Pharmacological Management Of Anxiety Disorders and Depression

Question 1

What is the function of the 5HT2-a receptor?

Answer 1

Located in the limbic system, involved in anxiety and panic attacks.

In the sleep centre, involved in insomnia and disruption of slow wave sleep.

In the basal ganglia, involved in muscle restlessness.

Question 2

What is the function of the 5-HT1a receptor?

Answer 2

Autoreceptor responsible for the delayed effect of anxiolytics, which eventually become desensitised over time.

Question 3

What is the function of the 5HT3 receptor?

Answer 3

Present in the hypothalamus and gut to cause vomiting, diarrhoea and muscle cramps.

Question 4

What is the function of the 5HT2-C receptor?

Answer 4

Located in the spinal cord and activation causes sexual dysfunction.

Question 5

What is the action of SSRIs?

Answer 5

Reduce the reuptake of serotonin in the synaptic cleft by SER/serotonin transporters on the presynaptic neurons to increase availability and reduce psychological symptoms.

Question 6

How is serotonin synthesised?

Answer 6

Dietary protein, in the form of the amino acid tryptophan -> serotonin

Question 7

Where is serotonin stored/found in the body?

Answer 7

-> Platelets

-> Neurons in the CNS

-> Enterochromaffin cells in the gut

Question 8

What are the general side effects of SSRIs?

Answer 8

They increase bleeding time, with possible risk in pregnant women for post-partum haemorrhage.

Prolonging of the QT interval

Vomiting, diarrhoea and muscle cramps

Arthralgia (joint pain)

Question 9

What is the first line SSRI commonly used in anxiety and depression?

Answer 9

Citalopram or Fluoxetine
Followed by Escitalopram, Paroxetine and Sertraline.

Question 10

What are the contraindications for SSRIs?

Answer 10

Poorly controlled epilepsy and QT interval prolongation.

Question 11

How are the catecholeamines synthesised?

Answer 11

Dietary protein in the form of phenylalanine -> tyrosine -> levadopa -> dopamine -> noradrenaline - > adrenaline

Question 12

What is the action of SNRIs?

Answer 12

Block action of SER and NE transporters on the presynpatic neurons to increase availability of serotonin and noradrenaline.

Question 13

Which SNRIs are first line treatment for anxiety and depression?

Answer 13

Venlafaxine and Duloxetine

Question 14

What is the action of venlafaxine?

Answer 14

It has a wider use than duloxetine; major depression, GAD, social anxiety and panic disorder. It is an SNRI with a greater affinity for serotonin than noradrenaline.

Question 15

What is the action of duloxetine?

Answer 15

Potent inhibitor of serotonin, noradrenaline and a lesser inhibitor of dopamine. It’s given for major depressive disorder and anxiety.

It decreases the transmission of painful stimuli; Increases vasoconstriction, hypertension and muscle contraction.

Question 16

What is the action of TCAs?

Answer 16

Tricyclic antidepressants inhibit serotonin transporters, noradrenaline transporters, histamine, muscarinic, Na+ channels and alpha 1 receptors.

They are a second line treatment for depression due to the risk of overdose and more significant side effects compared to SSRIs.

Question 17

What are the side effects of tricyclic antidepressants?

Answer 17

Tricyclic antidepressants are likely to induce mania amnd are contraindicated for mania during bipolar.

-> Inhibition of histamine= sedation and weight gain.

-> Inhibition of muscarinic receptors= orthostatic hypotension and dizziness.

-> Inhibition of Na+ channels= cardiac channel abnormalities

-> Increase in serotonin= sexual dysfunction, diarrhoea and vomiting

-> Increase in noradrenaline= hypertension

Question 18

What are the contraindications of tricyclic antidepressants?

Answer 18

Cardiovascular disease/arrythmias
Conditions related to hypertension such as Glaucoma, Urinary retention and Prostate hypertrophy.

Question 19

What are the primary tricyclic antidepressants?

Answer 19

Amitryptilline

Lofepramine

Imipramine

Question 20

What is the action of amitryptilline?

Answer 20

Given for major depressive disorder and those with neuropathic pain. Inhibits SER and NER transporters and inhibits the action of histamine, a1 receptors and muscarinic receptors.

Question 21

What is the action of MAO inhibitors?

Answer 21

Prevent the action of monoamine oxidase within the presynaptic neuron via the packaging of dopamine, serotonin and noradrenaline. They were divided into non-selective MAO inhibitors, MAO-A inhibitors and MAO-B inhibitors.

Question 22

What are the non-selective MAO inhibitors?

Answer 22

Phenelzine
Tranylcycloprine

Question 23

What is the action of monoamine oxidase A?

Answer 23

Greatest affinity for packaging of serotonin than noradrenaline and dopamine.

Question 24

What are the MAO-A inhibitors?

Answer 24

Moclobemide which targets serotonin to increase its availability. It is a treatment for depression and social anxiety.

Moclobemide is contraindicated for phaeochormocytoma and acute confusional state like delirium.

Question 25

What is the action of monoamine oxidase B?

Answer 25

Greatest affinity for packaging of dopamine.

Question 26

What is an important contraindication with the use of MAO?

Answer 26

When taking MAO, the ingestion of fermented foods high in tyramine, a precursor to monoamine like noradrenaline will result in its accumulation and a hypertensive crisis. -> Cardiovascular disease and cerebrovascular disease.

Question 27

What are the risks with the use of combination antidepressants such as SSRIs, SNRIs and mAO inhibitors?

Answer 27

Combination use of antidepressants results in accumulation of serotonin and serotonin syndrome, characterised by MAN: ->Mental state changes ->Autonomic dysregulation of hypertension and tachycardia ->Neuromuscular abnormalities such as clonus.

Question 28

What is the treatment of the somatic symptoms of anxiety?

Answer 28

Benzodiazepines which act on the modulators site on the GABA receptor, acting as a positive allosteric modulator. It causes a conformational change to occur on the receptor which enhances the effects of GABA for the influx of Cl-. -> Benzodiazepines are used for rapid tranquilisation to avoid physical intervention and acute treatment of anxiety.

Question 29

What are the side effects of benzodiazepines?

Answer 29

Sedation Respiratory depression Sleep induction with high drug concentration Anterograde amnesia (inability to form new memories following drug use) Anticonvulsant activity via reduction in muscle tone.

Question 30

What is monitored in rapid tranquilisation?

Answer 30

Temperature, pulse, BP, hydration, consciousness and respiratory rate.

Question 31

What is agomelatine?

Answer 31

Melatonin agonist and selective serotonin antagonist of 5HT2-C. It is indicated for major depression and can cause abdominal pain and anxiety.y

Question 32

What is reboxetine?

Answer 32

Noradrenaline reuptake inhibitor used for a treatment of major depression that can cause hypertension, akithisia and constipation.

Question 33

What are z drugs?

Answer 33

Non benzodiazepine drugs which act on the alpha subunit of the GABA receptor to cause sedation. These include zopiclome and zolpidem and have a similar risk profile like benzodiazepines for increased fill risk in elederly and intracranial pressure.

Question 34

What is an atypical antidepressant?

Answer 34

Bupropion used in smoking cessation which is a Weak dopamine and noradrenaline reuptake inhibitor to prolong the action of the neurotransmitters at the synaptic cleft and antagonises nicotinic anticholinergic receptors, used during smoking cessation and continued for weeks with gradual decline.

Question 35

Which antidepressant is commonly prescribed for those with anorexia?

Answer 35

Mirtazapine, indicated for major depression which increases noradrenergic and serotonin activity and induces weight gains and increased appetite.

Question 36

Which SSRI is ideal for use with an antidepressant?

Answer 36

Fluoxetine

Question 37

Which drugs should be avoided for prescribing with SSRIs?

Answer 37

NSAIDs due to bleeding risk Warfarin and heparin Aspirin Monoamine oxidase inhibitors due to risk of serotonin syndrome

Question 38

What is the risk of citalopram use?

Answer 38

Prolonged QT inerval