spectrum disorder Flashcards
what is the annual incidence of bipolar disorder
Bipolar presents in a variety of ways and is recurrent; treatment provides control but not a cure. Lifetime incidence is 1% and annual incidence is 4,500. Bipolar usually presents under 30.
what are the different sub categories of bipolar disorder
Acute mania – episode runs over a short course
Mixed affective disorder – manic & depressive episodes occur simultaneously, or within a short space of time
Rapid cycling – 4 episodes experienced in 12 months
Unipolar depression – only depression experienced
how long does mania last for
episodes can last 2 weeks-4 months, occurring less frequently than depression
what is meant by hypomania
elevated mood, but not quite manic state normal affect
how long does depression last
episodes may last 6-12 months
what is meant bye depression
Depressive episodes are associated with the disruption of noradrenaline, dopamine, serotonin & glutamate systems.
what are manic epsisodes due to
Manic episodes may be due to a hyperdopaminergic state, depletion of GAGA & excess of glutamate.
those who have bipolar disorder have an increased concentration of what?
Those with bipolar have a greater concentration of neurons in the Locus Coeruleus, responsible for arousal/ alertness and, via mesolimbic projections, have a role to play in motivation, drive and response to stress.
what is meant by bipolar 1
Characterised by at least one manic episode and one or depressive episodes, where manic episodes dominate. Affect both sexes equally.
what is meant by bipolar 2
Characterised by one or more major depressive episodes, accompanied by at least one hypomanic episode - depressive episodes dominate. The risk of suicide is highest during depressive episode. Higher prevalence in females.
what is meant by bipolar 2
Characterised by one or more major depressive episodes, accompanied by at least one hypomanic episode - depressive episodes dominate. The risk of suicide is highest during depressive episode. Higher prevalence in females.
how do you diagnosis bipolar disorder
•Distinct period of abnormal mood for more than 7 days
•Depressive symptoms: Lowered mood, anergia (abnormal lack of energy), anhedonia (loss of capacity to experience pleasure i.e. where pleasure was previously felt in a certain activity, pleasure is no longer found), weight changes, insomnia, suicidal ideation
•Manic symptoms: euphoric, expansive or irritable, with 3 or more associated features present to a significant degree:
oIncreased self-esteem
oGrandiosity
oIncreased, aberrant speech
oPsychomotor agitation/ overactivity
oFlight of ideas/ racing thoughts
oPleasure seeking
oReduced need for sleep – this is the perception of patients, not the physiological reality
oReduced ability to concentrate
what are the rating scales
Rating scales can be used to confirm diagnosis, asses severity, establish a baseline and monitor a response to treatment.
- Mood Disorder Questionnaire (MDQ.)
- Young Mania Rating Scale (YMRS)
- Montgomery Asperg Depression Rating Scale (MADRS)
what is the prognosis of bipolar disorder
In a 12-year follow up, patients with BPAD were found to be symptomatic for almost half of their lives (47%); the most common complaint at this time was depression (32%); mania or hypomania was reported in 9% of patients.
Mortality is high, due to the likelihood of self-neglect, accidental death via risk-taking behaviour. 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%. Annually, around 0.4% of patients with BPAD commit suicide; international average suicide rate of 0.017%.
what is the treatment of bipolar disorder
There is no cure for BPAD; the aim of treatment is to manage symptoms of mania & depression, preventing relapse, and to minimise side effects to enhance compliance.
what is the first line treatment for bipolar disorder
lithium
what is the concentration of lithium given for the treatment of bipolar disorder
• 0.4–1.2 g PO OD or BD. Adjust dose according to serum-lithium concentration, doses are initially divided throughout the day, but OD administration is preferred when serum-lithium concentration stabilised (0.4 and 1 mmol/L).
describe how lithium works in the treatment of bipolar disorder
• Interacts with the transport of monovalent or divalent cations in neurons. Lithium has been shown to change the inward and outward currents of glutamate receptors (especially GluR3), acting to keep the amount of glutamate active between cells at a stable, healthy level
what are the side effects of lithium in the treatment of bipolar disorder
• Tremor, muscle weakness, nausea/vomiting, increased urination, excess thirst
what should you do if there is signs of toxicity in lithium in the treatment of bipolar disorder
• Signs of toxicity require withdrawal of treatment and include increasing gastro-intestinal disturbances (vomiting, diarrhoea), visual disturbances, polyuria, muscle weakness, fine tremor increasing to coarse tremor, CNS disturbances (confusion and drowsiness increasing to lack of coordination, restlessness. With severe overdose, seizures, cardiac arrhythmias (including sino-atrial block, bradycardia and first-degree heart block), blood pressure changes, circulatory failure, renal failure, coma and sudden death reported.
what are the interactions associated with lithium for the treatment of bipolar disorder
• Lithium may enhance the neurotoxic effect of TCAs and antipsychotic agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Lithium may enhance the adverse/toxic effect of Tramadol. The risk of seizures may be increased and serotonin syndrome risk. NSAIDs may increase the serum concentration of Lithium. Opioid Agonists & SSRIs: serotonin syndrome. Sodium Chloride (salt): May increase the excretion of Lithium. Caffeine may decrease the serum concentration of Lithium.
what should be monitored when a patient is taking lithium for the treatment of bipolar disorder
• Renal and thyroid function should be monitored, and blood tests should be taken to monitor serum lithium levels – taken 12 hours after dose.
what are the contraindications of lithium in the treatment of bipolar disorder
- Care should be taken in elderly, impaired renal/thyroid function, poor symptom control/adherence, high plasma lithium level
- Lithium causes heart defects in foetus if given during pregnancy (Ebstein’s anomaly)
what is the dose for valproate
• 1–2 g daily; therapeutic plasma conc of 30-100 μg/mL. To prevent major seizures, valproate should not be discontinued abruptly, as this can precipitate status epilepticus
how does valproate work
• Na+ channel blocker & reduces T-type Ca2+ channel current, preventing repetitive and sustained firing of an action potential. Downregulates the arachidonic acid (AA) cascade, stabilising mood.
what are the side effects of valproate
• May cause hepatic/ renal failure and pancreatitis. The rate of congenital malformations among babies born to mothers using valproate is about four times higher than the rate among babies born to epileptic mothers using other anti-seizure monotherapies. Hyperammonaemia (nausea, vomiting, ataxia) – ammonia levels must be monitored.
what are the interactions associated with valproate
• Antipsychotics, anticonvulsant agents interact w Valproate (CYP2D9 & CYP3A4).
when someone is diagnosed with mania what should you give them
• Antidepressants must be withdrawn.
• Give prophylactic agent.
• Start antipsychotic
o Haloperidol (2-10mg daily)
o Risperidone (initially 2mg, titrated to 4-6mg)
o Olanzapine (5-20mg daily)
o Quetiapine (initially 50mg daily, titrated to 400–800 mg daily).
o Selective D2 antagonist causes D2 blockade in the mesolimbic pathway, producing the therapeutic relief of positive symptoms. D2-receptor binding is loose, allowing for fast dissociation. SGAs also have additional receptor occupancies that give secondary therapeutic effects. 5-HT2A antagonism reduces negative symptoms & 5-HT1A partial agonism reduces negative symptoms.
o Side effects include: anticholinergic/ sedative effects, metabolic disorders, due to interference with hypothalamus (significant weight gain, hyperglycaemia, raised cholesterol/ triglyceride levels), muscarinic side effects (dry mouth, blurred vision, tachycardia, agitation, urinary retention, constipation, delirium), dizziness, orthostatic hypotension.
• Consider BDZ
o Lorazepam > 4mg daily
o Clonazepam > 2mg daily
o Benzodiazepines, bind to GABA-a receptors, induces chloride ion conduction the threshold for AP firing, increases the inhibitory effects of gamma-aminobutyric acid (GABA), such as sleep induction, hypnosis, memory, anxiety, epilepsy and neuronal excitability.
o Side effects include Drowsiness, loss of coordination, and physical dependence – if stopping BDZ therapy, gradually decrease dose.
what should you give someone who has been diagnosed with depression
- Fluoxetine (25mg nightly) & olanzapine (6mg)
- Quetiapine (400-800mg) on its own, depending on the person’s preference and previous response to treatment.
- If the person prefers, consider either olanzapine (without fluoxetine)
- Lamotrigine on its own, if there is no response to fluoxetine combined with olanzapine, or quetiapine
If a patient develops depression and they are already taking lithium, check plasma-lithium level. If plasma-lithium is at max level, same pathway as above.
what are SSRIs
- Quetiapine initially 50mg daily, titrated to 400–800 mg daily
- Fluoxetine 20-60mg nightly
- Selective inhibition of the reuptake of serotonin at the presynaptic membrane results in an increased synaptic concentration of serotonin in the CNS. The serotonin response at 5-HT1A and 5-HT2A receptors is enhanced, causing enhanced serotonergic neurotransmission.
- The therapeutic effect of SSRIs may not be seen for 4-6 weeks.
- Side effects include drowsiness, nausea, dry mouth, akathisia (restlessness), insomnia, diarrhoea & sexual dysfunction are common side effects.
- Fluoxetine has the longest washout period, of 4-5 weeks; the risk of serotonin syndrome is high during transition.
- SSRIs are substrates for CYP450 3A4 metabolic enzyme. Drugs that are metabolised by 3A4 should not be given with SSRIs, as the risk of adverse side effects increases. NSAID use with SSRIs increases the risk of GI bleeding
what is Lamotrigine
- With valproate – initially 25mg, titrated to 100mg daily
- Without valproate – initially 25mg, titrated to 200mg daily
- Inhibits Na+ currents by selectively binding to the inactivated state of the sodium channel and subsequently suppresses the release of the excitatory amino acid, glutamate.
- Side effects include aggression, agitation, diarrhoea, dizziness, drowsiness, dry mouth, fatigue, headache, irritability, nausea & vomiting, sleep disorders
- Interacts with valproate (CYP2C9)
- Carry out a full blood count, urea and electrolytes and liver function tests
what is rapid cycling
Withdraw antidepressants
Evaluate triggers (substance misuse)
Optimise prophylactic agents – lithium is less effective in rapid cycling
Commence:
- Clozapine
- Lamotrigine
- Levetiracetam
- Nimpodipine
- Olanzapine
- Quetiapine
- Risperidone
- Thyroxine
what is meant by ADHD
ADHD is a heterogeneous behavioural syndrome. Inattention and hyperactive / impulsive symptoms are commonly seen in practice with up to 6% of children meeting criteria for ADHD. ADHD accounts for 30-50% of mental health referrals among children.
what are the causes of ADHD
The exact cause of ADHD is not clear, but there is a genetic link; approximately 40%-60% of parents with ADHD will have a child with ADHD. There is increased prevalence in the following groups, indicating that neurodevelopment plays a huge part:
• Premature birth
• Epilepsy
• Brain injury
• Mood disorders
• Neurodevelopmental disorders (e.g. autism & Tourette’s)
what are the characteristics and symptoms of ADHD
The core symptoms of hyperactivity, impulsivity and inattention.
list the symptoms of inattention 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
list the symptoms of impulsivity In ADHD
- Blurts out answers before questions have been completed
- Has difficulty awaiting turn
- Interrupts or intrudes on others (butts into conversations or games)
list the symptoms of hyperactivity 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
how does ADHD affect children ?
At pre-school age, behavioural disturbances are seen. During school, behaviour disturbances are still seen alongside additional development issues: academic problems, difficulty with social interactions, self-esteem issues. During adolescence, poorly managed ADHD may, there is an increased chance of smoking and drug-taking, injury/ accidents occurring, and high-risk sexual behaviour is probable. In adulthood, ADHD may cause academic failure, occupational difficulties, relationship problems, self-esteem issues, substance abuse, injury/accidents, risky sexual behaviour.
how are the symptoms presented
While these symptoms tend to cluster together, some people are predominantly hyperactive and impulsive, while others are principally inattentive.
what are some of the co-existing psyiatril problems that exist along ADHD
There are a number of co-existing psychiatric problems that may exist alongside ADHD. In all cases, the most impairing disorder should be treated first.
• Depression – If a patient has moderate to severe depression you would treat that first; be vigilant of the risk of suicidality, suicidal ideation, akathisia with SSRIs, SNRIs. With mild depressive disorder treat ADHD first and mood may then improve
• Bipolar disorder – Treatment of ADHD can be offered when bipolar disorder is stabilised
• Anxiety disorder – some patients may show worsening of anxiety and some may improve.
• Psychotic disorders – 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
how do you diagnose ADHD
The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V) diagnoses ADHD where there is the triad symptoms of inattention, impulsivity and hyperactive behaviour that are pervasive (all aspects of living are affected), of early onset, unexplained by other disorders and resulting in impairment and disability.
The International Classification of Mental and Behavioural Disorders 10th revision (ICD-10) uses a narrower, more restrictive diagnostic category, which includes people with more severe symptoms and impairment.
The American Academy of Paediatrics (AAP)’s diagnosis is based on very specific symptoms, which must be present in more than one setting and for at least 6 months.
Conners rating scale is used to help diagnose ADHD.
ADHD is thought to be under-recognised in girls and women, since they are less likely to be referred for assessment for ADHD, may be more likely to have undiagnosed ADHD and they may be more likely to receive an incorrect diagnosis of another mental health or neurodevelopmental condition.
Symptoms of ADHD can overlap with symptoms of other related disorders, and ADHD cannot be considered a categorical diagnosis. Therefore, care in differential diagnosis is needed. Common co-existing conditions in children with 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.
describe the mechanism of ADHD
Dysfunction in the cortico-striatal-thalamic-loops leads to decreased noradrenaline dopaminergic activity. This causes delayed brain growth; frontal lobes of affected children have been shown to be 10% smaller. ADHD is actually a result of lower levels of brain functioning.
what are the non-pharmacological interventions associated with ADHD
Psycho-educational measures (such as education & advice) should be the basis of any treatment offered; parent training and Family-Centred Behavioural Therapy is proven to be effective in randomised clinical trials. Behavioural interventions (school or pre-school) are effective in reducing hyperactive behaviour and promoting social adjustment.
what are the pharmacological interventions for ADHD
Medication is used to control symptoms rather than controlling/ treating the syndrome of ADHD. Pharmacological intervention with or without behavioural therapy is the most effective at treating the core symptoms of ADHD.
Treatment is selected based on efficacy, tolerability & acceptability (patient’s lifestyle). Ideally, medications used in the treatment of ADHD should have a rapid & long duration of action, but quick to dissipate (to avoid insomnia), be easy to administrate. They should not cause addiction, rebound effects or affect appetite or growth rate.
describe the assessment for people with ADHD before starting medication
Before starting medication for ADHD, people with ADHD should have a full assessment, which should include:
• A review to confirm they continue to meet the criteria for ADHD and need treatment
• A review of mental health and social circumstances, including:
o Presence of coexisting mental health and neurodevelopmental conditions
o Current educational or employment circumstances
o Risk assessment for substance misuse and drug diversion
o Care needs
• A review of physical health, including
o a medical history, taking into account conditions that may be contraindications for specific medicines
o current medication
o height and weight (measured and recorded against the normal range for age, height and sex)
o baseline pulse and blood pressure (measured with an appropriately sized cuff and compared with the normal range for age)
o a cardiovascular assessment & an electrocardiogram (ECG) if the treatment may affect the QT interval
list the treatment pathways for ADHD
- Methylphenidate - 5-10mg daily, increased to max of 60mg daily
- Lisdexamfetamine – 30mg OM, increased to max of 70mg daily.
a. If, after 6-week trial of methylphenidate, no substantial improvement seen - Dexamphetamine – 5mg daily, increased to max of 20mg daily.
a. If symptoms are responding to lisdexamfetamine but who cannot tolerate the longer effect profile - Atomoxetine – if < 70kg: 0.5mg/kg, increased to 1.2mg/kg; if > 70kg: 40mg, increased to 80-120mg
Guanfacine – 1mg daily, increased to 0.05–0.12 mg/kg daily
a. If they cannot tolerate methylphenidate or Lisdexamfetamine
b. If their symptoms have not responded to separate 6‑week trials of lisdexamfetamine and methylphenidate, having considered alternative preparations and adequate doses
Dosing should start low and go slow – initial dose should be low, and changes to the dose should be small increments.
Common prescribing errors see a failure to increase dose slowly until no further improvements are noted or where ADRs are manageable and initiating with an initial dose that is too high.
list 3 pyscho-stimulants
Methylphenidate, lisdexamfetamine & dexamphetamine
what are pyschostimulants
Stimulants are more effective in treating hyperactivity than inattention but overactivity, attention span, impulsivity, aggression and social Interaction should all improve; social skills & general academic achievement may not improve.
They have antagonist action at norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extra-neuronal space and prolonging their action. Stimulants raise brain-functioning-activity-level to within a normal range. In addition, stimulants also activate brain inhibitory and self-organizing mechanisms, which helps focus attention and manage impulses, thus allowing the person to have greater control over his or her own behaviour.
Side effects include appetite suppression thus weight changes, irritability, anxiety, sadness, tics, headaches, sleep disorders, dysphoria, BP changes – hypertension is most likely.
list 2 non-pyschostimulants
Atomoxetine & Guanfacine
MoA of Atomoxetine
Atomoxetine is known to be a potent and selective inhibitor of the norepinephrine transporter (NET), which prevents cellular reuptake of norepinephrine throughout the brain, which is thought to improve the symptoms of ADHD.
Atomoxetine may cause sexual dysfunction.
MoA of Guanfacine
Guanfacine is an alpha2A receptor agonist which modulates signalling in the pre-frontal cortex & basal ganglia, through modification of direct synaptic noradrenaline. Because guanfacine is non-selective, it reduces sympathetic nerve impulses from vasomotor centre to the heart & blood vessels, causing decreased peripheral resistance, blood pressure & heart rate. It may prolong the QT interval. Guanfacine is not indicated in adult ADHD.
what are the side effects of non stimulants
Side effects include dizziness, drowsiness, dyspepsia, decreased appetite, hypotension, bradycardia.
what monitoring should be done for non-stimulants
• Efficacy of treatment
o Conners rating scale
Sensitive (able to detect change)
Reliable
• Growth
o Height should be measured every 6 months in children and young people
o Weight should be measured every 3 months in children < 10; every 6 months in > 10
• Cardiovascular
o Monitor heart rate and blood pressure and compare with the normal range for age before and after each dose change and every 6 months
o If a person taking ADHD medication has sustained resting tachycardia, arrhythmia or significant increase in systolic blood pressure, measured on 2 occasions, reduce dose and refer to a paediatric hypertension specialist
• Signs of psychiatric illness
what is meant by OCD
OCD is a form of anxiety, where the sufferer is compelled to repeatedly perform compulsive acts. It can affect anyone, regardless of ethnicity, age, gender or socioeconomic status. OCD was once considered rare but advances in diagnosis and treatment have led to recognition that the disorder is a major worldwide health problem. Lifetime prevalence is 1-3%.
what is the characteristics/sy,ptoms of OCD
The compulsive acts are not enjoyable, nor do they result in the completion of inherently useful tasks; their function is to prevent an irrational, unlikely event (often involving harm) which the patient fears might otherwise occur. Usually, this behaviour is recognised by the patient as pointless or ineffectual and repeated attempts are made to resist; if compulsive acts are resisted the anxiety gets worse.
The magnitude of psychosocial impairment is high, so co-morbidly is common: depression, anxiety, social phobias, bi-polar may be seen.
how do you diagnose OCD
Recurrent obsessional thoughts (ideas, images or thoughts that are constantly repeated) or compulsive acts must be seen by HCP or expressed by patient. Mean age of diagnosis ranged from 20-25 years with nearly 50% of patients reporting that their symptoms had begun in childhood or adolescence.
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a rating scale that indicates the severity of ADHD & evaluates the efficacy of pharmacological treatments.
what is the treatment pathway for OCD
Treatment pathway:
- SSRI
- Clomipramine
For those at high risk of suicide, a limited amount of medication should be supplied. Frequent contact with HCPs should be ensured, with the patient aware of crisis procedure.
list SSRI drugs and their dose strength
Citalopram 20-40mg daily
Escitalopram 10-20mg daily
Sertraline 50-200mg daily
Fluoxetine 20-60mg nightly
what is the MoA of SSRIs
Selective inhibition of the reuptake of serotonin at the presynaptic membrane results in an increased synaptic concentration of serotonin in the CNS. The serotonin response at 5-HT1A and 5-HT2A receptors is enhanced, causing enhanced serotonergic neurotransmission.
The therapeutic effect of SSRIs may not be seen for 4-6 weeks.
what is the side effects of SSRIs
Drowsiness, nausea, dry mouth, akathisia (restlessness), insomnia, diarrhoea & sexual dysfunction are common side effects.
Fluoxetine has the longest washout period, of 4-5 weeks; the risk of serotonin syndrome is high during transition.
what are the interactions associated with SSRIs
SSRIs are substrates for CYP450 3A4 metabolic enzyme. Drugs that are metabolised by 3A4 should not be given with SSRIs, as the risk of adverse side effects increases. NSAID use with SSRIs increases the risk of GI bleeding
what are the discontinuation side effects of SSRIs
- Flu-like symptoms
- Sleep disorder
- Nausea
- Poor balance
- Sensory changes
- Anxiety
SSRIs are nearly twice as likely as placebo to produce a clinical response, compared to a placebo.
when is Clomipramine used
Used when a trial of at least one SSRI failed in efficacy, tolerability or acceptability (side effects), or if there has been a previous response.
what is the dose of Clomipramine
Clomipramine 25 mg daily, then increased to 100–150 mg daily.
MoA of Clomipramine
tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells
what are the side effects associated with Clomipramine
Dry mouth or eyes, peculiar taste in mouth, sensitivity to light of the eyes, blurry vision, constipation, urinary hesitancy, and others
what do you do if you have an overdose of Clomipramine
Doses of less than 20 mg/kg are unlikely to be fatal or cause severe complications. In overdose, the following is seen:
• Sinus tachycardia, due to inhibition of norepinephrine reuptake at nerve terminals
• Prolongation of the QRS complex and the PR/QT intervals, due to inhibition of the sodium current
• Seizures/ coma
• Anticholinergic action (dry mouth, blurred vision, hyperpyrexia)
• Sodium bicarbonate is indicated for the treatment.
what monitoring should be done for Clomipramine
Remission is where a meaningful response to treatment is seen and is defined as 25-35% improvement in baseline Y-BOCS, or a score of ≤ 7. Relapse is defined as worsening of baseline Y-BOCS of ≥ 50% or a total Y-BOCS of ≥ 19.
If no response is seen, compliance should be challenged, ensuring there is no interference from substance misuse. If there are no issues relating to compliance, dose titration should commence, accounting for therapeutic response (efficacy), and tolerability.
The decision to continue treatment should be reviewed 12 months after remission has started. The decision should depend on the severity and duration of illness, number of previous episodes and presence of symptoms.
what is meant by autism
Autism 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.
Autism affects ~ 700,000 in the UK and is 4x more prevalent in men than women. 1/3 of people with a learning disability may also have autism. Asperger’s syndrome is a form of autism.
what are the causes of autism
Genetic influences are likely most important risk factor, but it is not the only cause, since in twins, one may be autistic and the other may not be. Autism is NOT related to bad parenting, food allergies, vaccines or parents with high or low intelligence.
what are the different characteristics of autism
• Social characteristics
o Understanding or functioning of facial expressions, tone of voice, eye contact & body language
o Muteness or abnormal speech
o Inappropriate social approaches to others
o Bizarre, elaborate & repetitive routines
• Social interaction
o The ability to understand the emotions of themselves and others is affected
o Aloneness, and a lack of emotional contact
o A social intelligence test scores the ability to understand emotion from people’s eyes
• Social imagination
o The ability to comprehend abstract ideas, other’s actions/ emotions/ behaviour & solutions outside the individual’s own routine is affected
o Theory of mind refers to the ability to understand the desires, intentions and beliefs of others, and is a skill that develops between 3 and 5 years of age. Those with autism do not have a fully developed theory of mind.
what are the formulation requirements for children
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.
Depending on the severity of the condition, dosage forms can be given in different ways – this is due to bioavailability of dosage form.
what drug formulations can neonates and perterms have
o Drug cannot be given via oral route, since there is an inability to swallow. As a consequence, drugs are routinely given by injection, suppositories or nasogastric feeding tube. There may be physical/ chemical interactions with feeds/other drugs, and possible decreased serum drug concentrations. So, dose adjustments have to be made. Amiodarone and certain PPIs - omeprazole most variable
what drug formulation can infants 1month-23months have
o Drugs can be via oral route, by syringe, powder/ crushed tablet added to drink or liquids (administered using a syringe, suspensions and emulsions).
what formulation can children have 2-11 years
o Drugs can be given as liquids (solutions and suspensions), and children age 6 may be able to swallow tablets. The ability to swallow depends on the size/shape of tablet, taste (acceptability). Tablets are generally easier and cheaper to develop, manufacture, transport, store and dispense than liquid medicines.
why are power ratchets, soluble tablets and chewable tablets a viable option to liquid formulations
- For seriously-ill patients, IV route is used.
- For chronic but less seriously-ill patients, oral route is used. Buccal, nasal, transdermal & rectal routes may be used if no oral dosage form is available.
how do you improve acceptability to taking medicines
To increase acceptability, avoid unusual flavours and complex taste mixtures. The most common flavourings are citrus & red berry in the UK, bubble-gum & grape in the US, liquorice in Scandinavia’s.
Children prefer a higher level of sweetness than adults – saccharin, aspartame, sucralose. Sucrose may be used but should be avoided in long term therapy.
Few dyes are available from a regulatory perspective, but children prefer brightly coloured medicines. The use of dyes should be limited use due to risk of hypersensitivity and adverse reactions.
Smooth texture is preferred; viscosity can be modified to minimize grittiness in liquid oral dosage forms.
what are specials
- A licensed drug is used off-label when it’s used by an unlicensed route, indication, dose or outside age limits.
- Unlicensed medicines include alterations to dosage form (e.g. crushing tablets), unlicensed drug or imported with no license in the UK. If there are no child-friendly formulations, adult formulations may be manipulated (e.g. crushing tablets, opening capsules and mixing the content with food or drink, halving or quartering tablets, diluting concentrated liquid preparations). Manipulating an adult formulation is problematic because the stability and dosing is not assured.
what are the stats of using specials
50 – 90% medications used in children are ‘off-label’ or unlicensed. Therefore, children are being treated in non-evidence based, unregulated fashion. Even commonly prescribed drugs e.g. short-acting beta 2 agonists and anti-pyretic have not been adequately studied in young children (Hay et al 2006)
what is the normal route when choosing a drug
- Licensed drug & licensed use
- Licensed drug & off-label use
- Unlicensed use (specials)
what does limited enrolment of trials
Limited enrolment in trials results in an inability to demonstrate efficacy and safety in all paediatric groups and sub-populations. This is due to a small number of volunteers and issues relating to the ethics of testing in healthy children. Results can be extrapolated from adults or paediatric groups of different ages, but this can lead to dangerous errors due to pharmacokinetic variations.
what are the regulatory incentives
EU Regulation on Paediatric Medicines aims to encourage pharmaceutical companies to consider the paediatric population during drug development & marketing. The objectives are to:
• increase development of paediatric medicines
• ensure medicines are subject to high quality research and appropriately authorised for use in children, improve amount of information available
• achieve the above without unnecessary trials or delaying authorising of adult drugs
how does oral formulation affect the absorption
Gastric pH is 6-7 until 20-30 months of age. Drugs must be in their unionized form to dissolve and be absorbed, therefore the higher pH increases the bioavailability of basic drugs and decreases the bioavailability of weakly acidic drugs. As a consequence,
The dose of basic drugs should be reduced until the age of 2, to avoid toxicity & overdose; the dose of acidic drugs should be increased.
Bile salt formation is decreased in until ~6 months, so bioavailability of lipophilic drugs is reduced; an increased dose is required for these drugs.
Gastric emptying & GIT motility is decreased until childhood, so there is a slower rate of absorption.
how does IM route affect absorption
Decreased blood flow, so absorption is slower. There are fewer muscular contractions, decreasing dispersion of the drug.
how does rectal route affect absorption
More pulsatile contractions, moving the suppository from the body, decreasing absorption.
how does transdermal route affect absorption
Babies & children have a larger BSA: Mass ratio. The skin is thinner, and there is a greater blood supply to the skin, so absorption is increased. As a result, systemic exposure is increased so greater side effects may be seen.
how does formulations for paediatrics affect the distribution
Neonates and infants have a higher proportion of water, compared to fat. This affects how water soluble drugs are distributed, and causes a lower plasma concentration; higher doses of water-soluble drugs are needed.
There are lower levels of albumin, so highly protein-bound drugs should be given at lower doses.
how is the metabolism affected in paediatric formulations
Rate of metabolism appears to be highly age dependent; slower for first year, exceeding adult metabolism rates during childhood, and finally attaining adult rates during adolescence.
how is elimination affected in paediatric formulations
Many drugs are renally excreted therefore functioning of the kidney largely determines how quickly a drug is cleared from the body.
eGFR increases rapidly during the first 2 weeks of life due to changes in blood flow and maturing nephrons, and continues to increase as children gets older stops increasing at around 6 years.
what are the ideal properties of ADHD medications
- Long duration of action
- Ease of administration
- Rapid onset of action
what is Methylphenidate
Methylphenidate has a short half-life, and multiple dosing poses many issues: reduced compliance, inconvenience, social stigma, security issues (CD).
what is Concerta XL capsules and how does it work
it is a modified release tablet and works by • Immediate-release component (22% of the dose)
o Outer coating is absorbed rapidly after ingestion
• Modified-release component (78% of the dose)
o Penetration of gastric fluid through the semipermeable outer membrane expands an osmotic agent in the push layer of the core, causing it to slowly force the methylphenidate contained in the core out a laser-drilled opening in the tablet over 12 hours
Total daily dose of 15 mg of standard-release formulation is considered bioequivalent to Concerta® XL 18 mg once daily
what does compliance mean
Compliance refers to whether patients take their medications as prescribed. Adherence is defined as the active, voluntary, and collaborative involvement of the patient in a mutually acceptable course of behaviour to produce a therapeutic result.
why do children not adhere to medicines
Children lack rational thinking, so cannot understand that something that tastes foul will have a long- term benefit. Liquid formulations with strawberry and orange flavours have the highest adherence rates. Liquids are also preferred to tablets, in terms of overdose risk, because the volume of liquid needed to overdose is so high, it is unlikely to be consumed.
what are the issues of liquid formulations
• Failure to shake the suspension gives an uneven distribution
• Unstable due to water activity
• Susceptible to microbial contamination
• Hard to transport
• Expensive to manufacture
• Accuracy of measuring device (syringes)
o If volume is too small, it can lead to inaccurate dosing
o If volume is too big it can lead to adherence issues
• Need for excipients – possible safety issues (e.g. the use of alcohol as a co-solvent & sucrose as sweetener)
• Taste masking
o If a product’s taste is not masked non-adherence
o If a product tastes too good risk of overdose
what % of children can take oral tablets
91% of 6-11-year-olds can take tablets.
what is the public opinion about medicines
25% of parents show negative beliefs about medicines; this causes non-adherence.
Only 50% think it is a good idea for children to learn to take tablets and only 18% think pharmacists should teach tablet-taking techniques.
what methods can improve adherence to medicines
- Masking in other foods/drinks
- Force
- Bribery (offering biscuit or sweet drink)
- Reasoning – does not work with children due to lack of rational thought
what is the role of the school
Since 1st September 2014, governing bodies have a statutory duty under the Children and Families Act 2014 to ensure schools make arrangements to support pupils with medical conditions. School staff may be asked to provide support to pupils with medical conditions, including the administering of medicines, although they cannot be required to do so. Schools should only accept prescribed medicines that are in-date, labelled, provided in the original container as dispensed by a pharmacist and include instructions for administration, dosage and storage. Medicines should only be administered at school when it would be detrimental to a child’s health or school attendance not to do so.
