BMB 3 - Antidepressants & Anxiolytics; Antipsychotics; Sleep Aids Flashcards
What is the black box warning on all antidepressants?
Antidepressants increase the risk of suicidal thinking and suicide in patients < 24 years with major depressive disorder (MDD)
(NOTE: antidepressants may also “unmask” mania in patients with an underlying bipolar disorder.)
Name two of the hypotheses of the pathophysiology of major depressive disorder.
Amine hypothesis
Stress hypothesis
Describe the amine hypothesis of major depressive disorder.
Depression is caused by reduced levels of biogenic amines (e.g. 5-hydroxytrypatamine, dopamine, norepinephrine)
(_EVIDENCE_: reserpine depletes NE and 5-HT and can induce severe depression; TCAs and MAOIs have antidepressant effects.)
Describe the stress hypothesis of major depressive disorder.
Chronic stress →
↑ cortisol →
↓ brain-derived neurotrophic factor (BDNF) →
↓ neural plasticity →
depression
Why do antidepressants have a slow onset-of-action?
Monoamines stimulate signaling cascades →
↑ BDNF →
↑ neural plasticity
What is the onset-of-action of antidepressants?
> 3-4 weeks
How is resistant depression approached?
Increase dose,
switch type of antidepressant,
augment with a drug with a different mechanism
What pharmacological interactions put patients at greater risk of serotonin syndrome?
SSRIs or SNRIs combined with other serotonergic drugs (e.g. triptans or MAOIs)
Describe the symptoms of serotonin syndrome.
Hyperthermia,
hypertension,
muscle rigidity,
muscle jerks
How is serotonin syndrome treated?
Cyproheptadine
True/False.
Most antidepressants are CYP450 substrates or inhibitors.
True.
St. John’s Wort is commonly used as an antidepressant and is a P450 _________.
St. John’s Wort is commonly used as an antidepressant and is a P450 inducer.
Discontinuing antidepressants can cause withdrawal symptoms. How can this be mitigated?
Gradually reduce the dosage
What term refers to the fact that a period of several weeks may be needed before starting another drug after fluoxetine?
A washout period
What is the usual ratio of GABA to glutamate?
1 : 1
What happens if a person’s [glutamate] > [GABA]?
Hyperexcitability and anxiety
What happens if a person’s [GABA] > [glutamate]?
Hypoexcitability and sedation
What is the mechanism of action of tricyclic antidepressants?
Inhibits norepinephrine and 5-hydroxytryptamine reuptake
What is the mechanism of action of MAOIs?
Non-selectively increases monoamines
(5-hydroxytryptamine, dopamine, norepinephrine)
What is the mechanism of action of SSRIs?
Inhibits 5-hydroxytryptamine reuptake
(and some norepinephrine)
What is the mechanism of action of SNRIs?
Inhibits 5-hydroxytryptamine and norepinephrine reuptake
What is the mechanism of action of bupropion?
Inhibits dopamine and norepinephrine reuptake
What is the mechanism of action of lithium?
Inhibits phosphatidylinositol casade
What is the mechanism of action of barbituates?
Enhances GABA effect
(↑ duration of Cl- channel opening)
What is the mechanism of action of benzodiazepines?
Binds to GABA-A receptor + enhances GABA effect
(↑ frequency of Cl- channel opening)
Which medication type increases the frequency of Cl- channel opening?
Which medication type increases the duration of Cl- channel opening?
Benzodiazepines
Barbituates
What is the mechanism of action of buspirone?
5-HT1A partial agonism
What is the mechanism of action of Z drugs (zolpidem, zaleplon, eszopiclone)?
Binds to GABA-A receptors at α-1 subunit
What is the mechanism of action of suvorexant?
Orexin receptor antagonist
What is the mechanism of action of ramelteon?
Melatonin agonist
Tricyclic antidepressants should only be used with caution in what patient population?
The elderly
True/False.
Tricyclic antidepressants have a high overdose potential.
True.
What antidepressant class is used for treating neuropathic pain?
Tricyclic antidepressants
Name some of the treatment options for depression.
SSRIs
SNRIS
Tricyclic antidepressants
Bupropion
MAOIs are mainly used in treating what condition(s)?
Atypical depression
(also, MDD and panic disorder)
Name some of the major side effects of tricyclic antidepressant use.
Arrythmias, seizures, hypotension
Name some of the major side effects of MAOI use.
Hypotension and seizures
Name some of the major side effects of SSRI use.
Sexual dysfunction, serotonin syndrome
What should be avoided in patients taking MAOIs?
Wine and cheeses;
SSRIs and SNRIs
How long do SSRIs or SNRIs take for their onset of action?
3 - 4 weeks
What is a major side effect of bupropion?
Seizures
Bupropion should be avoided in what patient population(s)?
Bullemic or anorexic patients
Which antidepressant is useful in smoking cessation?
Bupropion
Lithium has a narrow ________ index.
Lithium has a narrow therapeutic index.
Name some of the potential side effects of lithium use.
Nephrogenic diabetes inspidus;
weight gain, sedation, seizures;
teratogenic effects
Buspirone is used to treat what condition(s)?
It is useful in what patient population(s)?
Anxiety;
those with histories of drug/alcohol abuse
Which sleep aid should be avoided in patients with narcolepsy?
Suvorexant
Describe the major four dopaminergic brain pathways with which antipsychotics interact.
Mesocortical - associated with positive symptoms
Mesolimbic - associated with negative symptoms
Nigrostriatal - involved in extrapyramidal side effects
Tuberohypophyseal - involved in prolactin side effects
Which dopamine pathway is associated with positive symptoms of schizophrenia?
Mesocortical
Which dopamine pathway is associated with negative symptoms of schizophrenia?
Mesolimbic
Which dopamine pathway is associated with the extrapyramidal symptoms of antipsychotic use?
Nigrostriatal
Which dopamine pathway is associated with the hyperprolactinemic symptoms of antipsychotic use?
Tuberohypophyseal
What receptor type is upregulated in patients with schizophrenia?
D2 receptors
Antipsychotics are ______ ___gonists that can treat psychosis,
Antipsychotics are D2 antagonists that can treat psychosis,
Drugs that increase _______ergic activity worsen psychosis.
Drugs that increase dopaminergic activity worsen psychosis.
Drugs that ___crease dopaminergic activity worsen psychosis.
Drugs that increase dopaminergic activity worsen psychosis.
Name the three typical (1st -generation) antipsychotics (indicate high potency with asterisks).
Haloperidol**
chlorpromazine, thioridazine
**high potency
Aside from D2 antagonism, what are the other incidental receptor interactions of typical (1st-generation) antipsychotics?
M1 antagonism
Alpha-1 antagonism
H1 antagonism
Name some of the side effects of typical (1st-generation) antipsychotic use due to M1, alpha-1, and H1 antagonism.
M1 - Dry mouth, blurred vision, urinary retention
Alpha-1 - Orthostatic hypotension
H1 - Sedation
The side effects of H1/M1/Alpha-1 antagonism are more associated with which form of typical antipyschotics, low potency (chlorpromazine and thioridazine) or high potency (haloperidol)?
Low potency
(chlorpromazine and thioridazine)
Name some of the more severe side effects associated with haloperidol use.
QT prolongation;
extrapyramidal Syndromes
List the extrapyramidal effects of haloperidol use.
Dystonia (after ≥ ~4 hours)
Akathisia (after ≥ ~4 days)
Bradykinesia
Tardive dyskinesia (after ≥ ~4 months)
A patient presents with QT prolongation. You find out they recently started on an antipsychotic.
Which ones are the potential causes?
Haloperidol
or
a 2nd-generation antipsychotic
A patient presents with altered mental status, an unstable HR and BP, and muscle rigidity.
They were recently started on haloperidol.
What is the diagnosis?
Neuroleptic malignant syndrome
Name four atypical (2nd-generation) antipsychotics.
Clozapine,
olanzapine,
quetiapine,
risperidone
The side effects of H1/M1/Alpha-1 antagonism are more associated with which form of antipyschotics, typical (1st-generation) or atypical (2nd-generation)?
Typical (1st-generation)
The extrapyramidal side effects are more associated with which form of antipyschotics, typical (1st-generation) or atypical (2nd-generation)?
Typical (1st-generation)
True/False.
Both typical and atypical antipsychotics are associated with QT prolongation.
True.
What syndrome is associated with atypical antipsychotics but not typical antipsychotics?
Metabolic syndrome
(dyslipidemia, diabetes, weight gain)
Which antipsychotic is especially associated with hyperprolactinemia?
Risperidone
Which antipsychotic is the ultimate for treatment-resistant disease?
Clozapine
Name some of the side effects associated specifically with clozapine.
Agranulocytosis,
myocarditis,
seizures
How do you monitor a patient taking clozapine to check for agranulocytosis?
Monitor WBC count weekly for 6 months
Besides D2, M1, H1, and alpha-1 antagonism, what other receptors are antagonized by atypical antipsychotics?
5-hydroxytryptamine2
Name the indications for electroconvulsive therapy.
Treatment-resistant major depressive episodes or bipolar disorder
___lateral lead placement in electroconvulsive therapy has less cognitive side effects.
Unilateral lead placement in electroconvulsive therapy has less cognitive side effects.
What is the typical frequency and number of treatments in electroconvulsive therapy regimens?
2 - 3 / week
6 - 12
What percentage of patients who failed medications respond to electroconvulsive therapy?
70%
(continuing antidepressants required to boost maintenance of improvements; maintenance ECT is an option)
