Antidepressants Flashcards
According to the biogenic amine theory, depression is due to a deficiency of which two neurotransmitters in the brain?
- Serotonin (5-HT)
2. Norepinephrine (NE)
MAOa inactivates which neurotransmitters?
5-HT; NE
MAOb inactivates which neurotransmitter?
Dopamine (DA)
What is the mechanism of action of MAOIs?
inactivation of MAO, thereby increasing levels of 5-HT, NE, and DA in presynaptic neurons with subsequent leakage of neurotransmitter into the synaptic cleft
Name 3 nonselective MAOIs:
- Transylcypromine
2l Phenelzine - Isocarboxazid
Selegiline is commonly used in the treatment of which disease?
Parkinson disease
MAOa also inactivates which monoamine commonly found in certain cheeses (aged), alcoholic beverages, fish, chocolates, red wines, and processed meats?
Tyramine (inactivated by MAO in the GI tract)
MAOIs are the drugs of choice for treating what type of depression?
Atypical depression
How long does it take to see antidepressant effects in patients who are started on an MAOI?
2-4 weeks
How long should a patient wait from the time o discontinuing an MAOI to the time of starting a new antidepressant med?
At least 2 weeks
What are the adverse effects of MAOIs?
Orthostatic hypotension; xerostomia; blurred vision; drowsiness; constipation; urinary retention
What life-threatening condition may develop when MAOIs and selective serotonin reuptake inhibitors (SSRIs) are used concomitantly?
Serotonin syndrome
What characterizes serotonin syndrome?
Rigidity; diaphoresis; hyperthermia; seizures; autonomic instability; myoclonus
What life threatening condition may develop when patients taking MAOIs ingest foods containing tyramine?
Hypertensive crisis
What characterizes hypertensive crisis?
Hypertension; headache; tachycardia; nausea; vomiting; stroke; cardiac arrhythmias
A serotonin-like syndrome may develop when MAOIs are used concomitantly with what common OTC med used to suppress cough?
Dextromethorphan
A serotonin like syndrome may develop when MAOIs are used concomitantly with which opiod analgesic?
Meperidine
What is the mechanism of action of tricyclic antidepressants (TCAs)?
Inhibit reuptake of 5-HT and NE into presynaptic neurons, thereby increasing neurotransmitter concentrations in the synaptic cleft
What other types of neurotransmitter and hormonal receptors, other than 5-HT and NE, are inhibited by TCAs?
Muscarininc; alpha-adrenergic; histaminergic
How long does it take to see antidepressant effects in patients who are started on a TCA?
4-6 weeks
Give examples of TCAs:
Amitriptyline; imipramine; clomipramine; nortriptyline; protriptyline; desipramine; doxeprin
What is the name of the active metabolite of amitriptyline that selectively inhibits NE reuptake?
Nortriptyline
Which TCA is also used for the treatment tot certain types of neuropathic pain and for the prevention of migraine headaches?
Amitriptyline
Which TCA is commonly used to treat OCD?
Clomipramine
Which TCA is also used to treat pediatric nocturnal enuresis?
Imipramine
Why is imipramine used for childhood enuresis?
Increases contraction of internal sphincter of bladder; decreases stage 3 & 4 sleep
What are the adverse effects of the TCAs?
Xerostomia; blurred vison; urinary retention; constipation; precipitation of acute glaucoma attacks; cardiac arrhythmias; seizures (lowers seizure threshold); orthostatic hypotension with reflex tachycardia; sedation; serotonin syndrome when combined with MAOIs and/or SSRIs; coma
What are the “3 C’s” of TCA toxicity?
Coma, convulsions, and cardiotoxicity
Compare TCA toxicity to SSRI toxicity
SSRI toxicity is much lower than that seen with TCAs, and mortality is most often reported only when SSRIs used in combo with another agent, such as alcohol. This is in contrast to TCAs, which can lead to death at much lower concentrations as compared to SSRIs.
What is the treatment for TCA overdose?
Activated charcoal to absorb the drug in the GI tract; sodium bicarbonate to correct acidosis and cardiac arrhythmias; phenytoin; magnesium
What is the mechanism of action of trazodone and nefazodone?
inhibits reuptake of 5-HT into presynaptic neurons, thereby increasing neurotransmitter concentrations in the synaptic cleft
What adverse effect is unique to trazodone?
Priapism
What is the mechanism of action of bupropion?
Weak inhibitor of DA, 5HT, and NE reuptake
Does bupropion cause sexual dysfunction?
NO, making it a useful alternative in patients that experience sexual dysfunction with other antidepressant medications such as SSRIs
Is bupropion safe to use in patients with epilepsy?
no, because it lowers the seizure threshold
What is the MOA of mirtazapine?
alpha2- adrenoceptor antagonist (results in increased release of NE & 5-HT)
What is the major side effect mirtazapine?
weight gain via appetite stimulation (may be beneficial in depressed patients who become anorexic)
Name an alpha2-antagonist that is used in the treatment of erectile dysfunction?
Yohimbine
What is the mechanism of action of venlafaxine?
Potent inhibitor of 5-HT and NE reuptake; weak inhibitor of DA reuptake
What is the major side effect of venlafaxine?
Hypertension
What is the mechanism of action of duloxetine?
Selective serotonin and norepinephrine reuptake inhibitor (SSNRI)
Give examples of SSRIs:
Fluoxetine Paroxetine Fluvoxamine Sertraline Citalopram Escitalopram
What is th prototype of the SSRI drug class?
Fluoxetine
What is the longest acting SSRI?
Fluoxetine
Fluoxetine is also used in what other settings (other than depression)?
Premenstraul dysphoric disorder (PMDD); bulimia nervosa; OCD; panic disorder; selective mutism
What kind of drug interactions may SSRIs produce?
Inhibition of cytochrome P-450 enzymes
Do SSRIs cause sexual dysfunction?
Yes, they can cause anorgasmia
Do SSRIs cause cardiac arrhythmias?
No, they do not, in contrast to TCAs
What are the adverse effects of SSRIs?
Sexual dysfunction; agitation; anxiety; seizures (with overdose); nausea; vomiting; diarrhea; sedation
What SSRI is also FDA approved for social anxiety disorder (GAD), and post traumatic stress disorder (PTSD)?
Paroxetine
Which SSRIs cause the least amount of drug-drug interactions
Citalopram; escitalopram; sertraline
