Chapter 14: Serotonergics Flashcards
What is the number one inducer of depressive episodes?
stress
What is serotonin made from (including rate limiting enzyme) and where is it located?
tryptophan–(tryptophan hydroxylase)–> serotonin
- in the raphe nuclei
what is norepinephrine made from (including rate-limiting enzyme) and where is it located?
tyrosine –(tyrosine hydroxylase)–> L-DOPA–>dopamine –>NE.
- in locus ceruleus
what does MAO-A oxidize?
what does MAO-B oxidize?
MAO-A: 5-HT, NE, dopamine
MAO-B: dopamine
What are characteristics of bipolar I disorder, and what would be an adverse effect taking antidepressants concurrently?
only one manic episode not superimposed on schizophrenia and no past depressive episodes.
- life-threatening switches into mania
What effect do transmitters have on the 5;HT2(A,C) receptors?
excitatory (increase IP3, DAG)
What effect do 5-HT4,6,7 receptors have?
excitatory (increase cAMP)
What is the monoamine hypothesis?
States that decreased serotonin and/or NE levels cause mood disorders
What are characteristics of typical depression, and what is the first line agent?
depressed mood w/ no cause 2+ weeks, early awakening/sleep disturbance, decreased appetite with weight loss, social disengagement, NO MANIC EPISODES.
- SSRIs
What are characteristics of atypical depression, and what are effective treatments?
hypersomnia, increased appetite, sensitivity, engagement in pleasure-seeking behaviors.
- bupropion, venlafaxine, methylphenidate, 2nd/3rd line = MAOIs
What are characteristics of bipolar II disorder?
1+ depressive episodes, 1+ hypomanic episodes, no manic or mixed episodes
What experimental drug induces depression by inhibiting transport of 5-HT, NE, and DA?
reserpine
What are the acute vs. chronic effects of treatment with antidepressants?
Acute: decreased neuronal firing, decreased 5-HT and NE.
Chronic(3+ weeks): downregulation of inhibitory autoreceptors, leading to enhancement of neurotransmission
What selective 5-HT2a/2c agonist prodrug is converted into mCPP used mostly for insomnia?
trazodone
What drug displaces 5-HT,dopamine, and NE from their storage vesicles in presynaptic nerve terminals, and is used as a 2nd line agent for atypical depression and depression in the elderly?
modafinil
What drugs that treat ADHD displace 5-HT,dopamine, and NE from their storage vesicles in presynaptic nerve terminals?
dextroamphetamine, lisdexamfetamine
What drug for ADHD has side effects of sudden death, hyperthermia, CNS stimulation, and psychotic disorder, and should not be used with CV disease or with MAO-Is?
dextroamphetamine
What drug for ADHD has side effects of sudden death, MI, ventricular hypertrophy, stroke, Gilles de la Tourette syndrome, seizure, and Stevens-Johnson syndrome, and should not be used with CV disease or with MAO-Is?
lisdexamfetamine
What drugs inhibit MAO (serotonin degradation) to treat depression, and are irreversible and nonselective so have the worst tyramine toxicity?
iproniazid, phenelzine, isocarboxazid (all Z)
What drugs that inhibit MAO-A are reversible, and have less tyramine toxicity than the irreversible drugs of their class?
moclobemide, befloxatone, brofaromine (mo, flo, bro)
What drug, as a transdermal patch, will have a decreased risk of tyramine induced crisis? It inhibits MAO-B at low doses and MAO-A at high doses.
selegiline
What 2 things should always be done prior to starting tricyclic antidepressant treatment
ECG to rule out conduction system disease, and make sure they’re not taking MAO-Is
What inhibits reuptake of serotonin to treat depression, anxiety, & OCD (1st line), post-traumatic stress disorder, and pain syndromes?
SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
What drugs will cause side effects of sexual dysfunction and GI distress, and when taken with MAO-Is, cause hyperthermia, muscle rigitity, myoclonus, and mental status fluctuations?
SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
((the group of symptoms with MAO-Is is called “serotonin syndrome”!))
What drugs block reuptake of 5-HT and NE by GENERALLY blocking their transporters, enhancing post-synaptic responses, and what do they generally treat
tricyclic antidepressants (-pramine/-ptyline) - depression, pain syndromes
What SSRI causes a side effect of constipation?
paroxetine
What tricyclic antidepressant treats OCD?
clomipramine
What are the major side effects with tricyclic antidepressants?
heart block, arrythmia, MI, conduction delays, AV block & BBB, orthostatic hypotension in elderly, agranulocytosis, suicidal thoughts, antihistaminergic effects (sedation, weight gain, confusion)
What should always be done prior to starting tricyclic antidepressant treatment
ECG to rule out conduction system disease
What inhibits reuptake of serotonin to treat depression, anxiety, OCD, post-traumatic stress disorder, and pain syndromes?
SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
What drugs will cause side effects of sexual dysfunction and GI distress, and when taken with MAO-Is, cause hyperthermia, muscle rigitity, myoclonus, and mental status fluctuations?
SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
What SSRI causes a side effect of diarrhea?
sertraline
What SSRI causes a side effect of constipation?
paroxetine
What happens if you stop administration of citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline?
serotonin discontinuation syndrome (anxiety, dysphoria, GI/flu-like symptoms, insomnia, hypomania)
What is the best drug for pain syndromes in the elderly/fragile or in patients where citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline did not work?
duloxetine
What drugs that block 5-HT reuptake and NE reuptake in a CONCENTRATION-dependent manner (low = 5-HT, high = NE) treat depression, anxiety, and panic disorders?
venlafaxine, duloxetine
What depression medications will give you neuroleptic malignant syndrome and hepatitis?
venlafaxine, duloxetine
What drug that blocks 5-HT reuptake and NE reuptake in a concentration dependent manner (low = 5-HT, high = NE) treats major depressive disorder, and has unique side effects like hyponatremia, GI hemorrhage/bleeding, interstitial lung disease, and pulmonary eosinophilia?
desvenlafaxine
What drug is used for fibromyalgia that causes abnormal bleeding and serotonin syndrome, and what is its class?
milnacipran (SNRIs)
What drug that selectively blocks NE transporter treats ADHD?
atomoxetine
What is the benefit of atomoxetine over amphetamines in treating ADHD, and what side effects remain?
lower abuse potential, but still can have MI, prolonged QT, sidden cardiac death, liver injury, suicidal thoughts, psychotic disorder, dyskinesia
What is the treatment for atypical depression and smoking cessation and what does it inhibit?
buproprion: inhibits 5-HT, dopamine, and NE reuptake
What is the biggest side effect with buproprion?
seizure
What are the biggest pros of buproprion over other antidepressants?
fewer sexual effects and less mania
What drug blocks 5-HT2a, 5-HT2c, and alpha-2 adrenergic receptors, decreasing 5-HT neurotransmission while increasing NE neurotransmission?
mirtazapine
What is a potent somnorific and appetite stimulant in the elderly, but can cause agranulocytosis?
mirtazapine
What blocker of post-synaptic 5-HT2 receptors causes a side effect of priapism?
trazodone
What blocker of post-synaptic 5-HT2 receptors causes a side effect of liver failure and orthostatic hypotension?
nefazodone
What atypical antidepressant drug should not be administered with MAO-I, pimozide, triazolam, or carbamazepine?
nefazodone
What drug is a 5-HT1a agonist for anxiety with nonaddictive properties?
buspirone
What serotonin receptor do the “triptans” for acute migraines work on?
5-HT1B, 5-HT1D
What should never be taken with “triptans”?
ergot agent or MAO-Is
What serotonin antagonist is used to treat glaucoma and HTN, and on which serotonin receptor?
ketanserin (“Ket smokes pot”), on 5-HT2a/2c
What serotonin antagonist is used for nausea in cancer chemotherapy, and on which serotonin receptor?
odansetron, on 5-HT3
What serotonin antagonist is used for IBS with constipation, and on which serotonin receptor?
tegaserod, prucalopride (“ROD up butt, PRIDE = stick up yer ass”), on 5-HT4
What serotonin antagonist is used for IBS with diarrhea, and on which serotonin receptor?
alosetron (“losing lots of stool/water”), on 5-HT3
What 2 contraindications should you check for before prescribing tegaserod or prucalopride?
history of bowel obstruction, gallbladder disease
What contraindications should you check for before prescribing alosetron?
constipation, fluvoxamine use, IBD, diverticulitis, hypercoaguable history
What is a treatment for irritability and impulsivity?
valproic acid
What are treatments for bipolar disorder?
lithium (major), carbamazepine, lamotrigine
What are 4 mechanisms of action of lithium?
1) enters via Na+ channels, inhibiting inositol phosphates that makes IP2 –>IP1–>inositol, which blocks PIP regeneration
2) increases 5-HT
3) decreases NE, DA
4) inhibit adenylyl cyclase
What are side effects of lithium?
intoxication (nausea, diarrhea, ataxia, tremor, confusion), hyperkalemia, hypotension, bradyarrythmia, pseudotumor cerebri, increased ICP/papilledema, polyuria, nephrogenic DI, hypothyroidism, goiter, ECG/EGG abnormalities
What are contraindications of lithium?
CV disease, hyponatremia/nephrogenic DI, renal impairment, lactation
What drugs & electrolyte state increase lithium absorption in the proximal tubules?
NSAIDs & hyponatremia
