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359 Cards in this Set
- Front
- Back
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dx of depression requires at least - symptoms persisting for at least - weeks
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5
2 |
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involves cycles of depression only
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unipolar
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involves a pattern of both depression and mania
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bipolar
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temporary occurring depression:
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seasonal affective disorder
premenstrual dysphoric dysfunction |
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pdd due to which phase
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luteal
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then monoamine deficiency theory due to hypofuncitonal -- and ---
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5HT
NE |
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t/f
monoamine deficiency due to too much 5HT and NE |
f
hypofunctional |
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the neuroendocrine hypothesis due to -- and --- releasing factors
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cortisol
thyroid |
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what can increase cortisol levels
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5HT 2A and C receptors
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if there's too much 5HT and NE there will be an increase in ---- and then --- feedback
this will --- cortisol levels |
cortisol
negative decrease so, a dysfunctional neg feedback system can cause depression |
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how can sleep related factors/circadain variables cause depression . . . due to --- melatonin
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increased
decreased 5HT |
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what's increased in suicide victims w/ major depression
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5HT 1A
5HT 2 |
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what's decreased in suidically depressed patients
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spinal fluid content of 5HIAA
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--- and ---- can improve symptoms of depression in selectev patient populations
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tryptophan
5-HTP |
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5-HTP is a --- precursor
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sertonin
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lesions of 5HT pathways prevent --- ---- receptor changes after antidepressant tx
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beta-adrenergic
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tx w/ ---- and ------ antagonist accelerate antidepressant effects
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5HT-1A/B/D
5HT-2A/C |
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t/f
5HT-1A/B/D and 5HT-2A/C better in efficacy |
f
they are not better in efficacy, but are faster |
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rate limiting step of serotonin
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amount of trytophan in diet
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the 5HT 1A postsynaptic: mediated --- release
---thermia ---- |
ACTH
hypothermia anxiety |
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5HT1A presynatpic mediates:
---phagia ----- regulate both ---, ----- and ----- firing |
hyperphagia
anxiolysis 5HT DA NE |
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5HT 1A regulate both ---, ----- and ----- firing
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5HT
DA NE |
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which med to use on 5HT-1A
|
buspirone
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buspirone + --- can help increase chances of getting better
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antidepressants
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presynaptically 5HT 1B/1D
regulate ------, ---- rate and --- release of 5HT and NE |
synthesis
firing vesicular |
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5HT1A presynatpic mediates:
---phagia ----- regulate both ---, ----- and ----- firing |
hyperphagia
anxiolysis 5HT DA NE |
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5HT 1A regulate both ---, ----- and ----- firing
|
5HT
DA NE |
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which med to use on 5HT-1A
|
buspirone
|
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buspirone + --- can help increase chances of getting better
|
antidepressants
|
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presynaptically 5HT 1B/1D
regulate ------, ---- rate and --- release of 5HT and NE |
synthesis
firing vesicular |
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which med used on 5HT-1B/1D
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sumatriptan
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whic receptor regulates mood, anxiety, and psychotomimetic
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5HT-2A
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the presynatpic 5HT-2A regulates
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NE
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whiehc agent works on 5HT-2A
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mCPP
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which receptor regualtes anxiety, migraine, disrupts sleep, and decreases eating
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5HT-2C
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5HT-2C regulates ----, ----, disrutps --- and decreases ----
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anxiety
migraine sleep eating |
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which agent works on 5HT-2C
|
mCPP
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t/f
sumatriptan is an antagonist at 5HT-1B/1D |
f
agonist |
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5HT-3 regulates --/--, vaso----, pain, delayed and impaired -----
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n/v
vasodilation ejaculation |
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agent that's an antag at 5HT-3
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ondansetron
|
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mCPP is an active metabolite of -- and ---
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trazodone
nefazone |
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what's an adjunct antag to some antidepressant and antipsychotics
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ondansetron
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tx for antidepressants:
severe ----- depression, --- and --- |
endogenous
SAD PDD |
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tx indications for depression
--- depression/---- - affective disorder |
psychotic
schizo |
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tx indications for antidepress include certain anxiety rxns such as
|
OCD
panic disorder MAD |
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which meds used for ocd
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SSRI's
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which meds used for panic dx
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SSRI
MAOI |
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which meds used for mixed anxiety depression
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MAOI
|
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antidepressants can be used for depression associated w/ --- dieseae or damage such as ---, --, ---
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neurological
tourette's PD AD |
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antidepressants can be used for bed wetting aka
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enuresis
|
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low dose of --- will contract internal sphincters which helps enuresis
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imipramine
|
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off label uses of antidepressants include:
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hyperactivity, hyperkinetic syndrome
narcolepsy migraine eating disorders chronich pain syndromes chronci fatigue fibromyalgia menopause |
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med for OCD
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SSRI
|
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panic disorder med
|
SSRI
MAOI |
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t/f
antidepressants can be used for ADHD |
t
it's a possible mood disorder |
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how long til u see full tx actions w/ antidepressants
|
4-6 wks
|
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which condition doesn't need 4-6 weeks to see full effects
|
PDD
just give during luteal phase SSRI |
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when can you start seeing se of antidepressants
|
hours to days
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t/f
se of antidepressants will last a lifetime |
f
may diminish over time |
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why's there a 20-30% failure rate of antidepressants:
instrinsic ------- to drug tx inadequate drug --- or ---- of tx non-------- (often due to SE or lag time) |
resistance
dosage duration noncompliance |
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natural remission in - to - months
|
6-12 months
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placebo has --- to ----% efficacy
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30-40%
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how many patients will experience recurrent episodes
|
50-70%
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t/f
SSRIs are more efficacious than TCAs |
f
they are no different in efficacy they have different side effect profiles |
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most TCA's have a higher affinity for ---
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NE
|
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tca's might have --- inhibition of --- - dependent NE transporter
|
competitive
sodium |
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tca's may also inhibit the -- - dependent --- transporter
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Na
5HT |
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|
increased impulse dependent synpatic levels of --- and ---- w/ tca's
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NE
5HT |
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another moa of tca's
complex ------ recpetor changes to elevated NE and 5HT |
secondary
|
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tca's will lead to a loss of presynatpic --- --- receptor fx
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alpha-2 adrenergic
|
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tca's will decrease ---- presynaptic receptors
|
5HT-1
|
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tca's will decrease --- postsynatpic recpetors
|
5HT-2
|
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tca's will alter ---- adrenergic receptors
|
beta-1
|
|
|
Gi?
Gq? Gs? |
Gi: 5HT-1
Gq: 5HT-2 Gs: beta-1 adrenergic receptors |
|
|
tca's can work by
net gain in ------- formation, increased --- and ----- |
cAMP
CREB BDNF |
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how do CREB and BDNF work
|
regulating gene transcription
|
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which can increase connections btw neurons
|
BDNF
|
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which receptors are blocked:
hypotension sexual dysfunction |
alpha-1 receptors
|
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which receptors are blocked:
autonomic se |
muscarinic receptors
|
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which receptors are blocked
sedation |
histamine
|
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by increasing the 5HT receptor these SE occur
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nausea
ha nervousness |
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|
se of increasing NE
|
tremor
tachycardia sexual dysfunction pressor responses |
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relief from depression may cause manic or agitated states esp if undiagnosed bipolar
|
rollback
|
|
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who's more prone to rollback
|
adolescences
|
|
|
why's there an important balance btw NE and 5HT
|
cuz the neurons have both 5HT and NE receptors on them
so a loss in one will lead to a loss in another |
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rollback: relief from depression may cause --- or ---- states esp if undiagnosed bipolar
|
manic
agitated (akathisia) |
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|
in the acute phase of tca's,after the uptake of ne and 5 ht are blocked, what's activated due to increased extracellular NE
|
alpha-2 autoreceptors on NE
alpha - heteroreceptors on the 5HT neurons |
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t/f
in the acute phase of tca's there will be decreased firing of NE and 5HT |
t
|
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in the acute phase of tca's there will be decreased --- and --- of NE and 5HT
|
synthesis
turnover |
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during the acute phase of tca's there 's non-selective blockade of ---, ---, ---, ----
|
muscarinic
histaminergice adrenergic seroternergic |
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|
in the chronic phase of tca's there's desensitized or decreased --- ---- ----- receptors
|
alpha-2 presynaptic
|
|
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in chronic phase of tca's what will return the firing rate and turnover back to normal
|
desensitized or decreased alpha-2 presynaptic receptors
|
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in the chronic tca's there will be decreased presynapatic ----- and postsynatpic ---- sensitivity and number
|
pre: 5HT-1 (A, B, D)
post: 5HT-2A |
|
|
in tca's chronic there's also decreased beta -- receptor sensitivity
|
1
less inhibition of 5HT |
|
|
what will lead to an increased 5HT and NE release in chronic for tca's
|
desensitized presynatpic 5HT-1 (A, B, D)
decreased postsyn 5HT-2A decreased beta-1 receptor |
|
|
a net gain in --- will lead to sitmualation of CREB and BDNF in tca's chronic stage
|
cAMP
|
|
|
in chronic tca's. . ..how do the cholinergic and histaminergic se eventually go away
|
due to cholinergic receptor blockage desensitization
|
|
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in chronic tca's there an upregulation of --- receptors
|
alpha 1
|
|
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in chronic tca's there a decreased GABA----- and ----- receptors
|
GABA B
NMDA |
|
|
in chronic tca's there's decreased D-- dopamine --, increased DA released
|
D-2
autoreceptor |
|
|
what will be normalized in chronic tca's
|
cortisol release and receptors
|
|
|
tca's have good --- solubility
|
lipid
easily absorbed cross bbb |
|
|
tca's have a large/small Vd
and --- absorption |
large
oral |
|
|
tca's metabolized by cyp ----
|
cyp1A2
CYP2D6 CYP2C19 CYP3A3/4 |
|
|
t/f
many metabolites of tcas are tx inactive w/ a short t1/2 |
f
active long t1/2 |
|
|
tca's must undergo --- conjugation for --- elimination
|
glucoronide
renal |
|
|
some cyp for tca's can be --- toxic
|
cardiotoxic
|
|
|
tca's have moder to high levels of --- ---
|
protein binding
|
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why DI w/ tca's
|
due to displacements from proteins
|
|
|
tca's anticholinergic activity can slow -- --- and ---- ---- time
|
GI motility
gastric emptying time |
|
|
who metabolize tca's faster
|
kids
possible higher dose |
|
|
tca's and elderly:
|
decreased hepatic metabolism
decreased renal clearnace more sensitive to SE |
|
|
t/f
assays for monitoring TCAs reliable redictors |
f
not reliable |
|
|
Drug interactions w/ TCA's . . . competition for --- --- --- and --- ---
|
plasma protein binding sites
liver enzymes |
|
|
di can potentiate --- ----
|
sedative actions
antihistamines and BDZ's |
|
|
what can induce metabolism of TCA's
|
ETOH
barbiturates smoking |
|
|
t/f
safe to give ssri's w/ bdz's |
true
cuz ssri's don't have antihistaminergic or muscarinic effects |
|
|
tricyclic tox:
dilated/constricted pupils ---cardia increased --- and ---- sweating, ---- skin |
dilated
tachycardia reflexes hyperactivity flushed |
|
|
serious overdose of tca's
hyper----- ---tension --- abnormalities coma |
hyperpyrexia
hypotension (cna mediation) cardiac abnormalities (arrhythmias, QT prolongation) coma |
|
|
some tolerance of tca's to ---- and ---- se
|
sedative
autonomic |
|
|
t/f
there's tca tolerance to tx effects (sensitization) |
f
can take for years and not lose benefits |
|
|
why should withdraw tca's slowly
|
to avoid:
sleep disturbances anxiety increased riks of remission w/ early and fast withdrawal |
|
|
t/f
if pt feeling better they can stop taking tca's |
f
body needs time to return to normal |
|
|
tca's have a higher affinity for NE/5HT
|
NE
|
|
|
tca's selective for Ne uptake
|
desipramine
protriptyline maprotiline nortriptlyine |
|
|
tca's that block both NE and 5HT
|
imipramine
doxepine amitriptyline clomipramine trimipramine |
|
|
which tca's that block both NE and 5HT have a higher affinitiy for 5HT
|
imipramine
amitripytlyine clomipramine |
|
|
which tca that block both NE and 5HT have a higher affinity for NE
|
doxepine
|
|
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which's tca that block both ne and 5ht has a metabolite that is opposite to it
|
clomipramine
|
|
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which tca that block both ne and 5ht is very weak at both receptors
|
trimipramine
|
|
|
which tca that block both ne and 5ht not metabolized to an active agent
|
trimipramine
|
|
|
name the antagonist
dizziness, orthostatic hypotension, priapism |
alpha 1 antag
|
|
|
name the antag
blurred vision, dry mouth, memory |
muscarinic antag
|
|
|
name the antag
sedation, weight gain, potentiate other sedatives |
h-1 antag
|
|
|
name the antag
ejaclatory disturbances, hypotension, alleviates migraies |
5HT-2 antag
|
|
|
name the antag
may contribute to antidepressant activity, contribute to antiHTN, 10% potenc of phentolamine |
alpha 2 antag
|
|
|
alpha 2 anta might contribute to both --- and --- activity
|
antidepressant
antihypertensive |
|
|
what might have antidepressant or anxiolytic actions
|
5HT-1 antag
|
|
|
5HT 1 antag might have --- or ---- actions
|
antidepressant
anxiolytic |
|
|
what ca contribute ot parkinson-like motor deficits and gynecomastia
|
D2 antag
|
|
|
proposed mech of ssri:
-- inhibition of -- dependent 5HT --- . .. increased ---- dependent synaptic levels of 5HT |
Competitive
Na transporter impulse |
|
|
w/ ssri's due to elevated 5HT what's decreased
|
5HT-1 presynaptic receptors
5HT-2 postsynatpic receptors |
|
|
w/ ssri's due to elevated 5T what's altered
what's there a net gain of |
altered beta 1
net gain in cAMP. . .. increased CREB and BDNF |
|
|
due to increased 5HT due to ssri's what reset
|
cortisol regulation
|
|
|
w/ ssri's there's very little ---, ---, and ---- blockade
|
cholinergic
adrenergic histaminergic |
|
|
what se can 5HT-3 cause
|
nausea
appetite loss |
|
|
general se of ssri
|
ha
|
|
|
what se can 5HT-2c cause
|
daytime restlessness
nighttime insomnia |
|
|
what se can 5HT -3 cause
|
impaired orgasm
ejaculation arousal |
|
|
dyregulation of 5T control of ADH release can cause what se
|
hyponatremia
|
|
|
ssri's there might be occasional ---- due to altered --- function
|
bruising
platelet |
|
|
ssri's can initially activate 2C and 2A which can lead to --- and ----
|
akathesia
insomnia |
|
|
decreaed sedation allows combinatin w/ --- for ssri's
|
anxiolytics (bdz's)
|
|
|
ssri's relief from depression may cause --- or -- states esp if undiagnosed bipolar disorder
|
manic
agitated (rollback) |
|
|
t/f
ssri's can cause rollback |
t
|
|
|
acute ssri's block 5HT --- and increase 5HT --- conc
|
uptake
extracellular |
|
|
acute ssri's acitvate 5ht --, ---, and ---- autoreceptors and ------
|
5HT 1A
1B 1D heteroreceptors |
|
|
in acute autoreceptor will decrease
|
5HT/NE neuronal firing
5HT synthesis and release NE release |
|
|
acutly ssri's activate 5HT-3 receptors to cause --- and --- ---
|
nausea
sex dysfunciton |
|
|
acutely ssri's active ---- to cause anxiety and agitation
|
5HT-2C
(akathesia) |
|
|
what's desensitized chronically w/ ssri's
|
5HT-1, 1B, 1d presynaptically
so firing rates and release return to normal |
|
|
chronically there's decreased ----- 5HT 2A inhibition of NE fx w/ ssri's
|
post-synaptic
|
|
|
what's increased chronically w/ ssri's
|
5HT and NE release per nerve impulse
|
|
|
what might be desensitized chronically w/ ssri's
|
beta-adrenergic receptors
|
|
|
chronically there's a net gain in ------ w/ ssri's
|
cAMP
increased CREB and BDNF |
|
|
chronically whats reset w/ ssri's
|
cortisol regulation
|
|
|
t/f
se of ssri's are lifelong |
f
most decrease w/ time |
|
|
ssri's well absorbed ---
|
orally
|
|
|
what' metabolizes ssri's
|
cyp
|
|
|
who metabolizes ssri's faster
|
kids
|
|
|
who metabolizes ssri's slower
|
elderly
|
|
|
elderly are slower metabolizer of ssri's except ---
|
sertraline
|
|
|
t/f
ok to give tca and ssri together |
f
wean off one before the other is started |
|
|
ssri's have a very high ---- ---
|
tx index
|
|
|
antidepressant that much safer to use in suicidal pts
|
ssri
|
|
|
t/f
ssri's in breast milk |
t
|
|
|
fetal/perinatal effects w/ ssri's
|
unknown
consider benefit:risk |
|
|
w/ ssri's there's some --- to sdative se
|
tolerance
|
|
|
t/f
there's a lot of tolerance to tx effects w/ ssri's |
f
|
|
|
to avoid ae what do you do w/ ssri's
|
withdraw slowly
|
|
|
ae of ssri's
|
sleep disturbances
anxiety increased recurrence w/ early and fast withdrawal |
|
|
what's fluoxetine metabolized to
|
norfluoxetine
|
|
|
t1/2 of fluoxetine
|
2-3 days
|
|
|
t1/2 of norfluoxetine
|
8 days
|
|
|
norfluoxetine is a ---- antagonist
|
5HT-2C
|
|
|
se of fluoxetine
|
anxiety
agitiation akathesia seizures |
|
|
ssri's that a weak alpha 1 antag
|
sertraline
|
|
|
t1/2 of sertraline
|
24 hrs
not different in elderly |
|
|
se of sertraline
|
dizziness
dry mouth diarrhea tremor |
|
|
fluvoxamine is a weak --- antagonist
|
D2
|
|
|
t1/2 of fluvoxamine
|
15 hrs
|
|
|
ssri's that a weak alpha 1 antag
|
sertraline
|
|
|
t1/2 of sertraline
|
24 hrs
not different in elderly |
|
|
se of sertraline
|
dizziness
dry mouth diarrhea tremor |
|
|
fluvoxamine is a weak --- antagonist
|
D2
|
|
|
t1/2 of fluvoxamine
|
15 hrs
|
|
|
se of fluvoxamine
|
dizziness
seizures sedation |
|
|
t1/2 of citalopram
|
35 hrs
|
|
|
se of citalopram
|
tremor
ha dry mouth |
|
|
S isomer of citalprom
|
Escitalopram
|
|
|
which has less side effects cita or escita
|
escitalopram
|
|
|
se of fluvoxamine
|
dizziness
seizures sedation |
|
|
t1/2 of citalopram
|
35 hrs
|
|
|
se of citalopram
|
tremor
ha dry mouth |
|
|
S isomer of citalprom
|
Escitalopram
|
|
|
which has less side effects cita or escita
|
escitalopram
|
|
|
what's the active metabolite of citalpram
|
norcitalopram
has more NE affinity |
|
|
selective NSRI that a NE reuptake inhibitor
|
Viloxazine
|
|
|
what does reboxetine have more affinity have for
|
NE > 5HT
|
|
|
paroxetine have some weak --- and ---- activity
|
anticholinergic
antihistaminergic |
|
|
se of paroxetine
|
dizziness
dry mouth sedation |
|
|
venlafaxine has a higher affinity for
|
5HT than NE
|
|
|
se of venlafaxine
|
nausea
sedation dizziness hypertension |
|
|
what does duloxetine have more affinity for
|
5HT > NE
|
|
|
milnacipran has more affinity for
|
5HT > NE
|
|
|
what has specific effects on fibromyalgia
|
milnacipran
|
|
|
bupropion is a -- uptake blocker and a weak --- uptake blockade
|
dopamine
5HT |
|
|
se of bupoprion
|
seizures
rashes anorexia tremor dry mouth |
|
|
atypical antidepressants have --- and --- uptake blockade plus direct receptor actions
|
5HT
NE |
|
|
amoxapine has higher affinity for
|
NE > 5 HT
|
|
|
amoxapine
--- and --- receptor blocker leads to an increased NE and 5HT release |
5HT-2
5HT-1 |
|
|
amoxapin has high affinity for --- DA receptor blocker, also ----, ---, ----
|
D-2
alpha-1 mACh H1 |
|
|
se of amoxapine
|
EPS
cardiotoxicity seizures |
|
|
trazodone is a weak --- uptake blocker
|
5HT
|
|
|
trazodone is a -- and ---- antagonist
|
5HT-1 autoreceptor
5HT-2A this will lead to increased 5HT and NE |
|
|
trazodone is metabolized to
|
mCPP
|
|
|
trazodone is a --- and ----- partial agonist
|
5HT-1A/B
5HT-2A/C |
|
|
SE of trazodone
|
sedation
priapism postural hypotension dizziness |
|
|
affinity of nefazodone
|
NE > 5HT > DA uptake inhibition
|
|
|
what antagonized by nefazodone
|
5HT-1 autoreceptor
5HT-2A antagonist this will increase 5HT and NE |
|
|
nefazodone has mod ---- --- and ----- ----- blockade
|
alpha-1 adrenergic
H1 hitaminergic |
|
|
what's nefazodone metabolized to
|
mCPP
hydroxynefazodone |
|
|
SE of nefazodone
|
sedation
priapism postural hypotension dizziness |
|
|
black warning on nefazodone due to
|
liver toxicity
check bilirubin regularly |
|
|
mitrazapine antagonizes
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alpha-2 adrenergic
|
|
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where does metirazapine antagonize alpha 2
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pre and postsynpatic receptors
|
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what does mitrazapine antagonize
|
5HT-2
5HT-3 alpha-2 adrenergic |
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|
se of mirtazapine
|
sedation
weight gain |
|
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mitrazapine can cause rare but dangerous -----
|
agranulocytosis
|
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buspirone is a partial agonist at ------ recpetors
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5HT-1A
|
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buspiraone generally used against --- but also increase efficacy of ---- when used together
|
antiaxiety
SSRIs |
|
|
mirtazapine is a strong ---- antagonist
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H-1
|
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|
mirtazapine is a mod ---- antagonist
|
alpha-1
|
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maoi are ----- inhibitors of mao
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irreversible
|
|
|
what are metabolized by both MAO - A and B
|
adrenaline
Dopamine Noradrenaline |
|
|
what's mainly metabolized by MAO-A
|
5-Hydroxytryptamine
|
|
|
what's metabolized by both MAO-A and B 50/50
|
tryptamine
|
|
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5HT, DA and NE neurons express primarily ------
|
MAO-A
|
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glia cells express mainly
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MAO-B
|
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tyramine mainly metabolized by
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MAO-B
|
|
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80% MAO activity in brain is MAO ----
|
B
|
|
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the most important subtype for antidepressant activity is MAO ---
|
A
|
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|
last choice antidepressant
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MAOI
|
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maoi . . . . cns sympathetic depression due to elevated brainstem --- causing depressied --- ganglionic transmission
|
NE
SNS |
|
|
maoi: CNS sympathetic depression due to elevated brainstem NE causing decreased ----- NE release
|
postganglionic
|
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|
maoi: CNS sympathetic depression due to elevated brainstem NE causing modest reduction in -----
|
BP
|
|
|
maoi
hyperadrengeric state causes: |
HA
diaphoresis mydriasis neuromuscular excitation cardiac dysrhythmia |
|
|
other se of maoi inclue
mild anticholinergic effects |
dry mouth
urinary retention |
|
|
se of maoi
hyper---- and --- gain |
hyperphagia
weight gain |
|
|
maoi se:
impaired ---- ---- |
sexual responses:
impotency anorgasmia |
|
|
maoi se include hypersomina/insominia
|
insomnia
|
|
|
maoi se include:
|
edema
orthostatic hypotension peripheral neuropathy: reversed or prevent by B6 |
|
|
how much mao inhibition do you need for optimal effect
|
> 85%
|
|
|
how long does it take for max ezyme inhibtion for maoi
|
5 days
|
|
|
w/ maoi there's acute elevattion of --- and ---
|
NE
5HT |
|
|
how long does it take for maximal clinical effects of MAOI
|
4-6 weeks
|
|
|
what does maoi decrease that leads to increase NE and 5HT
|
beta receptors
alpha-2 receptors 5HT-1 receptors 5HT2 receptors |
|
|
about 3 weeks of chronic tx, brain monoamine conc return to normal and -- -- rates increase slightly in -- and --- neurons
|
neuronal firing
NE 5HT |
|
|
maoi has good --- absorption
|
oral
|
|
|
--- less important for irreversible agents. . . maoi
|
half life
|
|
|
takes --- weeks to fully regenerate enzyme activity after d/cing maoi
|
2
so there might be interactions when switching |
|
|
htn crisis w/ maoi due to interaction w/ ---
|
tyramine
|
|
|
foods w/ tyramine increase NE release
|
cheese rxn
|
|
|
other than food what else can cause a htn crisis
|
sympthomimetics
|
|
|
tx of htn crisis
|
phentolamine (IV)
nifedipine (oral) prazosin |
|
|
what can block tyramine uptake. . . so no rxn
|
SSRIs
TCAs |
|
|
why not use ssris and maois
|
due to possible 5HT syndrome
|
|
|
5ht syndrome s/s
|
flushed face
dizziness sweating/hyperthermia tremor/myoclonus/rigidity gi disturbances HA |
|
|
possbile interaction w/ meripidine maoi leading ot syndrome of ---, hyper----, and hyper-----
|
coma
hyperpyrexia hypertension |
|
|
tox of maoi
|
agitation
hallucinations convulsions fever |
|
|
maoi
hydrazines : |
phenelzine
isocarboxazide |
|
|
acetylenic agents:
|
pargyline
clorgyline deprenly |
|
|
specfic maoi agents
|
hydrazines
acetylenic tranylcypormine |
|
|
which specific maoi has the least se
|
tranylcypromine
least irreversible |
|
|
tranylcypromine --- more rapid after cessasation of drug
|
reversal
|
|
|
tranylcypromine has --- like structuure and --- acitons
|
amphetmaine
sympathomimetic |
|
|
2nd gen maoi are mao --- selective
|
MOA-A
so less tyramine interaction |
|
|
t/f
2nd gen maoi are irreversible |
reversible w/ no need to synthesize new enzyme
so, don't have to wait two weeks to start a new med |
|
|
2nd gen maoi have fewer se than ---- or old -----
|
tca's
maoi's cuz less tyramine interactions |
|
|
2nd gen maoi that last 8-10 hrs
|
moclobemide
|
|
|
moclobemide has --- dose inhibition
|
single
|
|
|
other 2nd gen maoi
|
brofaromine
cimoxatone toloxatone |
|
|
this herbal prep has demonstrated efficacy for mild depression
|
st john's wort
|
|
|
t/f
st john's wort recommened for severe clinical depression |
f
|
|
|
most research done on what pharma active substance in st john's
|
hypericin
|
|
|
t/f
ok to combine st john's w/ ssri or maoi |
f
due to 5HT syndrome will have elevated NE and 5HT |
|
|
what will st. john's inhibit
|
monoamine/choline uptake
mao comt |
|
|
what will st john's suppress
|
cytokine expression
|
|
|
se of st. john's
|
dry mouth
confusion dizziness gi upset allergic rxn reproductive toxicity |
|
|
what will st. john's induce
|
cyp3A4
|
|
|
what will st. john's increse
|
p-glycoprotein
|
|
|
time course of st. john's?
|
similar to ssri's
|
|
|
most efficacious and rapid way to decrease manic symptoms
|
lithium
|
|
|
tx indications of Lithium
|
acute mania
manic stage of bipolar depression |
|
|
proposed mech of tx action
---/counter transport in cells |
Na
Na/Li exchange |
|
|
moa of lithium
na/- atpase activity increase in ---- and decrease in ----- |
RBC
brain |
|
|
lithium ---- decrease DA and -- release, may increase 5HT release
|
directly
NE |
|
|
mao of Li:
--- inhibition of --protein coupled signaling |
indirect
G |
|
|
mao of Li:
comptete for --- which keeps G proteins in less active ---- states |
Mg
alpha beta gamma |
|
|
li can attenutate both -- and -- fx
|
Gs
Gi |
|
|
Gi increase basal --- production
|
cAMP
|
|
|
Gs ---- stimulated cAMP production
|
decrease
|
|
|
li blocks --- turnover
|
phosphonisitide
|
|
|
li block --- phosphatase which prevents cycling of ---
|
IP
inositol |
|
|
Li decrease -- fx so less stimulation of phospholipase ---
|
Go
C |
|
|
Li decreases --- ---- -- translocations
|
Protein Kinase C
|
|
|
less stimulation of phospholipase C leads to less --- and -- which leads to less PKC
|
IP3
DAG |
|
|
Li affects --- regulatory factor, alter protein expression
|
nuclear
|
|
|
t/f
se w/ li very uncommon |
f
as many as 60% of pt will have se |
|
|
who's more prone to li se
|
african americans
due to Na regulation in body |
|
|
se of li include
poly --- poly ---- |
polyuria
poly dipsia decreased ADH responsiveness |
|
|
se of li include --- retention and ---
|
Na
edema initial response and will disappear in 3-5 days |
|
|
allergic rxn of li include ---, ---
|
dermatitis
acne excess inflammatory rxns |
|
|
se of li include hypo------
|
hypothyroidism. .. decreased thyroxine synthesis
|
|
|
t/f
li se does not include weight gain |
f
30-60% of pts show > 5% increase in BW |
|
|
gi se of li
|
n/v/d
|
|
|
seroius signs of li that shows beginning of toxicity
|
cardiac arrhythmias
hypotension hand tremor sedation |
|
|
w/ li there's decreased manic episodes when stable -- --- are achieved
|
blood levels
|
|
|
when do blood levels of li peak
when's it stable |
2-4 hrs after oral dose
10-12 hrs later |
|
|
t1/2 of li
|
24 hrs
|
|
|
slow release preps or divided daily doses decrease --- --- of Li
|
toxic peaks
|
|
|
some --- increase Li reabsorptions
|
diuretics ( thiazide)
so you need less Li |
|
|
---- ---- increase renal excretion of Li
|
osmotic diuretics
so you need more Li |
|
|
--- increase Li reabsorption
|
NSAIDS
so less needed |
|
|
what NSAID will increase li reabsorption more
|
indomethacin>ibuprofen = naproxen > ASA
|
|
|
tx index of Li
|
1.5--3
|
|
|
what can drastically affect steady state Li levels
|
Na loss
dehydration 95% eliminated in urine |
|
|
t/f
not necessary to monitor Li levels in all pts |
f
must in all pts |
|
|
tx range of Li
|
0.6-1.2 mEq/L 10-12 hrs after last oral dose
|
|
|
GI tox of Li
|
1.6-2.0 mEq/L
n/v/d |
|
|
CNS tox of Li
|
> 2.0 mEq
tremor dizziness ataxia coma convulsions |
|
|
when is li tetratogenic
|
first semester
consider risk vs benefit cv abnormalities in utero. . .can be surgically corrected |
|
|
what do you watch w/ postpartum babies who's moms took Li
|
fluid balance
|
|
|
what percent of serious toxicity require intervention
|
10-20%
|
|
|
any tolerance/withdrawal of Li
|
no
but recurrence of manic episodes even if controlled over years |
|
|
what;s less likely to cause withdrawal w/ Li
|
slow withdrawal
|
|
|
when do you give li alternatives
|
refractory pts that don't respond to Li
w/ other tx li toxicity decrease or time to when lithium needed |
|
|
alternative meds to Li
|
valproate
carbamazepine |
|
|
neuro symptoms of valproate
|
tremor
ataxia coma |
|
|
GI s/s of carbamazepine
|
n/v
|
|
|
allergic rx of carbamazepine
|
rash
|
|
|
carbamazapine can cause -- and -- toxicity
|
liver
bone marrow |
|
|
what can be elevated w/ valproate
|
hepatic transaminase
heptaotoxicity |
|
|
what does carbamazepine induce
|
cyp3A4
|
|
|
atypical antipsychotics that can be alternatives to li
|
aripiprazole
ziprasidone |
|
|
what can worsen manic symptoms
|
TCA and SSRIs alone
|
|
|
what can be combined w/ atypical antipsy to help w/ manic symtoms
|
olanzapine/fluoxetine ( symbyax)
|
|
|
this has moderate mood-stablizing effects used for manic s/s
change fatty acids then change prostaglandins , bind to different receptors |
omega-3 fatty acids
|
|
|
glucocorticoid receptor antag used for manic s/s
|
mifepristone
|
