Pharmacology of Antidepressant Drugs

Question 1

List the three major categories of drugs use in the treatment of depression

Answer 1

Uptake inhibitors, monoamine oxidase inhibitors, and atypical agents

Question 2

Describe the neurochemical characteristics and adverse effects of TCAs.

Answer 2

TCAs: mixed 5-HT and NE uptake inhibition

Adverse effects: Anticholinergic activity, moderate a adrenergic blockade, antihistamine activity, class IA antiarrhythmic-like activity (blockade of cardiac Na+ channels, potential serotonin syndrome

Question 3

Describe the neurochemical characteristics and adverse effects of reuptake inhibitors (SSRIs, SNRIs and NRIs).

Answer 3

SSRIs, SNRIs and NRIs (second generation uptake inhibitors)- not as problematic in overdose; No anticholinergic activity, a-adrenergic blockade, antihistamine acitivity

Adverse effects: Concern for serotonin syndrome: hyperthermia, flushing, GI disturbances, myoclonus and diaphroresis

Question 4

Describe the neurochemical characteristics and adverse effects of MAOI.

Answer 4

MAOI: inhibit the metabolism of 5-HT, DA and NE (brain isoform MAO-B, gut MAO-A) Act as covalent inhibitors and so effects persist after leave blood stream

Adverse effects: DC 2-3 before sympathomimetics and avoid tyramine containing foods

Question 5

List benefits of newer uptake inhibitors compared to first generation agents.

Answer 5

Second generation uptake inhibitors have low/no anticholinergic activity, a-adrenergic, antihistamine, no antiarrhythmic like activity and produce only minor problems in overdose

Question 6

List conditions other than depression for which antidepressant drugs are also useful.

Answer 6

• – Anxiety disorders (SSRI, TCA, MAOI): PTSD, OCD, social anxiety, generalized anxiety, panic disorder
• – Pain disorder (SNRIs, TCA): neuropathic pain, postherpetic neuralgia, phantom limb pain
• – premenstrual dysmorphic disorder (SSRIs)
• – Smoking cessation (buproprion, nortiphytriptyline)
• – Eating disorders (SSRIS)
• – Eneuresis (TCAs)

Question 7

Describe the risk associated with antidepressant treatment in a person with bipolar

Answer 7

Antidepressants can precipitate mania or hypomania in bipolar patients

Question 8

Describe the clinical presentation, course and risks of serotonin syndrome and contrast it with neuroleptic malignant syndrome

Answer 8

too much serotonergic activity cause serotonin syndrome include: clonus, hyperreflexia, hyperthermia, tachycardia, altered mental state

Neuroleptic malignant syndrome is caused by DA blocking includes: slow onset over days, extrapyramidal symptoms and rigidity

Question 9

Name the class, pharmalogical distinction and adverse effects of prototype serteraline.

Answer 9

SSRI: 5-HT uptake inhibitor, weak effects on NE, DA and no affinity for adrenergic, cholinergic, GABA, DA, H or 5-HT receptors

Adverse effects: Dizziness, somnolence, fatigue, NVD, ED, palpitations
Inhibits CYP2D6, long half-life

Caution with MAOI, serotonergic agents, avoid sudden DC and hepatic disease

Question 10

Discuss the following SSRIs and their salient features:
Citalopram
Escitalopram
Fluoxetine

Answer 10

Citalopram: clean, only 5-HT activity
Escitalopram: clean, only 5-HT activity
Fluoxetine: activity at 5-HT receptors and on 5-HT, NE and DA transporters

Question 11

Name the class, pharmalogical distinction and adverse effects of prototype venlafaxine.

Answer 11

SNRI: Inhibits 5-HT uptake more than NE uptake

anticholinergic effects on CNS, CV, GI, UG and hypercholestrolemia

caution with MAOI, dementia, psychosis, tardive dyskinesia or excessive tremor, peptic ulcers or sympthomimetics

Question 12

Name the class, pharmalogical distinction and adverse effects of prototype Nortriptyline.

How is this drug different from Amitriptyline?

Answer 12

2nd line tx of depression TCA, a metabolite of amitriptyline with H1, a1, and 5-HT receptors and 5-HT, NE transporters

adverse effects include anti-muscarinic activity

Question 13

Name the class, pharmalogical distinction and adverse effects of prototype Imipramine.

How is this drug different from Desipramine?

Answer 13

2nd line tx of depression TCA, a metabolite of Desipramine, inhibits 5-HT more than NE and blocks at ACh receptors

adverse effects: significant anticholinergic effects

caution with Cardiac disease, MAOI, blood
dyscrasias, hepatic disease (CYP2D6) and sensitize skin, avoid serotonergic agents and watch LFT

Question 14

Name the class, pharmalogical distinction and adverse effects of prototype Selegiline.

Answer 14

MAOI- B selective acting as a irreversible inhibitor, preventing metabolism of DA, used in treatment of Parkinson’s and off-label for depression

Adverse effects: Anxiety, confusion, insomnia and mania, orthostatic hypertension, hypertension and arrhythmias, pain, NVD

caution with MAOI, Dementia, psychosis, tardive dyskinesia or excessive tremor, peptic ulcers, sympathomimetics

Question 15

Name the class, pharmalogical distinction and adverse effects of prototype Tranylcypromine.

Answer 15

MAOI, 2nd line depression med for patients unresponsive to tx., effective in refractory anxiety disorders, quick action as non-selective, irreversible inhibitor of MAO, increases NE, 5-HT, DA and epi

Adverse effects: sympathomimtic effects: HTN, agitation, insomnia, tachycardia, mydriass, diaphoresis, tremor, aggressiveness, urinary retention

caution with CV and hepatic problems, pheochromocytoma, concern with radio- contrast (seizures) and DM

Question 16

Name the class, pharmalogical distinction and adverse effects of Bupropion.

Answer 16

1st line treatment for depression, has some affinity for nicotinic receptors, mechanism for inhibition of 5-HT, NE and DA uptake are unclear and varying affinity for Ach, NE, DA, 5-HT, a-1 receptors, and voltage activated Na and Ca channels

Fewer adverse sexual effects; significant agitation, anxiety, dizziness, tremor, HTN, tachycardia, constipation and xerostomia (muscarinic activity)

Caution with seizure disorder, eating disorders, sympathomimetic drugs and hepatic disease

Question 17

Discuss the following atypical psychotics and their salient features:
Miratazapine
Trazodone

Answer 17

mirtazapine: Antidepressant and anxiolytic, potent antagonist at 5-HT2a, 2c 3 and H1 receptors; antagonizes presynaptic a2 receptors (increases NE release) and is weak antagonist at 5-HT1 receptors
trazodone: serotonergic and noradrenergic systems, antagonism at 5-HT2A and a1 receptors and inhibition of 5-HT uptake

both produce sedation and drowsiness

Question 18

Describe the mechanism of action of ketamine?

Answer 18

activates mammalian mTOR pathways leading to increase synaptic signaling protein and increased spine synapses (NMDA receptor actor, like N2O)