Mania and bipolar disorder

Question 1

Name 3 classes of drug that might be used for mania and bipolar disorder and give examples of these (state the P drugs).

Answer 1

1) Lithium - Lithium carbonate.
2) Antoconvulsants used as mood stabilisers - Sodium valproate, carbamazepine, lamotrigine.
3) Atypical antipsychotics - Risperidone, Olanzapine, Clozapine, Aripiprazole, Quetiapine.

Question 2

1) State what lithium is used for.
2) State what anticonvulsant medications can be used for.
3) State what atypical antipsychotics can be used for.

Answer 2

1) Treatment and prophylaxis of mania, hypomania and depression in bipolar disorder.
2) Treatment and prophylaxis of mania, hypomania and depression in bipolar disorder.
3) Psychosis schizophrenia and rapid tranquillisation in mania.

Question 3

Give the 4 common clinical indications for the use of typical, first generation antipsychotic drugs.

Answer 3

1) Urgent treatment of severe psychomotor agitation, causing dangerous or violent behaviour or to calm patients to permit assessment.
2) Schizophrenia, particularly when the metabolic side effects of second generation antipsychotics are likely to be problematic.
3) Bipolar disorder, particularly in acute episodes of mania or hypomania
4) Nausea and vomiting, particularly in the palliative care setting.

Question 4

1) Name 3 first generation (typical) antipsychotics.
2) What receptors do first generation antipsychotics block?
3) Name the 3 main dopaminergic pathways in the central nervous system

Answer 4

1) Haloperidol, Chlorpromazine and Prochlorperazine.
2) Post-synaptic dopaminergic D2 receptors.
3) Mesolimbic/ mesocortical, nigrostriatal and tuberohypophyseal pathways.

Question 5

1) State where the mesolimbic/ mesocortical pathway runs and what the potential blockage of D2 receptors does.
2) What does the nigrostriatal pathway connect?
3) What does the tuberohypophyseal pathway connect?

Answer 5

1) Runs between the midbrain and the frontal cortex (limbic system) and D2 blockage here is probably the main determinant of antipsychotic effects.
2) Connects substantial nigra with corpus stratus of the basal ganglia.
3) Connects hypothalamus with pituitary gland.

Question 6

1) D2 receptor blockage in the CTZ accounts for what in the use of typical antipsychotics?
2) What effect of all antipsychotics, but particularly chlorpromazine may be beneficial in the context of acute psychomotor agitation?
3) What is the main drawback of first generation antipsychotics?

Answer 6

1) Their use in nausea and vomiting.
2) Sedative effects.
3) Extrapyramidal effects (movement abnormalities) that arise from D2 blockade in the nigrostriatal pathway.

Question 7

State and describe the major extrapyramidal side effects that can be caused through the use of typical antipsychotics.

Answer 7

1) Acute dystonic reactions: involuntary Parkinsonian movements or muscle spasms.
2) Akathisia: a state of inner restlessness.
3) Neuroleptic malignant syndrome: rare but life-threatening side effect - rigidity, confusion, autonomic dysregulation and pyrexia.

Question 8

1) Describe tardive dyskinesia.

2) State 5 other potential adverse effects of typical antipsychotics.

Answer 8

1) A late adverse effect occurring months to years after therapy. Comprises movements that are involuntary, pointless and repetitive, for example, lip smacking.
2) Drowsiness, hypotension, QT interval prolongation (consequent arrhythmias), erectile dysfunction and symptoms of hyperprolactinaemia.

Question 9

1) When taking typical antipsychotics, what causes symptoms of hyperprolactinaemia as a side effect?
2) State some symptoms of hyperprolactinaemia.

Answer 9

1) Tuberohypophyseal D2 blockade.

2) Menstrual disturbance, galactorrhoea and breast pain.

Question 10

1) Why do you need to start with lower doses of antipsychotics in elderly patients?
2) Ideally, why should antipsychotics NOT be used in patients who have dementia?
3) Why should antipsychotic use be avoided in patients who have Parkinson’s disease?

Answer 10

1) Because elderly patients are particularly sensitive to antipsychotics.
2) As they may increase the risk of death and stroke.
3) Due to their extrapyramidal effects.

Question 11

List the important interactions of typical antipsychotics.

Answer 11

Consult the BNF because there are extensive interactions, however, a prominent interaction is drugs that prolong the QT interval such as Amiodarone and Macrolides.

Question 12

1) Name a common dose of a typical antipsychotic drug used as a single dose to control acute or violent behaviour.
2) How is Haloperidol given for the control of nausea?
3) Which arrhythmia is more likely to occur when antipsychotics are given by injection or in high doses?
4) Which typical antipsychotic is licensed for use in controlling intractable hiccups?

Answer 12

1) Haloperidol 0.5-3.0mg IM.
2) Regular small oral or SC doses or as a component of a continuous SC infusion..
3) Torsades de Pointes
4) Haloperidol.

Question 13

Give the 3 main clinical indications for the use of second generation (atypical) antipsychotics.

Answer 13

1) Urgent treatment of severe psychomotor agitation leading to dangerous or violent behaviour or to calm such patients to permit assessment.
2) Schizophrenia, particularly when extrapyramidal side effects have complicated the use of typical antipsychotics or when negative symptoms are prominent.
3) Bipolar disorder, especially in acute cases of mania or hypomania.

Question 14

Give 3 features that distinguish first generation antipsychotics from second generation antipsychotics.

Answer 14

1) Improved efficacy in treatment resistant schizophrenia (particularly Clozapine).
2) Improved efficacy against negative symptoms.
3) Lower risk of extrapyramidal symptoms.

Question 15

Give 2 possible mechanisms for the differences between first and second generation antipsychotics.

Answer 15

1) Second generation antipsychotics have a higher affinity for other receptors, particularly 5-HT2 receptors.
2) Second generation antipsychotics have a characteristic of ‘looser binding’ to D2 receptors, especially in the cases of quetiapine and clozapine.

Question 16

1) What is a common problem with second generation antipsychotics?
2) What do antipsychotics do which can cause arrhythmias?
3) What is a side effect which is specific to Risperidone?
4) Give 2 more serious side effects specific to Clozapine.
5) Give a main side effect caused by most antipsychotic drugs.

Answer 16

1) Metabolic disturbance including weight gain, metabolic disturbance and lipid changes.
2) Prolong the QT interval.
3) Particular effects on dopaminergic transmission in the tuberohypophyseal pathway (responsible for regulating the secretion of prolactin and this can cause breast symptoms as well as sexual dysfunction.
4) Agranulocytosis (severe neutrophil deficiency) in about 1% of patients and can rarely cause myocarditis.
5) A degree of sedation.

Question 17

1) In what patients should second generation antipsychotics be used with caution in?
2) In what 2 conditions should Clozapine NOT be used?
3) When might sedating effects caused by antipsychotics be more pronounced?
4) What other 2 groups of drugs should antipsychotics not be combined with?

Answer 17

1) Those with cardiovascular disease.
2) Patients with severe heart disease or with a past medical history of neutropenia.
3) When they are combined with other sedating drugs.
4) Dopamine blocking antiemetics and drugs that prolong the QT interval (Amiodarone, Quinine, Macrolides, SSRIs).

Question 18

1) In what 2 situations might use of second generation antipsychotics be considered?
2) What might patients taking Clozapine need to be aware of?

Answer 18

1) Treatment of acute symptoms and prevention of subsequent attacks.
2) The need for regular blood test monitoring and the need to report infective symptoms immediately.

Question 19

What monitoring is required for patients taking second generation antipsychotics?

Answer 19

1) Blood tests at the start of treatment and periodically thereafter (FBC, renal and liver profiles).
2) Monitoring for metabolic and cardiovascular side effects (weight, lipid profile and fasting blood glucose at baseline and intermittently during treatment).
3) Intensive monitoring programme for Clozapine due to the risk of agranulocytosis.

Question 20

In patients taking antipsychotic drugs, what might be exacerbated by drugs administered for an acute problem?

Answer 20

A prolonged QT interval (may be exacerbated, for example, if macrolides are needed to treat and infection).

Question 21

Give the 2 main clinical indications for the use of Valproate.

Answer 21

1) Epilepsy: as a first choice drug for the control of generalised or absence seizures and as a treatment option got focal seizures.
2) Bipolar disorder: for acute treatment of manic episodes and prophylaxis against recurrence.

Question 22

Describe the apparent mechanism of action of Valproate.

Answer 22

1) Appears to be a weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability.
2) Increases brain content of GABA (principle inhibitory neurotransmitter) and this regulates neuronal excitability.

Question 23

Name the 5 most common dose-related adverse effects of Valproate.

Answer 23

1) GI upset (nausea, gastric irritation and diarrhoea).
2) Neurological effects (tremor and ataxia)
3) Psychiatric effects (behavioural changes)
4) Thrombocytopenia
5) Transient changes in liver enzymes

Question 24

What do hypersensitivity reactions to Valproate include?

Answer 24

Hair loss, with subsequent hair regrowth being curlier than original hair.

Question 25

Name the 4 life-threatening idiosyncratic adverse effects of Valproate.

Answer 25

1) Severe liver injury
2) Pancreatitis
3) Bone marrow failure
4) Antiepileptic sensitivity syndrome

Question 26

Name and describe the main contraindication for the use of Valproate.

Answer 26

Women of child bearing age, particularly around the time of conception and in the first trimester of pregnancy.

Valproate is the anti epileptic drug associated with the greatest risk of foetal abnormalities.

Question 27

name 5 foetal abnormalities that can be attributed to the use of Valproate.

Answer 27

1) Neural tube defects
2) Craniofacial, cardiac and limb abnormalities
3) Developmental delay

Question 28

When should Valproate use be avoided and when should a dose reduction in Valproate be used?

Answer 28

Avoided in patients with hepatic impairment and a reduced dose should be used in patients with severe renal impairment.

Question 29

1) What enzymes does Valproate inhibit?
2) What does this inhibition cause?
3) Describe how Valproate concentration can be affected by drugs such as Phenytoin and Carbamazepine and state the consequences.

Answer 29

1) Hepatic cytochrome P450 enzymes
2) Increased plasma concentration and toxicity of drugs metabolised by CYP450 enzymes (Warfarin and other anti epileptic drugs).
3) Valproate concentration may be reduced and the risk of seizures may be increased by cytochrome P450 inducers as Valproate is metabolised by these.

Question 30

1) Adverse effects of Valproate are increased by what?

2) What is the efficacy of anti epileptic drugs reduced by?

Answer 30

1) CYP450 inhibitors (macrolides and protease inhibitors).

2) Drugs that lower the seizure threshold ( SSRIs, TCAs, antipsychotics, tramadol).

Question 31

1) In what formulation is Valproate prescribed for epilepsy?

2) In what formulation is Valproate prescribed for bipolar disorder?

Answer 31

1) Sodium Valproate

2) Valproic acid.