Antidepressants & Anxiolytics Flashcards
What is the first line pharmacological therapy for depression?
SSRIs and SNRIs
MOA of SSRIs and SNRIs
Both work to increase dopamine transmission in the CNS
What are the other uses of SSRIs and SNRIs
SSRIs and SNRIs are first line therapy for:Generalized Anxiety DisorderPanic DisorderPTSDSSRIs management of OCD, depression, bulimia and social anxiety disorder
What is bulimia?Is it related to anorexia?
Bing eating and then purging out food either by vomiting or diarrheaNot related to anorexia
Explain the treatment of generalized anxiety disorder. What drugs are used for this?
Benzodiazepines provide much more rapid relief of anxiety, but SSRIs and SNRIs are just as effective for long-term treatment and do not carry the same risk of physical dependence & addiction that benzodiazepines do
What is a disadvantage of using SSRIs or SNRIs for treatment of anxiety disorder
Don’t provide acute relief, have to wait at least 1 to 2 months to determine if they are effective or not
What do we use for pain management? SSRIs or SNRIs?What kind of pain can be managed with this agent?
SNRIs are used for neuropathic pain disorder (such as back pain etc)
Name SNRIs used for pain management
Venlafaxine and duloxetine
What specific pain management can be achieved with SNRIs?
Both can be used for painful sensation associated with diabetic neuropathy, duloxetine specifically is used for pain associated with fibromyalgia
Name SSRIs
“Fly out” Fluoxitine, “Parrot Air” Paroxetine, “Desert Airline” Sertraline, and “The City” Citalopram
Name SNRIs
“Fax Machine” Venlafaxine, Duloxetine “Duel copy scanner”
MOA of SSRIs
Work by inhibiting the presynaptic Serotonin Reuptake Transporter (SERT)
MOA of SNRIs
Work by inhibiting the presynaptic reuptake of norepinephrine (NET) and serotonin (SERT)
What are the side effects of SSRIs
- Hyponatremia due to excessive ADH release2. Decreased libido, disrupted arousal, inorgasmia, and increased ejeculation latency 3. Weight gain4. Drowsiness
What are the side effects of SNRIs
SNRIs can cause hypertension d/t increasing norepinephrine in the synaptic cleft or just autonomic malfunction in general such as tachycardia, excessive sweating etc
What is a common side effect of SSRIs and SNRIs
Serotonin syndrome
What causes neuroleptic malignant syndrome?
Dopamine blockers such as anti psychotics
Explain serotonin syndrome and NMS and how do they differ
Serotonin syndrome shares many of the characteristics as neuroleptic malignant syndrome or NMS, however there is a subtle difference in the 2. Just like in NMS serotonin syndrome can present with (1) agitation, (2) autonomic instability, (3) hyperthermia and (4) hypertension but there is one thing that should clue us into thinking serotonin syndrome specifically, look for hyper reflexia and clonus whereas in NMS we see hyporeflexia and rigidity.NMS ALSO has Rhabdomyolysis
How do you treat serotonin syndrome
Involves discontinuation of the offending drug, stabilizing vitals, and possibly administration of a Serotonin inhibitor such as Cyproheptadine
What is cyprohepatidine
5HT-2 blocker
What happens when someone being treated with SSRIs or SNRIs suddenly stops taking their medication
Withdrawal symptoms from SSRIs and SNRIs include flu-like symptoms 1-2 days after stopping the medication - so you need to slowly taper patients of the medication
What are tricyclics used for
They have numerous side effects so are used as 2nd or 3rd line for treatment of depression
Tricyclics MOA
Tricyclic Antidepressants work by inhibiting the reuptake of Norepinephrine (NET) and Serotonin (SERT)
Explain the pathophysiology of depression
One of the leading hypothesis for the pathophysiology of depression is the monoamine hypothesis that suggests that depression is related to a deficiency in monoamines (central serotonin, norepinephrine, and dopamine)
Name tricyclics
Imipramine, desipramine, and clomipramineAmitriptyline, nortriptyline
What are other uses of TCAs
All TCAs have been used historically for neuropathic pain.
What is a specific use of Amitriptyline other than to treat depression
Migraine prophylaxis
What is a specific use of Clomipramine other than to treat depression
Treats OCD
Most important AE of TCAs
By far the most important side effect is the anti cholinergic effectDry mouth, constipation, blurred vision, and urinary retention
Which TCA is most closely associated with anti cholinergic effects.What TCAs have less of this side effect?
Amitripline has the most anti-cholinergic effects out of the Tricyclic AntidepressantsNortriptyline and desipramine are secondary amines that are associated with less anticholinergic effects than Amitripiline
What are the other major AE of TCAs.What is a clinical concequence of these AE?
- Blocks histamine receptors = sedation, increased appetite, weight gain and drowsiness2. Block alpha 1 receptors - orthostatic hypotension, can cause falls in the elderly and a fatal ↓CO3. Sexual dysfunction4. Can cause serotonin syndromeTCAs are relatively contraindicated in elderly patients due to severe anticholinergic and antihistamine effects -> increased risk of sedation, delerium, urinary retention, and falls.
What is the most common cause of death in patients with TCA overdose
The most common cause of death is fatal cardiac arrhythmia by blocking cardiac fast Na+ channels -> decreased slope of P1 -> QRS & QT prolongation -> QT prolongation can cause torsades
Treatment of TCAs overdose
Sodium-bicarb Therapy, it increases the pH of the blood and provides Na to increase conductance
What are the 3 Cs side effects of TCAs and how are they caused?
Tricyclic Antidepressants can cause 3 C’s: Cardiac, Coma, Convulsions (likely d/t antagonistic effect on GABA-A receptors).
Name monoamines
NE, dopamine, serotonin
What breaks down monoamines?
Monoamine oxidase (MOA)
How many types of MOA are there? What do they break down?
MAO-A - breaks down serotonin, norepinephrine, and dopamine MAO-B - breaks down dopamine
When are MOA inhibitors used?Are these reversible or irreversible?
ALL are irreversibleUsed for Parkinson’s supplementary to L dopa and atypical depression, can treat major depressive disorder but used as a last resort
Name MAO inhibitors
Tranylcypromine “try a sip of wine” Phenelzine “funnel” Isocarboxazid “boxed wine”These are non selective MAO inhibitors so they inhibit both MAO-A and B
Name MAO-B specific inhibitor
Selegiline “sledge hammer” - a selective irreversible MAO-B inhibitor
What is a use of Selegiline
Useful in treating the cogwheel rigidity of Parkinson’s in patients that are not responding well to Levodopa
AE of MAO inhibitors?
Similar side effects as SSRIs and SNRIs, highest rate of sexual dysfunction
What food should be avoided while on MOA inhibitors?
Tyramine containing foods so aged meats, fermented dairy products, and alcohol
MOA of tyramine
Release of stored catecholamines
What happens when tyramine is taken with MOA inhibitors
Tyramine is normally broken down by MAO-A in the GI tract - with inhibition of MAO-A, the Tyramine flows into the general circulation where it acts as a sympathomimetic agent, displacing NE from neuronal storage vesicles and sending an absurd amount of NE into the synapse -> can cause a hypertensive crisis (HTN, blurry vission, diaphoresis, stroke, and even MI).
What can be used to treat tyramine toxicity
Phentolamine
When do we use atypical antidepressants
Used for treatment in patients who have failed to respond to other therapy, these can also be 1st line agents in patients that are looking for specific drug results
Bupropione drug type and MOA
Atypical antidepressant, inhibits NET and DAT so it has no effect on serotonin
What are the uses of bupropione?
Resembles amphetamine structure so it has CNS activating effects, useful for treating depression associated with hyper somnolence and low energy. Can also be used to treat tobacco dependence, smoking.
What makes bupropion especially useful as an antidepressant?
Bupropion does not affect serotonin - so it does not cause sexual dysfunction, making it useful for patients that are distressed/anxious about lack of libidoBupropion also causes less weight gain than other antidepressants - it can even be used for weight maintenance
AE of bupropione
Can induce seizures especially at high doses and in older patients. Contraindicated in patients with history of bulimia and anorexia due to the drug’s ability to induce seizures
What is mirtazapine?
Alpha 2 blocker
What are the other MOA of mirtazapine?
Blocks 5HT-2 & 5HT-3 and H1 Histamine receptors
What does alpha 2 blockade by mirtazapine specifically lead to?
Mirtazapine blockage of α-2 receptors causes an increase in presynaptic release of Serotonin and NE
What are the 3 clinical scenarios where mirtazapine is especially useful?
(1) Blockage of H1-receptors can cause sedation -> making it one of the 1st-line options for patients with depression and insomnia. (2) Blockage of H1-receptors is assoicated with weight gain -> can be used in patients w/ depression and anorexia. (3) Does not cause sexual dysfunction -> can be preferred as a 1st-line treatment for depression due to its lack of sexual side effects
What is trazodone?
Atypical anti depressant, Inhibits serotonin by blocking 5HT 2 and 5HT3 receptors. It has NO effects of NE or dopamine.Also an H1-receptor antagonist -> useful for treating insomnia associated with depression
What is a major side effect associated with trazodone due to which it is colloquially called ‘trazo-bone’?
Antagonizes alpha 1 receptors, causes priapism (persistant erection lasting >4hrs) d/t vasodilatory effects.It is not a first line agent.
Explain in what condition is priapism more likely with trozadone?What does priapism lead to?
Patients with SCD or multiple myeloma are more likely to develop priapism It can lead to permanent damage to penile tissue and erectile dysfunction if left untreated
What are other AE of trozadone?
Orthostatic hypotension due to alpha 1 blockade, also blocks H1 receptor so can cause drowsiness, can cause sexual dysfunction and finally it can cause serotonin syndrome
