Week 10 Flashcards
(28 cards)
What are the 2 types of affective disorders?
1 - Unipolar depressive syndrome
2- Bipolar depressive syndrome
What are the symptoms of unipolar depressive syndrome?
What is it associated with?
- Depression without associated mania
- More common in older patients
- Can be associated with anxiety and agitation
What are the symptoms of bipolar depressive syndrome?
What causes it?
Hereditary?
- Oscillation between depression and mania
- Strong evidence for hereditary link
- Biochemical imbalance
There are 9 criteria for major depressive episodes. Name a few
- Depressed or irritable mood.
- Decreased interest in, or unable to experience, pleasurable activities.
- Low self-esteem: guilt, inadequacy, ugliness.
- Sleep disturbance - insomnia / hypersomnia.
- Fatigue / loss of energy.6. Indecisiveness and loss of motivation.
- Retardation of thought / concentration.
- Loss of appetite.
- Suicidality / thoughts of death.
There are 6 symptoms of mania. What are they? (hint, most of them are excessive)
- Excessive exuberance
- Excessive self-confidence
- Excessive enthusiasm
- Excessive physical activity
- Irritability, impatience and anger
What are the brain regions involved in mood regulation.
And what are the processes they are involved in
- Frontal cortex (FC)
- Hippocampus (HP)
Both of the above are involved in memory impairment, worthlessness, suicidality etc - Hypothalamus: Involved in sleep appetite, energy impairment, reduced interest in pleasurable activities
What is the Monoamine Theory of Depression?
Depression is due to a functional deficit of monoamine neurotransmission
What are the 3 main supporting points of Monoamine Theory of Depression?
- Drugs that increase or alleviate the symptoms of affective disorders have known effects on the 5-HT and NA systems
- Mania is regarded as being due to the opposite mechanism. I.e., functional excess of these neurotransmitters
- 5-HT and NA metabolites (5-HIAA and MOPEG respectively) are higher in the CSF of depressed patients (however, DA metabolite (HVA) is not increased)
What are the 3 monoamine neurotransmitter:
- Serotonin
- Noradrenaline
- Dopamine
In support of the monoamine hypothesis of depression, drugs that increase monoamine levels help to alleviate depressive symptoms. This can be done in 2 obvious ways. What are they? (Think synapse)
- Inhibiting reuptake of NA and 5-HT
- Preventing breakdown of NA and 5-HT
What do the drugs alpha-methyltyrosine and reserpine do? (Hint = think of the opposite ma hypothesis)
They decrease monoamine levels leading to an increase in depressive symptoms
alpha-methyltyrosine inhibits NA / 5-HT synthesis
Reserpine depletes vesicular stores of these neurotransmitters
There is a body of evidence that is inconsistent with the monoamine theory of depression. Mention some examples. (think specific drugs)
- Amphetamine releases NA and blocks NA re-uptake, but has no effect on depression
- Cocaine blocks NA re-uptake but has no effect on depression
- Tryptophan increases 5-HT synthesis but has inconsistent effects on mood
- L-dopa increases NA synthesis but has no effect on mood
Different to the previous question, there are 2 main problems with the hypothesis. These aren’t to do with specific drugs, but more overarching unexaplainables
- The biochemical actions of drugs are very rapid but antidepressant effects usually take days or weeks to develop
- Current antidepressants do not improve symptoms in all patients
Stress is also thought to be involved in depression, specifically, the dysregulation of the HPA axis.
What is the mechanism behind this?
- Corticotropin releasing factor (CRF) is released from the hypothalamus and stimulates cortisol production in the adrenal gland.
- The hippocampus exerts an inhibitory influence on CRF release
- The Amygdala exerts an excitatory effect.
- Dysregulation of hippocampal / amygdala function may therefore result in abnormal regulation of the HPA axis
- Both CRF and cortisol are elevated in many (~50%) depressed patients
- CRF action in the amygdala may influence emotional symptoms while it may promote insomnia, anxiety and depress appetite for food and sex
- High cortisol levels may damage hippocampal neurones reducing inhibitory feedback on cortisol production
- Reduced hippocampal volume has been observed in depressed humans using MRI and post-mortem analysis
In support of the stress hypothesis, antidepressants acting through monoamine pathways can reduce CRF and cortisol levels. What is the specific factor that mediates this and how?
High monoamine levels may reverse cortisol-induced damage by increasing growth factor production. The specific example is Brain-derived neurotrophic factor (BDNF).
Antidepressants are split into 2 groups, first and second generation. What are the classes of drug in each group and some specific examples?
First Generation:
- TCAs: Imipramine, Amitriptyline
- MOAIs: Phenelzine, Tranylcypromine
Second Generation:
- SSRIs: Fluoxetine (Prozac)
- Noradrenaline and Serotonin-specific antidepressants: Venlafaxine
- Noradrenaline and Serotonin receptor-targeted drugs: Mirtazapine
What do Imipramine and Amitriptyline do?
- They are TCAs
- Non-selective inhibitors of 5-HT and NA reuptake proteins
- Acute sedative effects useful for agitated patients
What are the pharmacokinetics of Imipramine? i.e., what is its action?
Non-selective NA and 5-HT reuptake inhibitors.
Converted to Desipramine
TCAs, along with other antidepressants, have unwanted effects.
a) What are some of them?
b) What can TCAs interact with?
a)
- Sedation (through H2 receptor blocking)
- Atropine-like autonomic side effects related to muscarinic AChR (general anticholinergic effects, dry mouth, constipation, blurred vision etc)
- Seizures
b)
- Alcohol
- MAOIs
And other CNS depressants
Is there a risk of overdose from TCAs? If so, from what?
Yes.
- Ventricular dysrhythmia
- Ventricular fibrillation
- Coma, respiratory depression
Developing a previous point, TCAs have interactions with other drugs. Name some of them (the interactions, not the drugs).
- Microsomal metabolism in the liver may be inhibited by competing drugs such as antipsychotics and steroids
- CYP enzymes are inhibited by competing drugs leading to increased TCA plasma levels
- TCAs potentiate the effects of alcohol
- TCAs can interact with some anti-hypertensive drugs (ACE-inhibitors) causing large and potentially hazardous swing in blood pressure
What are some examples of MAOIs
- Phenelzine
- Tranylcypromine
- Clorgyline
Phenelzine and other MAOIs have one common unwanted effect called the ‘Cheese Reaction’. What is this?
- Reaction with tyramine-containing foods.
- Causes anticholinergic side effects such as hypotension, insomnia, weight gain and liver damage
SSRIs (such as Fluoxetine (prozac) and fluvoxamine) are second generation antidepressants. What are the important
a) Interactions
b) Side effects
that SSRIs have?
a) Must not be taken with MAOIs as can cause serotonin syndrome
b) Nausea, anorexia, anxiety, dependence
