Antidepressants & Antipsychotics Flashcards
What are the 3 mechanisms of termination of NT synaptic activity?
Reuptake
Enzyme degradation
Diffusion
What are the two types of biogenic amines?
ACh and Monoamines
What are the two types of monoamines?
Serotonin and Catecholamines
What are the 3 types of catecholamines?
NE, epi, DA
What adverse effects are caused by blocking the DA2 receptor? (2)
EPS AE
Prolactin release
What are the AEs caused by blocking the H1 receptor?
Sedation, impaired cognition
What AEs are caused by blocking the M1 receptor?
Opposite of DUMBBELSS (Constipation, urinary retention, blurred vision, closed-angle glaucoma, tachycardia, hypomania, dry mouth/eyes, hypohidrosis) and altered cognition
What AEs are caused when blocking the alpha 1 adrenergic receptor?
Orthostatic hypotension, reflex bradycardia
Name 2 tricyclic antidepressants (TCAs).
Amitriptyline, nortriptyline
What is the MOA of TCAs?
Blocks NE and 5-HT uptake into presynaptic nerve terminal
Common indications for TCAs?
Depression unresponsive to SSRIs and SNRIs, insomnia, various pain syndromes
Name all receptors blocked by TCAs (besides blocking NET and SERT).
M1, H1, alpha 1 adrenergic
Name common TCA AEs (3)
Lower seizure threshold
Serotonin syndrome
Cardiac toxicity (Prolonged QT, cardiac depression, life-threatening arrhythmias with OD)
Describe TCA OD.
LD 8x average dose.
Symptoms - cardiotoxicity, seizures, respiratory depression, hypotension.
Arrhythmias can persist 10 days b/c t1/2 ~81 hours.
Name 4 drug classes with which TCAs can interact.
CNS depressants (ex., opioids)
Other serotonergic drugs
Sympathomimetics (hypertension with ex., epi)
Antimuscarinics (delirium, confusion, hypotension)
MOA of SSRIs?
Inhibit 5-HT reuptake transporter (SERT).
Why do SSRIs have a lower risk of AEs than TCAs?
No/minor blockade of H1, ACh, and NE receptors; also less risk of cardiac toxicity/death
Name 7 common SSRIs.
Fluoxetine, fluvoxamine, citalopram, escitalopram, sertraline, paroxetine
State 2 points regarding SSRI pharmacokinetics.
Metabolized in liver
Variable 1/2 lives (around 20-24 hours). EXCEPTION: fluoxetine 4-9 days.
Name 8 SSRI AEs
Serotonin syndrome Hyponatremia Withdrawal syndrome Bleeding Sweating Nausea/diarrhea Sexual dysfunction
Describe the s/s, time frame, and management of serotonin syndrome.
Agitation, confusion, hyperreflexia, clonus, diaphoresis, autonomic instability, fever, death
2-72 hours after treatment initiation
Discontinue drug and provide supportive care
Name 3 MOAs that can cause serotonin syndrome through DDIs
Drugs that decrease 5-HT reuptake (antidepressants, opioids, ondansetron, meth/coke)
Direct 5-HT receptor stimulators (triptans)
DDIs involving CYP enzymes
Which SSRIs affect CYP enzymes and in what way?
Fluoxetine and fluvoxamine INHIBIT CYP enzymes
Which SSRI is least likely to cause withdrawal syndrome?
Fluoxetine due to long t1/2
MOA of SNRIs?
Blocks SERT and NET activity
What aspect of SNRI MOA makes this class effective for treating pain syndromes?
NET blockade (on label for duloxetine)
Patients are at risk for what AE after taking SNRIs in addition to those imposed by SSRIs?
Hypertension (lower risk with duloxetine than venlafaxine)
Name 2 SNRIs.
Venlafaxine, duloxetine
Which atypical antidepressant does NOT cause sexual dysfunction?
Bupropion (Wellbutrin)
Major mechanism of bupropion?
Increase synaptic NE and DA activity (block NET and DAT and increase their release); noncompetitive antagonist of nicotinic receptors
Indications for bupropion?
Depression, smoking cessation
Bupropion AEs?
CNS stimulation (agitation, insomnia, tremor) DECREASED seizure threshold NO sexual dysfunction!
What serotonin modulator is mainly used as a hypnotic?
Trazodone
MOA of trazodone?
Blocks 5-HT2 receptors, H1, and alpha 1 adrenergic receptors; inhibits SERT at high doses
AEs of trazodone? (2)
Priapism
Postural hypotension
A 29-year-old male veteran with a 2-month history of progressively worsening lower back pain was admitted for revision of a discectomy. His routine medications included fluoxetine (Prozac) and tramadol (Ultram). His perioperative medications included several opioids.
One hour after return to his room he was found to be agitated , hypertensive, diaphoretic and with spontaneous clonus. He was subsequently diagnosed with the serotonin syndrome.
Which opioid is most likely to have triggered this response? A. Morphine B. Hydromorphone (Dilaudid) C. Oxycodone (Oxycontin) D. Fentanyl (Duragesic)
D
SSRI/SNRI will generally be (continued/discontinued) perioperatively unless …? In which case…?
continued; the patient is a high risk for bleeding; SSRI will be held
TCAs may be DC’s perioperatively depending on __ risk
CV
Drugs with what centrally-acting receptor can increase post-op confusion and delirium?
Muscarinic
Drugs blocking what receptor may decrease GI motility and cause urinary retention postoperatively?
Muscarinic
Where in the body are MAO enzymes active?
Gut, liver, and CNS
Monoamine oxidase inactivates what NTs?
5-HT, NE, DA
What does MAO-A inactivate?
NE, 5-HT, and dietary tyramine
What does tyramine cause? In the presence of MAOIs?
Release of NE from nerve terminals; dangerous hypertension
What does MAO-B do? What condition are MAO-B inhibitors used to treat?
Inactivates DA; Parkinson’s
Name some nonselective MAO irreversible inhibitors. (3)
Phenylzine, tranylcypromine, selegiline
What is unique about selegiline?
Available as a patch for depression
Also, lower concentrations mainly inhibit MAO-B for Parkinson’s
Why are MAOIs reserved for refractory or atypical depression?
The potential for life-threatening interactions with tyramine-containing foods (but less likely with selegeline patch)
Discuss MAOI impact on blood pressure (2)
Orthostatic hypotension at normal doses
Hypertensive crisis with tyramine-containing foods (aged meats/cheese, wine/beer, yeast extracts, cured fish, fermented soybeans)
Name 3 DDIs for MAOIs and their effects.
Sympathomimetics - increased hypertension
Other serotonergic drugs - serotonin syndrome
Meperidine - hyperpyrexia
What factors can increase risk of lithium toxicity?
Low sodium leading to the retention of chemically-similar lithium
Renal impairment
Pregnancy/lactation - teratogenic
DDIs with lithium?
NSAIDs ACEIs ARBs Thiazide diuretics (All of the above will decrease lithium excretion)
What are common AEs with normal levels of lithium?
GI efx, thirst, cardiac efx, tremor, polyuria
What are uncommon AEs with normal levels of lithium?
Hypo/hyperthyroidism, renal damage, leukocytosis, dermatologic reactions
What are AEs with toxic levels of lithium?
Tremor, ataxia, convulsions, hypotension, arrhythmias, coma, death
What commonly used anesthetic drug may be prolonged by lithium?
NM blockers
What labs should be checked perioperatively if the patient is on lithium?
Lithium levels, electrolyte levels, and thyroid hormone
Also maintain adequate hydration
A 57-year-old woman complains of persistent pain associated with fibromyalgia. She has lost interest in most her hobbies and often feels despondent. Which of the following medications is most likely to address her pain and depression?
A. Citalopram (Celexa) B. Bupropion (Wellbutrin) C. Duloxetine (Cymbalta) D. Selegiline (Emsam) E. Phenelzine (Nardil)
C
What is a non-psychiatric indication for antipsychotics?
Antiemetic
What kind of antipsychotics most effectively treat positive schizophrenia symptoms?
Conventional OR atypical
What class of antipsychotics most effectively treats negative symptoms of schizophrenia?
Atypical antipsychotics
Cognitive symptoms of schizophrenia are NOT worsened by what kind of antipsychotics?
Atypicals
What about the MOA of 1st generation antipsychotics (FGAs/neuroleptics) make them more likely to cause movement disorders than 2nd generation (SGAs/atypicals)?
FGAs have a higher affinity for DA2 receptor; SGAs moderately block 5-HT2 receptors and rapidly dissociate from DA2.
What other receptors are blocked by FGA and SGAs?
Alpha 1 adrenergic, muscarinic, and histamine
What is the MOA of the 3rd generation antipsychotic Abilify?
Dopamine system stabilizer - DA partial agonist; also 5-HT2 receptor antagonist
What lower potency 1st generation antipsychotic places the patient at higher risk for sedation, hypotension, and antimuscarinic effects?
Chlorpromazine
What medium potency antipsychotic is used primarily as an antimetic?
Promethazine
What high potency SGAs place the patient at a lower risk of sedation but a higher risk of EPS symptoms?
Haloperidol
Droperidol
What is a severe AE of antipsychotics caused by insufficient dopamine?
Acute dystonia (severe muscle spasm including torticollis, oculogyric crisis, trismus)
How is acute dystonia treated?
Centrally acting antimuscarinic (benztropine) and diphenhydramine
What is late-occurring EPS termed?
Tardive dyskinesia (oral, facial dyskinesias, lip smacking, choreoathoid movements)
What are some adverse effects common to all classes of antipsychotics?
Reduced seizure threshold
Prolonged QT/related arrhythmias
Neuroleptic malignant syndrome
What are risk factors for prolonged QT interval? (5)
Bradycardia, HF, prior MI, hypokalemia, hypomagnesemia
What commonly-used perioperative drug is most likely to cause QT prolongation?
Amiodarone Others (inhaled anesthetics, antiemetics, methadone)
What antipsychotics are most associated with prolonged QT? (3)
Haloperidol (esp. IV) Droperidol Ziprasidone (Geodon)
What s/s characterize neuroleptic malignant syndrome?
Fever, “lead-pipe” rigidity, dysautonomia, altered mental status
What dopamine blockers are most implicated in NMS?
FGA, SGA, D2 antagonist emetics, and dopaminergic withdrawal
Compare and contrast onset of SS and NMS.
Within 24 hours and within days, respectively
Compare and contrast NM findings with SS and NMS.
Hyperreactivity (tremor, clonus, reflexes) and bradyreflexia/severe muscular rigidity, respectively
Compare and contrast causative agents of SS and NMS.
Serotonin agonist and dopamine antagonist
Compare and contrast resolution timeline of SS and NMS
Within 24 hours and days to weeks, respectively
Describe 5 antipsychotic DDIs.
Epinephrine - blunted pressor effect with drugs that cause alpha blockade (such as chlorpromazine)
Antimuscarinics (additive)
CNS depressants (additive)
Levodopa (since it is metabolized to DA, antipsychotics will antagonize the effects - watch for psychosis)
Dopamine (decreased DA effectiveness)
Name 4 second generation antipsychotics
Olanzapine
Ziprasidone
Risperidone
Quetiapine
Why are SGAs preferred over FGAs?
They relive both positive and negative symptoms and generally have a lower SE profile
SGAs carry an increased risk of _________ AEs over FGAs.
metabolic - hyperglycemia, dyslipidemia
Which antipsychotic carries the highest risk of prolonged QT?
Ziprasidone
What is the 3rd generation antipsychotic/DA system stabilizer?
Aripiprazole (Abilify)
A patient that received promethazine (Phenergan) for post-operative nausea suddenly develops a sustained, involuntary muscle contraction involving the neck. Which of the following would most likely be used to treat this reaction? A. Diphenhydramine (Benadryl) B. Chlorpromazine (Thorazine) C. Dantrolene (Dantrium) D. Lorazepam (Ativan)
A
A 58-year-old man with a history of schizophrenia, generalized anxiety disorder and bradycardia is in the PACU following an appendectomy. He has received ondansetron and droperidol perioperatively. He took his home medications the day of surgery. Which of the following is most likely to increase his risk of arrhythmia? A. Aripiprazole (Abilify) B. Ziprasidone (Geodon) C. Sertraline (Zoloft) D. Duloxetine (Cymbalta)
B
