Major depressive disorder 1.1.1 Flashcards
(46 cards)
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NOTE: TCAs must be withdrawn slowly to avoid withdrawal syndrome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
