Antidepressants Flashcards
Therapeutic Use of MAOIs
Atypical depression (spending a lot of time in bed, eating a lot, etc)
Treatment-resistant depression
Treatment-resistant panic disorder
Treatment-resistant social anxiety disorder
Two MAOIs that I need to know
Phenelzine
Tranylcypromine
Inhibit both MAOA and MAOB
MAOI mechanism of action
Inhibit the degradation of biogenic amines in the presynaptic terminals. get an increase in serotonin, NE, DA.
What type of inhibitor are MAOIs?
Irreversible inhibitor, so it takes at least 2 weeks for enzymes levels to recover
MAOI side effects
Serotonin syndrome (if combined with other serotonergic drugs) Hypertension/hypertensive crisis (when given adrenergics (decongestants) or stimulants) also caused by tyramine, weight gain, insomnia
Serotonin syndrome
Autonomic effects (sweating, tremor, tachycardia) Mood effects (agitation) Motor effects (myoclonus, hyperreflexia)
Drugs that, when combined with MAOIs, can lead to serotonin syndrome
SSRIs, carbamazepine, meperidine, fentanyl, methadone, tramadol
Tyramine induced hypertensive crisis
Can be triggered by the ingestion of tyramine rich foods like cheese, red wine, soy, beer. Tyramine is a catecholamine releasing agent that is broken down by MAOa in gut, if it gets access to sympathetic neurons and will cause release of NE, causing increased BP.
When can somebody who was on MAOIs eat tyramine again?
Two weeks after to allow the enzyme to regenerate.
Selegiline transdermal
MAOI that is higher dose so it inhibits both MAOA and MAOB.
Why is selegiline better when given transdermally
Bypass GI and liver so patients can eat tyramine without having a hypertensive crisis.
Tertiary Amine Tricyclic Antidepressant
Amitriptyline (also used in migraine prevention)
Secondary Amine Tricyclic Antidepressants
Nortriptyline and Desipramine
Therapeutic uses for TCAs
Depression and treatment resistant depression, childhood bedwetting, GAD, Panic disorder, obsessive compulsive disorder, neuropathic pain, fibromyalgia
How do TCAs work?
The inhibit the reuptake of NE. Tertiary amines (like amitriptyline) inhibit some 5HT reuptake as well.
Side effects of TCAs?
Very dirty drugs: H1 blockade (weight gain, sedation) Na channel blockade (anti arrhythmic effects, but can lengthen QT intervals) M1 blockade (blurry vision, constipation, dry mouth) Overdose can cause heart block.
When to avoid TCAs?
In patients with narrow angle glaucoma, recent cardiac events, prolonged QT. Secondary amines preferable in elderly.
Are TCAs lethal in overdose?
Yes, absolutely. Cause heart block.
Anticholinergic toxicity
Red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask.
What happens to tertiary amines when they are broken down by CYPs?
Broken down into secondary amines.
Can TCAs be given with MAOIs?
No way jose. That would be terrible. Cause serotonin syndrome. Wait 14 days for MAOIs to wash out.
Dosing of TCAs?
Narrow therapeutic index, start low and titrate slowly.
SSRI therapeutic uses
MDD GAD Panic Disorder PTSD OCD PMDD Bulimia
Common side effects with SSRIs
GI upset, weight gain, loss of sex drive, headache, akathisia
Metabolism of SSRIs
Significant first pass metabolism. Metabolized in liver by CYPs
SSRIs with most drug interactions
Fluvoxamine and fluoxetine
SSRIs with the least drug interactions
Citalopram and escitalopram
SSRI with the longest half life and least withdrawal?
Fluoxetine
SSRI with the shortest half-life and most withdrawal?
Paroxetine
Most selective SSRI
Escitalopram
When does SSRI withdrawal occur and what are the symptoms?
Occurs as a result of abrupt discontinuation of SSRI after at least 6 weeks of treatment. Feels like the flu. Usually resolves in 3 weeks.
Why are SSRIs preferred over other agents?
No cardiac symptoms, simple dosing, typically not lethal. No special diet.
SNRIs include
Venlafaxine, duloxetine
SNRI therapeutic uses. Common problem?
MDD
GAD
Neuropathic pain
Fibromyalgia
May increase BP.
Venlafaxine mechanism and side effects.
At high doses, acts like an SNRI. Low doses, like an SSRI. High doses can cause increase diastolic BP and can cause tachycardia
Duloxetine
SNRI, for MDD GAD.
Buproprion
Wellbutrin– Used for MDD and smoking cessation, also can be used for ADHD. Weak NE and DA repute inhibitor, inhibitor of nAChRs. No sexual dysfunction/weight gain.
Buproprion adverse effect?
May cause seizures. Avoid in patients with eating disorders (who may have electrolyte balances)
Mirtazapine
Noradrenergic and Specific Serotonergic antidepressant. Antagonizes a2 receptors (enhancing adrenergic transmission because of the auto receptor), indirect agonist of 5HT1 because it blocks 5HT2A and 5HT3, so remaining serotonin shunted to 5HT1A. Weight gain mediated by H1 antagonism, also increased somnolence.
Trazodone
5HT2A receptor antagonist, mild SNRI, used as sleep aid. Orthostatic hypertension and priapism.
Why prescribe a SNRI?
If depression with a comorbid pain disorder.
