W20: CNS Conditions: Nausea & Labyrinth, ADHD

Question 1

Antiemetics- when are they prescribed?
Causes and treatments:

Answer 1

Antiemetics are generally only prescribed when the cause of vomiting is known because otherwise, they may delay diagnosis, particularly in children.

• Motion sickness – hyoscine hydrobromide, cinnarizine, cyclizine, promethazine (sedative)
• GI and biliary disease - Metoclopramide
• Underlying conditions – Antihistamines e.g. Cinnarizine, Cyclizine, Promethazine
• Chemotherapy – Dopamine antagonist prochlorperazine (buccal), ondansetron, dexamethasone, aprepitant, nabilone (cannabis)
• Palliative care – antipsychotic e.g. haloperidol and levomepromazine
• Post-op - 5HT3-receptor antagonists (e.g.ondansetron), dexamethasoneandhaloperidol
• Post-op N&V caused by opioids and GA– cyclizine

Question 2

Hyoscine 2 types:

Answer 2

Hydro bromide
**Butyl bromide ** e.g. Buscopan for muscle cramps

Hydro is more polar, and butyl is more non-polar and lipidic so can cross the BBB, some pt will smoke this to get a ‘high’ as it causes a neurotransmitter inbalance in the brain

Question 3

Nausea and Labyrinth:
Other treatments:

Answer 3

• Metoclopramide - acts directly on gastric smooth muscle stimulating gastric emptying. Can cause dystonia in young females. (central effects)
• Domperidone - acts at the chemoreceptor trigger zone (acts peripherally), less likely to cause central effects, such as sedation and dystonic reactions. It is a dopamine antagonist, but can be used at low doses in Parkinson’s disease (is cardiotoxic)
• Phenothiazines - act centrally by blocking the chemoreceptor trigger zone (risk of dystonic reactions) e.g. chlorpromazine, prochlorperazine (also for prevention of post-op N&V), trifluoperazine

Question 4

Nausea & Labyrinth – In Pregnancy
What are the treatments? (3)

Answer 4

• Common in 1st trimester
• Resolves within weeks 16-20
  1. Self-care advice (such as rest, oral hydration and dietary changes)
  2. Available support (e.g. self-help information and support groups)
  3. Antiemetics Chlorpromazine,cyclizine,metoclopramide,prochlorperazine,promethazine andondansetron.
• Persistent hyperemesis gravidarum – offer antiemetics via parenteral or rectal routes.
  -Offer Thiamine supplements to reduce the risk of Wernicke’s encephalopathy.

*=intractable vomiting during pregnancy, leading to weight loss and volume depletion, resulting in ketonuria and/or ketonemia

Question 5

Metoclopramide
MHRA/CHM advice?
Side-effects?

Answer 5

MHRA/CHM advice - risk of neurological adverse effects - restricted dose and duration of use
Metoclopramide should only be prescribed for short-term use (up to 5 days)
Usual dose is 10 mg, repeated up to 3 times daily; max. daily dose is 500 micrograms/kg

Side-effects:
Can induce acute dystonic reactions involving facial and skeletal muscle spasms and oculogyric crises this subsides within 24 hours of stopping

Question 6

Domperidone:
Indication?
MHRA/CHM advice about dose?
C/I?

Answer 6

MHRA/CHM advice - Domperidone for N&V: lack of efficacy in children; reminder of contraindications in adults and adolescents
* Not for children < 12 years or those weighing < 35 Kg
* Use the lowest effective dose for the shortest possible duration max. treatment duration should not usually exceed 1 week
* Patients advised on signs of arrhythmia and to seek medical attention if palpitation or syncope develops
* Contra-indications: cardiac disease, GI obstruction or haemorrhage.

Question 7

Quiz:
1. What is the dose of donepezil for mild to moderate dementia in Alzheimer’s disease

2. When is a prescription for donepezil for an elderly potentially inappropriate?
3. Counsel patients on the use of donepezil orodispersible tablets
4. What are the cognitive and non-cognitive symptoms of dementia?

Answer 7

1. 5mg OD for 1 month, then increased up to 10mg daily, taken at bedtime.
2. In patients with a known history of persistent bradycardia (heart rate less than 60 beats per minute)
   * In patients with a heart block (risk of cardiac conduction failure, syncope and injury).
3. Tablet should be placed on the tongue, allowed to disperse, and swallowed.
4. Cognitive:
   * Memory loss, Lack of concentration, Disorientated, Difficulty with speech

Non-Cognitive:
* Agitation, Aggression, Distress, Psychosis

Question 8

Quiz:
Causes and treatments of nausea and labyrinth:
Motion sickness —————————–
GI and biliary disease —————————–
Underlying conditions —————————–
Chemotherapy —————————–
Palliative care —————————–
Post-op —————————–
Post-op N&V caused by opioids and GA —————————–

Answer 8

• Motion sickness – Hyoscine Hydrobromide, cinnarizine, cyclizine, promethazine (sedative)
• GI and biliary disease - Metoclopramide
• Underlying conditions – Antihistamines e.g. Cinnarizine, Cyclizine, Promethazine
• Chemotherapy – Dopamine antagonist prochlorperazine (buccal), ondansetron, dexamethasone, aprepitant, nabilone (cannabis)
• Palliative care – antipsychotic e.g. Haloperidol and Levomepromazine
• Post-op - 5HT3-receptor antagonists (e.g.ondansetron), dexamethasone and haloperidol
• Post-op N&V caused by opioids and GA– cyclizine

Question 9

What is the definition of ADHD?

Answer 9

ADHD is characterised by a persistent pattern of inattention and/or hyperactivity-impulsivity, with onset during the developmental period, typically early to mid-childhood.

The degree of inattention and hyperactivity-impulsivity is outside the limits of normal variation expected for age and level of intellectual functioning and significantly interferes with academic, occupational, or social functioning.

Question 10

ADHD Neurobiology and Basis for Treatment:
Which neurotransmitters are involved in the treatment response?
What does DA modulate? (3)
What are the 2 firing modes of dopamine neurons?

Answer 10

• Both Dopamine (DA) and Noradrenaline (NA) are involved in the treatment response (Paradoxical effect to stimulants: calming effect)
• Other neurotransmitters thought to be involved include Glutamate and Serotonin, potentially shedding some light on the memory and mood aspects of ADHD
• DA modulates reward in the ventral striatum (tells the brain when a reward is particularly salient) - ADHD patients need higher rewards and show hypo-activation in reward circuits.
• DA modulates working memory and inhibitory functions in fronto-striatal circuits - ADHD patients have impaired prefrontal cognitive functions and show hypoactivation in prefrontal circuits.
• Two firing modes: tonic (background) and phasic (intermittent pulses) - ADHD patients have a reduced tonic pool of DA (and NA) and compensate with increased phasic release (reward and novelty seeking)

Question 11

ADHD – Treatment Targets

Answer 11

• Educate about the disorder and its management
• Support the individual (+/- family members)
• Improve the core symptoms
• Address the associated impairments
• Treat the psychiatric co-morbidity
• Monitor physical health

Question 12

ADHD – Different Treatments? (domains)

Answer 12

1. Medication
2. Psychological: Individual or group-based CBT, DBT, mindfulness
   Specialist (relationship/marital, family, vocational/educational)
3. Psychoeducation’ (inc bibliotherapy) & Lifestyle modification

Question 13

ADHD – Pre-medication Checks? (4)

Answer 13

1. Confirm the diagnosis of ADHD
2. Review of mental health comorbidities
3. Risk assessment for substance misuse and drug diversion
4. Review physical health:
   - medical history, current medications and contraindications
   - height and weight; pulse and BP
   -a cardiovascular ‘assessment’ (including FH of CVD)

• NICE September 2019: ECG is not needed before starting stimulants,
  atomoxetine or guanfacine if CV history and examination are normal and
  the person is not on medicine that poses an increased CV risk.

Question 14

ADHD:
What are physical health monitoring requirements and timing? (NICE 2018)

Answer 14

1. Blood pressure & pulse:
   -Recorded (at baseline) and before and after every dose change
   -Recorded routinely every 6 months thereafter
2. Weight:
   -Recorded at baseline then every 6 months thereafter

Annual review:
* At least once a year
* Consider trial periods of stopping medication or reducing the dose
* If the decision is made to continue medication, the reasons for this should be documented

Question 15

ADHD – Choice of Medication Checks:
What is first-line?

Answer 15

• Lisdexamfetamine or methylphenidate first-line
• Switch those who have not derived enough benefit (from the first trial) to lisdexamfetamine or methylphenidate following a 6-week trial (of the other) at an adequate dose
• Consider atomoxetine if poor response or tolerance to stimulants
• Other medications (e.g. clonidine (for children), guanfacine (for adults), atypical antipsychotics, ‘medication not included above‘ should only be used on the advice of tertiary care specialists

Question 16

Mechanisms of action:

Answer 16

1. Psychostimulants - DAT and NAT inhibitors
2. Non Stimulants:
   * Atomoxetine - NARI selective noradrenaline reuptake inhibitor
   * Clonidine and Guanfacine – NA agonists
   * Bupropion - DAT & NAT inhibitor & nicotinic receptor antagonist

Question 17

ADHD medications:

Methylphenidate CD2:
C/I?
Monitoring requirements?
Most common SE?

Answer 17

Methylphenidate CD2:
-M/R preparations should be prescribed by brand name
Contra-indications:
* CVD: arrhythmias, heart failure, structural abnormalities, cardiomyopathy, severe hypertension
* Hyperthyroidism, anorexia, psychosis
* Suicidal tendencies, uncontrolled bipolar disorder

Monitor:
* Growth-restriction in children
* For psychiatric disorders
* Pulse, BP, appetite, weight and height at
the beginning and then at least every 6
months

Most common side effects: appetite loss, weight loss, increased heart rate and blood pressure, tics and Tourette’s syndrome and growth restriction in children

Question 18

ADHD medications:

Lisdexamfetine & Dexamfetamine:
C/I?
Overdose symptoms?
Monitoring requirements?
Most common SE?

Answer 18

Lisdexamfetine & Dexamfetamine:
Contra-indications:
* CVD: moderate- severe hypertension, advances arteriosclerosis - increases blood pressure or heart rate
* Hyperthyroidism

Overdose:
* wakefulness, excessive activity, paranoia, hallucinations and hypertension followed by exhaustion, convulsions, hyperthermia and coma

Monitor:
* Aggressive behaviour or hostility
* Pulse, BP, psychiatric symptoms
* Weight and height in children and adults
every 6 months

Most common side effects: appetite loss, weight loss, increased heart rate and blood pressure, tics and Tourette’s syndrome and growth restriction in children

Question 19

SAQ:
1. List some important prescribing information that you need to remember for methylphenidate

Answer 19

All long-acting preparations of methylphenidate contain an immediate-release component and a modified-release component. The biphasic-release profiles of different preparations are not all equivalent and contain different proportions of immediate-release and modified-release components.
The MHRA has advised caution when switching between such preparations, due to differences in dosing frequency, administration with food, amount and timing of the modified-release component, and overall clinical effect.

Healthcare professionals are advised to:
*Follow the specific dosage recommendations for each preparation;
*Discuss the reasons for switching with patients or their carers, including any possible changes in symptoms and side-effects;
*Take patient preferences into account when considering a switch;
*Provide counselling on administration of the new preparation, especially with regards to food;
*Follow current clinical guidance on prescribing by brand name, or by manufacturer name if generic;
*Avoid frequent switching between different preparations.

Question 20

SAQ 2
List the monitoring requirements for methylphenidate

Answer 20

Monitor for psychiatric disorders. Pulse, blood pressure, psychiatric symptoms, appetite, weight and height should be recorded at initiation of therapy, following each dose adjustment, and at least every 6 months thereafter.

Question 21

SAQ:
List the monitoring requirements for Lisdexamphetamine?

Answer 21

• Manufacturer advises monitor for aggressive behaviour or hostility during initial treatment.
• Manufacturer advises monitor pulse, blood pressure, and for psychiatric symptoms before treatment initiation, following each dose adjustment, and at least every 6 months thereafter.
• Monitor weight in adults before treatment initiation and during treatment; in children, height and weight should be recorded before treatment initiation, and height, weight and appetite monitored at least every 6 months during treatment

Question 22

SAQ
Counsel the patient on the intake of Lisdexamphetamine capsules

Answer 22

Swallow whole or mix contents of capsule with soft food such as yoghurt or in a glass of water or orange juice; contents should be dispersed completely and consumed immediately.