6. Psychiatric Drugs

Question 1

What is the brain used for and consists of?

Answer 1

• Coordination of mental activity
• Consists of over 100 billion neurons – Neuron: nerve cell
  
  • Within cell → electrical transmission
  • Between cells → chemical transmission

Question 2

What can a neuron do? Explain what a neuron is comprised of.

Answer 2

• dentrites - receive info from other cells
• cell body (soma)
  -axon - carries info away from cell body
• axon terminal

*Within a neuron, an action potential can be generated and carried from dentrites –> cell body (soma) –> axon –> axon terminal

Question 3

How do neurons communicate with one another?

Answer 3

with a neurotransmitter

Question 4

What is neurotransmission and when does it occur?

Answer 4

• Occurs by means of specific neurotransmitters at the synapse
  
  • Neurotransmitter: chemical that is released from the presynaptic neuron in response to an electrical signal
  • Synapse: junction between two neurons
• A complex process involving neurotransmitter synthesis, storage and release, receptor activation, and neurotransmitter inactivation

Question 5

Explain the process of neurotransmission. (hint: 4 steps)

Answer 5

1. Synthesis
   
   • building blocks of a transmitter substance are imported into the terminal where the neurotransmitter is synthesized and packaged into vesicles
2. Release
   
   • in response to an action potential, the transmitter is released across the membrane by exocytosis
3. Receptor action
   
   • the transmitter crosses the synaptic cleft (presynaptic cleft –> postsynaptic cleft) and binds to a receptor
4. Inactivation
   - the transmitter is either taken back into the terminal (presynaptic cleft) or inactivated by enzymes in the synaptic cleft

Question 6

Is it male or females that visit physicians more?

Answer 6

Females

Question 7

Why is there an increased prevalence?

Answer 7

• inc awareness of disorders
• diagnostic criteria has broadened
• social behavour
• less stigmatized in receiving help
• diet
• affects of covid

Question 8

What are Psychiatric Disorders? Which age group do they usually affect?

Answer 8

• A group of medical conditions characterized by alterations in thinking, mood, and/or behaviour
• Associated with significant distress and impaired functioning over an extended period of time
• Major economic impact
  
  • Health care system
    
    • estimated public and private mental health expenditure: $15.8 Billlion
  • Lost productivity (self and society) –> inc work of absences
    
    • ex. inc need for community care and hospital care
• usually affects people in their 20s-30s
  
  • usually most productive, has burden in job and family wise

Question 9

What are the causes of psychiatric disorders?

Answer 9

• genetics
• Neurodevelopmental defects
  
  • ex. alcoholism, malnutrition
• Medical conditions
  
  • ex. infections, strokes
• psychosocial experiences
  
  • emotional, physical or sexual abuse
• Drugs
  
  • (e.g. substance abuse)
• Stress

Question 10

What are the 3 Subclassification of Psychiatric Disorders?

Answer 10

• Mood disorders: depression, bipolar disorder
  
  • Changes in emotional state
• Psychotic disorders: schizophrenia
  
  • Changes in thoughts and perception
• Anxiety disorders
  
  • Excessive, persistent worry and/or fear

–> Negative impact on the quality of life!
- relationships, jobs, schooling, day-to-day activities…

Question 11

What are Psychiatric Drugs used for and their fundamental requirements?

Answer 11

• For treatment of psychiatric disorders
• Fundamental requirements
  
  • Act in the central nervous system (the brain)
    
    • has to cross the blood-brain barrier
      
      • blood-brain barrier: prevent certain substances from getting in the brain
  • Influence neurotransmission by modulating neurotransmitter action
  • Cause changes in perception, mood, cognition and/or behaviour

Question 12

4 characteristics of Psychiatric Drugs.

Answer 12

• Do not “cure” → only decrease or relieve symptoms
  
  • we only know how to decrease symptoms
• Wide spectrum of therapeutic activity
  
  • ex. sleep disturbance in depression and anxiety
• Usually slow onset of therapeutic effects → may take weeks to improve symptoms
• Often many side effects
  
  • not selective in their mechanism of action –> target other receptors
    –> more side effects

Question 13

Explain the PK of Psychiatric Drugs.

Answer 13

• Often administered orally
  
  • Very lipid soluble –> allow to pass blood-brain barrier and absorb through GI tract
• Most are metabolised in the liver
• Generally eliminated from the body by renal excretion (metabolites are water soluble)

Question 14

What are the classifications of Psychiatric Drugs.

Answer 14

1. Antidepressants: MAOIs, TCAs, SSRIs, SNRIs
2. Mood stabilizers: lithium, anticonvulsants
3. Antipsychotics: typical, atypical
4. Anxiolytics: BZDs, azapirones

Question 15

What is depression?

Answer 15

• Characterized by feelings of severe despair over an extended period of time
• Some people experience only a single episode in their lifetime, but most often people have multiple episodes
• Affects ~8% of the population
• Nearly twice as prevalent in women
  
  • may be due to hormonal differences
  • men more likely to seek help and acknowledge their symptoms
• Average age of onset ~30 years old

Question 16

What are the symptoms of depression/What is required for you to be considered to have depression?

Answer 16

• need one of these…
  
  • depressed mood
  • apathy/loss of interest
• and need 4 of these…
  
  • weight/appetite changes
  • sleep disturbances
  • fatigue
  • worthlessness
  • executive dysfunction
    
    • difficulty memorizing and concentrating
  • suicidal ideation

Question 17

What are antidepressants? What is its Theory of Treatment?

Answer 17

• Indicated for the treatment of depression and anxiety disorders
• Affect serotonin and/or norepinephrine neurotransmission
• Theory of treatment: Monoamine Hypothesis
  
  • “Depression is associated with low levels of serotonin and norepinephrine in the brain”

*Please refer to slide 25 for procedure of how it works

Question 18

What are Monoamine Oxidase Inhibitors (MAOIs)?

Answer 18

• Inhibit the enzyme monoamine oxidase, which breaks down monoamines (serotonin and norepinephrine)
  
  • therefore increase [neurotransmitter] in nerve terminal, available for neurotransmission
• Must avoid foods and beverages that contain tyramine (e.g. cheese, red wine)
  
  • Risk of hypertensive crisis due to excessively high levels of norepinephrine
• Last-line treatment for depression

Question 19

What are foods to avoid and allowed because it has tyramine?

Answer 19

• Foods to avoid:
  
  • dried, aged, smoked, fermented, fish, and poultry
  • broad bean pods
  • aged cheeses
  • tap and unpasteurized beer
  • marmite and sauerkraut
  • soy products/tofu
• Foods allowed
  
  • fresh or processed meat, fish, and poultry
  • all other vegetables
  • processed and cottage cheese, ricotta cheese and yogurt
  • brewer’s and baker’s yeast

Question 20

What do Tricyclic Antidepressants (TCAs) do? What are the side effects?

Answer 20

• Prevent serotonin and norepinephrine reuptake by inhibiting the serotonin transporter (SERT) and the norepinephrine transporter (NET)
  
  • Increase [neurotransmitter] in synaptic cleft
• Not very selective
  
  • High affinity for other additional receptors
• Many side effects:
  
  • Anticholinergic effects
    
    • blurred vision, dried mouth and constipation
  • Orthostatic hypotension
    
    • dec in BP when a person goes from supine to upright position
  • Sedation, weight gain
  • Cardiac arrhythmia

Question 21

What do Selective Serotonin Reuptake Inhibitors (SSRIs) do? What are the side effects?

Answer 21

• Prevent serotonin reuptake by selectively inhibiting SERT
  
  • Increase [serotonin] in synaptic cleft
• Less side effects than TCAs and MAOIs, therefore safer and better tolerated
• Side effects: nausea, headache, drowsiness, sexual dysfunction
  
  • minor compared to TCAs
• First-line treatment for depression – Some approved for use in children

Question 22

What do Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) do? What are the side effects?

Answer 22

• Prevent serotonin and norepinephrine reuptake by selectively inhibiting SERT and NET
  
  • Increase [neurotransmitter] in synaptic cleft
• Side effects similar to SSRIs

*same mechanism as TCA, difference is that SNRIs has higher selectivity

Question 23

Conclusion in depressants.

Answer 23

• patients who have mild depression won’t get much benefits from antidepressants –> turn to other firms of treatment instead
• antidepressants are effective in acute depressive episodes that are moderate to sever but are not effective in mild depression

Question 24

What is Bipolar Disorder?

Answer 24

• Characterized by drastic mood changes – alternating between extreme “highs” (mania) and extreme “lows” (depression)
• Affects ~1% of the population
• Average age of onset ~25 years old

Question 25

What are the symptoms of Bipolar Disorder?

Answer 25

• 4 of these required for manic phase
  
  • high energy
  • higher self esteem
  • racing thoughts
  • very quick talking
  • impulsive behaviour
  • irritability
  • reduced need for sleep
• depressed phase (as previously said…)
  
  • lack of concentration
  • low self-esteem
  • suicidal thoughts
  • helplessness
  • loss of interest
  • low energy levels

Question 26

What are mood stabilizers?

Answer 26

• Indicated for the treatment of bipolar disorder
• Mechanism of action not clearly understood
• In general more effective in treating mania than depression, therefore often used in combination with antidepressants
  
  • Antidepressant monotherapy should be avoided in patients with bipolar disorder

*antidepressants should not be used alone for the treatment of bipolar disorder –> can induce manic episodes and cause rapid cycling in moods

Question 27

What is Lithium and what is it used for?

Answer 27

• A small monovalent cation (+1 charge)
• an effective treatment for reducing the risk of suicide in people with mood disorders
• Relatively slow onset of action (1-3 weeks)
• Mechanism of action unclear
  
  • May alter signal transduction pathways
  • Possibly influence neurotransmitters and receptors
• Not metabolised; excreted through the kidneys
• comes in 2 forms: Lithium carbonate and lithium citrate
• Very low therapeutic index (has narrow margin of safety)
  
  • Ineffective at blood levels <0.4 mmol/L while toxic when >1.5 mmol/L
  • Must monitor blood levels during treatment
• Over 80% of patients experience side effects:
  
  • Tremor (usually in the hands)
  • Weight gain
  • Polyuria (↑ urine), polydipsia (↑ thirst)
  • Hypothyroidism (inc metabolic rate: tired and cold)
  • GI symptoms (vomiting, diarrhea)

Question 28

What are Anticonvulsants used for?

Answer 28

• Only a few anticonvulsants are approved for the treatment of bipolar disorder
• Specific mechanism unknown
  
  • Possibly act by reducing neuronal excitability

Question 29

What are the 2 forms Anticonvulsants come in? Explain their mechanism of action.

Answer 29

• Carbamazepine: antagonist of MDA receptor
  
  • MDA - activated by excitatory neurotransmitter, glutamate. If MDA is blocked –> glutamate cannot bind = dec neuronal excitability
• Valproic Acid
  
  • inc GABA transmission in the brain. GABA is the main inhibitory transmitter. It helps stabilize mood by reducing excitability.

Question 30

What is Schizophrenia?

Answer 30

• Characterized by deficits in thought processes, perceptions, and emotional responsiveness
  
  • most lose contact with reality and don’t even realize it
• Affects ~1% of the population
• Typical onset in early adulthood
  
  • Late teens to early 30s
• Symptoms classified as “positive” or “negative”