SNRIs, MAOIs, thyroid hormones, and novel agents Flashcards
what are the three most commonly used SNRIs
duloxetine
venlafaxine
sdesvenlafaxine
Brand name of milnacipran
Savella
Band name of levomilnacipran
fetzima
Name all 5 SNRIs
Duloxetine
venlafaxine
desvenlafaxine
milnacipran
levomilnacipran
brand name of duloxetine
cymbalta
brand name for venlafaxine
effexor
brand name for desvenlafaxine
pristiq
which SNRIs cause increased sweating
duloxetine
venlafaxine
dosage range for duloxetine
30-120mg daily in 1-2 doses
FDA approved uses for duloxetine
MDD
peripheral neuropathy
fibromyalgia
GAD
musculoskeletal pain
geriatric considerations for duloxetine
lower doses
labs to monitor with duloxetine
BP
LFTs
baseline creatinine
pregnancy risk of duloxetine
low
which SNRIs must be tapered to dc
duloxetine
venlafaxine
desvenlafaxine
what conditions would cause you to avoid duloxetine
angle-closure glaucoma
heavy alcohol use
severe renal/hepatic impairment
which SNRI decreases the effectiveness of narcotic pain medications
duloxetine
interaction between duloxetine and THC
THC decreases concentration of duloxetine
which SNRIs increase bleeding risk when taken with NSAIDs, ASA, or anticoagulants
duloxetine
venlafaxine
dosage range for ER venlafaxine
37.5-225 qd
what considerations are there with dosing IR venlafaxine
divided in 2-3 doses
max is 375mg
FDA approved uses for venlafaxine
depression
GAD
social phobia
panic disorder
geriatric considerations with venlafaxine
lower doses
caution with cardiovascular disease
labs to monitor for venlafaxine
baseline creatinine
pregnancy risk for venlafaxine
low
when would you avoid venlafaxine
angle-closure glaucoma
venlafaxine dosage with renal/hepatic impairment
decrease by 50%
dose related side effects of venlafaxine
increased BP and HR
dosage range for desvenlafaxine
50-100mg qd
FDA-approved uses for desvenlafaxine
MDD
Which geriatric conditions should you be cautious with desvenlafaxine
caution with CV disease, HTN, liver/renal failure, glaucoma
labs to monitor for desvenlafaxine
baseline creatinine
pregnancy risk of desvenlafaxine
low
desvenlafaxine effect on UDS
false positive for PCP and amphetamines
contraindications for desvenlafaxine
angle-closure glaucoma
MAOIs
ETOH abuse
CNS depressants
desvenlafaxine dosage adjustment for renal impairment
50mg qd for moderate
50mg qod for severe
desvenlafaxine dosage adjustment for hepatic impairment
max 100mg qd
FDA approved indications for venlafaxine
MDD
GAD
social anxiety
panic disorder
FDA approved indications for desvenlafaxine
MDD
off-label indications for venlafaxine
OCD
ADHD
panic disorder
depression w/ cocaine addiction
chronic pain
most common SE of venlafaxine and desvenlafaxine
nausea
do venlafaxine and desvenlafaxine have anticholinergic side effects?
side effects that are suggestive but these medications have no affinity for muscarinic or nicotinic receptors
are venlafaxine and desvenlafaxine associated with discontinuation syndrome
yes
CYP enzyme that primarily metabolizes venlafaxine and desvenlafaxine
CYP2D6
initial dose of venlafaxine
75mg
may begin at 37.5mg x4-7 days to reduce GI side effects
how often can you increase venlafaxine and by how much
75mg q4 days
upper limit and max dosage of venlafaxine
225mg and 375mg
are dosages of venlafaxine typically higher or lower when used for anxiety
lower
duloxetine and food
delays max concentration by 6-10 hours and reduces absorption by 10%
which hepatic enzymes metabolize duloxetine
CYP2D6
CYP1A2
excretion of duloxetine
70% as metabolites in urine
20% in feces
duloxetine and blood glucose
risk for DM with long-term use d/t elevated glucose and A1C
why should you avoid duloxetine in patients with alcohol abuse
increased risk of hepatic impairment
contraindications for duloxetine
hepatic insufficiency
ESRD
uncontrolled narrow-angle glaucoma
is duloxetine associated with discontinuation syndrome
yes
duloxetine in pregnancy
not recommended
recommended therapeutic dose of duloxetine
60mg (also max dose)
what is milnacipran approved for in the US
only fibromyalgia
FDA approved indications for levomilnacipran
MDD
does levomilnacipran have greater potency for norepinephrine or serotonin
norepinephrine
6 available MAOIs
phenelzine
isocarboxazid
tranylcypromine
rasagiline
moclobemide
selegiline
MAOA primarily metabolizes which neurotransmitters
NE, serotonin, and epinephrine
which MAO enzymes metabolize dopamine and tyramine
MAOA and MAOB
for which indications are MAOIs more effective than TCAs
-atypical depression
-bipolar depression
switching from one MAOI to another
taper and dc 1st drug x14 days before starting new one
MAOIs with bipolar
associated with the induction of mania
MAOIs with schizophrenia
associated with psychotic decompensation
MAOIs in pregnancy
contraindicated as well as during lactation
how do MAOIs lead to tyramine induced HTN crisis
MAOI inactivates GI metabolism of dietary tyramine allowing intact tyramine to enter blood stream where it exerts a powerful pressor effect
how long do tyramine-containing foods have to be avoided in association w/ MAOIs
for at least 2 weeks after last dose
tyramine-containing foods
cheese
fish
cured meats and sausage
alcohol
sauerkraut
bananas
avocados
which medications can cause HTN crisis when administered with MAOIs
sympathomimetic amines:
ephedrine
pseudoephedrine
dextromethorphan
what else can precipitate HN crisis in those treated with MAOIs
bee stings
other sx requiring immediate clinical intervention when taking MAOIs
headache
stiff neck
diaphoresis
N/V
discontinuation of MAOIs
taper slowly over several weeks to avoid discontinuation syndrome
s/s MAOI OD
agitation that can progress to coma
hyperthermia
HTN
dilated pupils
hyperactive deep tendon reflexes
drugs that have fatal interaction with MAOIs
demerol
fentanyl
which thyroid hormones can be used to tx depression or rapid cycling
levothyroxine
liothyronine
thyroid hormones and food
absorption increased if taken on empty stomach
main uses of thyroid hormones as adjunctive tx
convert nonresponders to responders
lithium-induced hypothyroidism
contraindications to thyroid hormone use
cardiac disease
angine
HTN
adrenal insufficiency
acute MI
thyroid hormones and pregnancy
safe
minimally excreted in breast milk
medications that are contraindicated w/ thyroid hormones d/t risk of cardiac decompensation
sympathomimetics
ketamine
maprotiline
how long is an adequate trial of liothyronine
2-3 weeks
ketamine medication class
NMDA receptor antagonist
time frame of therapeutic effects of ketamine
relief within 4 hours and lasts several weeks but then depression will relapse w/o further intervention
approved ketamine enantiomer
esketamine
administration of esketamine
in clinical setting w/ observation for 2 hours post administration
medication class of brexanolone
neurosteroid
allosteric modulation of brexanolone
-positively modulates GABAA receptors
-negatively modulates nicotinic acetylcholine receptors
timeframe for response to brexanolone
within 2-3 days
schedule and availability of brexanolone
schedule 4
available only through national registry
administration of brexanolone
IV x60 hours in clinical setting
General contraindications for SNRIs
Renal/hepatic impairment
Glaucoma
Heavy alcohol use
CNS depressants
what distinguishes SNRIs from TCAs
SNRIs have a relative lack for of affinity for muscarinic, histaminergic, and a- and b-adrenergic receptors
What enzyme primarily metabolizes venlafaxine and desvenlafaxine
2D6
initial dose of duloxetine
20-30mg
which MAOI is a reversible inhibitor
moclobemide
which enzyme primarily metabolizes norepinephrine, serotonin, and epinephrine
MAOA
which enzymes primarily metabolize dopamine and tyramine
MAOA and MAOB
what is used to tx HTN crisis with MAOIs
a-adrenergic antagonists
(pentolamine or chlorpromazine)