antidepressant meds Flashcards
1
Q
First line tx of depression?
A
- SSRIs
- no real diff in efficacy
2
Q
List of SSRIs?
A
- prozac
- zoloft
- paxil
- celexa
- luvox
- lexapro
3
Q
SSRIs are used to tx what conditions?
A
- depression
- panic disorder
- OCD
- generalized anxiety disorder
- social anxiety disorder
- PTSD
- body dysmorphic disorder
- bulimia nervosa
- binge eating disorder
- premenstrual dysphoric disorder
- somatoform disorders
4
Q
Citalopram and escitalorpam similarities?
A
- isomers of eachother, same side effect profile
- less drug interactions b/c they inhibit less liver enzymes than other SSRIs
- good for pts who are already on mult. meds
5
Q
MOA of SSRIs?
A
- block presynaptic serotonin reuptake pump
- increases the time that serotonin is available in synapse
- increases postsynaptic occupancy - downregulate receptor sites
6
Q
SSRIs pharmacokinetics?
A
- well absorbed in GI tract
- reach peak plasma levels in 1-8 hrs
- bind to proteins that are then distributed throughout the body
- metabolism and elimination occur in the liver
- metabolites are inactive except for fluoxetine has an active metabolite
7
Q
What are the downstream effects of SSRIs?
A
- increased production of neuroprotective proteins such as brain-derived neurotrophic factor
- down-regulation of 5HT1A receptors ( when bound with serotonin inhibits neuron from releasing serotonin) so less inhibition = more firing and increased release of serotonin in presynaptic neuron
8
Q
Half lives of SSRIs?
A
- in general half life range: 20-30 hrs
- except fluoxetine (prozac) half life is up to 3 days and it’s active metabolite can last 4-16 days
- fluvoxamine’s (luvox) half life is about 15 hrs
9
Q
SSRIs inhibit what P450 enzymes? What happens when another drug is intro that also works at these enzyme sites?
A
- 2D6, 2C9, 2C19, 2B6, 3A4, 1A2
- diff ones in each SSRI
- citalopram and escitalopram don’t seem to be affected by these
- can have build up of other drugs and decreased metabolism or build up of SSRI - depends on which drug is the stronger inhibitor
10
Q
SSRI drug interactions - to use with caution?
A
- azole antifungals
- macrolide abx
- omeprazole
- hepatic impairment
- CI if taking MAOis w/in 2 weeks due to risk of serotonin sydrome
- paroxetine and fluoxetine are CI with tamoxifen - used to tx breast cancer
11
Q
SSRI side effects?
A
- sexual dysfxn (17%)
- drowsiness (17%)
- wt gain (12%)
- dizziness (11%)
- insomnia (11%)
- anxiety (11%)
- diaphoresis
- diarrhea
- hyperprolactinemia
- HA
- dry mouth
- blurred vision
- nausea
- rash or pruritus
- tremor
constipation - diarrhea
- SIADH
- hyponatremia
12
Q
Withdrawal syndrome if abrupt d/c of SSRIs?
A
- dyphoria
- dizziness
- GI distress
- fatigue
- chills
- myalgias
- more common with fluvoxamine and paroxetine (shorter half lives)
13
Q
Response time of SSRIs?
A
- some will feel better in a few weeks
- others 4-6 wks
14
Q
Admin. of SSRIs?
A
- usually once a day
- if it makes them sleepy - take at night
- if it causes insomnia - take in am
- warn of common SEs: HA, dizziness, nausea, diarrhea when first starting so they know that these are expected
15
Q
Duration of SSRI therapy?
A
- for many it is lifelong
- don’t stop it for 1 yr after resolution of sxs
- stopping med too early may cause recurrence of severe depressive episode
16
Q
When is citalopram (celexa) indicated? risks?
A
- 20-40 mg
- good to use when concerned about drug interactions (doesn’t hav P450 enzyme inhibition as strong as other SSRIs)
- risk of QT prolongation at doses over 40 mg, or in those on 20 mg and high risk for arrhythmia:
- hepatic impairment
- older than 60
on other Cyp219 inhibitors (cimetidine)
17
Q
Use of escitalopram (lexapro)?
A
- 10-20 mg
- isomer of citalopram
- similar to citalopram as has fewer drug interactions than others in the class
18
Q
Dosing, CI, pros of fluoxetine (prozac)?
A
- 90 mg delayed release capsule for weekly dosing - 20-40 mg daily
- CI with tamoxifen
- used to tx premenstrual dysphoric disorder
- more likely to cause activation than others - helps pts with low energy and motivation
- least problems with wt gain
19
Q
Dosing of fluvoxamine (luvox), SEs?
A
- 50-200 mg daily, 2x daily dosing if at 200 mg daily
- wt gain up to 2.6% of body wt
- **more likely to have nausea and sedation compared to most other SSRIs
20
Q
SEs and CI, dosing of paroxetine (paxil)?
A
- 20-40 mg daily
- Nausea and sedation more likely to occur than most others
- sig withdrawal sxs
- ***causes most wt gain among SSRIs (upt to 3.6% of baseline)
- CI in use with tamoxifen
21
Q
Sertraline (zoloft) dosing and most notorious SE?
A
- 50-200 mg daily
- Diarrhea
22
Q
Other more serious side effects of SSRIs?
A
- may increase risk of suicide as pt recovers (risk greatest in ages 18-24)
- may increase risk of abnorm bleeding - inhibit platelt fxn
- possible increase in bone fractures
- may affect male fertility: abnormal levels of DNA fragmentation in sperm were noted compared to baseline 50% vs 10%
23
Q
Common SNRIs? MOA? Indications?
A
- effexor
- cymbalta
- pristiq
- act on both serotonin and NE - leads to increased stimulation of post-synaptic receptors
- can use for tx of depression if intolerable side effects or poor response to first line SSRI therapy
- other uses;
panic disorder
generalized anxiety disorder
social anxiety disorder
OCD
PTSD
body dysmorphic disorder
diabetic periph. neuropathy
fibromyalgia
menopausal hot flashes
24
Q
Pharmacokinetics of SNRIs?
A
- food decreases rate of absorption but not degree of absorption - tell pt to eat and decrease rate and SEs - nausea
- desvenlafaxine (pristiq) and venlafaxine (effexor) don’t significantly inhibit P450 enzymes
- duloxetine moderately inhibits P450 enzymes so will have more drug interactions
25
Q
SNRI side effects?
A
- nausea*
- dizziness*
- diaphoresis*
- sexual dysfxn
- sedation
- agitation
- fatigue
- diarrhea
- constipation
- anorexia
- insomnia
- dry mouth
- orthostatic hypotension
26
Q
Most common SE of pristiq, dosing?
A
- 50-100 mg daily
- MC causes nausea
- monitor for elevation of blood pressure
27
Q
Cymbalta dosing, CI, avoid in what? Indications, SEs?
A
- 30-60 mg daily
- CI in uncontrolled angle closure glaucoma
- avoid in severe renal or liver impairment
- indicated for diabetic neuropathy and fibromyalgia
- **wt gain of 7% of baseline when tx with 80 mg
28
Q
Effexor dosing? SEs, adjustments?
A
- immed release: 75-375 mg daily (BID)
- extended releas: 75-225 mg daily (QD)
- essentially SSRI below (150 or 225 mg daily)
- may increase BP
- increased risk of upper GI bleed
- adjust dose in hepatic and renal impairment
- needs slow taper off of it to avoid withdrawal sxs
- can cause QT prolongation
29
Q
keypts of SNRIs?
A
- nausea occurs in 20%
- admin of food seems to help reduce nausea
- wt gain could be sig issue with duloxetine esp at higher doses
- sexual dysfxn occurs as frequently as SSRIs
- could elect to not taper up on starting dose
- watch BP
30
Q
TCAs diff amines?
A
- tertiary: amitryptyline,
clomipramine, doxepin, imipramine, trimipramine
more potent at blocking uptake of serotonin, more SEs - secondary: desipramine, nortriptyline, protriptyline
more potent at blocking uptake of NE
31
Q
When are TCAs usually avoided, when are they useful?
A
- usually avoided in tx of depression due to anticholinergic side effects
- highly sedating so often used for insomnia and for those with night time neuropathic pain or fibromyalgia
32
Q
MOA of TCAs?
A
- inhibit reuptake of serotonin and NE
- also block muscarinic, histamine, and alpha-adrenergic receptors
33
Q
Pharmacokinetics of TCAs?
A
- rapid and near complete absorption from small intestine
- 1st pass metabolism in the liver
- binds to proteins and only free protein is active
- elimination half life is about 24 hrs
- most have active metabolites
34
Q
Cardiac side effects of TCAs?
A
- heart block, ventricular arrhythmias, sudden death
- in pts over 40 need to screen for cardiac conduction system disease with EKG b/f initiation of therapy
35
Q
SEs of TCAs?
A
- lower seizure threshold
- increase in bone fractures
- block histamine receptors: causing sedation, increased appetite, confusion, delirium
- block acetylcholine receptors causing blurred vision, constipation, dry mouth, urinary retention
- very dangerous in overdose due to broad spectrum
36
Q
Why are TCAs not well tolerated in the elderly?
A
- orthostatic hypotension
- anticholinergic side effects
- heavily sedating
- cardiac side effects
37
Q
2 main MAOis used? Why are these not used very often?
A
- Nardil and Parnate
- drug-drug interactions: serotonin syndrome, hypertensive crisis, dietary restrictions: tyramine containing food - aged cheese
- poorly tolerated due to SEs
- leave prescribing these up to psychiatrists
38
Q
Use of trazodone? What is it? What to watch for?
A
- serotonin antagonist and reuptake inhibitor
- good for sleep at low doses
- if tolerated: fxns as antidepressant at higher doses
- watch for sedation, orthostasis, priapism
39
Q
Indications for bupropion (wellbutrin)? dosing? MOA?
A
- major depressive disorder
- ADHD
- smoking cessation
- IR 100-500 mg TID
- SR 12 hr 150-300 mg total daily dose
- XL 24 hr 150-300 mg once a day
- some inhibition of P450 2B6 pathway, inhibits reuptake of dopamine
40
Q
SEs and Caution in buproprion? Pros of bupropion?
A
- structurally related to amphetamines
- can cause anxiety
- lowers seizure threshold
- avoid in bulemia
- no withdrawal syndrome upon d/c
- preg Category C
pros:
mildly stimulating so good for pts with fatigue, hypersomnia or poor concentration - good for sleepy, slowed down pt - no sexual side effects or wt gain
- can be used as an add on to SSRIs for tx of sexual side effects (don’t use 1st line unless poor results with SSRis)
41
Q
MOA of mirtazapine (remeron)? SEs? Use?
A
- 15-45 mg
- blocks adrenergic receptors leading to increased release of NE and serotonin
- blocks serotonergic receptors and increases serotonin mediated neurotransmission
- high affinity for H1 receptors and low for cholinergic, alpha 1 adrenergic and dopaminergic receptors - going to have anticholinergic SEs (not as bad as TCAs) - sedation
- stimulates appetite - give to elderly pt who can’t sleep and needs to gain wt b/c they aren’t eating
- sedation: used off label for insomnia, more pronounced at doses of 15 mg vs higher dose
- wt gain: good for appetite stimulant
- good for pts with nausea
42
Q
What is Vilazodone (viibryd)? MOA?
A
- SSRI and 5-Ht1A receptor agonist
- appears to have same side effect profile of SSRIs (maybe less sexual SEs)
- 96-99% protein bound
- half life: 25 hrs
- spendy!
43
Q
What is vortioxetine (brintellix)?
A
- SSRI and %HT1A agonist, 5HT3 receptor antagonist - broader MOA - hitting 2 serotonin receptors and inhibiting serotonin reuptake
- same SE as SSRIs - less sexual SEs maybe
- CYP2D6 inhibitor
- half life: 66 hrs
- 98% protein bound
- spendy!
44
Q
What is serotonin syndrome?
A
- constellation of sxs caused by an excess of serotonin
- ranges in severity from mild to fatal
45
Q
Causes of serotonin syndrome?
A
- classically assoc with simultaneous admin of 2 serotonergic agents
- can occur after initiation of single serotonergic drug or increasing the dose
46
Q
What drugs can cause serotonin syndrome?
A
- psych meds: SSRIs, SNRIs, TCA, MAOIs, nefazadone, trazadone, buproprion, buspirone, lithium
- pain meds; pentaxcocine, meperidine (demerol), tramadol, fentanyl, cyclobenzprine
- migraine meds: triptans, ergots
- neuro meds: levodopa, carbidopa-levodopa, valproate, carbamezepine
- OTC: robitussin, St john’s wort
- antiemetics: zofran, kytril
- street drugs: cocaine, meth, ectasy, LSD
- ADHD: amphetamine derivatives, dextroamphetamine
- some wt loss drugs and metaclopramide (reglan) for gastric motility
47
Q
Time frame of serotonin syndrome?
A
- majority of cases of serotonin syndrome present within 24 hrs, and most within 6 hrs, of a change in dose or initiation of a drug
48
Q
Physical manifestations of serotonin syndrome?
A
- hyperthermia, agitation, ocular clonus
- tremor, akathisia, deep tendon hyperreflexia
- inducible or spontaneous clonus, muscle rigidity
- dilated pupils, dry mucus membranes
- increased bowel sounds, flushed skin, and diaphoresis
- neuromuscular findings are typically more pronounced in lower extremities
49
Q
HARM - serotonin syndrome?
A
- hyperthermia
- autonomic instability (delirium)
- rigidity
- myoclonus
50
Q
signs and sxs of serotonin syndrome?
A
- mental status change: anxiety agitated delirium restlessness disorientation
-classic: someone with fever, agitiated, pacing aroun, they don’t know where they are at
51
Q
Autonomic manifestations of serotonin syndrome?
A
- diaphoresis
- tachycardia
- hyperthermia
- HTN
- V/D
52
Q
Neuromuscular hyperactivity of serotonin syndrome?
A
- tremor
- muscle rigidity
- myoclonus
- hyperreflexia
- bilateral babinski sign
- hyperreflexia and clonus are common
- ankle clonus
- ocular clonus
53
Q
Hunter criteria for serotonin syndrome?
A
- has taken serotonergic agent plus 1:
- spontaneous clonus
- inducible clonus AND agitation or diaphoresis
- ocular clonus AND agitation or diaphoresis
- tremor and hyperreflexia
- hypertonia AND temp over 38 C and ocular clonus or inducible clonus
54
Q
Tx of serotonin syndrome?
A
- DC serotonergic agents
- sedate using benzodiazepines (lorazepam)
- supp O2
- IV fluids
- cardiac monitor
- if BZDs don’t improve agitation the antidote is cyproheptadine***
- if temp is above 41.1 C (105.98F) immed intubation and sedation
- avoid acetaminophen
55
Q
When does serotonin syndrome usually resolve? What drugs pose the greatest risk?
A
- within 24 hours of d/c serotonergic agent
- irreversible MAOIs carry greatest risk, and sxs can persist for several days
