Depression Drugs

Question 1

What are the 3 potential anatomical targets for antidepressants?

Answer 1

Cingulate cortex, amygdala, Hippocampus

Question 2

What is the MOA, clinical use, and toxicity of barbiturates?

Answer 2

Ex. Phenobarbital, pentobarbital, thiopental, secobarbital
MOA: Facilitate GABAa action by increasing duration of Cl- channel opening, thus decreasing neuron firing
Clinical use: Sedative for anxiety, seizures, insomnia, induction of anesthesia
Toxicity: Resp/CV depression; CNS depression (exacerbated by EtOH) use.. dependence. drug interactions (induces cytochrome P-450)
OD treatment is supportive (assist respiration and maintain BP)

Question 3

What is MOA, clinical use, toxicity of benzodiazepines?

Answer 3

Ex. Diazepam, lorazepam, triazolam, temazepam,
MOA: Facilitate GABAa action by increase frequence of Cl- channel opening. Decrease REM sleep. Most have long half lives and active metabolites
Clinical use: Anxiety, spasticity, status epilepticus, detoxification (especially alcohol withdrawal-DTs), night terrors, sleepwalking, general anesthetic
Toxicity: Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates

Question 4

Where do benzos, barbs,and EtOH bind?

Answer 4

All bind to GABAa receptor which is a ligand-gated Cl- channel

Question 5

SSRI
FLoxetine, PARoxetine, SEtraline, CITalopram "flashbacks paralyze senior citizens"
MOA
Clinical use
Toxicity

Answer 5

*Normally takes 4-8 weeks for antidepressants to have an effect
-5 HT specific reuptake inhibitor
-Depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social phobias, PTSD
-Fewer than TCAs (side effectS). GI distress, sexual dysfunction (anorgasmia and decreased libido)
Serotonin syndrome with any drug that increases 5-HT (e.g. MAO inhibitors, SNRIs, TCAs)-hyperthermia, confusion, diarrhea, seizures. Treatment: cyproheptadine (5-HT receptor antagonist

Question 6

SNRI
Venlafaxine, duloxetine
MOA 
Clinical use
Toxicity

Answer 6

• Inhibit 5-HT and norepinephrine reuptake.
• Depression. Venlafaxine is also used in generalized anxiety and panic disorders; duloxetine is also indicated for diabetic peripheral neuropathy.
• Increase BP most common; also stimulant effects, sedation, nausea.

Question 7

Tricyclic antidepressants
Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxapine (all
TCAs end in -iptyline or -ipramine except doxepin and amoxapine).
MOA
Clinical use
Toxicity

Answer 7

-Block reuptake of norepinephrine and 5-HT.
-Major depression, OCD (clomipramine), fibromyalgia.
-Sedation, α1-blocking effects including postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). 3° TCAs (amitriptyline) have more anticholinergic effects than 2° TCAs (nortriptyline) have. Desipramine is less sedating, but has a higher seizure incidence.
Tri-C’s: Convulsions, Coma, Cardiotoxicity (arrhythmias); also respiratory depression, hyperpyrexia. Confusion and hallucinations in elderly due to anticholinergic side effects (use nortriptyline). Treatment: NaHCO3 for cardiovascular toxicity.

Question 8

MAO oxidase inhibitors

Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline (selective MAO-B inhibitor). (MAO Takes Pride In Shanghai).

Answer 8

-Nonselective MAO inhibition

Question 9

Bupropion
MOA
Use
Toxicity

Answer 9

• Increase NE and dopamine via unknown mechanism
• Smoking cessation in addition to antidepressant use
• Toxicity: stimulant effects (tachycardia, insomnia), headache, seizure in bulimic patients. No sexual side effects

Question 10

Mirtazapine
MOA
Use
Toxicity

Answer 10

• Alpha-2 antagonist (increase release of NE and 5-HT) and potent 5-HT2 and 5-HT3 receptor antagonist
• atypical Antidepressant
• sedation (which may be desirable in depressed patients with insomnia), increased appetite, weight gain

Question 11

Trazodone
MOA
Use
Toxicity

Answer 11

• Primarily blocks 5-HT2 and a-1 adrenergic receptors
• Used primarily for insomnia as high doses are needed for antidepressant effects
• Sedation, nausea, priapism, postural, hypotension

Question 12

Major depressive disorder (sig e caps)

Answer 12

Sleep disturbance, loss of interest, guilt or feelings of worthlessness, energy loss and fatigue, concentration problems, appetite/weight changes, psychomotor retardation and agitation, suicidal ideation and depressed mood