CNS Affective Disorders and Their Treatment Flashcards
Define: Affective Disorder
A group of disorders characterised by clinically significant mood disturbances
What are the 3 major categories of affective disorders
Major depressive illness
Cyclothymic or Dysthymic disorder (Minor)
Bipolar depression (Mania)
What is the prevalence of depressive illness in the UK
Affects 1 in 38 adults in the UK at any one time
2-3 times more prevalent in women
Onset usually 25-35 years old
What are the two types of depressive syndrome
- Unipolar depression (25% of cases are familial)
- Bipolar affective disorder (depressive episodes fluctuate with episodes of mania)
What are the emotional symptoms of depressive illness?
- Misery, apathy, pessimism
- Low self-esteem, feelings of guilt, inadequacy
- Indecisiveness, loss of motivation/interest
What are the biological symptoms of depressive illness?
- Retardation of thought and action
- Loss of libido
- Sleep disturbance
- Loss of appetite
What are the two rating scales for depressive illness?
HAM-D and MADRS
What is electroconvulsive therapy? (ECT)
- Patients are lightly anaesthetised
- Paralysed by NMJ blockers
- Ventilated
- Electrodes on either side of head
What are the side effects of electroconvulsive therapy (ECT)?
Confusion and memory loss
How many forms of Monoamine oxidase (MAO) are there?
There are 2. A and B
Explain the two types of MAO
Type A: Responsible for enzymative degradation of 5-HT and catecholamines (only 6-8% of MAOs! Intraneuronal)
Type B: Majority (located extraneuronally)
How many chemical classes of MAOI are there and what are they?
There are 3 chemical classes
Hydrazines, Cyclopropylamines and Acetylenic propargylamines
Features of Hydrazines (class of MAOI)
Irreversible
Non-selective
Features of Cyclopropylamines (class of MAOI)
Irreversible
Non-selective
E.g Tranylcypramine
Features of Acetylenic Propargylamines
Irreversible
Selective
MAO-A: Clorgyline
MAO-B: Deprenyl, Pargyline
Antidepressant activity and main side-effects associated with MAO-A inhibition
What are the main side effects of MAOIs?
Hypotension (sympathetic block)
Atropine-like effects (dry mouth, blurred vision, photophobia, tachycardia)
Hepatocellular Jaundice
Drowsiness
Insomnia
CNS Stimulation and Agitation (tranylcypramine)
What are the main clinical uses of MAOIs?
Neurotic depression and anxiety
Mixed anxiety-depression and hypochondriasis
Phobic anxiety (e,g agoraphobia)
Explain the ‘cheese reaction’ in relation to MAOIs
Cheese is high in TYRAMINE content
The interaction of MAOIs and Tyramine can cause hypertensive crisis (displaces NA)
How can the ‘cheese reaction’ be avoided? (in relation to MAOIs)
Use reversible MAOIs (E.g moclobemide)
How many classes of TCAs are there and what are they called?
There are 2.
Dibenzazepines and Dibenzcycloheptanes
Examples of Dibenzazepines
Imipramine (non-sedative), Desipramine, Clomipramine
Examples of Dibenzcycloheptanes
Amitryptiline (Sedative) and Noriptyline
What are the major side effects of TCAs?
Sedation
Atropine-like (muscarinic blockade)
Postural hypotension
Dysrhythmia and heart block
What common drugs interact with TCAs?
Alcohol
Hypotensions
NSAIDs
MAOIs
How is the selectivity of monoamine reuptake inhibitors calculated?
IC50(5-HT)/IC50(NA)
What chemical is involved in the medial forebrain bundle?
NA
Biological components of depression are sensitive to antidepressant effects on which systems?
NA
Emotional components of depression are sensitive to antidepressant effects on which systems?
5-HT
Are SSRIs structurally similar to one another?
No
SSRIs vs TCAs
- No evidence to support greater efficacy
- No evidence of more rapid onset
- Better side-effect profile
- Safer in overdose
- However they are more expensive!
What is the general mechanism of MAOIs
They increase 5-HT, NA (and DA) by inhibiting breakdown
What is the general mechanism of TCAs
They increase 5-HT, NA (and DA) by blocking reuptake
What is the general mechanism of SSRIs
They increase 5-HT by blocking reuptake
What is the hippocampus responsible for?
Coping behaviour and resilience
What is the hypothalamus responsible for?
Emotional expression
What is the amygdala responsible for?
Anxiety and panic
What is a manic episode (mania)?
A distinct period of abnormally and persistently elevated, expansive or irritable mood.
Lasting at least 1 week
What classes of drugs can be used to treat mania?
Antidepressants
Antipsychotics
Lithium (only in acute episodes)
Antiepileptics (only in acute episodes)
Does lithium have a narrow therapeutic range?
Yes
What are the two mechanisms of action of Lithium?
Lithium, sodium and potassium
Lithium and second messengers
How does Lithium affect sodium and potassium?
It mimics the role of Na (as it is a monovalent cation)
It cannot be pumped out by NA/K ATPase and so accumulates in excitable cells (partial loss of intracellular K)
How does Lithium affect second messengers?
It affects the Phosphatidylinositol (PI) pathway
Blocks the conversion of IP1 to Inositol and P
Intracellular accumulation of IP
Causes signal transduction by Gq GPCRs
