazodone side effects (5)? 2) A distinguishing feature of Nefazodone?

Back 28

1) Highly sedating. 2) drowsiness and dizziness. 3) N/V. 4) hypotension. 5) Can cause priaprism. 6) Nefazodone is more moderate but can have rare liver failure (inhibits CYP3A4)

Front 29

Bupropion: MOA? 2) Purpose?

Back 29

Blocks NE and DA reuptake. 2) smoking cessation

Front 30

Bupropion side effects in relation to: 1) sedation. 2) cholinergic. 3) hypotension. 4) stimulation. 5) seizures

Back 30

1-3) Less sedative, anticholinergic, and hypotensive side effects. 4) Stimulation (agitation and insomnia) rather than sedation. 5) More likely to cause seizures.

Front 31

What is St. John's Wort? 2) What does it do?

Back 31

1) Herbal remedy for mild depression. 2) interferes with metabolism for many drugs

Front 32

Amoxapine blocks what? 2) 3 side effects?

Back 32

Blocks DA and NE activity. 2) hyperprolactinemia, TD, EPS

Front 33

What does maprotiline do? 2) side effects?

Back 33

1) Blocks NE reuptake. 2) highly sedating and seizures

Front 34

Mirtazapine blocks what? 2)Causes what? 3) Any specificity?

Back 34

1) Prejunctional alpha2 receptors. 2) Causes inc NE and 5HT transmission. 3) only 5HT1 receptors are activated since it blocks 5HT2 and 5HT3 which leads to less side effects leaving only sedation and wt. gain

Front 35

Clomipramine MOA? Use?

Back 35

Specific for inhibiting 5-HT uptake. 2) OCD

Front 36

Phenelzine is a what? 2) Other drug in this class? 3) used for? 4) Inactivated by?

Back 36

MAO Inhibitor. 2) Tranylcypromine. 3) Atypical depression or pts who respond poorly to SSRI or TCA. 4) inactivated by acetylation -> prolonged activity in slow metabolizers

Front 37

Phenelzine MOA? 2) halflife 3) How long until therapeutic effect?

Back 37

1) Blocks activity of MAO-A and MAO-B -> so dec metabolism of NE, 5HT, DA, and tyramine. 2) short plasma half life, but b/c it is a suicide inhibitor it has a long biological halflife. 3) month +- a week

Front 38

Phenelzine adverse effects (7):

Back 38

1) substantial excitation. 2) HA. 3) dry mouth. 4) sexual dysfxn. 5) wt. gain. 6) mild hypotension. 7) insomnia

Front 39

Phenelzine drug interactions (4):

Back 39

1) Indirectly acting sympathomimetic amines (tyramine). 2) directly acting sympathomimetic agents. Consider how a potentiating pressor effect could have N/V, tachycardia, HT. 3) SSRI, TCA, and opiods particularly meperidine. 4) drugs with CNS depressant activity.

Front 40

Venlafaxine and Duloxetine: 1) MOA. 2) Two uses. 3) Side effects.

Back 40

1) Blocks 5HT and NE reuptake. 2) Major depression and neuropathic pain (duloxetine is specific for diabetic peripheral neuropathy). 3) seizues, inc BP, inc HR

Front 41

Lithium use? 2) Therapeutic effect seen? 3) Limited by?

Back 41

1) Acute or prophylactice Tx of mania or bipolar disorder. 2) seen in 2-3 weeks. 3) limited by adverse side effects and compliance issues.

Front 42

3 drugs used for mania or bipolar disorder?

Back 42

Lithium, carbamazepine, valpriod acid

Front 43

What 2 things does Lithium inhibit to cause what?

Back 43

1) noncompetively inhibits inositol monophosphate (rate limiting enzyme for inositol). This affects phospholipid pathways and ultimately reduces hormone stimulated phospholipid turnover. 2) inhibits inositol polyphosphate 1-phosphatase. Together these limit PIP2 hydrolysis (Phospholipase C) to DAG and IP3

Front 44

Lithium efficacy and effects related to what? 2) Two kidney factoids related to elimination. 3) TI

Back 44

1) closely related to level in blood. 2) 80% passively reaborbed in PT and elimination unchanged by the kidney. 3) LOW TI

Front 45

Lithium drug interactions (3):

Back 45

1) Na depletion increases Li blood levels. 2) diuretics decrease Li renal clearance. 3) NSAIDs dec renal clearance like indomethacin, phenylbutazone

Front 46

Lithium adverse effects: 1) common at what therapeutic range? 2) GI. 3) CNS. 4) Kidney

Back 46

1) 0.5-0.9. 2) N/V/D. 3) tremor, lethargy, confustion/impaired concentration. 4) polyuria, polydipsia, inc water intake

Front 47

Lithium adverse effects: 5) wt. 6) skin. 7) thyroid. 8) Pregnancy

Back 47

5) wt. gain. 6) rashes. 7) thyoid enlargement -> hypothyroidism. 8) fetal malformations (Ebstein's!) and can be transported through mother's milk.

Front 48

Lithium toxicity above what? 5 side effects?

Back 48

> 2.5. 1) arrhythmias. 2) clonic movements. 3) circulatory collapase. 4) coma/death. 5) seizuires

Front 49

Lithium Tx?

Back 49

discontinue administration, anticonvulsants, diureteic, infusion of sodium fluids, hemodialysis