Drugs used in Psychiatric Disease

Question 1

What are the key symptoms of depression?

Answer 1

Core = low mood, anhedonia, decreased energy

Secondary = decreased appetite, sleep disturbance, hopelessness, irritability, reduced libido

Question 2

Outline the pathophysiological theories of depression

Answer 2

1) Monoamine hypothesis = def of monoamine neurotransmitters (NA, serotonin). Monoamine oxidase inhibitors (MAOIs) block the enzyme monoamine oxidase from destroying neurotransmitters
2) Receptor hypothesis = abnormality in receptors for monoamine transmission leads to depression
3) Gene expression = problem within the molecular events distal to the receptor

Question 3

Give an example of an SSRI

Answer 3

Citalopram

Question 4

What is the mechanism of SSRIs?

Answer 4

Inhibit the reuptake of serotonin into the presynaptic cell

Increased serotonin the synaptic cleft

Question 5

What are the ADRs of SSRIs?

Answer 5

Anorexia, nausea, diarrhoea

Overdose = reasonable safe on its own

Question 6

Give an example of a TCA

Answer 6

Amitriptyline

Question 7

What is the mechanism of TCAs?

Answer 7

1) inhibition of NA uptake = enhanced NA neurotransmission
2) muscarinic cholinergic blockade = reduced cholinergic neurotransmission
3) A1-adrenoceptor blockade = suppression of NA neurotransmission

Question 8

What are the ADRs of TCAs?

Answer 8

CNS – sedation, lower seizure threshold

ANS – reduction in glandular secretions

CVS – tachycardia, postural hypotension, impair myocardial contractility

GI - constipation

Overdose = Seizures, tachycardia, elevated temperature (pyrexia), cardiac arrest.

Question 9

Give an example of an SNRI

Answer 9

Venlafaxine

Question 10

What is the mechanism of SNRIs?

Answer 10

Developed as SSRIs with property of noradrenaline uptake inhibition grafted on

Question 11

What are the ADRs of SNRIs?

Answer 11

anorexia, nausea, diarrhoea

Sleep disturbance, increased BP, dry mouth, hyponatraemia

Question 12

Briefly outline the progression in medication one should follow when treating depression

Answer 12

FIRST LINE = SSRI’s (serotonin selective reuptake inhibitor)

TCAs = Tricyclic Antidepressants

SNRI’s (serotonin/noradrenergic reuptake inhibitor)

MAOI’s (monoamine oxidase inhibitor)

Try one antidepressant for at least 6 weeks before switching to another

Question 13

What are the key symptoms of schizophrenia?

Answer 13

Disturbances of thinking

Hallucinations = perception in the absence of an external stimulus-auditory, olfactory, visual, gustatory, tactile

Delusions = fixed false belief that it out of keeping with someone’s culture or religious beliefs

Unusual speech- thought disorder

Behavioural changes

Lack of insight

Negative symptoms

Question 14

Describe the pathophysiological mechanism underlying schizophrenia

Answer 14

1) dopamine theory = amphetamine causes symptoms very similar to positive symptoms of schizophrenia, some evidence of increased dopamine function in schizophrenics

Question 15

What are the main dopamine pathways?

Answer 15

Mesolimbic = emotional response and behaviour

Meso-cortical = important in arousal and mood

Nigrostriatal = key pathway damaged in Parkinson’s disease

Tuberoinfundibular = in hypothalamus and pituitary gland

Question 16

Outline the mechanism is dopamine D2 antagonists

Answer 16

Block D2 receptors present in dopamine pathways

Question 17

What are the ADR of dopamine D2 antagonists?

Answer 17

Haloperidole = tardive dyskinesia (involuntary repetitive body movements), QT interval prolongation, motor restlessness, muscle rigidity, parkinsonism (extra-pyramidal effects)

Question 18

What is the mechanism of 5-HT antagonists?

Answer 18

antagonists at 5HT-2A receptors

Question 19

What are the ADRs of 5-HT antagonists?

Answer 19

Clozapine = severe constipation, sedation, hypersalivation, weight gain ++++

Question 20

How do stats should an overall effectiveness for the treatment for schizophrenia over a 10 year period?

Answer 20

~1/4 improved but need support

~1/4 improved and relatively independent

~1/4 fully recovered

Question 21

What are the key symptoms of anxiety?

Answer 21

Fear out of proportion to situation

light headedness,

shortness of breath

hot and cold flushes

nausea

palpitations

numbness, pins and needles

Question 22

Describe the mechanism of GABA agonists

Answer 22

Binds GABA-BDZ receptor complex = enhanced GABA

Question 23

Give examples of benzodiazepines (GABA agonists)

Answer 23

Diazepam

Lorazepam

Question 24

What are the ADRs of benzodiazepine?

Answer 24

Drowsiness, dizziness, psychomotor impairment

Tolerance = need to increase dose to achieve the same effect

Withdrawal = insomnia, agitation, anxiety

Question 25

How can benzodiazapine be toxic?

Answer 25

Cleft lip/palate if used in preg

If taken late in preg = resp depression, feeding diff in baby

Question 26

How is a benzodiazepine overdose treated?

Answer 26

Flumazenil = antagonist/partial inverse agonist at BDZ receptors may be useful in reversing effects

Question 27

What are the symptoms of bipolar disorder?

Answer 27

Episodes of depression and mania

Mania = unusually excited, happy, overactive, poor concentration, poor sleep, rapid speech, poor judgement

Question 28

Name the range of drugs that can be used to treat mood disorders

Answer 28

Lithium

Sodium valproate

Carbamazepine

Lamotrigine

Antipsychotics

Question 29

What is lithium used to treat?

Answer 29

Prophylaxis of Mania and Depression in bipolar disorder

Augmentation of antidepressants in unipolar depression

Good evidence for reducing suicidality

Of all mood stabilisers Lithium has the best evidence

Question 30

What are the ADRs of lithium?

Answer 30

Memory problems

Thirst

Polyuria

Tremor

Drowsiness

Weight gain

Question 31

Online the toxic effect of lithium

Answer 31

Need to monitor blood levels closely

D+V, coarse tremor, dysarthria, cognitive impairment, restlessness, agitation