pharmacology of depression Flashcards
1
Q
biogenic amine hypothesis of depression
A
depression is caused by deficiency of monoamines, particularly NE and 5HT
2
Q
monoamine
A
neurotransmitter containing one amino group, e.g., serotonin, dopamine, epinephrine, norepinephrine
3
Q
receptor sensitivity hypothesis of depression
A
supersensitivity and upregulation - the post-synaptic neuron tries to compensate for a lack of stimulation due to deficiency of NE & 5HT
4
Q
lag period
A
time between starting medication and obtaining full symptom relief; believed to occur as a result of down regulation
5
Q
down regulation
A
reducing stimulation at the post-receptor (post-synaptic) site
6
Q
bruxism
A
teeth grinding
7
Q
sympathomimetics
A
compounds mimicking effect of sympathetic nervous system neurotransmitters: catecholamines, epinephrine, norepinephrine, dopamine
8
Q
monoamine oxidase (MAO)
A
inactivates norepinephrine, dopamine, epinephrine, and serotonin
- inhibit MAO, increase amount of circulating neurotransmitters
9
Q
antidepressant rule of thumb
A
NEVER MIX ANTIDEPRESSANTS
10
Q
antidepressant guidelines
A
start low, go slow
remember lag period
most side effects occur in first 1-2 weeks
suicide risk increases with energy level
11
Q
antidepressant discontinuation rule of thumb
A
TAPER TAPER TAPER
the shorter the half life, the more likely to have withdrawal
12
Q
SSRI side effect profile compared to others
A
much lower!
13
Q
serotonin level in depression is…
A
low 5HT
14
Q
fluoxetine (prozac)
A
SSRI - first one to be made!
15
Q
SSRI: moa
A
inhibition of 5HT reuptake
- result: increased availability, intensified transmission at post-synaptic site
- adaptive changes occur in response to prolonged uptake blockade
- smaller doses typically for older adults
16
Q
SSRI: pharmacokinetics
A
- highly pound to plasma proteins
- extensive hepatic metabolism, resulting active metabolites
- prolonged half life
- degree of inhibition (platelet aggregation)
17
Q
SSRI: steady state plasma levels in how long + why?
A
~ 4 weeks, due to prolonged half life
18
Q
SSRI: degree of inhibition significance (pharmacokinetics)
A
5HT needed to stimulate platelet aggregation!
higher inhibition of 5HT receptors = less 5HT to stimulate aggregation = higher risk of bleeding, hemorrhage (especially taken with NSAID)
19
Q
SSRI: side effects
A
nervousness, insomnia, anxiety headache nausea weight loss at first → weight gain sexual dysfunction common (70%) bruxism skin rashes *
20
Q
SSRI: adverse effects
A
risk for hemorrhage
risk for hyponatremia
serotonin syndrome
21
Q
serotonin syndrome
A
may begin within minutes to hours (up to 72) after initiation of ANY medication that increases serotonin levels
22
Q
SSRI: why risk for hemorrhage? (ae)
A
serotonin needed for platelet aggregation
- SSRI blocks reuptake, so aggregation CAN’T occur
- SSRI decreases coagulation!!!
23
Q
SSRI: why risk for hyponatremia? (ae)
A
5HT thought to be involved in production of ADH
- water leaves, salt leaves
- within first few weeks, more common in older adults
24
Q
too much serotonin is…
A
overly excitatory
25
zofran, reglan + SSRI = ?
serotonin syndrome. zofran and reglan already increase serotonin alone.
26
serotonin syndrome treatment
stop med, stop med combo, treat s/s
27
mild serotonin syndrome
mental status: restless
autonomic activity: diaphoresis, increased HR
neuromuscular: myoclonus (spasm)
28
moderate serotonin syndrome (full blown!)
mental status: agitation, LOC
autonomic activity: hypertension, shivering --> hyperthermia
neuromuscular: rigidity
29
severe serotonin syndrome
mental status: coma
autonomic activity: shock
neuromuscular: tonic-clonic seizures
30
SSRI interaction: TCA
potentiates
31
SSRI interaction: lithium
potentiates
32
SSRI interaction: MAOI
serotonin syndrome
NO NO NO NO NO NEVER MIX
33
SSRI: withdrawal + fix
abrupt, persists 1-2 weeks
severity depends on: duration, dosage, half life
s/s: GI, neuro, somatic, psychological
“fix” = take med again
34
tricyclic antidepressants (TCA): moa
- inhibits reuptake of NE and 5HT
- - moa varies by med (primarily NE, 5HT less)
intermediary neurochemical events and/or changes occur over time
35
TCA compared to SSRI
more effective, but worse side effect profile
36
TCA: why "dirty drug" and results
because varying affinity for MANY receptor sites
- block muscarinic receptors (anticholinergic side effects)
- block histamine receptors (sedation, weight gain)
- love adrenergic receptors (dizzy, hypotension, increased fall risk)
MANY SE DUE TO PERIPHERAL EFFECTS ON OTHER NT SYSTEMS
37
TCA: minimize AE by avoiding... (2)
```
anticholinergic drugs
cns depressants (alcohol, opioids, barbituates)
```
38
TCA: AE
```
hypotension
horrible anticholinergic SLUD
sedation
diaphoresis
cardiotoxicity
seizures
hypomania
yawngasm
muscarinic: flushing, pupil dilation, hyperthermia
```
39
TCA: most dangerous adverse effect & why
cardiotoxicity: decrease vagal influence, act directly on heart to slow conduction
40
hypomania + TCA, MAOI: why?
sudden increase in monoamines!
41
TCA interactions (4)
cns depressants
anticholinergics
sympathomimetics
MAOI
42
TCA + MAOI = ?
NEVER EVER EVER EVER DO THIS
| hypertensive crisis can result!!!!
43
TCA toxicity: cardiotoxicity
direct/indirect causes
44
TCA toxicity: anticholinergics
only takes 8x daily dose to be LETHAL
| --> atropine psychosis
45
atropine psychosis: cause + s/s
sign of TCA toxicity!
early s/s: agitation, confusion
late s/s: seizures, coma
aka anticholinergic delirium
46
TCA: what to monitor (2)
```
baseline EKG regardless of age
plasma levels (only in case of overdose)
```
47
MAOI rule of thumb
NEVER MIX MAOI WITH OTHER ANTIDEPRESSANTS
48
MAOI compared with SSRI
more effective, but more significant side effect profile
49
MAO action
degrades monoamines after reuptake
important role in metabolism of many drugs
- MAOI inhibits both MAO-A and MAO-B
50
MAO-A
inactivates dopamine
51
MAO-B
inactivates 5HT, NE
52
MAOI wash out period
10 - 14 days before new MAO is synthesized after discontinuing MAOI
53
MAOI appropriate for (disease + patient types)
depression, bulimia, ocd, panic disorders, more
give to patients highly likely to conform to restrictions (med, diet)
54
MAO: decrease in liver = ?
decreased metabolism of many drugs
| MAO plays important role in metabolism of many drugs
55
MAOI: moa
- prevents inactivation of NE and 5HT by mao
= increased transmitters released into synaptic cleft
- irreversible inhibition for 10-14 days
= effects continue up to 2 weeks after medication stopped
56
phenelzine sulfate (nardil)
MAOI in USA
57
tranylcypromine sulfate (parnate)
MAOI in USA
58
selegiline transdermal system (emsam)
MAOI in USA
less likely to react with food, but still needs regulation
59
isocarboxazid (marplan)
MAOI in USA
60
MAOI: drug interactions
- anesthesia
- narcotics
- antidepressants
- sympathomimetics
- cocaine
- antihypertensives
61
MAOI: food interactions
TYRAMINE!!!!
```
dairy
protein-rich (esp processed; salami, sausage, tofu, pickled fish)
fruits, veg (fig, banana, avocado)
desserts, sweets (chocolate!)
alcohol (red wine, beer)
some fats (salad dressing)
yeast products
soy sauce, meat tenderizers
ginseng (MANIC REACTION)
caffeinated bevs
```
62
tyramine
MAJOR INTERACTION WITH MAOI
moa: pressor, increases BP if not inactivated by MAO
- MAOI increases availability leading to
- - hypertension, hypertensive crisis
63
tyramine + MAOI = ?
hypertensive crisis!!!!
64
MAOI: interaction with anesthesia
- anesthesia
- narcotics
- antidepressants
- sympathomimetics
- cocaine
- antihypertensives
65
MAOI: interaction with narcotics
especially opioids
66
MAOI: interaction with SSRI
serotonin syndrome
DON'T MIX
67
MAOI: interaction with TCA
hypertensive crisis
DON'T MIX
68
MAOI: interaction with OTC
+ St. John's Wort = bad
+ cough medicine = bad
CONSULT PHARMACIST FIRST
69
MAOI: interaction with antihypertensives
excessive hypotension (MAOI already = hypotension, so potentiated hypotension)
70
MAOI: adverse effects
- hypertensive crisis!!!
71
hypertensive crisis: definition, cause, risk
sudden, severe increase in BP
- massive vasoconstriction of entire body
- excessive stimulation of the heart
- - due to high tyramine levels
- - result of MAOI interactions (+food/tyramine, +TCA)
risk: intracranial hemorrhage, stroke
72
hypertensive crisis: treatment
- call 911
| - take IMMEDIATE measures to decrease BP (nifedipine or other antihypertensive)
73
hypertensive crisis: s/s
```
major:
throbbing, occipital headache
retroorbital pain
stiff neck
apprehension
flushing of skin
palpitations
chest pain
```
minor: nausea, chills, fever, pallor, sweating
74
atypical antidepressant list (4)
SNRI (serotonin-norepinephrine reuptake inhibitor)
- venlafaxine (effexor)
NDRI (norepinephrine-dopamine reuptake inhibitor)
- bupropion (wellbutrin)
heterocyclic
- trazodone (desyrel)
NaSSA (norepinephrine and serotonergic specific antidepressant) OR TeCA (tetracyclic antidepressant)
- mirtazepine (remeron)
75
venlafaxine (effexor)
atypical antidepressant: SNRI (serotonin-norepinephrine reuptake inhibitor)
does not block cholinergic, histamine, alpha1-adrenergic
- very selective, no peripheral side effects
use: bipolar disorder (if more depressive)
side effects (common): headache, anorexia, insomnia
- increased 5HT = more excitatory!
- increased NE = excitatory (in this case)
adverse effects (less common): serotonin syndrome, neuroleptic malignant syndrome, hypertension, bleeding, increased serum lipids, activation of mania
76
bupropion (wellbutrin)
atypical antidepressant: norepinephrine-dopamine reuptake inhibitor
moa: inhibits nicotinic receptors
- does NOT block 5HT!!
smoking cessation (Zyban)
side effects: weight loss, dizziness, dry mouth (NE effects!)
nausea, headache, insomnia, tremor, agitation (direct stimulation effects!)
increased risk for seizures!
77
the only activating antidepressant is...
bupropion (wellbutrin): atypical antidepressant, SNRI
78
Zyban
atypical antidepressant: norepinephrine-dopamine reuptake inhibitor -- bupropion (wellbutrin)
EXCEPT USED FOR SMOKING CESSATION
79
trazodone (desyrel)
atypical antidepressant: heterocyclic
moa: SSRI and 5HT2 antagonist
use: adjunct
- sedation for insomnia, potentiates SSRI
- dose for depression alone too high
side effects: sedation, hypotension, nausea, vomiting, priapism
- sedative due to histamine activation
- similar to TCA (increase in 5HT and NE levels = added sedative effects)
- priapism due to alpha-adrenergic blocking
80
mirtazepine (remeron)
atypical antidepressant: NaSSA/TeCa -- norepinephrine and serotonergic specific antidepressant; also tetracyclic antidepressant
moa: moa: blocks alpha-2 adrenergic receptors (those inhibit release of NE & 5HT)
elimination half-life: 20 to 40 hours
side effects: somnolence (> 50%), increased appetite, cholesterol, dizziness, weight gain (significant: 50-60lbs/year)
- - give at bedtime
- - increase dose = somnolence decreases
dosing: 15mg QHS, max 30mg
quick dissolve - first antidepressant with this route
- great for compliance (can't hide in cheek, spit out)
- - esp. dementia patients with depressive features
81
atropine psychosis aka
anticholinergic delirium
82
trazodone + SSRI
augment each other, good combo
