Lecture 3 & 4: Anxiety And Insomina Pathiophysiology, Pharmacology & Pharmaceutical Care

Question 1

What is anxiety?

Answer 1

• Anxiety is a feeling of worry, tension, or fear about potential or upcoming events, often with an imprecise or unknown threat.
• Anxiety can manifest in various forms and intensities, affecting daily life and functioning.

Question 2

How is anxiety different from fear?

Answer 2

• Anxiety involves an imprecise or unknown threat, while fear involves a known or definite threat.
• This distinction is crucial in understanding emotional responses and treatment approaches.

Question 3

What are three types of symptoms of anxiety?

Answer 3

• Behavioral: Avoidance behaviours, Overly attached
• Psychological: Restlessness, Difficulty concentrating, irritability
• Physical: Fatigue,Muscle aches, insomnia

Question 4

Name some types of anxiety disorders.

Answer 4

• Generalized Anxiety Disorder (GAD)
• Panic Disorder
• Social Anxiety Disorder.
• Specific Phobias
• Post traumatic stress disorder
• Obsessive Compulsive Disorder

Question 5

What are the first-line pharmacological treatments for anxiety?

Answer 5

• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs).

These medications are often preferred due to their efficacy and safety profile.

Question 6

What neurotransmitter systems are targeted in anxiety treatment?

Answer 6

Serotonin, noradrenaline, and GABA systems.

Targeting these systems helps regulate mood and anxiety levels.

Question 7

What are common side effects of SSRIs?

Answer 7

Insomnia, nausea, dizziness, sexual dysfunction, serotonin syndrome (high doses) (can affect GI & CNS), hyponatraemia

Understanding side effects is important for patient management and adherence.

Question 8

What are the advantages of benzodiazepines?

Answer 8

Quick onset of action.

This makes benzodiazepines effective for acute anxiety episodes.

Question 9

What is the disadvantage of long-term benzodiazepine use?

Answer 9

They are highly addictive and can impair cognitive function and have withdrawal symptoms w/ long term use.

Long-term use is generally discouraged in favor of other treatment options.

Question 10

What does Pregabalin target?

Answer 10

• Similar effect to Benzos
• Modulation of neurotransmitter release: Binds to alpha-2-delta subunit on voltage gated Ca2+ channels
• Reduces release of excitatory neurotransmitters such as glutamate and norepinephrine

Pregabalin is used to treat anxiety and neuropathic pain.

Question 11

What is insomnia?

Answer 11

Difficulty falling asleep or staying asleep, often leading to fatigue during the day.

Insomnia can significantly impact quality of life.

Question 12

Name causes of insomnia.

Answer 12

• Stress and psychiatric conditions like depression.
• Other medical conditions: Alzheimers and Parkinsons
• Medication: SSRIs & MAOIs

Identifying underlying causes is essential for effective treatment.

Question 13

What brain circuits regulate sleep?

Answer 13

• Wake-promoting circuits (neurons releasing serotonin, noradrenaline, dopamine, acetylcholine & histamine)
• NREM-promoting circuits: Neurons releasing GABA in the forebrain
• REM-promoting circuits: Neurons releasing GABA in the brainstem

The interplay of these circuits is complex and crucial for healthy sleep patterns.

Question 14

Name some pharmacological treatments for insomnia.

Answer 14

• Z drugs (e.g., Zolpidem) not benzos but have similar mechanisms
• Prolonged-release melatonin.
• Daridorexant: inhibits actions of wake promoting orexin
• Antihistaminergic drugs

These medications target different aspects of sleep regulation.

Question 15

What is the mechanism of action of Zolpidem?

Answer 15

• Binding Site: Zolpidem binds to GABA-A receptor unlike benzodiazepines, which can bind to a variety of subtypes of GABA-A receptors, zolpidem has a more selective affinity for a specific subset of GABA-A receptors that contain the alpha-1 subunit.
• Zolpidem’s high selectivity for the alpha-1 subunit is why it has a stronger sedative effect with less impact on other cognitive functions
• Allosteric Modulation: When binds to the alpha-1 subunit of the GABA-A receptor, it enhances the effect of GABA. This increases the opening of the chloride ion channel, allowing more chloride ions to flow into the neuron. The influx of chloride ions hyperpolarizes the neuron, making it less likely to fire.
• This hyperpolarization results in overall CNS depression, leading to the sedative and hypnotic effects of zolpidem, which help promote sleep in individuals with insomnia.

Zolpidem enhances the effect of GABA, promoting sleep.

Question 16

Why were barbiturates (that can be used for insomnia) replaced with benzodiazepines?

Answer 16

Barbiturates have a narrow therapeutic dosage range and a high risk of overdose.

Benzodiazepines are considered safer alternatives with a better therapeutic index.

Question 17

What is the stress response system?

Answer 17

• Hypothalamus releases CRH
• Causes pituitary gland to release ACTH
• Goes to adrenal gland (on top of kidney) and causes the release of cortisol
• Hypothalamus responds to the level of cortisol

Question 18

What does the stress response system cause?

Answer 18

• Mobilisation of energy
• Increased cardio tone
• Suppression of digestion and growth
• Alter the immune system

Question 19

What are the different treatment strategies used in anxiety?

Answer 19

• Changes in lifestyle (quit smoking, reduce alcohol, physical exercise)
• Self help
• Psychotherapy (CBT)
• Pharmacotherapy: 6-12 months/ combination or switch

Question 20

What is second line treatment for anxiety?

Answer 20

• Benzodiazepines
• Pregabalin

Question 21

What are other treatments that can be used for anxiety?

Answer 21

• Tricyclic antidepressants (TCAs)
• 5 HT1A agonist (Buspirone)
• Monoaminoxidase inhibitors (MAOIs)

Question 22

What is the mechanism of SSRIs

Answer 22

• Serotonin Release: Released from presynaptic neuron. Transmit signals related to mood, anxiety, and behavior.
• Reuptake Process: After serotonin is released into the synaptic gap, it binds to receptors on the post-synaptic neuron. Serotonin is usually reabsorbed into the presynaptic neuron via a transporter protein called the serotonin transporter (SERT) (reuptake).
• SSRIs Block Reuptake: SSRIs work by inhibiting or blocking the serotonin transporter (SERT). This blockage reduces the reuptake of serotonin, leaving more serotonin available in the synaptic gap.

Question 23

Why do SSRIs have a delay period of 4-6 weeks?

Answer 23

• Serotonin binds to auto receptors which stops the firing of activation of neurons
• This inhibits further release of serotonin -> negative feedback
• After 4-6 weeks auto receptors are desensitised and stop the negative feedback process-> affect of drug starts

Question 24

What are examples of SSRIs?

Answer 24

• Citalopram
• Fluoxetine
• Paroxetine
• Sertraline

Question 25

What are the Advantages of SSRIs?

Answer 25

* Effective against different anxiety disorders * Long lasting effects * Less addictive than benzodiazepines * Potent antidepressants w/ fewer side effects

Question 26

What are the Disadvantages of SSRIs?

Answer 26

* Delay period * Health issues if taken w/ other drugs (alcohol, NSAID) * SSRIs can increase the risk of suicidal thinking and self-harm in patients under 30.

Question 27

What is neuroplasticity?

Answer 27

* Ability of the brain to change its activity in response to intrinsic or extrinsic stimuli by reorganising its structure, functions or connections * Increasing serotonin and noradrenaline may promote flexibility and make the brain more capable of changing * Change brain to resist anxiety more adaptable

Question 28

What is the mechanism of Benzodiazepines?

Answer 28

* GABA is the primary inhibitory neurotransmitter in the brain, meaning it reduces neuronal excitability and dampens overall brain activity & binds to GABA receptors. The main subtype GABA-A receptor for Benzo action. * Allosteric Modulation: Benzodiazepines don't directly activate GABA-A receptors, they bind to a specific site on the GABA-A receptor (a site distinct from where GABA itself binds) in a process called allosteric modulation. This enhances the effect of GABA (receptor more responsive to GABA) * Increased Chloride Ion Influx: Causes the receptor to open and allows chloride ions (Cl-) to flow into the neuron. This influx of chloride ions hyperpolarizes the neuron, making it less likely to fire an action potential (a signal). stronger inhibition of neuronal activity, which produces the calming and sedative effects associated with benzodiazepines. * Resulting Effects: -- Anxiolysis: Reduction of anxiety due to decreased activity in regions of the brain involved in stress and fear (e.g., the amygdala). -- Sedation and Hypnotic Effects: Depresses CNS. -- Muscle Relaxation: Reduce muscle tone -- Anticonvulsant Effects: controlling seizure*s.*

Question 29

What are tricyclic antidepressants also antagonists of?

Answer 29

* Various serotonin receptors * a1 adrenergic receptors * Histamine receptor * Muscarinic cholinergic receptor

Question 30

What are the main side effects of tricyclic antidepressants?

Answer 30

* Dry mouth * Sedation * Weight gain * Constipation * Dizziness * Heart rhythm problems

Question 31

What are some treatment strategies for insomnia?

Answer 31

* Changes in sleep patterns and/or lifestyle * Tackle stress/ anxiety * Psychotherapy (CBT) * Pharmacotherapy (short term less than 3 months)

Question 32

What are some risk factors for insomnia?

Answer 32

* Stress * Caffeine * Sleep hygiene (mindfulness, position)

Question 33

Why is diazepam not the most appropriate choice for short term insomnia and name some councelling points?

Answer 33

* Diazepam is a long-acting benzodiazepine, increasing the risk of daytime hangover effects. Short-acting benzodiazepines like temazepam, lormetazepam, or loprazolam are preferred for insomnia to minimize this risk. * Risk in pregnant women (lipohilic drug (penetrate brain) * Short term course (addictive) * Risk in elderly (risk of falls and lightheadedness)

Question 34

What are 2 over the counter remedies for insomnia?

Answer 34

* Antihistamines like diphenhydramine (found in Nytol) repeated requests indicate chronic, medication interactions * Valerian root extract, which has mild sedative effects.

Question 35

What are 3 characteristics of General Anxiety Disorder (GAD)

Answer 35

* GAD is characterized by disproportionate, pervasive, and uncontrollable worry * a range of somatic, cognitive, and behavioral symptoms * varying severity.

Question 36

What are some complications of untreated GAD?

Answer 36

* reduced quality of life * impaired social and occupational functioning * comorbidities like depression * increased risk of suicidal ideation and attempts.

Question 37

How do you diagnosis GAD

Answer 37

* International Diagnostic Criteria (DSM-V/ ICD-10) * Physical symptoms * Risk factors * GAD-7 (7 questions & count score)

Question 38

What is Step 1 of treatment of GAD

Answer 38

* Assess severity * Mental health history * Active monitoring

Question 39

What is Step 2 of the treatment of GAD

Answer 39

* Low intensity psychological interventions (CBT)

Question 40

What is Step 3 & 4 of the treatment of GAD

Answer 40

* High intensity CBT * Drug therapy: 1st line SSRI/ SNRI * Review every 2-4 weeks

Question 41

What are examples of SNRIs and name some side effects?

Answer 41

* Duloxetine and Venlafaxine * Caution in a range of conditions: bleeding disorders, history of seizures * Adverse effects: Nausea, dizziness, dry mouth