Lec 74 Antidepressants

Question 1

What are the classes of antidepressants?

Answer 1

• MAO inhibitors
• tricyclic antidepressants
• selective serotonin reuptake inhibitors
• antidepressants with multiple receptor targets

Question 2

What is therapeutic use of MAO inhibitors?

Answer 2

atypical depression
anxiety
hypochondriasis

treatment resistant depression/panic disorder/social anxiety disorder

Question 3

What is mech of action of MAO inhibitors?

Answer 3

• irreversibly inhibit degradation of MAOs in presynaptic terminals
• causes increase 5HT, NE, DA in presynaptic terminals and synaptic cleft

Question 4

What are substrates of MAO-A vs MAO-B?

Answer 4

MAO-A: 5HT, NE, DA

MAO-B: phenylethylamine, DA [NOT 5HT, NE]

Question 5

What is first aid mnemonic for MAO inhibitors?

Answer 5

MAO takes pride in shanghai

• MAO
• Tranylcypromine
• Phenelzine
• Isocarboxazid
• Selegiline

Question 6

What are the side effects of MAO inhibitors?

Answer 6

serotonin syndrome if combined w/ other 5HT drugs

hypertension if combined with tyramine diet or drugs that are adrenergic agonists

orthostatic hypotension, weight gain, insomnia, sexual dysfunction, rare hepatotoxicity [for phenelzine + iso]

Question 7

What are symptoms of serotonin syndrome?

Answer 7

symptoms: ab pain, diarrhea, sweating, tremor, hyperthermia, tachycardia, hypertension, myoclonus, irritability, delirium, death

Question 8

What causes serotonin syndrome?

Answer 8

selected drugs in combo with MAOI

• other antidepressants
• cyclobenzapine
• carbamazepine
• dextromethorphan
• opiaties: meperidine, fentanyl, methadone
• tramadol
• st johns wort
• SSRI

Question 9

What is a hypertensive crisis? symptoms?

Answer 9

defined by diastolic BP > 120

symptoms: headache, palpitations, stiff/sore neck, N/V, sweating, dilated pupils, photophobia

Question 10

What triggers hypertensive crisis? what drugs to avoid?

Answer 10

triggered by noradrenergic drug + MAO inhibitor

avoid

• decongestants
• stimulants [amphetamines]
• appetite suppressants
• antidepressants with NRI [TCAs, SNRIs, buproprion]

Question 11

What is a tyramine-induced hypertensive crisis?

Answer 11

• ingestion of tyramine-rich foods in presence of MAO-I can trigger hypertensive crisis
• tyramine is a catecholamine releasing agent
• intestinal wall MAO-A breaks down tyramine before absorption
• if tyramine gets access to NE sympathetic neurons –> will release NE; but don’t have to worry about it because MAO-A breaks down tyramine before it gets a chance

if you inhibit MAO-A –> can’t handle dietary tyramine, release NE and no MAO-A to destroy it –> increased BP

Question 12

What foods should you avoid on MAO-I?

Answer 12

avoid: soy, beer, red wine, aged cheese, dried sausage, fava beans, liver, smoked fish, sauerkraut

continue diet for 2 wks after stopping MAO-I to allow re-synthesis of MAO-A

Question 13

What is EMSAM?

Answer 13

selegiline transdermal path for treatment of depression

• at low levels selegiline inhibits MAO-B but at antidepressent level inhibits A and B
• goal to bypass GI tract and liver to minimize chance of hypertensive crisis if tyramine is ingested

dietary restriction at > 6mg/24 hr

Question 14

What kind of drug is phenelzine?

Answer 14

MAO inhibitor

Question 15

What kind of drug is tranylcypromine?

Answer 15

MAO inhibitor

Question 16

What kind of drug is selegiline?

Answer 16

MAO inhibitor –> selective for MAO-B at low doses; but acts on both at anti-depressant levels

Question 17

What is therapeutic use for tricyclic antidepressants?

Answer 17

• major depression
• OCD [clomipramine]
• fibromyalgia

depression + treatment resistant depression
childhood enuresis [imipramine]
generalized anxiety disorder
insomnia
obsessive compulsive disorder
migraine
cataplexy syndrome [imipramine]
fibromyalgia
prurits/dermatologic

Question 18

What is mech of action tricyclic antidepressants?

Answer 18

• block presynaptic reuptake of NE and 5HT
• secondary = NE only; tertiary = NE + 5HT
• causes NT accumulation in synaptic cleft

Question 19

What are side effects of TCAs?

Answer 19

sedation, weight gain [H1 block]

a1 blockade –> orthostatic hypotension, dizziness

atropine [anti-ACh] side effects: urinary retention, dry mouth, tachycardia

Question 20

What are side effects unique to despiramine?

Answer 20

• less sedating [H] but higher seizure incidence

- least alpha 1 blockade

Question 21

Do tertiary or secondary amines have more anticholinergic effects?

Answer 21

tertiary > secondary

Question 22

what are the Tri-C’s of tricyclic antidepressants?

Answer 22

TriC = convulsion, coma, cardiotoxicity [arrhythmias]

Question 23

Why should you use nortriptyline in elderly?

Answer 23

its a secondary amine = less anti-ACh effects

causes confusion and hallucination in elderly

Question 24

How do you treat tricyclic antidepressant cardio toxicity?

Answer 24

NaHCO3

Question 25

Which TCAs have least anticholinergic effects?

Answer 25

secondary amines [desipramine, nortriptyline]

Question 26

Which TCAs have most antihistamigeric effect?

Answer 26

doxepin

Question 27

Which TCAs have least alpha 1 blockade?

Answer 27

secondary amines [desipramine, nortriptyline]

Question 28

What happens in TCA overdose?

Answer 28

lethal

Question 29

Who should you avoid TCA in?

Answer 29

pts with narrow angle glaucoma, recent cardiac events, cardiac conduction delays, prolonged GTc

Question 30

Are tertiary or secondary amines beter in elderly?

Answer 30

secondary

Question 31

What is the phrase for anticholinergic toxicity?

Answer 31

``` red as a beet dry as a bone blind as a bat mad as a hatter hot as a hare full as a flask ```

Question 32

How are TCAs metabolized?

Answer 32

by cyp450 tertiary --> secondary 1/2 life 10-70 hrs

Question 33

What drug-drug interactions with TCAs?

Answer 33

- block effect of antihypertensives - additive tox with anti-arrhythmics/QTc prolonging agents, anticholinergics, CNS depressants, sympathomimetics - drugs that increase TCA level: cimetidine, fluoxetine, ritonavir - drugs that decrease TCA: carbamazepine, rifampin, phenytoin, nictonie, barbituates MAOIs: wait 14 days between MAOI and TCA

Question 34

What is dosing/monitoring of TCA?

Answer 34

- narrow therapeutic index - similar dose range and plasma levels for most - lower doses for pain - unclear value in monitoring drug levels

Question 35

What are uses for SSRIs?

Answer 35

- depression - generalized anxiety - panic disorder - PTSD - OCD - premenstrual dysphoric disorder - social phobias - bulimia

Question 36

What is mech of action SSRIs?

Answer 36

bind to serotonin transporter and inhibit reuptake of 5HT into presynaptic nerve terminals

Question 37

What is first aid mnemonic for SSRI names?

Answer 37

Flashbacks paralyze senior citizens - Fluoxetine - paroxetine - setraline - citalopraom

Question 38

Which SSRI has highest potency for DA?

Answer 38

setraline

Question 39

Which SSRIs have highest potency for NE?

Answer 39

fluvoxamine | paroxetine

Question 40

Which SSRIs are most selective for 5HT reuptake?

Answer 40

citalopram | fluoxetine

Question 41

What are common side effects of SSRIs?

Answer 41

``` GI distress sexual dysfunction (anorgasmia and decrease libido) weight gain tremor sweating ``` serotonin syndrome with any drug that increases 5HT [MAOI, SNRI, TCA] --> hyperthermia, confusion, myoclonus, flushing, diarrhea, seizures

Question 42

What is treatment for serotonin syndrome?

Answer 42

cyproheptadine = 5HT2 receptor antagonist

Question 43

What is metabolism of SSRI?

Answer 43

significant 1st pass | metabolized in liver by CYP enzymes

Question 44

Which SSRIs have less drug-drug interactions?

Answer 44

citalopram and escitalopram

Question 45

Which SSRIs have more drug drug interactions?

Answer 45

fluxoamine

Question 46

Which SSRI has longest half life and least withdrawal?

Answer 46

fluoxetine

Question 47

What are properties of fluoxetine?

Answer 47

- activating, may cause insomnia - long half life - least withdrawal symptoms - more drug-drug interactions than others

Question 48

What are properties of sertraline?

Answer 48

- activating | - mild DA reuptake inhibitor

Question 49

What are properties of paroxetine?

Answer 49

- short half life - withdrawal symptoms - control release form available - blocks NE reuptake, some anti-ACh activity, more sedation, dry mouth, weight gain

Question 50

What happens in SSRI withdrawal? treat?

Answer 50

- if abrupt discontinuation after >6 wks of treatment - dizziness, weakness, nausea, headache, anxiety, insomnia, paresthesias, flu-like symptoms, muscles aches usually resolves within 3 wks can treat with fluoxetine

Question 51

What are advantages of SSRIs over older agents?

Answer 51

standard dosing = easy to titrate often get clinical response at starting dose usually not lethal in overdose no arrhythmias/disturbance in BP/seizure/coma/resp depression fewer drug-drug interactions no special diet

Question 52

What is use of SNRIs?

Answer 52

- depression venlafaxine = also generalzie anxiety + panic disorders duloxetine = also diabetic peripheral neuropathy fibromyalgia, painful physical symptoms of depression, stress urinary incontinence, vasomotor symptoms

Question 53

What is mech of SNRIs?

Answer 53

at low dose < 150mg/day act as SSRI | at higher doses --> SNRI = inhibit 5HT and NE reuptake

Question 54

What are side effects of SNRIs?

Answer 54

increase BP [more in venlafaxine than duloxetine], stimulant effects, sedation, nausea

Question 55

What is unique about bupropion's side effects?

Answer 55

no sexual dysfunction or weight gain stimulant effects: tachycardia, insomnia; headache, seizure in bulimic pts

Question 56

What are side effects of mirtazapine?

Answer 56

Sedation [may be desirable in depressed pts with insomnia] increased appetite, weight gain [may be desirable in elderly or anorexic] dry mouth

Question 57

What is use of mirtazapine?

Answer 57

- depression - insomnia - appetite stimulation

Question 58

Which anti-depressant is known for its priapism effects?

Answer 58

trazodone

Question 59

What causes the therapeutic delay in onset of antidepressant action?

Answer 59

downregulation of serotonergic receptors may enhance neruonal regeneration process + restore cortical dendrites

Question 60

Which type of antidepressants best for co-morbid pain disorders?

Answer 60

SNRI