Drugs Used in Psychiatric Disorders

Question 1

What is the class of drugs commonly used as anxiolytics and as sleeping pills to treat the symptoms and behaviors caused by anxiety disorders?

Answer 1

Benzodiazepines

Question 2

Name 5 examples of Benzodiazepines

Answer 2

Short acting: Midazolam
Intermediate acting: Lorazepam, Alprazolam
Long acting: Diazepam, Clonazepam

think lam and pam

Question 3

What is the Mechanism of Action of Benzodiazepines?

Answer 3

BZD binds to specific BZD sites in the CNS and potentiates GABA actions by increasing the frequency of chloride channel opening induced by GABA.

It is GABA dependent. It does not open the channels in the absence of GABA so Cl- doesn’t enter the cells in the overdose of Benzodiazepines.

∴ Benzodiazepine is a safe drug in overdose

Question 4

What is the route of administration for benzodiazepines?

Answer 4

Oral - fast onset 0.5 - 1 h
IV - immediate onset

Parenteral IV: Midazolam, Lorazepam, Diazepam

Question 5

What are the active compounds of Diazepam, Lorazepam, Alprazolam and Midazolam?

Answer 5

Diazepam -> Nordazepam (L) -> Oxazepam (I)

Lorazepam (I) - active compound, trick question

Alprazolam (S) -> alpha-Hydroxyalprazolam (S)

Midazolam (S) -> alpha-Hydroxymidazolam (S)

NOTE: all active compounds then undergo glucuronidation

Question 6

List 6 adverse effects of Benzodiazepines

Answer 6

1. CNS: ↑ drowsiness, ↓ motor skills, ↑ reaction time
2. CNS: Anterograde amnesia. Memory disturbances are particularly profound after IV sedation
3. CVS: ↓ BP, ↓ respiration in predisposed patients
4. Paradoxical effects: excitement, garrulousness (talkative), irritability, hallucination, outburst of rage.
   Violent behaviour has been attributed to disinhibition by BZD (behaviour normally suppressed)
5. Neonatal toxicity: Floppy child syndrome
6. Tolerance, dependence and withdrawal

Question 7

What is the elimination half-lives of Benzodiazepine hypnotics?

Answer 7

2 - 24 h

Question 8

What is insomnia?

Answer 8

Not able to fall asleep, maintain sleep or early morning wakening, affecting the function of next day

Question 9

What causes insomnia?

Answer 9

A + 3Ds
Anxiety - increased emotional arousal
Depression
Drugs-induced (caffeine)
Drug withdrawal - after chronic use of alcohol or sleeping pills

Question 10

What are the characteristics of Benzodiazepine - induced sleep?

Answer 10

Reduced REM and deep (stage 4) sleep when compared to natural sleep

Question 11

Name 2 non-benzodiazepine hypnotics, their MoA and hypnotic effect

Answer 11

Zolpidem, Zopiclone

MoA & hypnotic effect similar to BZ

binds to specific BZD sites in the CNS and potentiates GABA actions by increasing the frequency of chloride channel opening induced by GABA

Question 12

Name 2 adverse effects of non-benzodiazepine hypnotics

Answer 12

Withdrawal anxiety
Abuse potential

Question 13

What is the elimination half-life of non-benzodiazepine hypnotics?

Answer 13

2 - 4 h

Question 14

What are the symptoms of depression?

Answer 14

Mood down
Interest down
Feeling of shame / guilt
Suicidal ideation

Sleep less (or more)
Psychomotor retardation
Appetite down (or up)
Concentration down
Energy down

Symptoms persist for at least 2 weeks, and severity of symptoms interfere with normal functioning

Question 15

What are non-pharmacological treatment for depression?

Answer 15

Psychological: Cognitive Behavioural Therapy, Interpersonal
Social
Behavioural
Relaxation

Counselling

Question 16

Name 4 classes of antidepressants

Answer 16

1. Selective Serotonin Re-uptake Inhibitors (SSRIs)
2. TriCyclics Antidepressants (TCAs)
3. Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs)
4. NorAdrenergic & Specific Serotonergic Antidepressants (NaSSAs)

Question 17

Name 4 examples of SSRIs

Answer 17

Fluoxetine, escitalopram, sertraline, paroxetine

Question 18

Name 2 examples of TCAs

Answer 18

Amitriptyline, imipramine

Question 19

Name 1 example of SNRIs

Answer 19

Venlafaxine
Act like TCAs

Question 20

Name 1 example of NaSSAs

Answer 20

Mirtazapine
Antagonist of alpha2-adrenergic receptor and certain serotonin receptors

Question 21

MoA of SSRIs / SNRIs / TCAs

Answer 21

SSRI blocks serotonin transporter → ↑ serotonin in the brain

SNRI and TCA block serotonin transporter and norepinephrine transporter
→ ↑ serotonin and norepinephrine in the brain

Question 22

List 5 adverse effects of SSRIs

Answer 22

1. Anxiety
2. Weight loss / gain
3. Headache, nausea
4. Sexual dysfunction
5. Hyponatremia

No fatality in overdose (unlike TCAs)

Question 23

What is the blood test that you need to do when a patient is treated with SSRI?

Answer 23

Blood Na+ levels

Question 24

SSRIs - DDIs

Answer 24

1. SSRIs inhibit various P450 enzymes
   Fluoxetine > paroxetine > sertraline > escitalopram
   ask for medication history when prescribing
2. Don’t take SSRIs with MAOI or St John’s wort

Risk of Serotonin syndrome: confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high body temperature, an extremely high BP or severe seizures

Question 25

List 5 adverse effects of TCA

Answer 25

1. CNS effects: sedation, fatigue 2. Cardiac rhythm: tachycardia, arrhythmias 3. Postural hypotension 4. Anticholinergic effects: glaucoma, blurred vision, urinary retention, constipation 5. FATALITY IN OVERDOSE | don't give TCA to old man bc of anticholinergic effects

Question 26

List 3 adverse effects of SNRIs

Answer 26

1. CNS effects: agitation, irritable or drowsy 2. CVS effects: BP may be raised at higher dose 3. Hyponatremia ## Footnote Unlike TCA, SNRI doesn't have anticholinergic effects, postural hypotension and cardiac rhythm abnormalities

Question 27

What are the symptoms of anxiety disorders?

Answer 27

Psychological symptoms: - Apprehension and fear Somatic symptoms: - CVS: Palpitations - Resp: Chest pain and shortness of breath - GIT disturbance - Headaches and dizziness - Tense muscle - Insomnia

Question 28

What are the symptoms of schizophrenia?

Answer 28

Positive symptoms: - delusion (abnormal belief), hallucination - disorganized thinking, speech and behavior Negative symptoms: - no volition, no emotion, no expression - no ability to plan, poor concentration duration of disturbances: 6 months deterioration in social / occupational function

Question 29

List 2 classes of antipsychotic drugs to treat symptoms of psychoses and examples

Answer 29

1. Typical (first generation): high potency Haloperidol 2. Atypical (second generation): Risperidone Olanzapine Quetiapine Clozapine Aripiprazole

Question 30

What is the MoA for **typical** (**first** generation) antipsychotics?

Answer 30

block **D2 > serotonin (5-HT2)** receptors block D1, cholinergic, histaminic and alpha adrenergic

Question 31

What is the MoA for **atypical** (**second** generation) antipsychotics?

Answer 31

block **serotonin (5-HT2) > D2** receptors block D1, cholinergic, histaminic and alpha adrenergic

Question 32

List 4 adverse effects of typical (first gen) antipsychotic drugs / Haloperidol

Answer 32

1. Extrapyramidal side effects (blocks dopamine) - characteristic of haloperidol 2. Sedation 3. Anticholinergic (blocks acetylcholine) 4. Rare cases of neuroleptic malignant syndrome

Question 33

List ADRs of atypical (2nd gen) antipsychotics

Answer 33

Less extrapyramidal side effects than typical (1st gen) antipsychotics Clozapine: agranulocytosis in 2% of patients, weight gain, sedation Olanzapine: severe WEIGHT GAIN and severe SEDATION Risperidone: Extrapyramidal side effects (dose dependent), weight gain Quetiapine: weight gain