Antidepressants

Question 1

What are the MAOs MOA, uses, AE, and DI?

Answer 1

MOA: inactivates excess NE, dopamine, and serotonin that may leak out of synaptic vesicles when neuron is at rest

• Phenelzine: irreversibly bind MAO-A/B
• Isocarboxazid: irreversibly bind MAO-A/B
• Tranylcypromine: irreversibly bind MAO-A/B
• Selegiline: MAO-B inhibitor and MAO-A at high doses

Uses: tx of depression when unresponsive to other antidepressants; Selegiline Tx early Parkinson’s disease (transdermal)

AE: drowsiness, insomnia, N, orthostatic hypotension, weight gain, muscle pain sexual dysfunction

DI: serotonin syndrome, cheese reaction (pseudoephedrine and phenylpropanolamine)

Question 2

How can you manage Serotonin Syndrome and Cheese Reaction?

Answer 2

• Serotonin Syndrome: Benzodiazepine (sedation) and Cyproheptadine (serotonin antagonist)
• Cheese Reaction: Phentolamine or Prazosin to manage tyramine-induced HTN

Question 3

What are the TCAs MOA, AE, and what is used to Tx overdose?

Answer 3

MOA: block SERT and NET

• Amitriptyline
• Nortriptyline
• Clomipramine
• Desipramine
• Imipramine

AE: block alpha-andrenergic, muscarinic, histamine, and cardiac fast sodium channels

OD: Sodium Bicarbonate to reverse conduction block

Question 4

SSRI MOA, uses, AE?

Answer 4

MOA: inhibit SERT with little other activity

• Citalopram
• Escitalopram
• Fluvoxamine
• Fluoxetine
• Paroxetine
• Sertraline

Uses: DOC depression; OCD, PD, GAD, PTSD, SAD, Premenstrual Dysphoric Disorder, Bulemia, Premature ejaculation

AE: N/D, GI upset; less of the TCAs AE; overdose can cause seizure

Question 5

SNRIs MOA, uses?

Answer 5

MOA: block SERT and NET without other effects of TCAs

• Venlafaxine: potent inhibitor 5HT uptake, inhibits NE uptake at high doses, weak inhibitor of dopamine uptake
• Duloxetine

Uses: Tx depression when SSRIs are ineffective

Question 6

NDRIs MOA, uses?

Answer 6

MOA: inhibits NE and dopamine uptake and increase release

• Bupropion

Uses: not associated with sexual dysfunction because it is not serotonergic and smoking cessation; overdose and cause seizures

Question 7

SARIs MOA, uses?

Answer 7

MOA: weak inhibitors of SERT and NET and also 5HT2 antagonist

• Nefazodone: no longer prescribed bc of hepatotoxicity
• Trazodone: also blocks alpha1 and H1 so extremly sedating and used as a hypnotic

Question 8

NASSA MOA, uses

Answer 8

MOA: antagonist of central presynaptic alpha2 receptors > enhance release of NE and 5HT; antagonist at 5HT2/3 receptors; H1 antagonist

• Mirtazapine

Uses: may be useful if insomnia or agitation is prominent

Question 9

What is Antidepressant Discontinuation Syndrome, symptoms, drugs most likely to cause it?

Answer 9

• abrupt discontinuation of antidepressants causing symptoms:
• Anxiety/irritability/tearfulness, dizziness, HA, lethargy, flu-like symptoms, electic-shock sensation, insomnia, N/V/D
• By discontinuation of SSRI/SNRI specifically Paroxetine and Venlafaxine because of short half life

Question 10

Which classes of antidepressants can be used for chronic pain?

Answer 10

• TCAs and SNRIs mainly for neuropathic pain because block NE and 5-HT

Question 11

Lithium MOA, Uses, AE?

Answer 11

MOA: uncompetitive inhibitor of inositol polyphosphatase and monophosphatase to block regeneration of inositol

Uses: prophylactically in treating manic-depressive pts and in tx of manic episodes

AE: tremor/sedation/ataxia/aphasia, seizure, weight gain, hypothyroidism, nephrogenic diabetes insipidus, edema, dermatitis, alopecia, leukocytosis; category D

Question 12

How are the adverse effects of tremor and nephrogenic diabetes insipidus from Lithium treated?

Answer 12

• Tremor: Propranolol or Atenolol
• Nephrogenic Diabetes Insipidus: Amiloride (Thiazides and NSAIDs)

Question 13

What should be regularly monitored when taking Lithium and what drugs reduce its renal clearance?

Answer 13

• Monitor: Serum lithium concentrations, Thyroid function, Renal function
• Reduce renal clearance: Thiazide, NSAIDs, ACE inhibitors, ARBs