49 - Drug Dependence and Antidepressants

Question 1

Monoamine theory of depression

Answer 1

Alteration of monoaminergic transmission (noradrenaline, serotonin, dopamine) influences mood.
Depletion leads to depression.
Acute elevation in synapse can elevate mood

Question 2

1st generation of antidepressants
1
2

Answer 2

Tricyclics

Monoamine oxidase inhibitors

Question 3

2nd generation of antidepressants
1
2

Answer 3

SSRIs

Selective serotonin/noradrenaline uptake inhibitors (SSNRIs)

Question 4

3rd generation (atypical) antidepressants
1
2

Answer 4

Novel monoaminergic drugs

Non-monoaminergic drugs

Question 5

Treatments for bipolar disorder
1
2

Answer 5

Lithium
Some antiepileptics (EG carbamazepine)

Question 6

Tricyclic structure

Answer 6

Structurally similar to phenothiazines used to

treat schizophrenia

Question 7

Tricyclic mechanism of action
1
2
3

Answer 7

– Inhibit neuronal uptake of noradrenaline and serotonin
– Antagonise α-adrenoceptors, muscarinic receptors,
histamine receptors and serotonin receptors
– Quinidine-like membrane stabilising action at very high
concentrations

Question 8

Clinical effect of tricyclics
1
2
3

Answer 8

– Takes weeks to develop despite pharmacological effects
manifest in hours
– Adaptive changes in neuronal function likely underlie
antidepressant activity
• Changes in receptor sensitivity / density
– Increased levels of transmitter can down-regulate receptor number / function
≈ β-adrenoceptors, α-adrenoceptors and 5-HT2 receptors

Question 9

Therapeutic window of tricyclics

Answer 9

Narrow

Question 10

Side-effects of tricyclics 
1
2
3
4

Answer 10

Sedation, anti-muscarinic (dry mouth, blurred vision, constipation), postural hypotension, weight gain

Question 11

Effects of overdose on tricyclics 
1
2
3
4
5

Answer 11

Confusion, mania, cardiac dysrhythmias, seizures, impotence

Question 12

Effects of MAOIs on neurotransmitter levels

Answer 12

Increase levels of NA, 5-HT and DA

Question 13

MAOI cheese reaction

Answer 13

Monoamine oxidase present in gut walls, breaks down dietary amines (particularly tyramine) present in food (in cheese, wine, chocolate, bananas).

Tyramine can release NA from storage vesicles in peripheral nerve terminals (indirectly acting sympathomimetic, like amphetamine)

Inhibiting MAO allows tyramine to be absorbed, stops breakdown by nerves, enhancing sympathomimetic effect

Question 14

Irreversible MAOIs
1
2

Answer 14

Iproniazid, Tranylcypromine

Question 15

Reversible MAOI

Answer 15

Moclobemide

Question 16

Moclobemide

Answer 16

• MAO A selective
• Now the most commonly used
– less likely to cause ”cheese reaction”
» some tyramine breakdown in gut due to competition
– Interaction with other drugs
• Side effects
– Dizziness, nausea, insomnia

Question 17

Examples of SSRIs
1
2
3

Answer 17

Fluoxetine, Paroxetine, Sertraline

Question 18

Example of SSNRI

Answer 18

Venlafaxine

Question 19

Features of SSRIs

Answer 19

– Selective for 5-HT uptake
– Few adrenergic, histaminergic and cholinergic actions
– High therapeutic index

Question 20

When can SSRIs become toxic?

Answer 20

When combined with other drugs.
– MAOI and TCA - “serotonin syndrome”
» Hyperthermia, muscle rigidity, cardiovascular collapse

Question 21

Side effects of SSRIs

Answer 21

Nausea, insomnia, agitation, weight change, loss of libido

Question 22

Example of a noradrenaline reuptake inhibitor

Answer 22

Reboxetine

Question 23

Examples of non-monaminergic antidepressants 
1
2
3
4
5

Answer 23

– Corticotrophin receptors
• Hypothalamic-pituitary-axis in depression
– Glutamate receptors
– Opioid receptors
– Neurokinin (Substance P) receptors
– Growth factors
• The role of supporting cells?

Question 24

How does lithium carbonate work?

Answer 24

Interacts with inositol phosphate secondary messengers (regulates Ca2+ in nerves).

Question 25

Therapeutic index of lithium

Answer 25

Very low

Question 26

Side effects of lithium carbonate 
1
2
3
4
5

Answer 26

Nausea, tremor, impaired renal, thyroid & neurological

function