AntiDepressants Flashcards
Typically, how long do anti-depressants take to exert their therapeutic effects?
4-6 weeks, though adverse effects from these drugs may start after the first dose
The effect at the drug’s target site is immediate, but clinical improvement takes weeks-months
What is the function of MAOs? How about MAO-A and MAO-B specifically?
Breakdown 5-HT and NE in serotonergic and dopaminergic axon terminals
MAO-A: metabolizes NE, Epi, and 5HT
MAO-B: metabolizes trace amines and 5HT when at high concs
MAOIs
MOA
Inhibit MAO enzymes to prevent breakdown of NE and 5HT in the axon terminals. More is thus released into the synaptic cleft
MAOIs
What are the two main kinds? What drugs are in each class?
Irreversible Inhibitors:
Phenelzine
Tranylcypromine
Selegiline
Reversibel Inhibitors:
Meclobemide (not available in USA)
MAOIs
Irreversible Inhibitors MOAs
Phenelzine and Tranylcypromide block MAO-A and MAO-B by irreversibly binding and inhibiting the enzyme
Selegiline preferentially blocks MAO-B. Acts as an antidepressant at high doses.
MAOIs
Pharmacokinetics (half life, etc)
Brief half life
Irreversible – bind enzyme and that’s it. Once bound to MAO, enzyme must be replaced, which could take 10-14 days
Reversible– drug and enzyme can uncouple in certain situations
MAOIs
Adverse Effects
- Hypertensive Crisis
- Serotonin Syndrome
Excess 5HT:
Nausea, vomiting
Sexual Dysfunction
Sleep disturbance
Excess NE:
Orthostatic hypotension
When could a hypertensive crisis occur in a patient taking a MAOI?
MAOI blocks MAOs in the liver, which can prevent metabolism of some compounds in foods (tyramine in cheeses). If they consume foods high in tyramine, tyramine levels are elevated in the blood and tyramine can act as a pressor
What is special about selegiline’s dosage that it may be used to prevent hypertensive crisis?
Used in a transdermal patch so it travels directly to brain without going through first pass metabolism in the liver. Minimizes risk for HTN crisis because MAOs in brain are inhibited before MAOs in the liver
MAOIs
Describe signs and symptoms of Serotonin Syndrome
Caused by excess 5HT
Myoclonus Increased reflexes High BP Fever Cardiovascular collapse Altered mental status
Why are OTC cold remedies and antidepressants often a bad combination?
Could cause HTN crisis
List the Tricyclic Antidepressants (tertiary and secondary)
Tertiary
Imipramine
Amitryptaline
Secondary:
Desipramine
Nortriptyline
Clomipramine and Doxepin are tertiary, but act like secondary
How do the functions of tertiary and secondary TCAs differ?
Tertiary
NE = 5HT reuptake inhibitors
Secondary
NE > 5HT reuptake inhibitors
TCAs
Pharmacokinetics (Solubility, Vd)
High lipid solubility
High Vd
TCAs
Side Effects
Sedation – block H1, M1 muscarinic, a1 adrenergic receptors
Sexual dysfunction
HTN
Sweating
In what patients might you avoid using TCAs?
Elderly – avoid oversedation and confusion
Anyone on pain meds (CNS depressants) – risk of oversedation
Worried about people who might overdose. Worried about people who are on other drugs that will inhibit TCAs’ metabolism
SSRIs
MOA
Block the 5HT reuptake pump on the presynaptic axon terminal, thus leaving 5HT in the synapse longer so it can bind its receptor
List the SSRIs available
Fluoxetine Sertraline Paroxetine Citalopram Escitalopram Fluvoxamine
Why are SSRIs beneficial over TCAs?
SSRIs have very low risk of side effects involving histamine, Ach, and NE receptors
Which SSRI has the longest half life?
Fluoxetine (1-4 days) and its metabolite (7-15 days)
What effects do SSRIs have on CYP450 enzymes?
Inhibitory effects on CYP450 enzymes
Fluoxetine and Paroxetine are strong inhibitors of CYP 2D6 enzymes
Which SSRIs have the shortest half lives?
Paroxetine and Fluvoxamine
Which SSRIs have the highest risk of discontinuation syndrome (withdrawal) if they are abruptly stopped?
Paroxetine and Fluvoxamine
SSRIs
Side effects
GI upset
Anxiety
CNS
Sexual dysfunction
May only happen once or twice and then go away, or be intermittent. You need them to deal with side effects for some time (4-6 weeks) until they might actually see clinical improvement in symptoms
SNRIs
MOA
Block reuptake at both the serotonin and NE reuptake pumps, leaving both 5HT and NE in the synaptic cleft longer
What is the most commonly used SNRI?
Venlafaxine
Note: has a very short half life, so may have a discontinuation syndrome if abruptly stopped
What are the two atypical antidepressants?
Buproprion
Mirtazipine
Mirtazipine
MOA
Blocks alpha 2 adrenergic autoreceptors on NE and 5HT neurons
Also blocks histamine receptor, 5HT-2A, 2C, 3 (prevents potential side effects of excess serotonin)
Mirtazipine
Side Effects
Weight gain
Sedation
Buproprion
MOA
NE and DA reuptake inhibitor
Buproprion side effects
No 5Ht or H1 related side effects
Increased seizure risk at high doses
Nefazodone
MOA and Side Effects
Blocks 5HT reuptake
5HT-2A receptor antagonist
No sexual side effects, mild sedation
Vilazodone
MOA and Side Effects
Blocks 5HT reuptake
Partial agonist at 5HT-1A receptors
Insomnia
GI upset
Vortioxetine
MOA and Side Effects
Blocks 5HT reuptake
Agonist of 5HT-1A receptors
Partial agonist of 5HT-1B receptors
Antagonist 5HT-3 and 5HT-7 receptors
No sexual side effects or weight gain
If you are switching from an MAOI to an antidepressant, how long should you wait to start the new med?
Need to wait for neurons to regenerate new MAO enzymes (they need to replenish those that have been irreversibly inhibited).
Wait 10-14 days
Which two antidepressants are most likely to produce interactions with other drugs?
Fluoxetine and Fluvoxamine
