Drugs in Psychiatric Disease

Question 1

Describe the symptoms of depression

Answer 1

• Core symptoms
  
  • Low mood
  • Anhedonia - loss of enjoyment in activities and live
  • Low energy
• Secondary symptoms
  
  • Biological - poor sleep, low appetite, poor libido
    
    • Cognitive - negative cognition, poor concentration, hopelessness, thoughts of self harm

Question 2

What are non-pharmacological treatments of depression

Answer 2

• Cognitive behavioural therapy

- Interpersonal therapy

Question 3

Describe the theories of depression

Answer 3

• Depression due to monoamine neurotransmitters deficiency - noradrenaline, serotonin
• Neurotransmitter receptor hypothesis - abnormality in the receptors for monoamine transmission
• Monoamine hypothesis of gene expression

Question 4

List the drugs types used in depression

Answer 4

• Selective serotonin reuptake inhibitors
• Tricyclic antidepressants
• Serotonin noradrenaline reuptake inhibitors
• Monoamine oxidase inhibitors

Question 5

Describe the use of monoamine oxidase inhibitors

Answer 5

• Inhibit monoamine oxidase and thus reduces degradation of serotonin and noradrenaline
• Not used much due to many side effects

Question 6

Describe the mechanism of selective serotonin reuptake inhibitors

Answer 6

• Eg. Fluoxetine, citalopram
• Limit reuptake of serotonin into the presynaptic neurone, thus increasing the serotonin in the synaptic cleft available to bind to the postsynaptic receptor and carry on its action potential

Question 7

Describe the PK of antidepressant drugs

Answer 7

• Metabolised in the liver so can increase concentration of other drugs such as antiepileptics
• SSRI and TCA have long half life so single doses and be aware of long elimination half life
• SNRI has short half life

Question 8

Describe the ADRs of SSRI

Answer 8

• Nausea, sexual dysfunction, insomnia, anorexia, diarrhoea
• Can precipitate mania - especially in patients with bipolar syndrome
• Citalopram has cardiac side effects

Question 9

Describe the mechanism of tricyclic antidepressants

Answer 9

• Act largely as SNRI to prevent serotonin and noradrenaline reuptake (symptomatic effect)
• Muscarinic cholinergic inhibitor - anticholinergic effect by decrease cholinergic transmission

Question 10

Describe the ADRs of TCAs

Answer 10

• CNS: sedation, impairment of psychomotor performance (cannot participate in skills requiring attention or motor skills), lowering of seizure threshold , hallucinations
• Anticholingeric - constipation (lowered GI mobility), urinary retention, dry mouth, dry eyes, blurry vision
• CVS - tachycardia, postural hypotension
• More dangerous in overdose than SSRI

Question 11

What is given to reverse TCA overdose

Answer 11

Sodium bicarbonate given to reverse effects of amitriptyline

Question 12

Describe the mechanism of SNRI

Answer 12

• Eg. Venlaflaxine, duloxetine

- Mechanism - limit reuptake of serotonin and noradrenaline, thus increasing postsynaptic propagation

Question 13

Describe the ADRs of SNRI

Answer 13

• SSRI side effects
• Sleep disturbance, hypertension, dry mouth, hyponatraemia
• Short half life - may have withdrawal effect

Question 14

Describe the mechanism of antipsychotic drugs

Answer 14

• D2 antagonists which prevent dopamine from acting within the basal ganglia
• Has positive benefits on the mesolimbic pathway (reduces overactivity)
• Has negative benefits on the mesocortical pathway, and nigrostriatal pathway (Parkinson’s symptoms)
• Commonly given depot rather than oral as patients who are very unwell will not take medication properly
• Action
  
  • Sedation - within hours
  • Tranquilisation - within hours
  • Antipsychotic - several days or weeks

Question 15

Describe the length of antidepressant prescription

Answer 15

• Try one anti-depressant for at least 6 weeks before switching to another and continue prescription for at least 1 year to reduce relapse risk
• Some drugs require 6 weeks before benefits occur

Question 16

Describe the ADRs of typical antipsychotics

Answer 16

• Extrapyramidal side effects - dystonia, akathisia (constant restlessness), tardive dyskinesia (abnormal, involuntary, repetitive movements), pseudo-Parkinson’s (rigidity, tremor, hypertonia)
• Anti-cholinergic
• Serotonergic
• Neuroleptic malignant syndrome - life threatening reaction to antipsychotics: fever, altered mental status, muscle rigidity, autonomic dysfunction (tachycardia, flushing, labile BP)

Question 17

Describe the use and mechanism of atypical antipsychotics

Answer 17

• First line treatment of schizophrenia
• Eg. Risperidone, olanzapine, clozapine (most effective), quetiapine
• Mechanism - act as serotonin receptor agonists and dopamine antagonists
  - More effective in reducing negative symptoms of schizophrenia

Question 18

Describe the ADRs of atypical antipsychotics

Answer 18

• Extrapyramidal side effects (less than typical), weight gain (olanzapine), increased prolactin (risperidone)
• Serotonergic - nausea, sexual dysfunction, insomnia
• Anti-cholinergic
• Clozapine has more severe side effects including neutropenia, severe constipation - FBC monitoring needed

Question 19

Describe the symptoms of anxiety

Answer 19

• Fear out of proportion to situation
• Behavioural - avoidance
• Psychological - fear of dying, going crazy
• Physical - palpitations, sweating, chest tightness, shortness of breath, hot and cold flushes, light headedness, numbness

Question 20

Describe the treatment options for anxiety

Answer 20

• Cognitive behavioural therapy - first line as not only treats symptoms but finds underlying cause
• Exposure therapy - face your fears and working through a process to face them
• Benzodiazepines
  - Eg. Diazepam, lorazepam

Question 21

Describe the ADRs of benzodiazepine

Answer 21

• Becomes addictive in the long term as tolerance increases (greater dose needed for same effect)
• Withdrawal symptoms - insomnia, agitation, anxiety
• Common - drowsiness, dizziness, psychomotor impairment
• Occasional - dry mouth, blurred vision, GI upset, reduced blood pressure
• Cleft lip and palate in pregnancy

Question 22

How is benzodiazepine overdose treated

Answer 22

• Flumazenil reverses effect of benzodiazepine

Question 23

Describe the symptoms of mood disorders

Answer 23

• Includes bipolar disorder, which is a spectrum of mania/hypomania and depression
• Mania - excited, optimistic, cannot stop talking, overactive, poor concentration, poor sleep, poor appetite, short attention span

Question 24

List the treatments for mood disorders

Answer 24

• Lithium
• Sodium valproate
• Carbamazepine
• Lamotrigine
• Antipsychotics

Question 25

Describe the PK of lithium

Answer 25

• Eg. Lithium carbonate
• Renal secreted, slow release so 1 dose a day
• Lithium doses need to be monitored - narrow therapeutic window
• Renal and thyroid function need to be assessed before dosing

Question 26

List the ADRs of lithium

Answer 26

• Memory problems, thirst, polyuria, tremor, drowsiness, weight gain
• Toxic effects - vomiting, diarrhoea, coarse tremor, restlessness, agitation

Question 27

Give examples of antiemetic drugs

Answer 27

• Cyclizine - H1 antagonist (anticholinergic + antihistamine)
• Metoclopramide, domperidone - dopamine D2 antagonist
• Ondansetron - selective serotonin receptor antagonists (antagonize vagal input to gut stimulating vomiting)
• Hyoscine

Question 28

Give examples of antipsychotic drugs

Answer 28

• Typical - Haloperidol, chlorpromazine

- Atypical - Risperidone, olanzapine, clozapine (most effective), quetiapine

Question 29

Give examples of antidepressant drugs

Answer 29

• SSRI - Fluoxetine, citalopram, sertraline
• TCA - Amitriptyline, imipramine, lofepramine
• SNRI - Venlaflaxine, duloxetine