PH3113 - Psychiatric Disease and its Pharmacology 8

Question 1

What are the side effects of lithium to treat bipolar disorder?

Answer 1

Rapidly absorbed from GI tract
- excreted unchanged via kidney
Narrow therapeutic range
- 0.4 - 1.0 mmol/L
Signs of toxicity
- > 1.5 mmol/L
- nausea
- diarrhoea
- ataxia
- confusion
- coarse tremor
- > 2 mmol/L
- seizures
- loss of consciousness

Long term increases risk of
- hypothyroidism
- regular TFT monitoring
- hyperparathyroidism
- Ca2+ monitoring recommended
- renal impairement
- monitor creatinine/GFR

Question 2

What counselling is needed when using lithium to treat bipolar disorder?

Answer 2

Lithium card
Prior checks
- renal
- thyroid
- cardiac
Keeping appointments for regular monitoring
OTC NSAIDs interactions
Seek medical attention
- diarrhoea
- vomiting
Maintain fluid intake
- low salt a danger
Seek advice about stopping lithium for up to 7 days if they become seriously ill

Question 3

What is Attention Deficit Hyperactivity Disorder (ADHD)?

Answer 3

Prevalent debilitating disorder
Persistent developmentally, inappropriate levels of
- overactivity
- inattention
- impulsivity
No biomedical test
Diagnosis base on observation of behavioural symptoms
- 9 symptoms across 2 domains
- hyperactivity/impulsivity
- inattention

Question 4

What are the characteristics of Inattentive ADHD?

Answer 4

Fails to give close attention to details or makes careless mistakes
Has difficulty in sustaining attention
Does not appear to listen
- may actually be listening
Struggles to follow through on instructions
Has difficulty with organisation
Avoids or dislikes tasks requiring sustained mental effort
Loses things
Easily distracted
Forgetful in daily activities

Question 5

What are the characteristics of Hyperactive/Impulsive ADHD?

Answer 5

Fidgets with hands or feet or squirms in chair
Has difficulty remaining seated
Runs about or climbs excessively
Difficulty engaging in activities quietly
Acts as if driven by a motor
Talks excessively
Blurts out answers before questions have been completed
Difficulty waiting or taking turns
Interrupts or intrudes upon others

Question 6

How is ADHD diagnosed?

Answer 6

Sensory impairment
Epilepsy and related states
Effects of head injury
Acute or chronic medical illness
Poor nutrition
Sleep disorders
Side effects of medication
School or classroom difficulties

Question 7

What is the neuropathology of ADHD?

Answer 7

Reduced brain size
Reduced size of particular nuclei
- striatum
- ventral region of reward processing
- prefrontal cortex white matter
- connectivity in limbic system
- executive function
- corpus callosum
- connectivity

Dopamine receptor D4 polymorphism associated with reduced cortical thickening
- resolved in adolescence

Question 8

How can ADHD be treated?

Answer 8

Psychological treatments
Medical treatments
- reserved for severely affected
Educational interventions
Social interventions

Question 9

What is the NICE guidance for treating ADHD?

Answer 9

In all pre-school children and school-age children and young people with mild-moderate ADHD, drug treatment should not be offered as the first-line treatment
First line approach
- parent-training/education programmes
- parent and child
- group based sessions or individual if there are particular needs
Drug treatment is reserved for severe ADHD in school-age children and young people
- form part of a comprehensive treatment plan
- psychological
- behavioural
- educational advice and interventions

Question 10

What is the pharmacotherapy for ADHD?

Answer 10

Early trials were done with DL-amphetamine
- d-amphetamine and methylphenidate have been proven as the best therapy

Most effective
- enhance dopamine and noradrenaline function
- rapid onset of action
- no ceiling effect
- increase in dopamine efflux
- not limited to cortex

Question 11

What is the mechanism for ADHD treatment?

Answer 11

Deficits in dopamine in synapse

Question 12

Which drugs are preferred to treat ADHD?

Answer 12

Methylphenidate
Atomoxetine
- tics
- Tourette’s
- anxiety disorder
- stimulant misuse
- risk of stimulant diversion
D-amphetamine
- only if other drugs ineffective at raised doses

Question 13

What should ADHD treatment decisions be based on?

Answer 13

Co-morbidities
- tics
- Tourette’s syndrome
- epilepsy
Different adverse effects
Potential problems with compliance
- mid day dose needed at school?
Potential for drug diversion and misuse
Preferences of the child or young person and their parent/carer

Question 14

What are the properties of methylphenidate?

Answer 14

Simulant
CD Schedule II
Dopamine/noradrenaline reuptake inhibitor
- increased dopamine and noradrenaline levels
5-HT(1A) agonist
alpha-2 activation
VMAT relocation

Question 15

How should methylphenidate be used to treat ADHD?

Answer 15

Initial treatment
- low doses of immediate-release or modified-release preparations
- dose should be titrated against symptoms and side effects over 4 - 6 weeks until dose optimisation is achieved
Modified-release preparations
- given as single dose in morning
Immediate-release preparations
- in two or three divided doses

Question 16

What are the properties of D-amphetamine used to treat ADHD?

Answer 16

Stimulant
- heightens vigilance
- increase focus
- increase concentration
CD schedule II
Dopamine reuptake inhibitor
- initially increased dopamine uptake
- decreased with long term use and reversal of transporter
- similar to SSRI
- VMAT 2 inhibitor
- vesicular pools displaced and noradrenaline and dopamine released via reverse transport of DAT

Question 17

How should D-amphetamine be used to treat ADHD?

Answer 17

Initial treatment
- low doses consistent with BNF
- dose should be titrated against symptoms and side effects over 4 - 6 weeks
Treatment in divided doses
- increasing to a max of 20 mg/day
Children aged 6 - 18 years
- doses up to 40 mg/day may occasionally be required