Anti-depressant Flashcards
What are emotional/psychological symptoms of depression
Misery, apathy, pessimism, low self esteem, loss of motivation, anhedonia (loss of enjoyment from activities)
What are biological symptoms of depression
Slowing of action/thoughts, loss of libido, loss of appetite, sleep disturbances
What are the two types of depression
Unipolar depression
Bipolar depression
Describe unipolar depression
A depressive disorder with mood swings that only swing in one direction:
What are different types of unipolar depression
reactive depression
endogenous depression
Describe bipolar depression
Manic depression with oscillations between depression and mania
What is a drug treatment for bipolar depression but what is the fault with it
Lithium - can stabilise the swings between mania and depression but has a narrow therapeutic window
When are the different types of depression onset
Unipolar depression is relatively late onset but bipolar, although less common, has an early adult onset
What is the monoamine theory of depression
Depression is a functional deficit of central MA transmission; mania is a functional excess of MA transmission - this is related to NA and serotonin deficits/excesses
What is biological evidence that counteracts the monoamine theory of depression
- A reduction in NA metabolites is not concurrent with a worse depression
- Delayed onset of clinical effect of drugs (a few weeks sometimes) - possibly due to an adaptive change and not MA theory (downregulation of alpha2, beta and serotonin receptors)
What is another name for serotonin
5 HT
What is the mechanims of action of TCAs
They are monoamine reuptake inhibitors that also act on alpha2, mAChR, histmine receptors, serotonin receptors.
They down regulate beta adrenoceptors and 5-HT2 receptors
Administation, metabolism, half life of amitriptyline
Oral,
Hepatic metabolism to active metabolites that are secreted in urine,
Plasma t1/2 10-20 hrs
What are unwanted effects to therapeutic doses of amitriptyline
Atropine like effects - anti PNS effects eg dry mouth, constipation
Postural hypotension - effect vasomotor
Sedation - effect on H1 antagonism
What are effects of acute toxicity of amitriptyline?
CNS - excitement, delirium, seizures -> coma, respiratory depression
CVS - cardiac dysrhythmias -> VF and sudden death (often used to commit suicide)
What are the drug interaction of amitriptyline with plasma protein binding
As it is very plasma protein binding, there can be a massive increase in bioavailability if co-administered with something that displaces it from plasma proteins eg aspirin, phenytoin
What are the interactions of amitriptyline with hepatic enzymes
The drugs compete with the metabolising hepatic enzymes
What are drugs that can potentiate the effects of CNS depression from amitriptyline
Alcohol for example
What is the mechanism of action of MAOI (monoamine oxidase inhibitors)
MAO enzymes: MAO-A breaks down NA and 5HT, and MAO-B breaks down DA eg selegiline
What are the rapid effects of MAOI
increase cytoplasmic (not enhanced release but more leakage) NA and serotonin
What are the delayed effects of MAOI due to
Delayed clinical response due to down regulation of beta adrenoceptors and 5HT2 receptors
What leads to the side effects of MAOI
It inhibits other enzymes
Describe the administration, half life and metabolism of MAOI - phenelzine
Oral administration
Short plasma half life but longer duration of action
Metabolised in liver, excreted in urine
What are unwanted effects of phenelzine
Atropine like effects - anti PNS but less than tCA Postural hypotension Sedation Weight gain Hepatotoxicity
What is the reaction between phenelzine and tyramine containing foods (cheese reaction) and why
Tyramine containing foods + MAOI -> hypertensive crisis
Tyramine is metabolised by MAO so high leves of tyramine compete with NA and so higher levels of NA leading to a hypertensive crisis
what is the reaction between MAOIs and TCAs
Hypertensive crisis
What is the reaction between MAOIs and pethidine
Hyperpyrexia, restlessness, coma, hypotension
What does meclobemide do?
It is a reversible, selective MAO-A inhibitor (RIMA - reversible inhibitor of MAO-A) leading to reduced drug interactions and reduced DoA
Give an example of an SSRI
Fluoxetine
What is the mechanism of action of SSRIs
5HT reuptake inhibitor
when are SSRIs a better choice than other anti depressants and when is it not and why
It has less bad side effects so is safer in ODs but is less effective vs severe depression
Describe the administration, half life, onset of action and metabolism of SSRIs
Oral administration
Half life 18-24 hrs
Delayed onset of action 2-4 weeks
Fluoxetine competes with TCAs for hepatic enzymes so avoid co-adminstration
What are unwanted effects of SSRIs?
Nausea
Diarrhoea
Insomnia
Loss of libido
What is the effect of SSRIs on suicidality
It increases suicidality in <18s but due to less side effects than others, it is the currently most prescribed antidepressant
Give 2 antidepressant drugs that aren’t SSRI, TCA or MAOIs
Venlafaxine and mertazapine
What does venlafaxine do? When is it used
dose dependant reuptake inhibitor leading to 5HT>NA>DA
Is 2nd line in severe depression
What does mertazapine do? When is it useful
alpha 2 receptor antagonist that inhibits negative inhibition of NA release and increases NA and 5-HT release.
Useful in SSRI intolerant patients
