Pharmacological Management for Autism and ADHD 2.2.1 Flashcards
What are the drugs used for ASD?
Risperidone
Glutamatergic drugs
Oxytocin
Fluoxetine
Methyphenidate, atomoxetine (symptoms of ADHD)
Melatonin
What are the drugs used for ADHD
Dexamphetamine
Methylphenidate
Atomoxetine
Clonidine
Why are antipsychotics used in ASD?
- Psychotropic drugs cannot cure ASDs but they can reduce the severity of some symptoms.
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What drugs are used for the following core symptoms of ASD
A) Restricted repetitive behaviours and interests domain(RRBI)
B) Social and communication impairment domain
C) Inattention, overactivity & impulsiveness in ASD (symptoms of ADHD)
D) Irritability
E) Sleep disturbance
A)
- SSRI = fluoxetine
B)
- Role of risperidone, glutamatergic drugs and oxytocin
C)
- Methylphenidate
- Atomoxetine
D)
- Risperidone
E)
- Melatonin
What do all children with autism experience difficulty in?
Developing social, speech and behavioural skills.
- Behavioural therapy is usually first line treatment with pharmacological therapies added to help patients function in their daily activities
MOA of risperidone?
Antagonist – D1 and D2 receptor
5-HT2A antagonism enhances or complements D2 receptor antagonism = lower EPS incidence
Antagonism of D3, D4 and other receptors may also contribute to the favourable clinical profile of risperidone
What are the adverse effects of antipsychotics?
Adverse effects on Dopaminergic pathways
- Psychological effects (mesolimbic/mesocortical)
- Movement disorders (nigrostriatal)
- Neuroendocrine (tuberoinfundibular)
Blockade of a1 receptors
- Hypotension, reflex tachycardia
Blockade of histamine H1-receptor
- Sedation and weight gain
Anti-cholinergic effects
- Blurred vision, dry mouth, constipation, urinary retention
Adverse effects due to immune reaction
- Hypersensitivity reactions, dermatitis, rashes, photosensitivity, urticaria
Adverse effects due to individual drug
- Clozapine cause agranulocytosis - neutropenia, bone marrow depression
Idiosyncratic reaction
- Neuroleptic malignant syndrome
Most common side effects of risperidone is weight gain, increased appetite, anxiety and fatigue
What is the medical cause of ADHD?
- Genes involved in the regulation of neurotransmitter (NT) catabolism and release have been implicated
- Dopamine (DA) and noradrenaline (NA) NT systems dysfunction is important for onset, progression and tmt response
- Certain regions of brain, rich in dopamine and noradrenaline are structurally altered and functionally different
- Regions involved in visual spatial and verbal attention, working memory and impulse control = ↓ abilities in children affected with ADHD
What are the drug treatments used for ADHD?
- Psychostimulants (methylphenidate and dexamphetamine)
- Atomoxetine
- Clonidine
- TCA’s (imipramine)
- Neuroleptics
What are the psychostimulants for treatment of ADHD?
- Dexamphetamine
- Methylphenidate
How do dexamphetamine and methylphenidate help with ADHD?
Thought to be equally effective
> dexamphetamine = higher affinity for NA receptors
> methylphenidate = higher affinity for dopamine receptors
- Immediate and dramatic improvement in impulsive behaviour
- Less effective in managing aggressive behaviours
- Have similar range and incidence of adverse effects
What are the mechanism of action of psychostimulants?
↑ functional activity of DA and NA by:
- Inhibiting their pre-synaptic uptake
- Increase release of dopamine, NA & serotonin
> Help compensatory brain neural networks which promote more cognition, behaviour and emotions
> Effects are dose dependent for hyperactivity and impulsiveness.
> Attention and working memory improve at low doses but can be impaired at high doses
- Amphetamine enters the nerve terminal via the NA transporter
- Amphetamine will then enter synaptic vesicle via the VMAT (vesicular monoamine transporter) in exchange for NA
- Some NA is degraded by MAO and some escapes, in exchange for amphetamine via the NA transporter
- The released NA will act on the postsynaptic receptors
Compare dexamphetamine and amphetamines? Long or shorter doa compared to methylphenidate
Amphetamine has both dextro- and levoisomers
> Dexamphetamine - greater CNS action and less peripheral action = active dextro isomer of amphetamine
> Has slightly longer duration of effect than methylphenidate
CIR AE of Dexamphetamines?
Common
- Headache – Nausea – ↓appetite – Anxiety – Insomnia – Dry mouth – Tachycardia – Palpitations – Changes in BP (↑ adults)
Infrequent
- Movement disorders – Tics – Rash – Weight loss – Growth retardation
Rare
- Pyschosis and liver dysfunction
For methylphenidate:
A) What are its effects
B) What does large doses do
C) What are its properties
A)
- Mild CNS stimulant
- More effects on mental rather than motor activities
B)
- Larger doses can over stimulat CNS –> convulsions
- Pharmacological properties similar to amphetamine
C)
- Similar to amphetamine
- Readily absorbed –> peak plasma conc after 2 hours
- Can be taken every day of the week with a break on weekends
Why is methylphenidate controlled release formulation used? Which patients get PBS-authority?
One daily dosing for ADHD
- Eliminates need for in school and after school dosing
- Efficacy lasts for 12 hours
- Minimal potential for abuse
PBS-Authority for ADHD patients who
- have a demonstrated response to immediate release methylphenidate
- have not experience any adverse effects
- require continuous coverage over 12 hours
CIR AE of methylphenidate (similar to dexamfetamine)
Common
- insomnia – ↓ appetite = weight loss – nausea – Anxiety – Irritability – Dry mouth – Tachycardia – Palpitations – Changes in BP (↑adults)
Infrequent
- – Movement disorders – Tics – Rash – Growth retardation
Rare
- Psychosis – Neuroleptic malignant syndrome – Liver dysfunction
Precautions and contraindications for dexamphetamine and methylphenidate?
Substance abuse- CI
Active psychotic disorders- CI
Tx with or within 14 days of stopping MAOI’s-CI
Tic disorders or Tourette’s syndrome-may worsen, monitor, consider other Tx e.g. clonidine or atomoxetine.
Angina, arrhythmia,↑BP, hyperthyroidism, glaucoma, anxiety, agitation, phaeochromocytoma- may worsen __> caution especially in patients who are children, especially those on anticoagulants, anticonvulsants and TCAs
Structural cardiac abnormalities –> caution
For atomoxetine (used in ADHD)
A) What is its MOA?
B) Compare it to psychostimulants
C) Metabolism
D) Precautions
A)
- Selectively inhibits presynaptic noradrenaline reuptake in CNS
- Increase noradrenaline and dopamine in pre-frontal cortex and nucleus accumbens therefore low potential for abuse = not a psychostimulant
B)
- Longer duration of action than psychostimulants
- Subsidised by PBS for patients who cannot take psychostimulants
- Well absorbed orally
- Not possible to confirm whether atomoxetine is as efficient or as well tolerated as the psychostimulants
C)
- Metabolised by CYP2D6 in liver and excreted through the kidneys
- CYP2D6 prone to genetic polymorphism thus poor metabolisers of atomoxetine may occur
- Poor metabolisers show 4 fold ↑ in mean elimination half life
D)
- Tx with or within 14 days of stopping MAOI- CI
- Closed angle glaucoma- CI
- History of seizures-caution when starting
- Hypertension, tachycardia, cerebrovascular disease- ↑ BP and heart rate
- Structural cardiac abnormalities- assess risk factors
CIR AE of atomoxetine?
Common
– N, V – Abdominal pain – Dyspepsia – ↓ appetite – Dry mouth – ↑BP – Dizziness – Somnolence – irritability
Infrequent
Palpitations and tachycardia
Rare
– Suicidal thoughts and behaviours
– Hepatic dysfunction
Drug interactions of atmoxetine?
- Risk of serotonin syndrome when atomoxetine is administered with other drugs that raise serotonin levels.
- Thus avoid combining atomoxetine with drugs that raise serotonin levels e.g. SSRI’s
- Potent CYP2D6 inhibitors e.g. fluoxetine and paroxetine ↓ metabolism of atomoxetine
Why is imipramine used for ADHD
TCA
> third line tx for ADHD
> virtually phased out of routine practice
> increase potential for adverse cardiac effects such as cardiac arrhythmias
Why is clonidine used in ADHD? How does it work? Which patients to avoid in?
Central adrenergic alpha 2 agonist →
↓ presynaptic release of noradrenaline
Used when other options are ineffective or CI
↓ hyperactivity, impulsiveness symptoms more than inattention at low doses •
Some evidence shows improved attention at higher dose
In Australia clonidine is more commonly prescribed with a psychostimulant than alone
DONT USE IN CHILDREN WITH HISTORY OF DEPRESSION –> worsens depression
AE = dry mouth and sedation
When to use antipsychotics for ADHD?
Atypical antipsychotics e.g. risperidone and sedative antipsychotics e.g. pericyazine are of limited benefit on core ADHD symptoms
BUT they can be beneficial if there is severe aggression or irritability or affective disability
Specialist consultation is required
