5: Pharmacology of antidepressants and mood stabilisers

Question 1

Are antidepressants only given for depression?

Answer 1

No

eating disorders, anxiety, chronic pain as well

Question 2

What is dysthymia?

Answer 2

Persistent low-grade depression

Question 3

What are some examples of monoamine neurotransmitters?

Answer 3

Noradrenaline (excitatory)

Dopamine (excitatory)

5-HT / Serotonin (inhibitory)

Question 4

What is 5-HT?

Answer 4

Serotonin

Question 5

NA, 5-HT and dopamine are examples of ____ neurotransmitters.

Answer 5

monoamine

Question 6

Serotonin is widely distributed in the brain.

What are its functions

a) superiorly
b) at the nucleus raphe magnus?

Answer 6

a) Mood, sleep, appetite, perception

b) Analgesia

Question 7

What effects does NA produce in the brain specifically?

Answer 7

Arousal

Emotional response

fight or flight in the brain

Question 8

Which part of the brain releases NA in response to signals from the periaqueductal grey?

What general effect does this cause?

Answer 8

Locus caeruleus

Analgesia

Question 9

Which enzyme metabolises monoamine neurotransmitters to clear them out of the pre-synaptic terminal?

Answer 9

Monoamine oxidase

Question 10

What happens if you inhibit monoamine oxidase?

Answer 10

Neurotransmitter isn’t cleared up

It sticks around in the synapse for longer

Increased excitation

Question 11

What are two examples of monoamine oxidase inhibitors?

Answer 11

Phenelzine (irreversible)

Moclobemide (reversible)

Question 12

Which monoamine oxidase inhibitor is

a) reversible
b) irreversible?

Answer 12

a) Moclobemide

b) Phenelzine

Question 13

What is a major side effect, involving diet, of monoamine oxidase inhibitors?

Answer 13

If you eat products containing lots of tyramine e.g cheese, gravy you’ll have a hypertensive crisis

Question 14

Why aren’t monoamine oxidase inhibitors e.g phenelzine, moclobemide widely used?

Answer 14

Side effects

Question 15

What are some side effects of monoamine oxidase inhibitors?

Answer 15

Hypertensive crisis w/ high tyramine diet

Postural hypotension

Peripheral oedema

Insomnia

Question 16

How do tricyclic antidepressants work?

Answer 16

Block re-uptake of monoamine neurotransmitter into pre-synaptic terminal

Question 17

What are some examples of tricyclic antidepressants?

Answer 17

Imipramine

Dosulepin

Amitriptyline

Lofepramine

Question 18

What are some side effects of TCAs?

Answer 18

Anticholinergic effects - reduce smooth muscle activity; blurred vision (can’t accomodate), dry mouth, constipation, urinary retention

Cardiovascular problems - tachycardia, postural hypotension, (fatal) arrhythmia

Sedation

Weight gain

Question 19

What are some anticholinergic effects of TCAs?

Answer 19

Dry mouth and eyes

Blurred vision (failure of accommodation)

Constipation

Urine retention

Question 20

What are some cardiovascular side effects of TCAs?

Answer 20

Postural hypotension

Tachycardia

Arrhythmia (fatal in overdose)

bad for the heart in general

Question 21

What can patients suffer if they overdose on TCAs?

Answer 21

Fatal arrhythmias

Question 22

How do SSRIs work?

Answer 22

Same action as TCAs, prevent reuptake of monoamine neurotransmitter into pre-synaptic terminal

but act selectively on 5-HT

Question 23

SSRIs act selectively on ___.

Answer 23

5-HT (serotonin)

Question 24

What are some examples of selective serotonin reuptake inhibitors?

Answer 24

Fluoxetine

Citalopram

Sertraline

Question 25

What are some **side effects** of **SSRIs**?

Answer 25

**N&V** (opposite: anti-emetics which INHIBIT a type of 5-HT) **Headache** (opposite: triptans which INHIBIT a type of 5-HT) Sweating Sexual dysfunction

Question 26

The **nausea** and **headache** typically caused by **SSRIs** is \_\_\_.

Answer 26

**transient** meaning it goes away after a while

Question 27

Which symptoms are a) **5-HT1** b) **5-HT₃** receptors responsible for?

Answer 27

**a) Headache** (antagonists are the -triptans, for migraine) **b) Nausea** (antagonists are -setrons, or anti-emetics)

Question 28

**SSRIs** may initially ___ the symptoms of anxiety or depression.

Answer 28

**worsen** especially in young people

Question 29

In young people, what do **SSRIs** increase the risk of?

Answer 29

**Thoughts of self-harm / suicide**

Question 30

Why shouldn't **SSRIs** be given to patients under 25?

Answer 30

**Increase in thoughts of self-harm / suicidal ideation**

Question 31

**SSRIs** can cause a degree of ___ dysfunction.

Answer 31

**sexual dysfunction**

Question 32

Which class of antidepressant has a similar **mode of action to SSRIs** but **less side effects**?

Answer 32

**SNRIs** duloxetine blocks uptake of NA AND 5-HT

Question 33

Which antidepressant can be added alongside an **SSRI** to block its nausea and headache side effects?

Answer 33

**Mirtazapine** look at receptors to see why

Question 34

In the treatment of depression, you **don't combine drugs** because you get more side effects without more benefit. What is the one exception to this?

Answer 34

**Addition of mirtazapine to SNRI (duloxetine) therapy to reduce side effects**

Question 35

What is the **onset of action** of antidepressants?

Answer 35

**2 - 6 weeks**

Question 36

What should you ask about in the drug history of someone with a mood disorder?

Answer 36

**Drugs they've been on previously** They may help again

Question 37

The more **severe** a patient's depression is, the **(more / less) effective antidepressants** tend to be.

Answer 37

**more severe \> more effective**

Question 38

Which **mood stabiliser** is the gold standard treatment for **bipolar disorder**?

Answer 38

**Lithium**

Question 39

**Lithium** has a **narrow** ___ \_\_\_.

Answer 39

**narrow therapeutic index** effective dose is v close to toxic dose

Question 40

**Lithium** has a lot of ___ side effects.

Answer 40

**renal**

Question 41

**Lithium** may cause renal impairment when given with which class of drug?

Answer 41

**NSAIDs**

Question 42

Which **mood stabiliser** is **toxic** when given in high doses?

Answer 42

**Lithium**

Question 43

Which **class of antidepressant** can cause **fatal arrhythmias** when an overdose occurs?

Answer 43

**TCAs** imipramine, amitriptyline, dosulepin

Question 44

Which drugs, used in epilepsy, can also be given to stabilise mood in **bipolar disorder**?

Answer 44

**Anticonvulsants** sodium valproate lamotrigine carbamazepine remember sodium valproate is teratogenic and carbamazepine makes myoclonic epilepsy worse

Question 45

Which **class** of **antidepressant drug** can cause a fatal hypertensive crisis when the patient eats mature cheese? Why?

Answer 45

**Monoamine oxidase inhibitor** (phenelzine, moclobemide) **Tyramine** is a substrate of monoamine oxidase, accumulation causes **noradrenaline release** - BP skyrockets \> pulmonary oedema, palpitations, subarachnoid haemorrhage