Flashcards in Katzung 12th ed - Chapter 30 - Antidepressant Agents (1 and 2) Deck (31):
Briefly describe the monoamine hypothesis for depression.
The monoamine hypothesis suggests that it is a defect in serotonin, noradrenaline or dopamine pathways that causes depression.
Briefly describe the neurotrophic hypothesis for depression.
The neurotrophic hypothesis suggests that it is a defect in trophic factors in the brain (such as BDNF) that result in abnormalities of neural plasticity and resilience. This leads to a depressed state, in which neural connections are lost.
What is SERT?
This is the serotonin transporter that allows the re-uptake of serotonin from the synaptic cleft to the pre-synaptic nerve terminal.
Name as many SSRIs as you can (up to six).
Sertraline, Fluoxetine, Citalopram, Escitalopram, Fluvoxamine, Paroxetine
What is an SNRI? Give three examples of SNRIs.
Selective Serotonin and Noradernaline Reuptake Inhibitor. e.g. Venlafaxine, Desvenlafaxine, Duloxetine.
Which receptors do SNRIs bind to?
They all bind to both SERT and NET.
Describe the basic chemical structure of TCAs.
There are three rings all in a straight line. The first ring and the third ring are hexacarbon rings. The middle ring has variable structure and variable R groups attached to it.
What is Lyrica?
What is Endep?
Name as many TCAs as you can.
Imipramine, Desipramine, Amitriptyline, Doxepin, Protryptyline.
What are the basic mechanisms of action of TCAs?
TCAs block SERT and NET to varying degrees (they are serotonin and noradrenaline reuptake inhibitors), but they also block many other receptors, causing multiple side effects.
What class of antidepressant is mirtazepine?
It is a tetracyclic antidepressant.
Name one of the current MAOIs. What is the basic mechanism of action?
Moclobemide. It blocks Monoamine-Oxidase A, which is an enzyme that metabolizes serotonin and noradrenaline.
Name as many features of serotonin syndrome as you can.
This occurs when a person has had an excess of serotonergic drugs (e.g. SSRI + MAOI).
- their BP / RR / HR and Temp can all be raised
- have large pupils (mydriasis)
- muscle rigidity, convulsions, rhabdomyolysis
- vomiting and diarrhoea.
What is the average half-life of an SSRI?
Roughly 24hrs. Fluoxetine is more like 48-72 hours.
What is the half-life of venlafaxine?
What is the average half-life of the TCAs?
What is CYP2D6 and what does it do?
CYP2D6 is an enzyme system (one of the cytochrome P450 enzymes) that metabolizes TCAs, most opioids, tramadol, beta-blockers and haloperidol.
What does serotonin do at the SERT?
It binds to a receptor site on SERT, which induces a conformational change, allowing the entry of serotonin, Cl- and Na+ into the cell.
How do SSRIs inhibit serotonin reuptake?
SSRIs bind allosterically to SERT (at a site different to the binding site for serotonin), and inhibit the opening of SERT.
In addition to blocking SERT and NET, the TCAs also block other receptors. Which ones?
TCAs also block alpha-adrenergic receptors, muscarinic cholinergic receptors, sodium channels, and histamine receptors.
What are some of the adverse effects of TCAs, and why?
TCAs block muscarinic cholinergic receptors, and therefore exhibit anticholinergic side effects, such as dry mouth and constipation. TCAs can also cause orthostatic hypotension due to their blockade of alpha-adrenergic receptors. TCAs can also cause a broad-complex sinus tachycardia due to the sodium channel blockade.
For each of the following monoamines, explain whether they are metabolised by MAO-A or MAO-B:
Serotonin - MAO-A
Noradrenaline - MAO-A
Adrenaline - MAO-A
Dopamine - Both
What is the risk of overdose with TCAs? How does this compare to SSRIs?
TCAs can be lethal in overdose. SSRIs are much safer in overdose.
Name one condition that can be treated with TCAs apart from depression and other mental health issues.
Pain. In particular, chronic pain and fibromyalgia.
What are some of the anticholinergic adverse effects of TCAs?
Dry mouth, dry eyes, urinary retention, constipation, blurred vision, confusion.
What are some adverse effects of H1-receptor blockade by TCAs?
Sedation and weight gain.
How do TCAs cause death in overdose?
They can cause arrhythmias such as VT and VF. The anticholinergic effects can lead to confusion, reduced GCS and seizures.
How much of a TCA is required to produce a lethal effect?
Less than 7 days' supply of amitriptyline (1500mg) can be lethal.
If you are giving fluoxetine, which drugs should you avoid giving concurrently? If you want to give a strong analgesic to a patient on fluoxetine, what is safe to give?
Avoid giving beta-blockers, TCAs, tramadol, opioids (except fentanyl), and haloperidol - because these drugs require CYP2D6 for metabolism, and CYP2D6 is inhibited by fluoxetine. Fentanyl is metabolised by CYP3A4.