Drugs of Dependence and Antidepressants 2

Question 1

What receptor does LSD act on?

Answer 1

Various 5-HT receptors

Question 2

What mediates LSD’s psychotomimetic effects?

Answer 2

5-HT2A receptor agonist actions

Question 3

What does LSD’s agonist activity at the 5-HT2A receptor cause?

Answer 3

Release of glutamate in cortex

Question 4

What is the effect of LSD in the raphe nuclei?

Answer 4

Inhibits firing of 5-HT containing neurons

Question 5

How does LSD inhibit the firing of 5-HT containing neurons in the raphe nuclei?

Answer 5

Acts as agonist on inhibitory autoreceptors of these cells

Question 6

What are affective disorders?

Answer 6

Those that influence mood

Question 7

What is unipolar/major depression?

Answer 7

Extreme melancholia and withdrawal

Question 8

What is reactive depression?

Answer 8

Due to known cause

Question 9

What is endogenous depression?

Answer 9

No known/apparent cause

Question 10

What is bipolar depression?

Answer 10

Mood swings from extreme elation and hyperexcitability to extreme melancholia and withdrawal

Question 11

What does the monoamine theory of depression state?

Answer 11

Drugs that interfere with monaminergic transmission influence mood

Question 12

What are the monoamine transmitters?

Answer 12

Noradrenaline
Serotonin
Dopamine

Question 13

What does a depletion in monoamine transmitters cause?

Answer 13

Depression

Question 14

What does an acute elevation of monoamine transmitters in the synapse do?

Answer 14

Can enhance mood

Question 15

Why do drugs that elevate mood not necessarily make good antidepressants?

Answer 15

Dependence - dopamine related
Toxicity
- Cardiovascular because given systemically
- Psychoses with overuse

Question 16

How long can antidepressants take to take effect?

Answer 16

2-6 wks

Question 17

What are the first generation drugs used to treat unipolar depression?

Answer 17

Tricyclic antidepressants = "ipramines"
Monoamine oxidase (MAO) inhibitors

Question 18

What are the second generation drugs used to treat unipolar depression?

Answer 18

Selective serotonin uptake inhibitors (SSRIs)

Selective serotonin/noradrenaline uptake inhibitors (SSNRIs)

Question 19

What are the third generation drugs used to treat unipolar depression?

Answer 19

Atypical antidepressants

• Novel monoaminergic drugs
• Non-monoaminergic drugs

Question 20

What drugs are used to treat bipolar depression?

Answer 20

Lithium

Some antiepileptics; eg: carbamazepine

Question 21

What are the pharmacological actions of tricyclic antidepressants?

Answer 21

Inhibit neuronal uptake of noradrenaline and serotonin
Antagonise
- Alpha adrenoceptors
- Muscarinic receptors
- Histamine receptors
- Serotonin receptors
Quinidine-like membran stabilising action at very high concentrations > acts as local anaesthetic

Question 22

How long do the clinical effects of tricyclic antidepressants take to develop?

Answer 22

Wks despite pharmacological effects taking hrs

Question 23

What is likely to underly the antidepressant activity of tricyclic antidepressants?

Answer 23

Adaptive changes in neuronal function

• Change in receptor sensitivity/density
• Change in 2nd messenger activity

Question 24

What is the therapeutic window of tricyclic antidepressants?

Answer 24

Narrow > limited efficacy

Question 25

What is the consequence of the longish half-life of tricyclic antidepressants?

Answer 25

Gradual accumulation possible | Slowly developing side effects

Question 26

What are the side effects of tricyclic antidepressants?

Answer 26

Sedation Anti-cholinergic = SLUD Postural hypotension Weight gain

Question 27

What happens in overdose of tricyclic antidepressants?

Answer 27

``` Confusion Mania Cardiac dysrhythmias Seizures Impotence ```

Question 28

What is the pharmacological effect of MAO inhibitors?

Answer 28

Increase levels of - Noradrenaline - Serotonin - Dopamine

Question 29

Are MAO inhibitors slow or fast acting?

Answer 29

Delayed antidepressant effect

Question 30

Do MAO inhibitors reversible or irreversible?

Answer 30

Irreversible

Question 31

What is the cheese reaction?

Answer 31

Monoamine oxidase present in gut wall to break down dietary amines (mainly tyramine) Tyramine can release noradrenaline from storage vesicles in peripheral nerve terminals > indirectly sympathomimetic MAO inhibitors stop breakdown of tyramine > absorbed > enhanced sympathomimetic effect

Question 32

Where is tyramine commonly found?

Answer 32

Cheese Wines Chocolate Bananas

Question 33

What are the sympathomimetic effects of the cheese reaction?

Answer 33

Acute hypertension Throbbing headache Intracranial haemorrhage

Question 34

What is moclobemide?

Answer 34

``` MAO inhibitor - most commonly used Monoamine oxidase A selective > prefers noradrenaline and serotonin Reversible Less likely to cause cheese reaction Interaction with other drugs ```

Question 35

What are the side effects of moclobemide?

Answer 35

Dizziness Nausea Insomnia

Question 36

What are some examples of SSRIs?

Answer 36

Fluoxtine = prozac Paroxetine Sertraline

Question 37

What is the selectivity for SSRIs?

Answer 37

Selective for 5-HT uptake | Few adrenergic, histaminergic, and cholinergic actions

Question 38

What is the therapeutic index of SSRIs?

Answer 38

High

Question 39

What is the toxicity of SSRIs?

Answer 39

Minimal unless combined with other drugs

Question 40

What is the serotonin syndrome?

Answer 40

``` SSRI + MAO inhibitor + tricyclic antidepressant Highly anxious Hyperthermia Muscle rigidity Cardiovascular collapse ```

Question 41

What effect do SSRIs have in adolescents?

Answer 41

Anxiety and suicidal tendencies on commencement

Question 42

What are the side effects of SSRIs?

Answer 42

``` Nausea Insomnia Agitation Weight change Loss of libido ```

Question 43

What is venlaflaxine?

Answer 43

SSNRI

Question 44

What is reboxetine?

Answer 44

Atypical antidepressant | Monoaminergic mechanism: re-uptake inhibitor

Question 45

What is mianserin?

Answer 45

Atypical antidepressant | Monaminergic mechanism: blocks alpha2 adrenoceptors, histamine, and serotonin receptors

Question 46

What is mirtazepine?

Answer 46

Atypical antidepressant Monoaminergic mechanism: blocks alpha2 adrenoceptors and serotonin receptors Good for people with low mood with basis in anxiety

Question 47

What are some pro-cognitive therapies used in the treatment of depression?

Answer 47

Breathing exercise Physical exercise Deep brain stimulation

Question 48

What could be the long term changes of depression be caused by, and what should new drug targets focus on?

Answer 48

Long term changes because of neuronal death | Targets should include focus on cell survival

Question 49

What is the pharmacological effect of lithium carbonate?

Answer 49

Interaction with inositol phosphate 2nd messengers | Tends to reduce Ca in nerves

Question 50

What is the therapeutic index of lithium carbonate?

Answer 50

Very low | Plasma levels must be monitored

Question 51

What are the side effects of lithium carbonate?

Answer 51

Nausea Tremor Impaired renal, thyroid, and neurological function