E1: Antidepressants Flashcards
What is the MOA of TCAs?
- Inhibits re-uptake of NE and serotoninc
- blocks alpha-adrenergic, histamine, and muscarinic receptors
What are the uses of TCAs?
- Depression
- Chronic pain (TMJ), fibromyalgia
- enuresis
What kind of drugs are amitriptyline, Imipramine, Nortriptyline, and desipramine?
TCAs
Which TCAs are tertiary amines?
Amitripyline and Imipramine
Which TCAs primarily inhibit serotonin re-uptake and which primarily block NE re-uptake?
Serotonin: Amitriptyline and Imipramine
NE: Nortriptyline and Desipramine
What are the side effects of the tertiary amine TCAs?
- Produces more seizure than secondary amines
- more sedating than secondary amines
How are TCAs metabolized?
- well absorbed orally, given once per day
- Metabolized by CYP2D6 and drug interactions are very common
What are the side effects of TCAs?
- Weight gain
- Histamine receptor blockade (drowsiness, fatigue, and sedation)
- Cholinergic blockade (blurred vision, tachycardia, constipation, dry mouth)
- Alpha1 receptor blockade (Cardiac depression and arrhythmias
- Analgesia
- SIADH
- Sexual dysfunction
- Decrease seizure threshold
- tolerance
Why does analgesia happen with TCAs?
-Results from activation of descending noradrenerigc pathways in the spinal cord (NE acts on Alpha2 receptors to decreased glutamate input into the brain)
What are the toxicites associated with TCAs?
- TORSADES DE POINTES
- Prolonged QT
- Cardiac arrhythmias
- severe hypotension
- seizure
What is the treatment of TCA overdose?
- Magnesium, isoproterenol, and cardiac pacing for Torsades
- Lidocaine, propanaolol, phenytoin for arrhythmias
- sodium bicarb and potassium chloride to restore acid/base balance
What can occur if TCAs and MAOIs are combined?
-Serotonin syndrome: severe CNS toxicities manifested by hyperpyrexia, convulsions, and coma
What happens when TCA and SSRIs are combined?
TCAs complete for metabolism of SSRIs, so combo can lead to toxic levels of TCAs
What can happen when TCAs and amphetamines are combined?
Hypertension
What are the uses of SSRIs?
- Depression
- Panic disorder
- OCD
- Social anxiety
- Bulimia
- Alcoholism
- Children and teenagers
What are the 5 SSRIs?
-Fluoxetine, Sertraline, Paroxetine, citalopram, and Escitalopram
What is unique about Fluoxetine when compared to the other SSRIs?
-Most likely to inhibit CYP450 enzymes and therefore has more drug interactions than other SSRIs
What is currently the DOC for depression?
Citalopram or escitalopram
What is the MOA of SSRIs?
- Selectively inhibits serotonin reuptake
- 2-3 weeks to be effective
What are the common side effects of SSRIs?
- Mostly mild
- GI (nausea, loss of appetite)
- Weight loss or gain
- CNS stimulation
- possible sedation
- sexual disinterest
What happens when SSRIs are combined with Phenytoin or Carbamazepine?
Increases levels and toxicity
What are the 3 opioids that should be avoided with SSRIs?
-Codeine, Meriperidine, and tramadol
What kind of drugs are Venlafaxine and Duloxentine?
SNRIs
What are the uses of SNRIs?
Depression, neuropathic pain, and post menopausal hot flashes
What is the main side effect of Venlafaxine?
May increase BP
What are the side effects of Duloxetine?
- Hepatotoxicity
- May cause bilateral acute angle closure glaucoma
What is the MOA of MAOIs?
-Irreversibly inhibits MAOs which metabolize NE, NA, and serotonin
What is the difference between MAO-A and MAO-B?
- MAO-A metabolizes NE, DA, and serotoninc in both the CNS and the periphery
- MAO-B selectively metabolizes DA in the CNS but not in the GI tract
What kind of drugs are Phenelzine and Selegiline?
MAOIs
What is the MOA of Phenelzine?
- Inhibits both MAO-A and MAO-B
- Increases NE, serotonin, and DA
** drug of last choice due to serious side effects
What is the MOA of Selegiline?
- selectively inhibits MAO-B
- Increases DA
- Fewer side effects
- May be used in Parkinson’s
What is the use of MAOIs?
-Used for depression which doesn’t response to other drugs
What are the side effects of Phenelzine?
Hypertensive crisis: MAO-A is inhibited in the GI tract, tyramine causes release of amines, and with limited metabolism by MOA-A, can lead to severe HTN
-Avoid foods with tyramine
What are the general side effects of MAOIs?
- Orthostatic hypotension
- weight gain
- Anticholinergics effects
What is the MOA of Buproprion?
-Inhibits DA and to a minimal extend, NE and 5HT re-uptake
What are the uses of Buproprion?
- ADHD, alcoholism
- Extended release for quitting smoking
What are the side effects of Bupropion?
- Seizures
- CNS: anxiety, insomnia
- tachycardia
- sexual dysfunction side effects are RARE
What is the MOA of Mirtazapine?
- Blocks presynaptic alpha2 receptors which inhibit release of NE and serotonin
- increases release of NE and serotonin
If a patient has significant side effects with SSRIs, what could you consider switching them to that eliminates the side effects associated with SSRIs?
Mirtazapine
What is the MOA of Atomoxetine?
Selective inhibitor of NE reuptake
-first non stimulant for treatment of ADHD
What is the MOA of trazosone?
5-HT2A receptor antagonists
Why is atomoxetine a good drug for addicts?
It does not cause euphoria
What can happen when St Johns Wort is combined with other anti-depressants?
Serotonin syndrome
