Antidepressants Flashcards
2 possible etiologies of depression
Monoamine hypothesis suggests decreased 5HT, DA, or NE.
Neurotrophic hypothesis suggests decreased BDNF activity.
Comparing Serotonin Syndrome to Neuroleptic Malignant Syndrome Causative medication Time course Vitals Pupils Bowel Sounds Neuromuscular tone Reflexes Mental status
Meds: SS from serotonergic drugs. NMS from DA antagonist
Time: SS less than 12 hrs. NMS 1-3 days.
SS vitals: HTN, tachycardia, tachypnea, hyperthermia (41+ C)
NMS vitals: HTN, tachycardia, tachypnea, hyperthermia (41+ C)
Pupils: SS shows mydriasis. NMS shows normal pupils.
Bowel sounds: SS is hyperactive. NMS is normal or decreased.
Neuromuscular tone: SS shows increased tone, mainly in lower extremities. NMS shows “lead pipe rigidity” in all muscle groups.
Reflexes: SS shows hyperreflexia / clonus. NMS shows bradyreflexia.
Mental status: SS shows agitation / coma. NMS shows stupor, alert, mutism, or coma.
Tricyclics
What generation?
General mechanism
Side effects
1st gen uptake inhibitors.
Mixed 5HT and NE uptake inhibition.
Anticholinergic (xerostomia, difficulty peeing), moderate alpha adrenergic blockade (orthostasis), and antihistamine activity (sedation). Blockade of cardiac Na channels may be lethal. Possible serotonin syndrome.
Imipramine Type of antidepressant Use Mechanism What time of day should you take it? How quickly does it work? Metabolism Precautions
Early TCA.
•Use – 2nd line for depression. Enuresis.
•Mechanism – inhibits 5HT uptake more than NE uptake. Anticholinergic effects allow for enuresis.
•Take before bed to avoid daytime sedation.
•2-6 week latency period.
•Metabolized by CYP2D6 (lots of genetic variability)
•Precautions – Cardiac disease, ileus, and MAOI therapy
Desipramine Type of antidepressant Use Mechanism Speed of onset Precautions
Later TCA. Active metabolite of imipramine.
•Use – Depression, bulimia, diabetic neuropathy, and adjunct for cocaine cessation
•Mechanism – inhibits NE uptake more than 5HT. 5HT agonist at high doses. Less sedation, hypotension, and anticholinergic activity than imipramine.
•2-6 week latency
•Precautions – Cardiac disease and MAOI therapy
Amitriptyline Type of antidepressant Use Mechanism Speed of onset Adverse rxns Precautions
Early TCA
•Uses – Depression, neurogenic pain, and childhood enuresis
•Mechanism – inhibits 5HT uptake more than NE uptake. Anticholinergic, antihistaminergic, and a1 blocking effects.
•2-6 week latency
•Adverse rxns – xerostomia, constipation, sedation, cycloplegia (paralysis of ciliary muscle → loss of accommodation), orthostasis, and dysrhythmia.
•Precautions – Cardiac disease, MAOI therapy, and ileus
Nortriptyline Type of antidepressant Use Mechanism Adverse rxns Precautions
Later TCA. Active metabolite of amitriptyline.
•Use – Depression, ADHD, neurogenic pain, smoking cessation, and childhood enuresis.
•Mechanism – Inhibits NE uptake more than 5HT uptake. Anticholinergic, antihistaminergic, and a1 blocking effects, but less than amitriptyline.
•Adverse rxs – xerostomia, constipation, sedation, cycloplegia, orthostasis, and dysrhythmia.
•Precautions – Cardiac disease, MAOI therapy, and Ileus
2nd generation uptake inhibitor characteristics
What classes of drugs?
Low / no anticholinergic activity, alpha-adrenergic blockade, or antihistamine activity. May still cause serotonin syndrome.
SSRI’s and SNRI’s
Paroxetine Brand Name Type of antidepressant Use Mechanism Speed of onset Adverse rxns Precautions
Paxil
SSRI
•Use – Depression, anxiety, panic disorder, OCD, PTSD. Off-label includes premature ejaculation and hot flashes.
•Mechanism – High specificity for 5HT uptake transporters. Slight anticholinergic activity.
•Onset usually 1-4 weeks.
•Adverse rxns
• CNS: drowsiness, dizziness, insomnia, tremor
• GI: NVD, xerostomia, constipation
• UG: erectile dysfunction, delayed ejaculation
• MSK: asthenia
•Precautions – MAOI Therapy
Sertraline Brand Name Type of antidepressant Use Mechanism Pharmacokinetics Adverse rxns Precautions
Zoloft
SSRI
•Use – Depression, anxiety, panic disorder, OCD, PTSD, pre-menstrual dysmorphic disorder. Off-label for premature ejaculation and hot flashes.
•Mechanism – 5HT uptake inhibitor. No affinity for adrenergic, cholinergic, or histaminergic receptors.
•Pharmacokinetics – Inhibits CYP2D6. Long half-life.
•Adverse rxns –
• CNS: dizziness, somnolence, fatigue
• GI: NVD, dyspepsia
• UG: erectile dysfunction, delayed ejaculation, decreased libido
•Precautions – MAOI therapy
3 other SSRI’s
Citalopram (Celexa), Fluoxetine (Prozac), and Escitalopram (Lexapro)
Duloxetine Type of antidepressant Use Mechanism Adverse rxn Precaution
SNRI
•Use – Depression, GAD (first line), diabetic neuropathy, and chronic MSK pain
•Mechanism – 5HT and NE uptake inhibitor. Does not inhibit MAO.
•Adverse rxns
• CNS: drowsiness, dizziness, fatigue, insomnia
• GI: ALT, NVD, xerostomia
• Sweating
•Precautions – MAOI therapy
Venlafaxine Type of antidepressant Use Mechanism Adverse rxns Precaution
SNRI •Use – Depression, GAD, social anxiety, and panic disorder •Mechanism – Inhibits 5HT uptake more than NE uptake. No anticholinergic, histaminergic, or a1 activity •Adverse rxns • CNS: drowsiness, dizziness, insomnia • CV: tachycardia / HTN • GI: NV, xerostomia, constipation •Precautions – MAOI therapy
MAOI's Gut form Brain form Time course Avoid what? Why?
- Gut isoform is MAO-A. Brain isoform is MAO-B.
- Effects last 2-3 weeks after DC of drug b/c enzyme needs to be made again. Must wait 2-3 weeks before starting sympathomimetics to avoid serotonin syndrome.
- Avoid tyramine containing foods: wine, beer, aged cheeses, soy sauce, meats, pickled food, etc. Tyramine causes NE release and can cause a hypertensive crisis (HTN, tachycardia, severe headache, fever, mydriasis).
- Must also avoid OTC sympathomimetics (phenylephrine and pseudoephedrine).
Tranylcypromine Type of antidepressant Use Mechanism Adverse rxns Precautions
MAOI
•Use – 2nd line for depression. Used for refractory anxiety disorders, OCD, social anxiety disorder, and panic disorder.
•Mechanism – nonselective, irreversible inhibitor (forms covalent bond) of both MAO-A and MAO-B → increased NE, 5HT, DA, and Epi.
•Adverse rxns
• Sympathomimetic effects – HTN, agitation, insomnia, tachycardia, mydriasis, diaphoresis, tremor, aggressiveness, urinary retention. Most effects subside over time.
•Precautions – CV, hepatic disease / jaundice, pheochromocytoma, and radiographic contrast administration (may cause seizures)
