Spectrum Disorder Case Flashcards
1
Q
what is meant by learning disability?
A
- A significantly reduced ability to understand new or complex information or learn new skills (impaired intelligence) with
- A reduced ability to cope independently (social function) which started before adulthood, with a lasting effect on development.
- Also called “special needs”
2
Q
what is considered as having a mild learning disability?
A
85% of the LD population
Can generally learn reading, writing and maths.
May have jobs and live independently
3
Q
what is considered as having a moderate learning disability?
A
10% of LD population
May be able to learn basic reading and writing.
Able to learn functional skills such as safety and self-help.
Require some type of supervision/oversight
4
Q
what is considered as having a severe learning disability?
A
5% of LD population
Probably not able to read and write although may they may learn self-help and routines. Require supervision in their daily activities and living environment
5
Q
what is considered as having a profound learning disability?
A
1% of LD population
Requires intensive support. May be able to communicate by verbal or other means. May have medical conditions that require ongoing nursing and therapy
6
Q
what is not a learning disability?
A
• Problems with reading, writing or numeracy only = learning difficulty
• Emotional difficulties not linked
• Always linked to conditions like
– Attention Deficit Hyperactivity disorder (ADHD)
– Autism including Asperger’s syndrome
– what is a learning disability- Having a learning disability means that people find it harder to learn certain life skill eg DS
7
Q
what is the definition of autism?
A
Autism spectrum disorder (ASD) is a lifelong developmental disability that affects how a person communicates with, and relates to, other people. It also affects how they make sense of the world around them.
They don’t interact with someone in the same way
8
Q
why is autism known as spectrum?
A
• Autism is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms people experience. ASD occurs in all ethnic, racial, and economic groups. Occurs more in males than females
9
Q
what is meant by high functioning autism spectrum?
A
requiring support, difficulty initiating social interactions, inflexibility of behaviour, difficulty switching activities. problems with organisation
10
Q
what is characteristics of autism?
A
requiring substantial support. marked deficits with social interactions: inflexibility of behaviour . difficulty or distress coping with change. repetitive behaviours
11
Q
what are the characteristic of severe autism?
A
requiring substantial support. marked deficits with social interactions: inflexibility of behaviour . extreme difficulty or distress coping with change. repetitive behaviours interfere with functioning
12
Q
what are the causes of autism?
A
• NOT related to bad parenting, food allergies, vaccines or parents with high or low intelligence
• No one cause of autism has been identified
• Genetic influences are likely most important risk factor
– But not only cause (MZ twin studies < 100%)
• Cause is likely multifactorial- doesn’t know what it means
• Physiology and environment are ALWAYS interacting from day 1
• May be several types of autism with different causes
13
Q
what are the characteristics of autism?
A
People with autism generally experience three main areas of difficulty: how you relate to other people
- Social Communication,
- Social Interaction
- Social Imagination
14
Q
how does social communications affect people with autism?
A
Social communication is where people understand:
• Facial expressions
• Tone of voice
• Common gestures
• Eye contact
• Body language
People with autism may struggle with this
15
Q
how does social interactions affect people with autism?
A
Social interaction is where people:
• Understand their own and other people’s feelings and emotions
• Social Intelligence test - Read the eyes
• Form relationships and making friends.
People with autism may struggle with this and can appear aloof, indifferent
and withdrawn.
16
Q
how does social imagination affect people with autism?
A
. Social Imagination
Social imagination is the ability to comprehend:
• Abstract concepts and ideas
• People’s actions, emotions,
behaviours and consequences
• Solutions to life outside of their routines.
Those with autism may find this very difficult
17
Q
what is meant by theory of mind?
A
- refers to the notion that many autistic individuals do not understand that other people have their own plans, thoughts, and points of view.
- A demonstration
- Questionnaire from University of Cambridge professor Simon Baron-Cohen
18
Q
what is meant by adherence?
A
- Adherence has been defined as the “active, voluntary, and collaborative involvement of the patient in a mutually acceptable course of behaviour to produce a therapeutic result.”
- Compliance usually refers to whether patients take their medications as prescribed (eg, twice daily)
19
Q
what is meant by non- adherence?
A
- estimated, in adults, to be between 30 and 50% for prescribed medication, depending on the disease and the health care system
- estimated, in children, to be between 4% and 92% and between 30-40% in chronic illness
- E.g. in patients with ADHD, it is estimated that most discontinue therapy after 4 months and approximately 20% stop after the first prescription.
20
Q
what can we do to give medicine to children ?
A
- Manipulate adult formulations
- Liquid formulations
- Tablets
21
Q
how can we manipulate adult formulations to give to children?
A
- Crushing tablets or opening capsules and mixing the content with food or drink
- Halving or quartering tablets
- Diluting concentrated liquid preparations
- Cutting or ‘halving’ suppositories
22
Q
what are the problems with manipulating adult formulations?
A
- Increased risk of error
- Possible bioavailability issues. Higher bioavailability when there is a greater surface area and then may cause side effects
- Increased risk of ADRs
- Issues with supply – not licenced and the pharmacist will be held liable if things go wrong
- Child refusal
23
Q
what considerations must be taken when giving liquid suspensions to children?
A
• Shaking the suspension- settles so the dosing is inaccurate if not shaken.
• Stability of medicine. Things in water is not stable as bacteria is a medium for bacteria growth.
• Transportation & Cost
• Accuracy of measuring device
• Volume – too small – inaccurate
too large – adherence problem
• Need for excipients – possible safety issues
• Taste masking but too nice overdose problem?
24
Q
what considerations must be taken when giving tablets to children?
A
• What age can children take tablets? 6 yrs old
• Few studies show children around age 6 can swallow tablets
• By 11 year olds - 91% can take tablets
• Depends on:
– Size & shape tablet
– Taste of alternative
– Delayed in certain conditions
25
what is the links between fussy eaters and adherence to medication?
• Studies show fussy eaters have a higher rejection rate for all medications
26
what Psychological approach to dealing with fussy eaters
* Remain calm.
* Address the anxiety.
* Talk about it.
27
adherence to medication in older children
* Once a child can reason (from 7 onwards), adherence increases, then in adolescents some studies show it drops, why?
* Control medication moves to teenager
* Evidence of peer-pressure and fear of stigma
28
what other factors affects the adherence of taking medicines?
* Family factors
* Family size, parental marital status, general stress, and stability may be contributing factors to adherence in children.
* Parents’/Carers’ Beliefs about medicine
29
how does beliefs about medicines affect adherence
It is known that patients’ beliefs affect adherence rates. So there are 2 questions:
1. What beliefs do patients have about medicines?
2. What happens to your beliefs when it is not you taking the medicine but you are giving it to your child?
Beliefs about medicines…
• In General
– Harm
– Overuse
• Specific to prescribed medication
– Necessity
– Concerns
Comparison of beliefs about medicines - parents vs patients
• Views about medicines in general similar
• However, parent’s beliefs about a specific medicine differ
• More parents (approx. 25%) show negative beliefs about the medicine (concerns) which result in anxiety and possible non-adherence
30
how do parents get their children to take medicine?
```
• Masking in other foods/drinks
• Force
• Bribery
– Offering biscuit or sweet drink after
• Reasoning
```
31
How giving medication affects the carers psychologically
guilt
desperation
anxiety
32
what impact does giving medication on family life
* Need for a routine
* “Holidays can be very difficult as he has to take his melatonin more often”
* Problems in School
* “School refused to administer when my son was on a linctus as they did not want the responsibility of anything going wrong
33
Define ADHD
ADHD is a heterogeneous behavioural syndrome characterised by the core symptoms of hyperactivity, impulsivity and inattention. While these symptoms tend to cluster together, some people are predominantly hyperactive and impulsive, while others are principally inattentive.
34
what are the two main diagnostic criteria
the International Classification of Mental and Behavioural Disorders 11th (ICD-11) and the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V).
ICD-11 uses a narrower (more restrictive) diagnostic category, which includes people with more severe symptoms and impairment. ICD-11 was published early 2019, May 2019 presented to WHO congress – widespread use from January 2022.
DSM-V has a broader, more inclusive definition, which includes a number of different ADHD subtypes.
35
what comes under ICD-11- 6A05 Attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder is characterized by a persistent pattern (at least 6 months) 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. Inattention refers to significant difficulty in sustaining attention to tasks that do not provide a high level of stimulation or frequent rewards, distractibility and problems with organization. Hyperactivity refers to excessive motor activity and difficulties with remaining still, most evident in structured situations that require behavioural self-control.
Impulsivity is a tendency to act in response to immediate stimuli, without deliberation or consideration of the risks and consequences.
The relative balance and the specific manifestations of inattentive and hyperactive-impulsive characteristics varies across individuals, and may change over the course of development. In order for a diagnosis of disorder the behaviour pattern must be clearly observable in more than one setting.
36
what is ADHD?
Attention deficit hyperactivity disorder is characterized by a persistent pattern (at least 6 months) of inattention and/or hyperactivity-impulsivity, with onset during the developmental period, typically early to mid-childhood.
37
what does inattention mean?
Inattention refers to significant difficulty in sustaining attention to tasks that do not provide a high level of stimulation or frequent rewards, distractibility and problems with organization.
38
what does hyperactivity mean?
Hyperactivity refers to excessive motor activity and difficulties with remaining still, most evident in structured situations that require behavioural self-control.
39
what does impulsivity?
is a tendency to act in response to immediate stimuli, without deliberation or consideration of the risks and consequences.
40
what common co-existing conditions exist in children who have ADHD?
are disorders of mood, conduct, learning, motor control and communication, and anxiety disorders.
In adults they include personality disorders, bipolar disorder, obsessive compulsive disorder and substance misuse.
41
why cant ADHD be considered a categorical diagnosis?
A categorical approach to a diagnosis results in labelling each subject as either having (D+) or not having (D) a disorder. The DSM-V categorises a patient as being depressed or not depressed. A dimensional approach results in labelling each subject with an ordinal score (D), with higher scores a stronger indicator of the presence of the disorder. Higher scores on the Hamilton depression scale are associated with a stronger likelihood of ‘‘being depressed’’ as well, perhaps, of greater impairment, or greater resistance to treatment
42
what is the DSM-V diagnosis of ADHD?
Extremes of the triad symptoms of inattention, impulsivity and hyperactive behaviour. These are
• Pervasive
• Of early onset
• Unexplained by other disorders
• Resulting in impairment and disability.
43
what symptoms is required in the ICD-11 hyperkinetic disorder?
• The ICD-11 ‘hyperkinetic disorder is more restrictive and requires symptoms to be more:
Pervasive
•Impairing
44
what is the diagnostic criteria for ICD-11
```
• Inattention
• Overactivity
• Impulsiveness, have all been present:
1. From an early age
2. Persist in more than 1 setting
3. Impair; social function, learning and ‘normal’ development.
```
45
How is ADHD diagnosed?
* The diagnosis is based on very specific symptoms, which must be present in more than one setting.
* Children should have at least 6 attention deficit symptoms and / or 6 hyperactivity/impulsivity symptoms, with some symptoms presenting before age 7.
* The symptoms must be present for at least 6 months, seen in two or more settings, and not caused by another problem.
* The symptoms must be severe enough to cause significant difficulties in many settings, including home, school, and in relationships with peers.
46
what are the inattentive symptoms in ADHD?
* Fails to give close attention to details or makes careless mistakes in schoolwork
* Has difficulty keeping attention during tasks or play
* Does not seem to listen when spoken to directly
* Does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace
* Has difficulty organising tasks and activities
* Avoids or dislikes tasks that require sustained mental effort (such as schoolwork)
* Often loses toys, assignments, pencils, books, or tools needed for tasks or activities
* Is easily distracted
* Is often forgetful in daily activities
47
what are the hyperactivity symptoms in ADHD?
* Fidgets with hands or feet or squirms in seat
* Leaves seat when remaining seated is expected
* Runs about or climbs in inappropriate situations
* Has difficulty playing quietly
* Is often "on the go," acts as if "driven by a motor," talks excessively.
48
what are the Impulsivity symptoms in ADHD?
* Blurts out answers before questions have been completed
* Has difficulty awaiting turn
* Interrupts or intrudes on others (butts into conversations or games)
49
what is the Epidemiology of ADHD>
Inattention and hyperactive / impulsive symptoms are commonly seen in practice with up to 6% of children meeting criteria for ADHD.
Up to 78% continue to exhibit symptoms at 10 yr follow-up, and inattentive symptoms are more likely to persist into adulthood.
ADHD accounts for 30-50% of mental health referrals among children
3 – 4 times more likely in boys than girls.(However, refer to later slide.)
High co-morbidity ~ conduct disorder most common.
50
what type of people may have increased prevalence of ADHD compared to the general population?
* people born preterm
* looked-after children and young people (i.e. in the ‘care’ system)
* children and young people diagnosed with oppositional defiant disorder or conduct disorder
* children and young people with mood disorders (for example, anxiety and depression)
* people with a close family member diagnosed with ADHD
* people with epilepsy
* people with neurodevelopmental disorders (for example, autism spectrum disorder, tic disorders, learning disability [intellectual disability] and specific learning difficulties)
* adults with a mental health condition
* people with a history of substance misuse
* people known to the Youth Justice System or Adult Criminal Justice System
* people with acquired brain injury.
51
what are the long term effects that can occur in ADHD?
ADHD is a chronic condition:
Commonly continues through adolescence and then into adulthood (with consequent high co-morbidity ~ depression, anxiety.
If untreated associated with:
Educational, Employment Difficulties, relationship problems. High incidence of substance misuse (Most common is Alcohol and / or Cannabis)
52
what is the initial management of ADHD?
Diagnosis must follow extensive and comprehensive mental health assessment by a specialist clinician;
Paediatrician
Child Psychiatrist
In addition the diagnosis should follow a full assessment by an:
• Educational + / or a Clinical Psychologist
53
onset of ADHD?
Usually before aged 3 yrs ~ often some symptoms arise in infancy .
Duration:
6 months and to a maladaptive level inconsistent with ‘normal development.’
Severity:
Clinically significant severity in at least 2 different settings
54
what non- Pharmacological interventions can be carried out for people with ADHD?
• Psycho-educational measures~ education + advice should be the base / basis of any treatment offered.
• Parent training and Family-Centred Behavioural Therapy. Effectiveness shown in RCT’s
• Behavioural Interventions (school or pre-school):
Effective in reducing hyperactive behaviour and promoting social adjustment.
No single scheme has been shown to be superior to others.
55
what Pharmacological Treatment is used for people with ADHD?
Increasingly, medication is used for symptoms rather than syndromal control.
Experimental studies are difficult both ethically + practically
P’kinetics +P’dynamics have been extrapolated from adult studies, therefore:
• Off-Licence, beyond terms of licence.
• Must discuss openly and fully with carers (pts if appropriate)
• Obtain informed consent
56
why should we not assume that drugs are not necessarily more hazardous at younger end of the age spectrum
Bioavailability is often lower in children due to:
• Rapid metabolism
• Distribution in a relatively larger ECF
Conversely, drugs cross the Blood Brain Barrier more readily.
Prescribing and subsequent titration should be on a mg/kg dosing range.
57
what are the ideal properties of medication used in the treatment of ADHD?
```
• Longer duration of action
• Not potentially addictive
• Ease of administration
• Absence of ‘rebound’ effects
• No effect on appetite, growth
• Rapid onset of action
• Effective in treating associated symptoms
~ depression, anxiety etc
• Dissipates rapidly - hence will not induce insomnia
```
58
what things should healthcare professionals be aware of before initiating medication for ADHD?
* be familiar with the pharmacokinetic profiles of all the short- and long-acting preparations available for ADHD
* ensure that treatment is tailored effectively to the individual needs of the child, young person or adult
* take account of variations in bioavailability or pharmacokinetic profiles of different preparations to avoid reduced effect or excessive adverse effects.
59
what does the baseline assessment contain for the initial diagnosis of ADHD?
• a review to confirm they continue to meet the criteria for ADHD and need treatment
• A review of mental health and social circumstances, including:
1. presence of coexisting mental health and neurodevelopmental conditions
2. current educational or employment circumstances
3. risk assessment for substance misuse and drug diversion
4. care needs
60
what review of physical health include in the assessment for ADHD?
* a medical history, taking into account conditions that may be contraindications for specific medicines
* current medication
* height and weight (measured and recorded against the normal range for age, height and sex)
* baseline pulse and blood pressure (measured with an appropriately sized cuff and compared with the normal range for age)
* a cardiovascular assessment
* an electrocardiogram (ECG) if the treatment may affect the QT interval.
61
what medication should be offered for children aged 5 and over and young people?
• Offer methylphenidate (either short or long acting) as the first line pharmacological treatment for children aged 5 years and over and young people with ADHD.
• Consider switching to lisdexamfetamine for children aged 5 years and over and young people who have had a 6 week trial of methylphenidate at an adequate dose and not derived enough benefit in terms of reduced ADHD symptoms and associated impairment.
• Consider dexamfetamine for children aged 5 years and over and young people whose ADHD symptoms are responding to lisdexamfetamine but who cannot tolerate the longer effect profile.
• Offer atomoxetine or guanfacine to children aged 5 years and over and young people if:
1. they cannot tolerate methylphenidate or lisdexamfetamine or
2. their symptoms have not responded to separate 6 week trials of lisdexamfetamine and methylphenidate, having considered alternative preparations and adequate doses.
62
name psychostimulants
Methylphenidate, Lisdexamfetamine, Dexamfetamine
Centrally-acting sympathomimetics ~ Atomoxetine
should only be used after:
• Specialist assessment
And as part of a Care Package that includes:
• Educational
• Psychological
• Behavioural assessment + intervention.
63
stimulants
Stimulants are effective in at least 70% of hyperactive children
{Swanson et al, 1991}.
Dysfunctional dopamine pathways (decreased Dopaminergic activity) in the fronto-basal ganglia are thought to be responsible for the Clinical Symptoms of ADHD.
Frontal lobes of affected children have been shown to be 10% smaller compared to control children.
64
what does stimulants improve?
```
Stimulants are more effective in treating hyperactivity than inattention. However:
• Over-activity
• Attention span
• Impulsivity
• Aggression
• Social Interaction
Should all improve
Social skills and general academic achievement may not improve.
```
65
Methylphenidate:
* Licensed for ADHD as part of a comprehensive treatment programme.
* Reserved for when remedial interventions have not been effective / proved sub-optimal.
* Patient must be under specialist supervision.
* Not licensed in children under 6 yrs.
66
MoA of Methylphenidate
```
Mechanism of Action (M of A): Inhibits uptake of monamines (NT’s) into the presynaptic neurone, thereby increasing dopamine ‘hit’ at post-synaptic receptor sites.
Dosing schedule (child >6yrs):initially 5-10mg,OD/BD, increment weekly, versus efficacy and tolerability, by 5-10mg to a maximum 60mg daily in divided doses.
If no response after 1 month at maximal dose(and with assured compliance) decrement and stop.
A m/r prep (Concerta XL, 18mg, 36mg) was licensed in 2003 ~ enhances compliance and may reduce ‘rebound’ effects via smoother kinetics hopefully minimising ‘peaks and troughs.’
```
67
what are the side effects of stimulants
• Insomnia
• Decreased appetite
• Euphoria / Depression / Anxiety
• Psychosis (rare)
(Hepatic dysfunction and blood dyscrasias have been reported with Methylphenidate.)
Stimulant use should be proactively assessed and the drug should be withdrawn periodically (12/12) for a drug-free assessment.
The stimulants are usually finally withdrawn during or after puberty.
68
what age is Lisdexamfetamine and Dexamfetamine licenced for in kids with ADHD?
Lisdexamfetamine licensed for children aged 6 yrs +
| Dexamfetamine licensed for children aged 3 yrs +
69
MoA for Lisdexamfetamine and Dexamfetamine
Amfetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity.
The mode of therapeutic action of amfetamine in ADHD is not fully established, however it is thought to be due to its ability to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extra-neuronal space.
As with methylphenidate, pharmacological efficacy centres on increasing post-synaptic dopamine receptor occupancy.
70
what is the dosing schedule for Lisdexamfetamine
* Dosage should be individualised according to the therapeutic needs and response of the patient. Careful dose titration is necessary at the start of treatment with Lisdexamfetamine.
* The starting dose is 30 mg, taken once daily in the morning. When in the judgment of the clinician a lower initial dose is appropriate, patients may begin treatment with 20 mg, once daily in the morning.
* The dose may be increased by 10 or 20 mg increments, at approximately weekly intervals. Lisdexamfetamine should be administered orally at the lowest effective dosage.
* The maximum recommended dose is 70 mg/day; higher doses have not been studied.
71
what is the doing schedule for
* Careful dose titration is necessary at the start of treatment with dexamfetamine. Dose titration should be started at the lowest possible dose.
* The recommended starting daily dose is 5 mg once or twice daily (e.g. at breakfast and lunch), increasing if necessary by weekly increments of 5 mg in the daily dose according to tolerability and degree of efficacy observed.
* In the treatment of hyperkinetic disorders / ADHD, the times at which the doses of dexamfetamine tablets are administered should be selected to provide the best effect when it is most needed to combat school and social behavioural difficulties.
* Normally the first increasing dose is given in the morning. Dexamfetamine tablets should not be taken too late after lunch time to avoid disturbances of sleep.
* The regimen that achieves satisfactory symptom control with the lowest total daily dose should be employed.
* The maximum daily dose in children and adolescents is usually 20 mg, although doses of 40 mg may in rare cases be necessary for optimum titration.
72
what is the MoA of Atomoxetine?
Atomoxetine;
Licensed in the UK in May 2004; children aged 6 yrs +, adolescents and adults
Highly selective inhibitor of the pre-synaptic Noradrenaline transporter ~ minimal effect on serotonergic or dopaminergic transporters.
Atomoxetine is not a psychostimulant, nor an amphetamine derivative and has limited abuse potential.
73
what is the dosing schedule for Atomoxetine
Children < 70Kg:
0.5mg/Kg, 7 days post initiation go to 1.2 mg/Kg
Children >70Kg:
initiate at 40mg, titrating after 7 days to 80mg as maintenance
Adults: initiate at 40mg titrate to 80-120mg
74
what is the MoA of Guanfacine
Guanfacine is a selective alpha2A-adrenergic receptor agonist in that it has 15-20 times higher affinity for this receptor subtype than for the alpha2B or alpha2C subtypes.
Guanfacine is a non-stimulant. MoA not fully established. Preclinical research suggests guanfacine modulates signalling in the PFC & BG through direct modification of synaptic noradrenaline transmission at the alpha 2- adrenergic receptors.
Pharma-codynamic effects
Guanfacine is a known antihypertensive agent. By stimulating alpha 2A-adrenergic receptors, guanfacine reduces sympathetic nerve impulses from the vasomotor centre to the heart and blood vessels. This results in a decrease in peripheral vascular resistance and blood pressure, and a reduction in heart rate.
75
what is the dosing for Guanfacine
• Careful dose titration and monitoring is necessary at the start of treatment with guanfacine since clinical improvement and risks for several clinically significant adverse reactions (syncope, hypotension, bradycardia, somnolence and sedation) are dose- and exposure-related. Patients / carers should be advised that somnolence and sedation can occur, particularly early in treatment or with dose increases. If somnolence and sedation are clinically concerning or persistent, a dose decrease or discontinuation should be considered.
76
what is the maintenance and monitoring of Guanfacine?
* Monitor effectiveness of medication for ADHD and adverse effects, and document in the person's notes.
* Encourage people taking medication for ADHD to monitor and record their adverse effects, for example, by using an adverse effect checklist.
* Consider using standard symptom and adverse effect rating scales for clinical assessment and throughout the course of treatment for people with ADHD. (Conners et cetera)
* Ensure that children, young people and adults receiving treatment for ADHD have review and follow up according to the severity of their condition, regardless of whether or not they are taking medication.
77
height and weight monitoring
* measure height every 6 months in children and young people
* measure weight every 3 months in children 10 years and under
* measure weight at 3 and 6 months after starting treatment in children over 10 years and young people, and every 6 months thereafter, or more often if concerns arise.
* plot height and weight of children and young people on a growth chart and ensure review by the healthcare professional responsible for treatment.
78
cardiovascular monitoring
* Monitor heart rate and blood pressure and compare with the normal range for age before and after each dose change and every 6 months.
* Do not offer routine blood tests (including liver function tests) or ECGs to people taking medication for ADHD unless there is a clinical indication.
* If a person taking ADHD medication has sustained resting tachycardia (more than 120 beats per minute), arrhythmia or systolic blood pressure greater than the 95th percentile (or a clinically significant increase) measured on 2 occasions, reduce their dose and refer them to a paediatric hypertension specialist or adult physician.
* If a person taking guanfacine has sustained orthostatic hypotension or fainting episodes, reduce their dose or switch to another ADHD medication.
79
other ADHD concerns and what to monitor
```
Tics – if stimulant induced switch to atomoxetine, guanfacine or clonidine
Sleep – monitor e.g. with sleep diary.
Sexual dysfunction (atomoxetine – switch )
Epilepsy (stop, review, gradual re-introduction)
Worsening behaviour (Monitor the behavioural response to medication, and if behaviour worsens adjust medication and review the diagnosis.)
```
80
other pharmacological agents (non-stimulating) is used in ADHD?
TCA’s (Imipramine) at 1mg/Kg ~ lower dose, faster onset (3-4 days) than for depression
Clonidine : slight +ve effect on hyperactive behaviour, no / little effect on cognitive performance.
Risperidone: some effect versus hyperactivity but risk:benefit ratio not favourable. NOT recommended by NICE
Buproprion: A Noradrenaline and Dopamine re-uptake inhibitor
Modafinal: A psychoanaleptic – centrally-acting sympathomimetic
81
adults and ADHD?
Adults with ADHD are more likely to have been arrested, to be divorced or separated, have been diagnosed with a Sexually Transmitted Disease and be unemployed.
Approximately 40%-60% of parents with ADHD will have a child with ADHD.
25% of children with ADHD will have a parent with the disorder.
82
name stimulants medication for ADHD?
(Lis-)Dexamfetamine (dopamine re-uptake blockade, presynaptic release)
Methylphenidate (dopamine re-uptake blockade)
83
name non-stimulant medication for ADHD?
Atomoxetine(noradrenaline re-uptake inhibitor)
Guanfacine (alpha 2Aagonist) – modulates signalling in the pre-frontal cortex and basal ganglia through modification of direct synaptic noradrenaline transmission via alpha 2Aagonist receptor agonism.
84
what is ADHD?
ADHD is associated with dysfunctional cortico-striatal-thalamic-loops.
Results in dysfunction of catecholamine transmission – Noradrenaline and Dopamine.
Delayed brain growth, smaller basal ganglia, cerebellum and frontal lobes have all been detected on MRI scans on patients with ADHD.
85
adverse effects of stimulants?
Appetite suppression, weight, irritability, anxiety, sadness, tics, headaches, sleep disorders, dysphoria, BP changes (hypertension most likely)
Non-stimulants:
Dizziness, drowsiness, dyspepsia, decreased appetite, hypotension, bradycardia
86
monitoring patients on ADHD medication ?
Monitor efficacy – use accepted rating scale;
Conners rating scale.
Monitor growth – i.e. height, weight and BMI, sleep charts, cardiac function (care with Guanfacine re; QTc2 prolongation)
NB: Be alert to the potential for rare psychotic ADRs – hallucinations, mania-type symptoms. These almost universally occur with the stimulants only – and then only rarely - visual hallucinations (formication) most often reported.
87
what are the common prescribing errors
Failure to increase dose slowly until no further improvements are noted or ADRs are manageable
Beginning with an initial dose that is too high.
It is often observed in clinical practice that the duration of effect is either longer or shorter than that reported in the literature (SPC et cetera)
88
what special consideration when prescribing for adolescents and adults?
* See adolescents alone
* Tailor treatment to their needs, their concerns.
* Review: ADRs, signs of overmedication and under medication;
* Drug : drug interactions
* Driving risks
* Sexual behaviour risk taking
* Empower adolescents – give them more control over their treatment
* When prescribing stimulants – short amounts often is the best defence versus misuse / diversion.
89
what are the co-morbid psychiatric problems associated with ADHD?
Affective (mood) disorders:
Major Depression:
treat the most impairing order first. Moderate to severe depression – pharmacological interventions is first line. Consider risk of suicidality, suicidal ideation, akathisia with SSRIs, SNRIs
With dysthymia, mild depressive disorder – treat ADHD first – mood may then improve
(Consider bupropion and desipramine; may reduce ADHD symptoms but with a reduced effect size c.f. psychostimulants.)
Bipolar Disorder:
Treat bipolar disorder. Treatment of ADHD can be offered when Bipolar Disorder is stabilised – refer to specialist. Pharmacological treatment of BPAD is complex, various sub-set presentations exacerbate the complexity – refer to BPAD presentation
Anxiety Disorders:
This would include GAD, panic disorder, social phobia, OCD, PTSD
Treat the most impairing order first.
Some patients may show worsening of anxiety and some may improve. ADHD treatments can be less well tolerated in this patient population.
Note possible drug : drug interactions with medications metabolised via P450 2D6.
Start low, go slow. Consider switch to atomoxetine.
Psychotic disorders:
Treat psychotic disorders first. Note that treatment of ADHD can trigger a psychotic relapse in a predisposed patient.
Stable patients who are in remission (from psychosis) may benefit from ADHD treatment.
90
define Bipolar affective disorder: BPAD
Previously known as Manic Depression
• Diverse ~ variety of presentations
• Recurrent ~ relapsing / remitting
• Life-long ~ treatments provide control not cure
Patient experiences mood disturbances at opposite ‘poles’ ~ Mania / Hypomania
Versus
Depression
91
what is the progression of BPAD?
• Manic episodes last 2 weeks - 4 months
• Depressive episodes may last from 6 -12 months
• Manic episodes occur less frequently than depression
• Patient may return to normality between polar swings
Mania does not always = euphoria
92
name the 2 classifications of BPAD?
Bipolar 1: (Classic mania)
• Mania predominates
• Usually one or more depressive episodes
• Characterised by one or more manic (or mixed affective state) episodes
Bipolar 2:
• Depression dominates
• Usually one or more major depressive episodes accompanied by at least one hypomanic episode
93
what is acute mania in BPAD
Acute mania has a relatively short time course
In Mixed Affective Disorder the pt experiences rapid alternation or co-existence of manic + depressive symptoms
Rapid Cycling is when 4 episodes are experienced in 12 months
Unipolar depression is when pts experience depression only (MDD)
94
what is manic episode in BDAD?
Manic episodes are less fully understood.
Postulated that mania is due to: Hyperdopaminergic state ~ hence efficacy of Dopamine Antagonists.
Depletion of the inhibitory NT Gamma -Amino Butyric Acid (GABA).
95
how is the brain structured different in people who have BPAD?
Neuro-anatomical changes are detected in Post-Mortem studies:
Pts with BPAD and Unipolar depression have subtle structural deficits in areas of the brain (Medulla Oblongata).
BPAD patients have a greater concentration of neurones in the Locus Coeruleus than Unipolar patients. Significance??
Locus coeruleus neurones are in part responsible for arousal and alertness
Locus coeruleus neurones, via meso-limbic projections, have a role to play in motivation, drive and response to stress.
Increased LC neurones in BPAD patients may account, in part, for symptoms of mania / hypomania.
96
what are the clinical features in patients who have BPAD?
Diagnosis: essential to use a categorised system, establishing presence or absence of recognised clinical features
- Distinct period of abnormal mood for > 7/7.
Euphoric, Expansive or Irritable with 3 or more associated features present to a significant degree:
Increased: self-esteem/grandiosity, speech, activity / psychomotor agitation, flight of ideas/ racing thoughts ‘pleasure but no pain’
-Reduced:
• Need for sleep,( this is the perception of patients not the physiological reality.)
• Ability to concentrate.
Marked social / occupational impairment
Psychotic features ~ mood congruent (c.f. depression)
97
what symptoms of depression is used to diagnose BPAD?
• Depressed mood
• Anhedonia
• Weight loss / gain… or decrease / increase appetite.
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness or excessive, inappropriate guilt.
• Diminished ability to think or concentrate or indecisiveness.
• Recurrent thoughts of death or suicidal thoughts, or a suicide attempt.
Sx must be severe enough to cause significant distress or impairment in social, occupational or other areas
98
why are rating scales used in BPAD?
Scales should be valid, sensitive and reliable.
Rating scales should be used to confirm a diagnosis.
To measure objectively, the response to treatment.
To identify and evaluate side effects of medication administered.
To inform patients and carers about their treatment and progress.
Can also be of great value in audit, research, E&T etc
99
what are the appropriate scales used for BPAD?
* Mood Disorder Questionnaire (MDQ.)
* Young Mania Rating Scale (YMRS)
* Montgomery Asperg Depression Rating Scale (MADRS)
100
what is the morbidity and mortality for patients with BPAD?
In a 12 yr follow up, pts with BPAD were found to be symptomatic for almost half of their lives (47%).
Most common complaint at this time was depression (32%)
Mania or Hypomania (9%)
Rapid cycling or mixed episodes (6%)
101
what are the causes for increased morbidity and mortality in BPAD?
* Possible self–neglect
* Accidental death
* Suicide ~ Mixed Affective Disorders are noted to be the most disabling and have the highest suicide rate of all sub sets of BPAD.
* Lifetime risk of death by suicide in BPAD estimated at 19%
102
what is the QoL in patients who have BPAD?
* BPAD classically follows a pattern of stability followed by relapse.
* Quality of Life is reduced even when post symptomatic and in remission.
* A review from 2003 confirmed the above finding, revealing that asymptomatic patients experienced significant impairment in functioning and well-being.
103
what is the treatment for BPAD?
It must first be understood that there is no cure for BPAD ~so, the aims of treatment:
• Control of both manic + depressive symptoms
• Minimal side effects + enhancing compliance
• And, ultimately, preventing relapse
104
what are the main treatment for BPAD?
Firstly, what are we trying to attain?
• Stability from mood enhancement / depression : Prophylactic agents (preferred term) required ~ Lithium, Valproate.
• If manic / hypomanic then Anti-manic agents are required ~ Antipsychotics, BDZ’s, Lithium
• If depressed then antidepressants should be initiated ~ follow NICE guidelines.
105
what is the treatment of acute mania or hypomania in BPAD?
Step 1:
Start antipsychotic ~ haloperidol, olanzapine , quetiapine, risperidone.
Hypomania in a pt not receiving prophylactic agents:
Start valproate*, or lithium. Consider adding BDZs
Mania or Mixed Affective Disorder:
Optimise prophylactic agent, start antipsychotic.
In all patients antidepressants MUST be WITHDRAWN.
Also, consider caffeine, medications and substances of abuse.
Step 2:
Add benzodiazepine ~ relaxant, hypnotic, anxiolytic, can also raise seizure threshold.
Examples: Lorazepam up to 4mg/day (available as PO tabs and IM)
Clonazepam up to 2mg/day ( tabs and IV)
Step 3:
Consider other antimanic agents + strategies
Aripiprazole, clozapine, gabapentin, lamotrigine, phenytoin, topiramate ~ refer to Maudsley Prescribing Guidelines.
NB: We are now firmly ‘off-licence.’
106
what monitoring is required of acute mania or hypomania in BPAD?
For all agents always: balance of efficacy versus tolerability
Assess objectively using rating scales whenever appropriate.
Lithium and Valproate have TDM requirements.
107
lithium profile for BPAD?
Lithium: range: 0.4-1.0mmol/L
t1/2 = 24 hrs ~ Cpss after 5 days.
Take sample 12 hrs post dose
Also, monitor: Renal function, Thyroid, FBC
Some drug interactions are clinically significant, e.g. avoid NSAID’s
Liquid, tablets and caps available.
108
valproate profile for the treatment in BPAD?
Valproate: range 50-100mg/L
t1/2 ; short ~ gets to Cpss in 5 days.
Monitor also LFT, FBC, Prolactin, Ammonia
Available as Depakote (SSV) liquid, caps , tabs, MR tabs.
Not for use in women of child-bearing age. If unavoidable MUST have adequate contraceptive cover.
109
Treatment of Bipolar Depression
When compared to Unipolar Depression, the depression in BPAD is:
• More rapid in onset
• Of shorter duration
• More severe
• Neurovegetative Symptoms more likely; Hyperphagia, Hypersomnia
110
what medication should be offered if a persons BPAD becomes moderate or severe?
* If a person develops moderate or severe bipolar depression and is not taking a drug to treat their bipolar disorder, offer fluoxetine combined with olanzapine, or quetiapine on its own, depending on the person's preference and previous response to treatment.
* If the person prefers, consider either olanzapine (without fluoxetine) or lamotrigine on its own.
* If there is no response to fluoxetine combined with olanzapine, or quetiapine, consider lamotrigine on its own.
111
what should you do if a person develops moderate/severe BPAD and is already taking lithium? is there anything you can offer?
* If a person develops moderate or severe bipolar depression and is already taking lithium, check their plasma lithium level. If inadequate, increase the dose of lithium; if it is at maximum level, add either fluoxetine combined with olanzapine or add quetiapine, depending on the person's preference and previous response to treatment.
* If the person prefers, consider adding olanzapine (without fluoxetine) or lamotrigine to lithium.
* If there is no response to adding fluoxetine combined with olanzapine, or adding quetiapine, stop the additional treatment and consider adding lamotrigine to lithium.
112
what is meant by Rapid-cycling bipolar affective disorder.
Rapid-cycling bipolar affective disorder.
(Arbitrarily) Defined as BPAD in which 4 or more episodes of (hypo) mania or depression have occurred in any 12 month period.
Less responsive to drug treatment c.f. non-rapid cycling BPAD
113
what is the 4 step approach of treating Treatment strategies for Rapid-Cycling BPAD
Step 1: Withdraw antidepressants.
Step 2: Evaluate possible exacerbating factors or ‘triggers’.
Examples range from erratic compliance to (excessive) use of illicit drugs such as psychostimulants (e.g. Amphetamine)
Step 3: Optimise prophylactic agent
If necessary, response still sub-optimal then try combinations of prophylactics. (Lithium is considered to be less effective in rapid cycling.)
Step 4: Here are some treatment options. Please note that the evidence base is not extensive. This is a notoriously difficult sub-set of BPAD to treat.
* Clozapine (usual dosing)
* Lamotrigine (up to 225mg/day – Levels can be taken)
* Levetiracetam (up to 2000mg/day)
* Nimpodipine (180mg/day)
* Olanzapine (usual doses; 5-20mg)
114
For all the above treatment options consider patient factors as there is no comparative efficacy data available. This is highly specialised area with no firm evidence base.
* Quetiapine (300-600mg/day)
* Risperidone (up to 6mg/day)
* Thyroxine (150mcg-400mcg/day)
115
what does NICE guidelines say for the treatment of mania
• Haloperidol, olanzapine, quetiapine and
risperidone are the antipsychotics of
choice for the treatment of mania.
• Fluoxetine is the recommended antidepressant in treating bipolar depression, in combination with the SGA olanzapine or quetiapine. If no response or patient prefers – offer olanzapine (on its own) or lamotrigine.
116
what does NICE guidelines say about lithium
```
Lithium is the most effective long-term
option for bipolar disorder and should be
used as first-line treatment.
Lithium levels should be measured every
six months after one year of monitoring.
```
117
what type of people are at high risk when taking lithium for the treatment of BPAD?
Older patients.
Patients taking medicines that interact
with lithium.
Patients at risk of impaired renal or thyroid function.
Hypercalcaemia.
Patients with poor symptom control / patients with
poor adherence.
Patients whose last plasma lithium level was 0.8mmol/l
or higher.
118
what is meant by OCD?
Compulsive acts (or rituals) are stereotyped behaviours that are repeated again and again. They are not inherently enjoyable, nor do they result in the completion of inherently useful tasks. Their function is to prevent some objectively unlikely event, often involving harm to or caused by the patient, which he or she fears might otherwise occur. Usually, this behaviour is recognised by the patient as pointless or ineffectual and repeated attempts are made to resist. Anxiety is almost invariably present. If compulsive acts are resisted the anxiety gets worse.
119
what are the essential features recurrent obsessional thoughts or compulsive acts
recurrent obsessional thoughts or compulsive acts.
Obsessional thoughts are ideas, images or impulses that enter the patient’s mind again and again in a stereotyped form.
These are distressing and the patient tries , unsuccessfully, to resist them. They are, however, recognised as his or her own thoughts, even though they are involuntary and often repugnant
120
DSM-V in OCD?
The presence of repetitive, intrusive thoughts and / or compulsions that are felt to be unreasonable or irrational and that interfere significantly with function or cause marked distress.
Compulsions are designed to neutralise or prevent some dreaded event.
121
OCD often occurs alongside other disorders (co-morbidities)?
* Depression*
* Tic disorders
* Anxiety disorders*
* Social phobias*
* Schizophrenia
* BPAD*
* ADHD
122
placebo referenced efficacy in adulthood OCD has been established for:
* Fluvoxamine
* Fluoxetine
* Sertraline
* Paroxetine
* Citalopram
* Escitalopram
123
name pharmacological interventions for OCD
| SSRIs
* fluoxetine
* fluvoxamine
* paroxetine
* sertraline
* citalopram
124
what advise should a healthcare professional say to the patient both verbally and in writing?
* craving and tolerance do not occur
* discontinuation/withdrawal symptoms may occur on stopping the drug, or missing or reducing doses
* there is a range of potential side effects (including worsening anxiety, suicidal thoughts and self-harm) that need to be carefully monitored, especially in the first few weeks of treatment
* onset of effect is commonly delayed for up to 12 weeks (although depressive symptoms improve more quickly)
* taking medication should not be seen as a weakness.
125
when should you consider Clomipramine for the treatment of OCD?
Consider clomipramine when:
• an adequate trial of at least one SSRI was ineffective, or
• an SSRI was poorly tolerated, or
• the patient prefers clomipramine, or
• there has been a previous good response to clomipramine.
For people at significant risk of cardiovascular disease:
• carry out an ECG and a blood pressure measurement before prescribing clomipramine.
For people at significant risk of suicide:
• prescribe only a small amount of clomipramine because of its toxicity in overdose
• monitor the patient regularly until risk has subsided.
126
what of the following should not normally be used without comorbidity in the treatment of OCD?
• Tricyclic antidepressants (except clomipramine)
• Tricyclic-related antidepressants
• SNRIs (including venlafaxine)
• MAOIs
• Anxiolytics (except cautiously for short periods to counter early activation of SSRIs).
Antipsychotics as monotherapy should not normally be used for OCD
127
what monitoring should be done for people with OCD?
• Be aware of the increased risk of drug interactions when prescribing SSRIs if the patient is using other medication.
• For adults who are not considered to be at increased risk of suicide or self-harm, monitor closely and see them on an appropriate and regular basis (agree this with the patient and record in the notes).
For people at high risk of suicide:
• prescribe a limited amount of medication
• consider, particularly in patients with comorbid depression, additional support such as more frequent direct contacts with primary care staff, or telephone contacts, especially in the first few weeks of treatment.
• Around the time of dose change, monitor for any new symptoms or worsening of the condition.
• If marked and/or prolonged akathisia*, restlessness or agitation develop, review use of the drug. Change to a different SSRI if the patient prefers.
* Consider recent reports and recommendations re; use of SSRIs in adolescents, young adults
128
what is the monitoring risk for people with OCD
Actively seek out (particularly in initial stages):
• signs of akathisia or restlessness
• suicidal ideation
• increased anxiety and agitation.
• Advise patients to seek help promptly if these are at all distressing.
• Monitor carefully and frequently because of increased risk of suicide and self-harm (particularly in early stages of SSRI treatment):
• adults younger than 30 years
• people with comorbid depression
• people at increased risk of suicide.
• Consider involving family/carers, where appropriate, until risk is not significant. Agree arrangements for monitoring with patient and record in notes.
129
what to do if no response to treatment of SSRIs in OCD?
Non-response to SSRIs
If there has been no response to a full course of SSRI treatment, check that:
• the patient has taken the drug regularly and at the prescribed dose
• there is no interference from alcohol or substance use.
• If there has not been an adequate response to a standard SSRI dose and there are no significant side effects at 4–6 weeks:
• consider a gradual dose increase in line with the summary of product characteristics.
– Dose increase rate should take account of therapeutic response, adverse effects and patient preference.
– Warn patients about and monitor for side effects during dose increases.
130
what to do if no response to the treatment of clomipramine in OCD?
If effective, continue treatment for at least 12 months to prevent relapse and allow for further improvement.
Review continued use of the drug with the patient 12 months after remission (symptoms are not clinically significant and the patient is fully functioning for at least 12 weeks).
Consider:
• the severity and duration of the initial illness
• the number of previous episodes
• the presence of residual symptoms
• concurrent psychosocial difficulties.
• If continued beyond 12 months after remission, regularly review the need for continued treatment, agree this with the patient and record in the notes
131
what to do if discontinuing SSRIs and clomipramine in the treatment of OCD?
Discontinuing treatment with SSRIs
• When reducing or stopping SSRI treatment, taper the dose gradually over several weeks, according to the patient's need.
• Take account of the starting dose, drug half-life and particular profile of adverse effects when determining rate of reduction.
• Encourage the patient to seek advice if they experience significant discontinuation/withdrawal symptoms.
Discontinuing treatment with clomipramine
• Reduce the dose gradually to minimise potential discontinuation/withdrawal symptoms.
132
what is the paediatric market and what is the ages for each category?
* Pre-term newborn infants
* Term newborn infants, neonates (0-27 days)
* Infants and toddlers (28 days – 23 months)
* Children (2 – 11 years)
* Adolescents (12 – 16 years)
* Widely varying needs
133
what dosage forms are used for preterm and neontes?
```
• Drug administration
by injection
• Suppositories
• Enteral feeding tube
e.g. nasogastric
```
134
Enteral feeding tube drug administration Potential problems
• Physical/chemical interactions with feeds/other drugs
• Interaction with delivery device
– Possible decreased serum drug concentrations
• Amiodarone [1]
• Certain PPIs [2] - omeprazole most variable
135
what is the most appropriate dosage form for infants?
* Drugs administered via oral route by syringe or added to drink
* Liquids
* What types of formulations can these be?
* Solutions and suspensions
136
what is the most appropriate dosage form fro children?
• Liquids
• A few studies show children around age 6 can swallow tablets
• 91% of 6-11 year olds [3]
• Depends on:
– Size & shape of tablet
– Taste of alternative – some children may have a delay in their ability to swallow tablets
– Delayed in certain conditions
137
A licensed drug is used off-label when it’s used:
* By an unlicensed route
* Lorazepam injection given orally
* For an unlicensed indication
* Sildenafil for pulmonary hypertension
* At an unlicensed dose
* Salbutamol nebules up to 60 mg/day in children
* Haven’t done clinical trials in children
* Outside stated age limits
* Diazepam rectal solution not licensed for children under 1 year
* Contraindicated in children
* Aspirin used in some cardiac patients
138
Unlicensed medicines include:
* Unlicensed dosage form (DF)
* Crushing tablets
* Unlicensed drug
* Novel medicines
* Imported medicines
139
what manipulation methods can be used in adult dosage forms?
* Crushing tablets
* Opening capsules and mixing the content with food or drink
* Halving or quartering tablets
* Diluting concentrated liquid preparations
* Cutting or ‘halving’ suppositories
140
what are the varying needs?
• Pharmacokinetic variations with age
• Potentially different doses for different ages. Absorb and metabolise differently of different age groups
• Dose calculated based on body mass or body surface area
– Leads to requirement of measurable doses
• What does this mean? How can it be achieved?
– Leads to taste issue
• Formulation preferences for different ages and abilities
141
how can the needs be met of varying needs?
```
• Range of dosage forms
– Age
– Ability
– Condition
• IV injection/infusion– seriously ill
• Oral dosage forms - chronic, less serious illness
• Dosage forms for other routes – buccal, nasal, transdermal, rectal
• Range of strengths or concentrations
• Correct age-related dose
• Liquid formulations
• Can be given to a broad age group
• Pharmaceutically challenging
```
142
16 types of oral paediatric formulations
```
Ready to use
solution
syrup
suspension
tablet/scored tablet/chewable tablet
orally-disintegrating tablet
thin strip (OTC)
```
143
what formulation requires manipulation?
powder or drops for reconstitution to susp.
conc soln for dilution
effervescent tablets
bulk oral granules or powder
solid in a capsule to mix with food or drink
144
How can widely different needs of paediatric population be met?
* Range of dosage forms
* IV – seriously ill
* Oral route - chronic, less serious illness
* Other routes – buccal, nasal, transdermal, rectal
* Range of strengths or concentrations
* Liquid formulations
* Pharmaceutically challenging
145
Rarely commercially viable
Paediatric practice requires a range of dosage forms that are acceptable at different ages and abilities and a range of strengths or concentrations allowing administration of correct age-related dose.
Seriously ill will req IV and prefer this to multiple IM inj.
Less seriously ill and for long term illness, oral route preferred but other route such as buccal, nasal, transdermal and rectal can be useful in certain circumstances.
Development of multiple dosage forms is rarely commercially viable.
Liquid formulations – which can be given to a broad age group – present particular pharmaceutical challenges.
Many drugs taste bitter and masking this can be costly and may not be achievable.
146
Regulatory incentives required for the Pharmaceutical Industry
* Aim to encourage pharmaceutical companies to consider paediatric population during two time periods.
* Throughout drug development
* During marketing
146
Regulatory incentives required for the Pharmaceutical Industry
* Aim to encourage pharmaceutical companies to consider paediatric population during two time periods.
* Throughout drug development
* During marketing
147
what are the clinical challenges for medication?
Clinical challenges
• Pharmacokinetic variations with age
– Potentially different doses for different ages
– Dose calculated upon body mass or body surface area
• Requirement of measurable doses
• Taste issues
• Formulation preferences for different ages
148
what considerations for children when making a liquid formulations in terms of taste?
* Sweetness
* Brightly coloured
* Aroma important
* Smooth texture
149
ages and ability of different dosage formulations?
* Small volume liquids
* Younger children
* Liquids/melt formulations
* Most ages
* Tablets/capsules
* Adolescents/school age
* IV injection/infusion
* Seriously ill
150
tablets and capsule consideration for different ages
* Age
* Avoid inhalation and choking
* School age
* Easier and cheaper than liquid medicines
* To develop, manufacture, transport, store and dispense
* Different types
* Melts, chewable, oro-dispersible, melts
* Technically possible to produce an appropriate tablet for most ages - but at a cost
151
what is the ideal properties of medication used in the treatment
```
• Longer duration of action
• Not potentially addictive
• Ease of administration
• Absence of ‘rebound’ effects
• No effect on appetite, growth
• Rapid onset of action
• Effective in treating associated symptoms
~ depression, anxiety etc
• Dissipates rapidly - hence will not induce insomnia
```
152
Why have long-acting formulations of MPH been developed?
• short half-life of MPH (2.5 h children)
• varied issues associated with
– multiple daily dosing of immediate-release MPH formulations
• social stigma
• reduced adherence
• inconvenience
• security issues associated with controlled substances in the school or workplace)
153
names of Methylphenidate HCl modified release
* Xaggitin XL tablets
* Concerta XL tablets
* Equasym XL capsules
* Delmosart modified-release tablets
* Medikinet XL capsules
* Matoride XL tablets
* Xenidate XL tablets
* Ritalin-SR tablets
154
Concerta XL tablets
• consist of an immediate-release component (22% of the dose) and a modified-release component (78% of the dose)
155
• Equasym XL capsules
• consist of an immediate-release component (30% of the dose) and a modified-release component (70% of the dose)
156
• Medikinet XL capsules
• consist of an immediate-release component (50% of the dose) and a modified-release component (50% of the dose)
157
counselling points of Concerta XL tablets 18 mg
* Counselling
* Tablet membrane may pass through gastro-intestinal tract unchanged
* Note
* Total daily dose of 15 mg of standard-release formulation is considered equivalent to Concerta® XL 18 mg once daily
158
mechanism of action of Concerta XL tablets 18 mg
3 layer system
- When drank with water osmotic material occurs which causes the drug to swell and starts to push the drug out of the drilled hole to allow for immediate release.
- Yellow bit is the immediate release dose which is drug gets released. Has a semi permeable membrane to allow water to enter.
159
can Concerta XL tablets be crushed?
- No because you wouldn’t get the modified release over a long period of time and instead you will get an overdose due to the drug being released all at once
160
Ritalin LA - Spheroidal Oral Drug Absorption System (SODAS) MoA
- When you open the capsule lots of granules and in the middle is the drug with different layers of coating to release the drug at different rates will give you the sustained release
161
when is Equasym XL capsules be given?
* Equasym XL should be given in the morning before breakfast.
* The capsules may be swallowed whole with the aid of liquids, or alternatively, the capsule may be opened, and the capsule contents sprinkled onto a small amount (tablespoon) of apple sauce and given immediately, and not stored for future use. Drinking some fluids, e.g. water, should follow the intake of the sprinkles with apple sauce. The capsules and the capsule contents must not be crushed or chewed.
162
Bipolar disorder
• Lithium carbonate (250 mg IR)
• Camcolit tablets MR 400 mg (NL in children)
• Liskonum tablets MR 450 mg
• Priadel MR 200 mg, 400 mg
• Lithium citrate tetrahydrate
– not licensed for use in children
• Li-liquid 509 mg/5 mL (509 mg equiv. to 200 mg LiCO3)
• Priadel liquid 520 mg/5 mL (520 mg eq. to 204 mg LiCO3
163
Matrix tablets
• Lipid excipient to provide prolonged release e.g. glycerol distearate in Priadel prolonged release
• Role of other excipients – see SPC
– Water soluble drug
– other excipients to draw in water/break up tablet
