SECTION 2A

Question 1

Outline the positive symptoms of Schizophrenia

Answer 1

Perceptual Hallucinations (esp. auditory)
Delusions
Thought Broadcasting
Disorganised Speech

Question 2

Outline the negative symptoms of Schizophrenia

Answer 2

Lack of Motivatiion 
Blunting of emotional responses
Poverty of Speech (alogia)
Social withdrawal 
Catatonia

Question 3

Describe some of the theories explaining the causes of Schizophrenia

Answer 3

Viral infection during Development
Genetic Inheritance
Developmental brain abnormality

Question 4

Describe the possible neuronal mechanisms that lead to Schizophrenia.

Answer 4

1) Excessive 5-HT transmission - 5-HT2a/2c activation by LSD leads to hallucination
2) Excessive Dopamine transmission - Amphetamine blocks DA uptake and induces psychosis resembling Schizophrenia
3) Excessive Glutamate Transmission - Phenycyclide blocks NMDARs and mimics positive and negative symptoms of Schizophrenia.

Question 5

What is meant by Extra-Pyramidal Side Effects?

Answer 5

Neuroleptics that target Dopaminergic systems aim to antagonise DA action in the mesolimbic and Mesocortical pathways (pyramidal effects) but they inevitably effect other DA systems such as nigrostriatal and tuberoinfundibular pathways (extra-pyramidal) can result in a pseudo Parkinson’s

Question 6

Name a typical neuroleptic

Answer 6

Chloropromazine
Flupenthixol
Haloperidol

Question 7

What are the advantages the typical neuroleptics?

Answer 7

They relieve the positive symptoms of Schizophrenia

They are sedatives as well (can be disadvantageous)

Question 8

What are the main disadvantages of the typical neuroleptics

Answer 8

Ineffective against the negative symptoms of Schizophrenia
EPS effects- dystonia (abnormal muscle tone), akathisia (restlessness)
Tardive Dyskinesia (repeated stereotyped movements enduring after cessation of drug)
Hyperprolactinaemia which can lead to reduced gonadal function.

Question 9

What are the molecular targets of the typical neuroleptics?

Answer 9

Antagonism of D2 receptors
Antagonism of H1 (histamine) receptors –> sedation
Antagonism of mAChRs –> relief of pseudo PD effects
Antagonism of alpha 1 and 2 adrenoceptors –> hypotension

Question 10

Name two of the atypical neuroleptics

Answer 10

Clozapine

Risperidone

Question 11

What are the advantages of Clozapine, an atypical neuroleptic?

Answer 11

It relieves both positive and negative symptoms of Schizophrenia.
It’s capable of relieving psychosis resistant to typical neuroleptics
It has a lower incidence of EPS

Question 12

What are the disadvantages of Clozapine, an atypical neuroleptic?

Answer 12

Dribbling
Agranulocytosis (loss of granulocytes, a type of white blood cell) 
Weight gain (systemic and visceral fat) --> diabetes/CVD
Elongation of QT interval

Question 13

What are the molecular targets of Clozapine, an atypical neuroleptic?

Answer 13

Antagonist Affinity for D4 (D2 family)
Antagonism of 5-HT2a/2c receptors (possibly causes the weight gain)
Weak Partial agonist at 5-HT1a receptors (increase DA release in Mesocortical pathway relieving negative symptoms)
Antagonism of Muscarinic ACh receptor alpha 2 adrenoceptor

Question 14

List three main symptoms of Depression

Answer 14

Anhedonia (inability to feel pleasure)
Weight gain/loss
Insomnia

Question 15

Describe the treatment of Electroconvulsive Therapy

Answer 15

ECT is procedure done under general anaesthesia where small electric currents are passed through the brain inducing a brief seizure. ECT is thought to sensitize the brain to 5-HT and Na. It is only given unilaterally to minimize amnesic effects

Question 16

What is the Monoamine Hypothesis of Depression?

Answer 16

The hypothesis states that depression is caused by a functional deficit of NA, 5-HT and possibly DA in the brain

Question 17

What pharmacological evidence supports the Monoamine hypothesis of Depression?

Answer 17

Reserpine (used to treat Schizophrenia) depletes Monoamine storage in vesicles by irreversibly binding to VMAT2. It was found to induce depression in 15% of people.
Iproniazid (used to treat tuberculosis) caused euphoria in patients as it is a non-selective inhibitor of MAO

Question 18

Name a first generation Monoamine Oxidase inhibitor and its mechanism of action

Answer 18

Iproniazid: it is an irreversible non-selective inhibitor of MAOs

Question 19

What is the Cheese Reaction?

Answer 19

Tyramine is present in cheese. When patients taking non-selective MAO inhibitors have tyramine in their diet, it is able to enter the CNS as MAOs in the periphery which normally block its entry are inhibited. In the CNS, the tyramine acts a false transmitter and disrupts the VMAT2 causing a build up of monoamine.

Question 20

Name a second generation Monoamine Oxidase inhibitor

Answer 20

Clorgyline. It is a reversible MAOA selective inhibitor.

Question 21

What are the benefits of second generation Monoamine Oxidase inhibitors?

Answer 21

They are reversible so the effects of a tyramine diet are less severe
They are MAOA selective so are likely to have less widespread effects than the non-selective 1st generation inhibitors.

Question 22

What are the adverse effects of both types of Monoamine Oxidase inhibitor?

Answer 22

Hepatotoxicity
CNS overstimulation –> insomnia, convulsions
Postural Hypotension
Sympathetic NS overstimulation –> dry mouth, sweating

Question 23

Name a tricyclic antidepressant and outline its usefulness in treatment of Depression

Answer 23

Imipramine
5-HT reuptake inhibition
NA reuptake inhibition
Relatively weak DA reuptake inhibition

Question 24

What are the side-effects Imipramine? What molecular targets are responsible for them?

Answer 24

Antagonism at alpha 1 receptor –> tachycardia
Antagonism at mACh receptors –> tachycardia
Antagonism at H1 receptors –> sedation

Question 25

What class of drug is Venlafaxine?

Answer 25

Serotonin Noradrenaline Reuptake Inhibitor (SNRI)

Question 26

What advantage do SNRIs have over the tricyclic antidepressants?

Answer 26

SNRIs don’t have additional effects on mAChRs, adrenoceptors or histaminergic receptors.