Anti-depressants Flashcards
What are the 2 types of psychoses?
- Affective disorders
- Schizophrenia
What are the 2 types of affective disorders?
- Depression
- Mania
What are the different types of depression - the 2 main types and the 2 subtypes for one of these?
- Bipolar depression
- Unipolar depression - reactive and endogenous
1) What is unipolar depression and what are the 2 types and describe these 2 types, including the hereditary pattern of it?
2) Describe the onset of unipolar depression
1)
- Unidirectional mood swings
- Reactive - in response to stressful life events - non-familial pattern
- Endogenous - unrelated to external stresses - familial pattern
2)
- Late onset in adulthood
1) What is bipolar depression?
2) Describe the onset of bipolar depression?
3) What is the main treatment for bipolar depression and what does it do?
1)
- Bipolar depression - oscillating depression and mania (hyper-excitability with opposite symptoms to depression)
2)
- Strong hereditary tendency - early onset
3)
- Lithium - mood-stabilising drug
Briefly describe the monoamine theory of depression and mania
- Depression = ↓ central monoamine transmission
- Mania = ↑ central monoamine transmission
Apart from monoamine transmission, what else may be involved in the pathophysiology of the depression that is observed in depressed patients?
- HPA axis involvement potentially → ↑ CRH in depressed patients
How might depression affect memory?
- Hippocampal degeneration due to chronic depression
Name an example of a TCA?
- Amiltryptiline
Describe how TCAs work as anti-depressants, and also what receptors do they act on?
- Neuronal monoamine reuptake inhibitors (NA, 5-HT, little dopamine)
- By antagonising alpha-2 receptors, TCAs prevent inhibition of NA release that alpha-2 receptors normally have - therefore they enhance NA release
- Act on alpha-2, muscarinic AChRs, histamine receptors, 5-HT receptors
Describe the pharmacokinetics of TCAs
- V. plasma protein bound
- Hepatic metabolism generates active metabolites
- Renal conjugation via glucuronide conjugation
- Long half-life
Give 3 unwanted efffects of TCAs at therapeutic dose
- Amiltryptiline gives atropine-like effects - dry mouth, blurry vision, constipation, urinary retention
- Postural hypotension - vasomotor centre mediated central effect
- Sedation due to H1 (histamine) antagonism
Give 2 unwanted effects of TCAs at a high dose - i.e. in acute toxicity
- CNS - excitement, delirium, seizures - coma, respiratory depression
- CVS - cardiac dysrhythmias - ventricular fibrillation and sudden death
List 5 drug interactions that TCAs can have
- ↑ TCA effects with co-administration with aspirin and phenytoin - to do with plasma protein bound TCA
- Warfarin displaces TCAs from binding sites → moves plasma levels to toxic range
- Hepatic microsomal enzymes metabolise TCAs, so if co-administered with other drugs which are also metabolised by hepatic microsomal enzymes → ↑ TCAs
- TCAs potentiate CNS depressants like alcohol
- TCAs interact with anti-hypertensive drugs unpredictably
Name one structural feature of TCAs
- 3 rings
Name an example of an Monoamine Oxidase Inhibitor
- Phenelzine
Describe the action of monoamine oxidase, mentioning the 2 isoforms involved and their specific actions
- Monoamine oxidases break down neurotransmitters such as the monoamines in the reuptake 1 mechanism
- MAO-A: NA + 5-HT
- MAO-B: Dopamine
Describe the basic mechanism for how monoamine oxidase inhibitors work as anti-depressives
- They bind irreversibly (covalently) with monoamine oxidases and prevent their action to degrade neurotransmitters via reuptake-1 mechanism
- They are mostly unselective in regards the monoamine oxidase isoforms they inhibit
- Thereby prolonging the action of the neurotransmitters as they can persist in the synaptic cleft and avoid degradation
- Monoamines such as NAs, 5-HTs and Dopamine persist
Describe the structure of monoamine oxidase inhibitors and particularly of phenelzine and how it allows it to have its functional capabilities
- Single-ring structure
- Phenelzine has a hydrazine end group which can bond covalently with the monoamine oxidase enzyme, thereby irreversibly binding and inhibiting it
In terms of the pharmacokinetics of monoamine oxidase inhibitors…
1) What is the rate of absorption?
2) Is the half life long or short?
3) Is the duration of action long or short, and why?
1)
- Rapid oral absorption
2)
- Short half-life
3)
- Long duration of action due to irreversible binding
Give the unwanted effects that monoamine oxidase inhibitors can have
- Atropine-like effects
- Postural hypotension
- Sedation
- Weight gain due to ↑ appetite
- Hepatotoxicity
1) Describe the main drug interaction that monoamine oxidase inhibitors have
2) List some other drug interactions that monoamine oxidase inhibitors have
3) Name a monoamine oxidase inhibitor which does not have as many drug interactions and name a downside of this drug
1)
- ‘Cheese’ reaction
- TYRAMINE interaction with monoamine oxidase inhibitors
- Tyramine is a sympathomimetic amine found in food like cheese or in red wine
- Tyramine is metabolised by monoamine oxidase
- So monoamine oxidase inhibitors interfere with the metabolism of tyramine, resulting in symptoms
- Symptoms: Hypertensive crisis, headache, ↑ BP, intracranial haemorrhage
2)
- Interaction with TCAs → hypertensive episodes
- Interaction with pethidine → hyperpyrexia, restlessness, coma, HOTN
3)
- Moclobemide - it is reversible and more selective. Therefore it has fewer drug interactions but also means it has a shorter duration of action
Name an SSRI
- Fluoxetine - ‘prozac’
What is the basic mechanism of SSRIs?
- SSRI = serotonin reuptake inhibitor - does what it says on the tin - prevents 5-HT reuptake, thereby prolonging 5-HT actions
Name an advantage to SSRIs and a disadvantage over other anti-depressants
- +ve: safer - fewer side effects
- -ve: less effective
What is an important consideration to do with the indirect interaction that an SSRI has with another class of anti-depressive drugs?
- Fluoxetine competes with TCAs for hepatic enzymes so avoid co-administration as it prevents metabolism of TCAs
List some unwanted effects of SSRIs
- GI side effects - nausea, diarrhoea
- Insomnia
- Loss of libido
Apart from TCAs, Monoamine oxidase inhibitors and SSRIs, name 2 other anti-depressant drugs and briefly outline their mode of actions - just their class of drugs quick title
- Venlaxafine - SNRI
- Mirtazapine - alpha-2 receptor antagonist
Describe the mechanism of action of venlaxafine
- SNRI
- Dose-dependent reuptake inhibition of 5-HT, NA, dopamine in order of how it inhibits them i..e. at low dose it inhibits reuptake of 5-HT, at higher dose NA, then finally of dopamine
1) Describe the mechanism of action of Mirtazapine
2) In who is mirtazapine useful?
1)
- Alpha-2 receptor antagonist - increases NA and 5-HT release in the brain
- Sedative - histamine antagonism
2)
- Useful in SSRI-intolerant patients
What type of type 2 metabolism do TCAs undergo?
- Glucuronidation
What is the tyramine reaction - what triggers it and describe the pathophysiology?
- Tyramine is a sympathomimetic amine
- It is found in cheese and wine
- It is usually metabolised by MAOs
- So MAOis inhibit their metabolism and so it can have its sympathomimetic effect - HTN crises, headache, intracranial haemorrhage
What is Moclobemide, what type of anti-depressant class does it belong to and what is a benefit and disadvantage in its use?
- Monoamine oxidase inhibitor
- Reversible (unlike all other MAOis) and more selective - therefore it has fewer drug interactions
- But also means it has a shorter duration of action
