Antidepressants

Question 1

Explain the difference between voltage-gated and ligand-gated ion channels.

Answer 1

Voltage gated channels:
o Respond to changes in membrane potential
o Found on axons of nerve cells (Na+ channels); cell bodies, dendrites (K+, Ca2+)

Ligand gated channels:
o Respond to chemical NTs that bind to receptor subunits
o Can be modulated by G protein-coupled receptors
o Found on cell bodies, an on both presynaptic and postsynaptic sides of synapses

Question 2

List the major chemical and peptide neurotransmitters and their receptors in the brain.

Answer 2

• Acetylcholine: M1, M2, Nicotinic
• Dopamine: D1, D2
• Norepinephrine: α1, α2, β1, β2
• Serotonin: 5-HT1A, 1a, 3, 4
• Glutamic acid: NMDA, KA, AMPA, mGLU1-7
• GABA: GABAA, GABAB
• Peptide transmitters
• Endocannabinoids

Question 3

List the SSRIs

Answer 3

Citalopram
Escitalopram
Fluoxetine 
Paroxetine
Sertraline

Question 4

List the SNRIs

Answer 4

Duloxetine

Venlafaxine

Question 5

List the MAO inhibitors

Answer 5

Selegiline

Tranylcypromine

Question 6

List the Tricyclic antidepressants

Answer 6

Amitriptyline
Desipramine
Imipramine
Nortriptyline

Question 7

List the Atypical Antidepressants

Answer 7

Bupropion
Mirtazapine
Trazodone

Question 8

List the major categories of drugs that are used in the treatment of depression.

Answer 8

• SSRIs
• SNRIs
• MAO inhibitors
• Tricyclic
• Atypical

Question 9

Describe differences in the neurochemical effects of the different classes of reuptake inhibitors

Answer 9

TCAs:
o Inhibit reuptake mechanisms that terminate synaptic actions of both NE and 5-HT
o Result = potentiation of NT action at post-synaptic receptors

SSRIs:
o Selective action on serotonin transporter (SERT)
o Allosterically inhibit transporter
o Minimum effects on NE transporter

SNRIs:
o Bind to transporters for BOTH serotonin and NE
o Different than TCAs because no significant blocking effects on peripheral receptors (including histamine H1, muscarinic, or alpha-adrenergic)

Question 10

Compare the pharmacokinetics of the reuptake blockers and the monoamine oxidase inhibitors.

Answer 10

Reuptake inhibitors:
o Require hepatic metabolism
o Half-life: 18-24 hours

MAOI’s:
o Inhibit both MAO-A (metabolizes NE, 5-HT, and tyramine) and MAO-B (metabolizes dopamine)
o Prolonged action (1-3 weeks)
o Inhibit hepatic drug-metabolizing enzymes → cause drug interactions

Question 11

Describe the adverse effects associated with the use of TCA’s

Answer 11

• Anticholinergic activity → variety of autonomic effects
• Moderate a adrenergic blockade → orthostatic hypotension
• Moderate antihistamine activity → sedation
• Class IA antiarrhythmic-like activity: blockade of cardiac Na+ channels; extremely dangerous in high doses
• Potential serotonin syndrome

Question 12

Describe the pharmacological differences, adverse effects, and precautions associated with the use of uptake inhibitors (SSRIs and SNRIs)

Answer 12

o Low or no anticholinergic activity
o Low or no a-adrenergic blockade
o Low or no antihistamine activity
o Newer agents produce only minor problems in overdose
o Serotonin syndrome: hyperthermia, flushing, GI disturbances, myoclonus, diaphoresis

Question 13

Describe the pharmacological differences, adverse effects, and precautions associated with the use of MAOIs

Answer 13

o Increase monoamine neurotransmitter activity by inhibiting MAO metabolism of 5-HT, DA, NE
• Gut isoform is mostly MAO-A
• Brain isoform is mostly MAO-B
o Effects persists after parent drugs are undetectable in blood, must DC 2-3 weeks before giving sympathomimetic drugs
o Tyramine-containing foods must be avoided with MAOIs
o Can produce a hypertensive crisis: hypertension, tachycardia, severe headache, fever, mydriasis
o OTC sympathomimetics must be avoided: Phenylephrine, Pseudoephedrine

Question 14

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

Answer 14

Anxiety disorders (SSRIs, TCAs, MAOIs)
o	PTSD
o	OCD
o	Social anxiety disorder
o	Generalized anxiety disorder
o	Panic disorder

Pain disorder (SNRIs, TCAs)
o Neuropathic pain
o Postherpetic neuralgia
o Phantom limb pain

Premenstrual dysmorphic disorder (SSRIs)
Smoking cessation (bupropion, nortriptyline)
Eating disorders (SSRIs)
Enuresis (TCAs)

Question 15

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

Answer 15

• Antidepressants can precipitate mania or hypomania

* Need to screen before prescribing

Question 16

Describe the clinical presentation and course of serotonin withdrawal (discontinuation syndrome).

Answer 16

• Occurs after interruption, dose reduction or discontinuation or SSRI or SNRI drugs

Symptoms:
o “Brain shocks” or “pulses”
o Dizziness, electric shock-like sensations, sweating, nausea, insomnia, tremor, confusion, nightmares, vertigo

Question 17

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

Answer 17

Serotonin syndrome:
o Life-threatening
o Includes: severe muscle rigidity, myoclonus, hyperthermia, cardiovascular instability, marked CNS stimulatory effects (seizures)
o Drugs involved: MAOIs, TCAs, dextromethorphan, meperidine, St. John’s wort, ecstasy

Mneumonic: Sinner SELl Drugs That Make ME TRIp
•	St. Johns Wort
•	SSRI
•	Dextromethorphan
•	TCAs
•	MAOIs
•	Meperidine 
•	Triptans

Treat: antiseizure drugs, muscle relaxants, 5-HT receptor blockers (cypoheptadine)

Neuroleptic malignant syndrome:
o Life-threatening
o From use of anti-psychotic drugs
o Includes: hyperthermia, rigidity, and autonomic dysregulation