Major depressive disorder 1.1.1 Flashcards
What are some of the emotional symptoms of major depressive disorder?
- Misery
- Apathy
- Pessimism
- Low self esteem
- Feelings of guilt or inadequacy
- Suicidal thoughts
- Indecisiveness
What are some biological symptoms is major depressive disorder?
Disturbances in
- appetite
- energy
- sleep
- ibido
- psychomotor function
How would you explain reuptake?
- reuptake allows for the recycling “reabsorbing” of neurontransmitters
- it regulates the level of neurontransmitters in the synapse
- so it controls how long a signal from neurontransmitter release lasts
- by BLOCKING reuptake, more 5HT & NA is available to pass messages between cells
What are SIX examples of TCAs?
AINCDD
- Tricyclic antidepressants
Amitriptyline
Imipramine
Nortriptyline
Clomipramine
Dosulepin (Dothiepin)
Doxepin
What is the MOA of TCAs? Are they reversible?
How long does it take to reach therapeutic effect?
- they inhibit the 5HT & NA reuptake transporters into the presynaptic terminal
- so you get an increase in synaptic levels of NA & 5HT
- Reversible
Why does it take 2-4 weeks for TCAs to reach therapeutic effect?
- due to adaptive receptor changes
- leads to downregulation of receptors
- get inhibitory presynaptic a2-adrenoceptors
- get inhibitory presynaptic 5HT1A autoreceptors
- get postsynaptic B-adrenoceptors
- get postsynaptic 5HT2A receptos
Do TCAs have long or short half lives?
- long half lives
- ~18-70 hours
*
Which TCAs block NA uptake more than 5HT uptake?
Secondary or tertiary amines?
- Nortriptyline
- Desipramine
Secondary amines
Which TCAs block 5HT more than the secondary amines?
- Amitriptyline
- Clomipramine
- Imipramine
What are some of the adverse effects of TCAs?
Antagonism of muscarinic receptors
- dry mouth, blurred vision, constipation, urinary retention, cognitive impairment, delirium
Antagonism of a1- adrenoreceptors
- postural hypotension, sedation, sexual dysfunction
Antagonism of H1 receptors
- sedation, weight gain
What are the symptoms of TCA withdrawal syndrome?
CRASH
NOTE: TCAs must be withdrawn slowly to avoid withdrawal syndrome
Cholinergic rebound
Runny nose
Abdominal pain, D
Sleep & sensory disturbances
Hypersalivation
- these last no longer than 2 weeks
- more common in amitriptyline, doxepin
- similar withdrawal syndromes with SSRIs, venlafaxine
Why does overdose occur in TCAs? What happens?
- TCAs have a low TI & a low therapeutic window
- it can be life threatening
- causing respiratory depression, seizures & cardia toxicity followed by COMA
What are some associated drug interactions for TCAs?
MAOIs
- severy hypertension
DIRECT ACTING SYMPATHOMIMETICS
- NA, adrenaline
- increase sympathetic activity, accumulation of NA
INDIRECT ACTING SYMPATHOMIMETICS
- ephedrine, amphetamine
- reduce the effects of indirect- acting agents
ANTICHOLINERGICS
- TCA has antocholinergic activity hence will intensify anticholinergic effects
CNS DEPRESSANTS
- sedation of TCAs exacerbated by agents such as alcohol, antihistamine, opiods, barbiturates, benzos
What are SIX examples of SSRIs?
CEFFPS
- Selective serotonin reuptake inhibitors
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Explain the MOA of SSRIs? How are they different to TCAs?
- selectively inhibit presynaptic 5HT reuptake transporters
- more commonly prescribed, have a higher TI, as effective BUT much safer, better tolerated than TCAs & don’t cause significant cardiotoxicity
What are some SSRI withdrawl syndrome symptoms?
FLUSH
Flu like
Light headness
Uneasiness
Sleep & sensory disturbances
Headache
- withdrawal symptoms not dangerous
- last no longer than 2 weeks
- more common with paroxetine (short acting)
What are some adverse effects for SSRIs?
- n, d, anorexia
- insomnia, anxiety, irritability, restlessness, tremor, headache, fatigue, drowsiness, dry mouth
- decreased libido, delayed orgasm
- weight gain, fever, sweating, palpitations
What are some noteable SSRI drug interactions?
MAOIs- serotonin syndrome
Warfarin- avoid as it may cause bleeding, fluoxetine is highly plasma bound
TCAs & lithium- fluoxetine can increase plasma levels of TCAs & lithium, giving rise to toxicity
What is serotonin syndrome? What are some symptoms of SS?
- it a toxic state when theres excess 5HT in the brain
- mental confusion, hypomania, agitation, headache, coma, fever, HTN, tachycardia, N, D, muscle twitching, tremor
>avoid SSRI w MAOI or RIMA
>avoid drugs that elevate 5HT levels
>avoid opiod analgesics that also ingibit 5HT reuptake; tramadol, pethidine, dextromethorphan
What drugs should be avoided to prevent serotoninsyndrome when a patient is on an SSRI?
- avoid SSRI w MAOI or RIMA
- avoid drugs that elevate 5HT levels
- avoid opiod analgesics that also ingibit 5HT reuptake; tramadol, pethidine, dextromethorphan
What are THREE examples of SNRIs?
VDD
- Serotonin & noradrenaline reuptake inhibitors
Venlafaxine
Desvenlafaxine
Duloxetine
WHat is the MOA of SNRIs?
- they reversibly inhibit 5HT & NA transporters
- lower doses selectively inhibit 5HT reupatke
Why are SNRIs safe than TCAs?
- venlafaxine (SNRI), lacks affinity for muscarinic, a1, h1 receptors & it doesn’t impair cardiac conduction significantly
What are some adverse effects associated with SNRIs?
- similar to SSRIs
- N, V, anorexia, headache, sweating, rash, anxiety, dose related increase in diastolic BP, orthostatic hypotension, tremor
What is the half life of venlafaxine?
- about 5 hours
- slow release allows for daily dosing
What are some noteable drug interactions associated with SNRIs?
- TCAs, MAOIs, SSRIs, selegiline, mianserin, moclobemide- possible serotonin syndrome combination contraindicated
- lithium- neurotoxicity or serotonin syndrome
- fentanyl, pethidine, tramadol-possible serotonin syndrome
What are TWO examples of MAOIs?
- Monoamine oxidase inhibitors
Phenelzine
Tranylcypromine
What is the MOA of MAOIs? Is it irreverible?
- Irreversible
- inhibition of MAOA & MAOB resulting in a decrease in the intraneuronal breakdown of NA & 5-HT
- MAOA selectively inactivates 5-HT & NA
- MAOB selectively inactivates DA
- In liver, MAOA inactivates dietary tyramine
What are the adverse effects of MAOIs?
- similar to TCAs
- can produce anxiety, agitation, hypomania & even mania
- postural hypotension
- patients should be informed of signs of hypotension, dizziness, light headedness
- sedation, cardiotoxicity
- in OD- hyperthermia, convulsions; can be life threatning
What foods should be avoided when taking a MAOI? And why? How long does it take to recover?
- cheese, pickles, wine, avocadoes
- foods rich in tyramine
- CHEESE/ TYRAMINE RXN
- tyramine can increase BP by displacing NA from sympathetic nerve terminals
- ingestion of tyramine by patients on MAOIs can result in hypertensive crisis
- Can take up to 2 weeks to recover
What are some other antidepressants?
- Agomelatine
- Mirtazapine
- Moclobemide
- Reboxitine
- Mianserin
- Vortioxetine
What are the drug interactions associated with MAOIs?
IN DIRECT ACTING SYMPATHOMIMETICS
- Ephedrine, amphetamine- hypertensive crisis
ANTIDEPRESSANTS
- TCAs- hypertensive crisis
- SSRIs- serotonin syndrome
ANTIHYPERTENSIVE AGENTS
- excess lowering of BP
MEPERIDINE (DEMEROL)
- can cause hyperpyrexia
What class of drug is reboxatine?
- NRI
- noradrenaline reuptake inhibitor
What is the MOA of raboxetine?
When is raboxetine used?
- it selectively inhibits NA transporters
- it doesn’t the reuptake of 5HT & DA?
- Can be used in major depression
What class of drug is moclobemide?
- reversible MAO-A inhibitor
What is the MOA of moclobemide?
- its selectively inhibits MAOa
- resulting in a decrease in the intraneuronal breakdown of NA & 5HT
What is moclobemide used for?
- fatigued depressed patients
- can be used if sexual dysfunction produced by a SSRI becomes a problem
What are some side effects of moclebomide?
- safer than MAOs
- nausea, dizziness, agitation, insomnia, headache
What class of drug is mirtazapine?
- NaSSA
- Noradrenaline- serotonin specific antidepressan
When is mirtazapine used?
- Used in depressed patients requiring sedation
- or as an alternative to a SSRI if insomnia or sexual dysfunction is problematic
What is the MOA of mirtazapine?
- mirtazapine antagonises presynaptic a2- adrenergic autoreceptors, 5HT2A, 5HT2C, 5HT3, H1 receptors
- antagonism of inhibitory presynaptic a2- adrenoceptors on NA & 5-HT nerve terminals cause an immediate increase in synaptic levels of 5-HT & NA (major therapeutic effect)
What are the common side effects of mirtazapine?
- weight gain, excessive drowsiness
- dizziness, dry mouth, constipation
What is a precaution/ important note for mirtazapine?
- it shouldn’t be combined with CNS depressants such as alcohol & benzodiazepines
- an anti depressant with a depressant makes depression harder to treat
For agomelatine
a) What is the MOA?
b) What is the indication?
c) What are the precautions?
d) What are some common adverse effects?
a) Its a melatonin receptor agonist, serotonin 5HT2C antagonist
b) Major depression
c) Potent CYP1A2 inhibitors, hepatic impairment
d) Abdominal pain, dizziness, up aminotransferase
For vortioxetine?
a) What is the MOA?
b) What is the indication?
c) Common adverse effects?
d) What are some pre cautions?
a) it enhances CNS serotonergic activity, inhibits serotonin reuptake
b) Major depression
c) N/D are dose dependent. Similar to other antidepressants.
d) co administration with CYP2D6 inhibitors & CYP3A4 inducers
What are some drug interactions associated wth vortioxetine?
A) Co-administration with serotonergic medications - triptans, other antidepressants, and tramadol; serotonin toxicity
B) Anticoagulants (eg, warfarin), aspirin, or NSAIDs (eg, ibuprofen, intranasal ketorolac); risk of bleeding
C) Diuretics (eg, furosemide, hydrochlorothiazide); Risk of low blood sodium levels
D)Carbamazepine, phenytoin, or rifampicin; Decreased effectiveness
