Antidepressants Flashcards
__-__% of depression patients will improve with placebo treatment.
30-40%
Antidepressants of all classes may increase the risk of _____________________ in children.
Suicidal thinking and behavior
_________________ are the standard for antidepressant efficacy.
Tricyclic antidepressants
What are some common examples of tricyclic antidepressants?
- Tertiary amines
- Imipramine
- Amitryptyline
- Secondary amines
- Desipramine
- Nortriptyline
Pharmacological activity of tricyclic antidepressants:
- All are about equally efficacious
- All have 2-3 week latency
- Don’t elevate mood in non-depressed patient
- May be combined with lithium when treating bipolar disorder
- Used for treatment of chronic neuropathic pain (greatest use today)
- May cause insomnia
Imipramine and Amitryptyline, tertiary amine tricyclic antidepressants, more effectively inhibit the reuptake of (serotonin/norepinephrine).
Serotonin
Desipramine and Nortriptyline, secondary amine tricyclic antidepressants, more effectively inhibit the reuptake of (serotonin/norepinephrine).
Norepinephrine
PCKN of tricyclic antidepressants:
-
Slowly absorbed
- Peak plasma levels in 2-8 hours
- Delay in gastric emptying time
-
Significant “first pass” effect
- Enterohepatic circulation
- Significant protein binding
- Large volume of distribution
- T1/2 ranges from 12-72 hours
What are the CNS adverse effects of tricyclic antidepressants?
- Delirium, confusion, and manic reactions
- Sedation and/or weight gain
- Tremors
- Reduced seizure threshold
What are the autonomic adverse effects of tricyclic antidepressants?
- Significant antimuscarinic activity
- Tertiary amines > secondary amines
- Dry mouth (teeth loss), blurred vision, constipation, urinary retention
-
α-adrenergic antagonist activity
- secondary amines > tertiary amines
- Orthostatic hypotension, reflex tachycardia, and arrhythmias
What are the drug interactions of tricyclics?
Causes hypertensive crisis when combined with MAO inhibitors
What is the contraindication of tricyclic antidepressants?
Do not use in patients with narrow angle glaucoma.
Why should tricyclics only be prescribed in 1 week supplies?
Acute overdoses of lethal levels can be achieved with amounts that are readily available to the patient.
What is the treatment course for an acute overdose of tricyclics?
- Maintain respiration
- Gastric lavage (stomach pump) with activated charcoal
- Supportive care
- Antiarrhythmic agents for arrhythmias
- Benzodiazepines for seizures
- Bicarbonate to correct acidosis and to increase plasma protein binding
When tricyclics are combined with MAO inhibitors, what crisis results?
Hypertensive crisis
When switching to a MAO inhibitor from a tricyclic, allow a __ week washout period.
1 week
When switching to a tricyclic from a MAO inhibitor, allow a __ week washout period.
2 week
What are the withdrawal signs of tricyclics?
- Sleep disturbances and nightmares
- GI upset
- Irritability
What are some common examples of selective serotonin reuptake inhibitors (SSRIs)?
- Fluoxetine
- Paroxetine
- Sertraline
- Citalopram
“Flashbacks Paralyze Senior Citizens”
What is the pharmacological activity of SSRIs?
- Can be combined with lithium in bipolar disorder
- Do not elevate mood in normal patients
- Main advantage over tricyclics is safety
What are SSRIs used to treat?
- Bipolar disorders (with lithium)
- Panic disorders
- Generalized anxiety disorder
- Obsessive compulsive disorder
(T/F) Fluoxetine is 10x more potent than sertraline.
False. Sertraline is 10x more potent than fluoxetine.
PCKN of SSRIs:
- Well absorbed orally
- Rate of metabolism is age dependent
- Children > young adults > over 60
- Exception: Fluoxetine and sertraline are metabolized to active metabolites by the liver
- Fluoxetine T1/2: 2-3 days
- Paroxetine T1/2: 22 hrs
- Sertraline T1/2: 25 hrs
- Citalopram T1/2: 33-38 hrs
The active metabolite of fluoxetine is _____________.
Norfluoxetine (7-15 day half-life)
Acute overdose is more serious in (tricyclics/SSRIs).
Tricyclics
What are some adverse effects of SSRIs?
- CNS stimulation
- Nausea and vomiting
- Headache
- Sexual dysfunction
- Black Box warning for cardiac birth defects
Sexual dysfunction is more common in (tricyclics/SSRIs).
SSRIs
What are the contraindication of citalopram?
-
Citalopram may cause QT prolongation
- Not to be prescribed to patients with history of congenital long QT syndrome
- If QT is >500msec, citalopram should be discontinued
When SSRIs are combined with MAO inhibitors, what condition may result?
Serotonin syndrome
What are the drug interactions of SSRIs?
- Causes serotonin syndrome when combined with MAO inhibitors
- SSRIs inhibit mixed function oxidases (CYP2D6)
- Reduces metabolism of other drugs
- Sertraline and citalopram do not inhibit P450 system
- Fluoxetine binds to plasma proteins
- Displaces warfarin and digoxin
What are the symptoms of serotonin syndrome?
-
SMARTS
- Sweating
- Myoclonus
- ANS instability
- Rigidity
- Temperature increase (hyperthermia)
- Seizures
What are the symptoms associated with withdrawal from SSRIs?
- Less symptoms with longer T1/2 compounds
- Dizziness
- Nausea
- Paresthesias
- Tremors
- Anxiety
- Palpitations
What are some common examples of selective serotonin and norepinephrine reuptake inhibitors (SSNRIs)?
- Venlafaxine
- Duloxetine
What is the pharmacological activity of SSNRIs?
Block reuptake of both serotonin and norepinephrine (equally) with minimal antimuscarinic and α-adrenergic antagonist effects
Venlafaxine has a 10x (higher/lower) affinity for 5-HT than sertraline, an SSRI.
Lower
Venlafaxine has a 11x (higher/lower) affinity for 5-HT than amitriptyline, a tricyclic.
Higher
Venlafaxine, an SSNRI, is more selective for (5-HT/NE) transporters.
5-HT
What are some common examples of miscellaneous antidepressants?
- Bupropion
- Trazodone
- Nefazodone
- Mirtazapine
What is the pharmacological activity of miscellaneous antidepressants?
- Effective in treating bipolar disorder in combination with lithium
- Does not elevate mood in normal patients
(T/F) The mechanism of action for bupropion might involve dopamine and norepinephrine transporters, but has little to no effect on 5-HT and MAO.
True.
The active metabolite of bupropion is _______________.
Hydroxybupropion
What is the mechanism of action for Trazodone?
- Blocks 5-HT 2a receptor
- Modest antagonist at H1 receptor (histamine receptor)
- Weak but selective inhibitor of SERT with little effect on NET
- Weak to moderate antagonism of α-2 adrenergic receptors
What is the mechanism of action for Nefazodone?
- Blocks 5-HT 2a receptor
- Inhibits SERT and NET
What are the adverse effects of Mirtazepine?
- Sedation (opposite of Bupropion)
-
Increased appetite and weight gain (opposite of Bupropion)
- Can be used to an advantage, such as in anorexic patients
- Dry mouth and constipation
- No sexual side effects
What are the drug interactions associated with miscellaneous antidepressants?
Do not combine any with MAO inhibitors
- Bupropion
- Trazodone
- Nefazodone
- Mirtazapine
What are some common examples of monoamine oxidase inhibitors (MAO inhibitors)?
- Phenelzine
- Tranylcypromine
- Selegiline
What is the pharmacological activity of MAO inhibitors?
- Used in depression only when refractory to other drugs
- Narcolepsy
What is the mechanism of action for MAO inhibitors?
- Inhibition of both MAO-A and MAO-B
- Selegiline is specific for MAO-B
- Increase norepinephrine, dopamine, and serotonin levels
- Takes 2-3 days for optimum inhibition of 70% to be reached
What is the pharmacokinets of MAO inhibitors?
- Good oral absorption
- Slow elimination
- Termination of activity is dependent upon the synthesis of new enzyme
What are some adverse effects of MAO inhibitors?
- Insomnia
- Agitation
- Hyperthermia
- Convulsions
- Hypo or hypertension
- Rare hepatotoxicity
What are the drug and food interactions of MAO inhibitors?
- Interacts with:
- Sympathomimetics
- Tricyclics
- SSRIs
- Foods (such as wine and cheese - tyramine)
What are some common examples of atypical antipsychotics?
- Aripiprazole
- Quetiapine
- Olanzapine
- Risperidone
_____________, taken from the Hypericum perforatum plant, is commonly prescribed for mild to moderate depression in Europe.
St. John’s wort
(T/F) St. John’s wort activates CYP3A4 and CYP2C9. It also activates CYP1A2 only in females.
True.
What are the adverse effects of St. John’s wort?
- GI symptoms
- Dizziness
- Confusion
- Sedation
- Photosensitivity
- May aggravate mania in bipolar patients and psychosis in schizophrenics
(T/F) Ketamine has a rather slow onset and short-lasting antidepressant effects in otherwise treatment-resistant patients.
False. Ketamine has a fast onset and a sustained antidepressant effect in otherwise treatment-resistant patients.
What are the two first line treatments of major depression?
- SSRIs
- SSNRIs
__________ is the only SSRI approved for depression in children and adolescents.
Fluoxetine
(T/F) 2nd generation antidepressants (the miscellaneous antidepressants) are not effective in the severely depressed. Bupropion is the exception to this rule.
True.
_____________, a tricyclic, has the cheapest generic form of medication.
Imipramine
Which two antidepressants have lowest incidence of sexual side effects?
- Bupropion (decreased appetite and awake)
- Mirtazepine (increased appetite and sedation)
What are some adverse side effects seen with Trazodone (2nd generation antidepressent)?
- Drowsiness
- Priapism (permanent impotence)
What are some adverse side effects seen with Nefazodone (2nd generation antidepressent)?
- Hepatotoxicity
- Dry mouth
What are some adverse side effects seen with Bupropion (2nd generation antidepressant)?
- Agitation (most frequent reson for discontinuation)
- Decreased appetite (opposite of Mirtazepine)
- Sedation (opposite of Mirtazepine)
- No sexual side effects
