Pharmacology of antidepressants and anxiolytics

Question 1

What are the four main classes of antidepressants?

Answer 1

TCAs

Monoamine oxidase inhibitors

SSRIs

Others

Question 2

Give two examples of TCA drugs

Answer 2

Imipramine

Amitryptilline

Question 3

What is the mechanism of TCAs?

Answer 3

Inhibit the reuptake of the neurotransmitters Serotonin and Noradrenaline but may also act on muscarinic and histamine receptors

Do this by competition for binding site on pre-synaptic neurone

Question 4

What are the adverse effects of TCAs?

Answer 4

Sedation

Confusion

Motor incoordination

Weight gain

Question 5

Describe the side effects of anti-muscarinics such as atropine?

Answer 5

Blurred vision

Dry mouth

Constipation

Urinary retention

Question 6

What side effects can occur as a result of blocking alpha-1 receptors?

Answer 6

Postural hypotension

Reflex tachycardia
=> ventricular dysrhythmias, QT prolongation

Question 7

Give some examples of monoamine oxidase inhibitors

Answer 7

Phenelzine
Isocarboxazid
Tranylcypromine

Moclobemide

Question 8

What is the mechanism of action of monoamine oxidase inhibitors?

Answer 8

Inhibits monoamine oxidase enzyme
 => inhibit breakdown of:
   - serotonin
   - noradrenaline
   - adrenaline
   - dopamine

Question 9

What are the two subtypes of monoamine oxidase inhibitors?

Answer 9

MAO-A: preference for serotonin

MAO-B: preference for phenylethamine and dopamine

Question 10

What are the adverse effects of MAO inhibitors?

Answer 10

Postural hypotension (sympathetic block)

Atropine like effects

Weight gain

CNS stimulation: Restlessness, Insomnia, Hallucinations

Question 11

Which drug interacts with tyramine containing products and what is the reaction?

Answer 11

MAO inhibitors

Interaction causes severe hypertension

Question 12

Give examples of SSRIs?

Answer 12

Fluoxetine (Prozac)

Fluvoxamine

Paroxetine

Citalopram

Sertraline

Question 13

What is the mechanism of SSRIs?

Answer 13

Inhibit reuptake of serotonin

Question 14

What are the adverse effects of SSRIs?

Answer 14

Common:

• Nausea
• Anorexia
• Insomnia
• GI disturbances
• Loss of libido and failure or orgasm

Other SEs:

• Hyponatraemia
• GI bleeding
• Serotonin syndrome: tremor, hyperthermia
• QT prolongation

Question 15

What is the mechanism of hyponatraemia in SSRI use?

Answer 15

Innappropriate ADH hypersecretion

Question 16

What are the signs of hyponatraemia?

Answer 16

Dizzines

Lethargy

Nausea

Cramps

Confusion

Seizures

Question 17

What are the risk factors of hyponatraemia as a result of taking a SSRI?

Answer 17

Old age

Female

Low body weight

Low baseline Na+ concentration

Concurrent drug treatments

Reduced renal function

Comorbidity

Question 18

How should hyponatraemia as a result of SSRIs be treated?

Answer 18

Withdraw drug but not immediately, must titrate down

Question 19

Which patients are SSRIs contraindicated in?

Answer 19

Patients under 18 years of age due to increased risk of self harm and suicidal thoughts

Question 20

Which SSRI is particularly associated with QT prolongation?

Answer 20

Citalopram

Question 21

What are the interactions of SSRIs?

Answer 21

Drugs increasing bleeding risk
- antiplatelets, anticoagulants, NSAIDs, Steroids

Other antidepressants, esp. MAO inhibitors

Patients with lower seizure threshold

Question 22

What does Mirtazapine do?

Answer 22

Antagonises pre-synaptic alpha-2 receptors which engances noradrenaline and serotonic release from synapse

Also antagonises H1 receptors

Question 23

What does Trazadone do?

Answer 23

Blocks 5-HT2a and 5-HT2c receptors (serotonin receptors) => blocks reuptake of serotonin

Question 24

What are the side effects of Mirtazapine and Trazadone?

Answer 24

Sedative

Increased appetite and weight gain

(Relatively safe)

Question 25

Give examples of non-selective reuptake inhibitors

Answer 25

Venlofaxine

Duloxetine

Question 26

Which antidepressant are you likely to prescribe if insomnia is a problem?

Answer 26

Amitriptyline

Mirtazapine

• both have anxiolytic sedative effects

Question 27

Which antidepressant are you likely to prescribe if lethargy and slowness is a problem?

Answer 27

Imipramine or SSRI

• less sedative

Question 28

Which antidepressant are you likely to prescribe if there is a problem with cardiotoxicity?

Answer 28

Sertraline

• 1st line post MI

Question 29

Which antidepressant are you likely to prescribe if there is a problem with anticholinergic activity e.g. glaucoma, prostatism?

Answer 29

Lofepramine

• TCA with less anti-cholinergic activity

Question 30

What is the first line antidepressant treatment?

Answer 30

SSRI: routinely Citalopram

Question 31

How long do antidepressants take before any benefit?

Answer 31

2-3 weeks

MAO inhibitors quicker

Question 32

Which antidepressant is associated with a greater risk of death in overdose?

Answer 32

Venlafaxine

TCAs due to risk of ventricular dysrhythmias

Question 33

Which drugs can be used to augment antidepressants?

Answer 33

Lithium

Antipsychotics

Another depressant

Benzodiazepine
- if anxiety is a problem, no > 2 weeks though

Question 34

Which benzodiazepines are used to treat insomnia?

Answer 34

Temazepam

Nitrazepam

Z-related compounds

• zopiclone
• zolpidem
• zaleplon

Question 35

Which benzodiazepines are used to treat anxietty?

Answer 35

Diazepam

Chlordiazepoxide

Lorazepam

Oxazepam

Question 36

What is the mechanism of action of benzodiazepines?

Answer 36

Agonists which bind to benzodiazepine site on GAGAa receptor

=> enhances inhibitory effect of GABA by opening Cl- channels

=> produces an increased inhibitory neurotransmission, which leads to sedation and reduced anxiety

Question 37

What are the adverse effects of benzodiazepines?

Answer 37

Drowsiness and falls

Impairs judgement and dexterity

Increased risk of experiencing RTAs

Forgetfulness, confusion, irritability, aggresion,…

Addiction