Antidepressants Pharmacology Flashcards
List a irreversible MAOI. What is its MOA?
- Phenelzine
- MOA: inhibit MAO -> increase biological availability of monoamines
- Non-selective for MAO-A, selective for MAO-B
MAO-A breaks down ________, and both MAO-A and MAO-B breaks down ____________.
5-HT
Dopamine and NE
What are the SEs of MAOIs?
- Postural hypotension
- Restlessness and insomnia
Explain the drug-food interaction of MAOIs (type of food, SEs, mechanism of interaction, management)
- Tyramine-rich foods e.g. cheese, marmite
- SE: acute HTN, severe headache, occasionally ICH
- MAO breask down tyramine in intestines and liver
- when MAOIs are used, tyramine is not broken down and gets taken up into adrenergic terminals -> competes with NA for vesicular compartment
- Tyramine displaces NA -> increase in NA release in synapses -> sympathomimetic effect
- Management: less likely with moclobemide (reversible, MAO-A selective)
True or false?
The SE of postural hypotension in MAOIs, TCAs, SSRIs and SNRIs are all caused by the same mechanism
False
* MAOIs: ↑dopamine in cervical ganglia, where it acts as an inhibitory transmitter → sympathetic block → ↓response of blood vessels, ↓vasoconstriction → ↓blood supply to brain
* TCAs, SSRIs, SNRIs: due to α-adrenergic antagonism
List 3 TCAs. What are their MOA?
- Non-selective for SERT: imipramine, amitriptyline, notriptyline, dothiepin
- Selective for NET: desipramine, clomipramine
- MOA: block reuptake of NE and serotonin
SERT: serotonin transport
NET: NE transport
List 3 SEs of TCAs
- Anticholinergic: sedation, weight gain, orthostatic hypotension, arrhythmias, seizure
- H1 antagonism: sedation, drowsiness (tolerance develop in 1-2w)
- α-adrenergic antagonism: postural hypotension
- GI and sexual dysfunction
List 3 SSRIs. What are their MOA?
- Fluoxetine, fluvoxamine, paroxetine, sertaline, escitalopram, citalopram
- Block reuptake of 5HT selectively
List 2 SNRIs. What are their MOA?
- Venlafaxine, desvenlafaxine, duloxetine
- Block reuptake of NE and 5HT
List 3 SEs of SSRIs and SNRIs
- Nausea, insomnia (due to discontinuation/ rebound sx of withdrawal when plasma lvls of drug ↓btw doses)
- Headache, transient nervousness during initiation
- Hyponatremia (SIADH)
- GI and sexual dysfunction, EPSE
- Bleeding risk (↑risk in elderly on concomitant NSAIDs, warfarin, and steroids, consider adding PPI + discontinuing 2w before surgery if high bleeding risks (agomelatine safest))
True or false?
Paroxetine is the most favoured SSRI, as it has the least SEs
False!
Paroxetine is the most anticholinergic and sedating, ↑weight, short t1/2 (withdrawal) → least favoured!
True or false?
Citalopram and escitalopram can cause QTc prolongation
True
When in high doses in elderly
True or false?
Duloxetine has an added SE of urinary hesitation
True
True or false?
Venlafaxine has an added SE of hypotension
False
It causes an increase in BP!
True or false?
SNRIs are less favoured than SSRIs
True
SNRIs has more SEs (e.g. anticholinergic SEs, orthostatic hypotension, sedation) compared to SSRIs
Briefly list out the signs and symptoms of serotonin syndrome
Fever, anxiety/ restlessness/ disorientation/ flushing/ muscle rigidity, ↑↑ BP/ HR/ body temp, tremors, jerking movements, loss of consciousness, cardiovascular collapse
What is the drug class and MOA of mirtazapine?
Noadrenergic and specific serotonergic antidepressant (NaSSA)
α2- adrenoceptor and 5-HT2&3 antagonism -> ↑5-HT and NE
Also antagonises H1 histamine receptors, peripheral
α1-adrenergic receptors, & muscarinic receptors
What antidepressant is the least sedating?
MOAIs (moclobemide less sedating than phenelzine)
What are the advantages and disadvantages of mirtazapine according to its SEs?
SEs: somnolence, increased appetite, weight gain
Less GI and sexual SEs than SSRIs/ SNRIs
What is the drug class and MOA of bupropion?
Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)
Block reuptake of NA and dopamine
What are the advantages and disadvantages of bupropion according to its SEs?
SEs: seizure-risk, insomnia, psychosis
Not suitable for eating disorders, and not to be taken at bedtime (stimulating in nature)
Less GI and sexual SEs than SSRIs/ SNRIs
Bupropion is a potent CYP_____________
CYP2D6 inhibitor
What is the drug class and MOA of aglomelatine?
Melatonin Receptor Agonist
MT1 and MT2 agonist, 5HT2C antagonist → ↑dopamine and NE
What drugs have reduced GI and sexual SEs when compared to SSRIs/ SNRIs?
GI and sexual: mirtazapine, bupropion
Sexual only: aglomelatine
What are the advantages and disadvantages of aglomelatine according to its SEs? What drugs are C/I with aglomelatine?
GI SEs, hepatic SEs
Less sexual dysfuntion and risk of bleeding
C/I: fluvoxamine, ciprofloxacin
Helps in sleep disorders
What is the drug class and MOA of vortioxetine?
Serotonin Modulators and Stimulators (SMS)
Multimodal serotonergic antidepressant, blocks reuptake of 5HT
What are the advantages and disadvantages of vortioxetine according to its SEs?
As for SSRI
May ↑risk of suicidal thoughts/ actions in children and teens
May be efficacious in pts resistant to other antidepressants
What is the drug class and MOA of trazodone?
Serotonin antagonist and reuptake inhibitor (SARI)
Blocks reuptake of 5HT
Antagonises 5HT2A, H1 and α1 adrenoreceptor
What are the advantages and disadvantages of trazodone according to its SEs?
As for SSRI + sedation, orthostatic hypotension
Rare: priapism
Used for insomnia rather than depression
What is the drug class of ketamine and esketamine?
Glutamate NMDA receptor antagonist
What are the advantages and disadvantages of ketamine and esketamine according to its SEs?
SEs: dissociation, dizziness, anxiety, nausea, sedation, increased BP
Ketamine: used as anesthestic
Esketamine: adjunct to SSRI/ SNRI for tx-resistant depression
Which antidepressant is the most/ least sedating?
Most: TCAs, trazodone, mirtazapine
Least: SSRIs
Which antidepressant produces the most/ least anticholinergic effects?
Most: TCAs
Least: SSRIs
Which antidepressant has the highest/ lowest risk of orthostatic hypotension?
Highest: TCAs, trazodone
Lowest: SSRIs
