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
SNRI side effects?
- nausea*
- dizziness*
- diaphoresis*
- sexual dysfxn
- sedation
- agitation
- fatigue
- diarrhea
- constipation
- anorexia
- insomnia
- dry mouth
- orthostatic hypotension
26
Most common SE of pristiq, dosing?
- 50-100 mg daily
- MC causes nausea
- monitor for elevation of blood pressure
27
Cymbalta dosing, CI, avoid in what? Indications, SEs?
- 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
Effexor dosing? SEs, adjustments?
- 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
keypts of SNRIs?
- 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
TCAs diff amines?
- 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
When are TCAs usually avoided, when are they useful?
- 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
MOA of TCAs?
- inhibit reuptake of serotonin and NE
| - also block muscarinic, histamine, and alpha-adrenergic receptors
33
Pharmacokinetics of TCAs?
- 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
Cardiac side effects of TCAs?
- 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
SEs of TCAs?
- 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
Why are TCAs not well tolerated in the elderly?
- orthostatic hypotension
- anticholinergic side effects
- heavily sedating
- cardiac side effects
37
2 main MAOis used? Why are these not used very often?
- 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
Use of trazodone? What is it? What to watch for?
- 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
Indications for bupropion (wellbutrin)? dosing? MOA?
- 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
SEs and Caution in buproprion? Pros of bupropion?
- 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
MOA of mirtazapine (remeron)? SEs? Use?
- 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
What is Vilazodone (viibryd)? MOA?
- 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
What is vortioxetine (brintellix)?
- 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
What is serotonin syndrome?
- constellation of sxs caused by an excess of serotonin
| - ranges in severity from mild to fatal
45
Causes of serotonin syndrome?
- classically assoc with simultaneous admin of 2 serotonergic agents
- can occur after initiation of single serotonergic drug or increasing the dose
46
What drugs can cause serotonin syndrome?
- 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
Time frame of serotonin syndrome?
- 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
Physical manifestations of serotonin syndrome?
- 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
HARM - serotonin syndrome?
- hyperthermia
- autonomic instability (delirium)
- rigidity
- myoclonus
50
signs and sxs of serotonin syndrome?
```
- mental status change:
anxiety
agitated delirium
restlessness
disorientation
```
-classic: someone with fever, agitiated, pacing aroun, they don't know where they are at
51
Autonomic manifestations of serotonin syndrome?
- diaphoresis
- tachycardia
- hyperthermia
- HTN
- V/D
52
Neuromuscular hyperactivity of serotonin syndrome?
- tremor
- muscle rigidity
- myoclonus
- hyperreflexia
- bilateral babinski sign
- hyperreflexia and clonus are common
- ankle clonus
- ocular clonus
53
Hunter criteria for serotonin syndrome?
- 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
Tx of serotonin syndrome?
1. DC serotonergic agents
2. sedate using benzodiazepines (lorazepam)
3. supp O2
4. IV fluids
5. cardiac monitor
6. 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
When does serotonin syndrome usually resolve? What drugs pose the greatest risk?
- within 24 hours of d/c serotonergic agent
| - irreversible MAOIs carry greatest risk, and sxs can persist for several days
