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Pharmacology of CNS > CNS Affective Disorders and Their Treatment > Flashcards

CNS Affective Disorders and Their Treatment Flashcards

1
Q

Define: Affective Disorder

A

A group of disorders characterised by clinically significant mood disturbances

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2
Q

What are the 3 major categories of affective disorders

A

Major depressive illness
Cyclothymic or Dysthymic disorder (Minor)
Bipolar depression (Mania)

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3
Q

What is the prevalence of depressive illness in the UK

A

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

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4
Q

What are the two types of depressive syndrome

A
  • Unipolar depression (25% of cases are familial)

- Bipolar affective disorder (depressive episodes fluctuate with episodes of mania)

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5
Q

What are the emotional symptoms of depressive illness?

A
  • Misery, apathy, pessimism
  • Low self-esteem, feelings of guilt, inadequacy
  • Indecisiveness, loss of motivation/interest
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6
Q

What are the biological symptoms of depressive illness?

A
  • Retardation of thought and action
  • Loss of libido
  • Sleep disturbance
  • Loss of appetite
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7
Q

What are the two rating scales for depressive illness?

A

HAM-D and MADRS

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8
Q

What is electroconvulsive therapy? (ECT)

A
  • Patients are lightly anaesthetised
  • Paralysed by NMJ blockers
  • Ventilated
  • Electrodes on either side of head
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9
Q

What are the side effects of electroconvulsive therapy (ECT)?

A

Confusion and memory loss

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10
Q

How many forms of Monoamine oxidase (MAO) are there?

A

There are 2. A and B

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11
Q

Explain the two types of MAO

A

Type A: Responsible for enzymative degradation of 5-HT and catecholamines (only 6-8% of MAOs! Intraneuronal)

Type B: Majority (located extraneuronally)

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12
Q

How many chemical classes of MAOI are there and what are they?

A

There are 3 chemical classes

Hydrazines, Cyclopropylamines and Acetylenic propargylamines

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13
Q

Features of Hydrazines (class of MAOI)

A

Irreversible

Non-selective

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14
Q

Features of Cyclopropylamines (class of MAOI)

A

Irreversible
Non-selective
E.g Tranylcypramine

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15
Q

Features of Acetylenic Propargylamines

A

Irreversible
Selective

MAO-A: Clorgyline
MAO-B: Deprenyl, Pargyline

Antidepressant activity and main side-effects associated with MAO-A inhibition

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16
Q

What are the main side effects of MAOIs?

A

Hypotension (sympathetic block)

Atropine-like effects (dry mouth, blurred vision, photophobia, tachycardia)

Hepatocellular Jaundice

Drowsiness

Insomnia

CNS Stimulation and Agitation (tranylcypramine)

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17
Q

What are the main clinical uses of MAOIs?

A

Neurotic depression and anxiety
Mixed anxiety-depression and hypochondriasis
Phobic anxiety (e,g agoraphobia)

18
Q

Explain the ‘cheese reaction’ in relation to MAOIs

A

Cheese is high in TYRAMINE content

The interaction of MAOIs and Tyramine can cause hypertensive crisis (displaces NA)

19
Q

How can the ‘cheese reaction’ be avoided? (in relation to MAOIs)

A

Use reversible MAOIs (E.g moclobemide)

20
Q

How many classes of TCAs are there and what are they called?

A

There are 2.

Dibenzazepines and Dibenzcycloheptanes

21
Q

Examples of Dibenzazepines

A

Imipramine (non-sedative), Desipramine, Clomipramine

22
Q

Examples of Dibenzcycloheptanes

A

Amitryptiline (Sedative) and Noriptyline

23
Q

What are the major side effects of TCAs?

A

Sedation
Atropine-like (muscarinic blockade)
Postural hypotension
Dysrhythmia and heart block

24
Q

What common drugs interact with TCAs?

A

Alcohol
Hypotensions
NSAIDs
MAOIs

25
Q

How is the selectivity of monoamine reuptake inhibitors calculated?

A

IC50(5-HT)/IC50(NA)

26
Q

What chemical is involved in the medial forebrain bundle?

A

NA

27
Q

Biological components of depression are sensitive to antidepressant effects on which systems?

A

NA

28
Q

Emotional components of depression are sensitive to antidepressant effects on which systems?

A

5-HT

29
Q

Are SSRIs structurally similar to one another?

A

No

30
Q

SSRIs vs TCAs

A
  • No evidence to support greater efficacy
  • No evidence of more rapid onset
  • Better side-effect profile
  • Safer in overdose
  • However they are more expensive!
31
Q

What is the general mechanism of MAOIs

A

They increase 5-HT, NA (and DA) by inhibiting breakdown

32
Q

What is the general mechanism of TCAs

A

They increase 5-HT, NA (and DA) by blocking reuptake

33
Q

What is the general mechanism of SSRIs

A

They increase 5-HT by blocking reuptake

34
Q

What is the hippocampus responsible for?

A

Coping behaviour and resilience

35
Q

What is the hypothalamus responsible for?

A

Emotional expression

36
Q

What is the amygdala responsible for?

A

Anxiety and panic

37
Q

What is a manic episode (mania)?

A

A distinct period of abnormally and persistently elevated, expansive or irritable mood.

Lasting at least 1 week

38
Q

What classes of drugs can be used to treat mania?

A

Antidepressants
Antipsychotics
Lithium (only in acute episodes)
Antiepileptics (only in acute episodes)

39
Q

Does lithium have a narrow therapeutic range?

A

Yes

40
Q

What are the two mechanisms of action of Lithium?

A

Lithium, sodium and potassium

Lithium and second messengers

41
Q

How does Lithium affect sodium and potassium?

A

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)

42
Q

How does Lithium affect second messengers?

A

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

Pharmacology of CNS (15 decks)

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