Class 9-Ped Flashcards
1
Q
Gastrointestinal absorption
A
- Different gastric pH
- Unpredictable gastric emptying
- Irregular intestinal transit
- Undiversified intestinal flora
2
Q
Other routes of administration
A
- Low muscle mass àIM more painful / irregular absorption
- Good absorption under the skin
- Erratic rectal absorption (as in adults)
3
Q
Distribution
A
- Age-variable plasma proteins (e.g. less albumin affinity in newborns)
4
Q
Metabolism
A
- Immature metabolic pathways (e.g. cytochromes)
- Examples : CYP1A2 in the first months of life, CYP2D6 in the first days of life
- Once the maturity of metabolic pathways : ↑ liver activity
5
Q
Renal elimination
A
- ClCr formula not applicable for children, variation in creatinine
production by age - ↑ kidney activity
6
Q
CAN CHILDREN SWALLOW TABLETS?
Alternatives
A
- Liquid formulations (solutions, suspensions)
- Preparations at the pharmacy
- Powder, capsules
- Some drugs taste really bad… if possible mix in small amounts of puree or liquid
7
Q
ETIOLOGY ADHD
A
GENETIC
• Significant contribution (40-90%)
• If patient affected: risk increased by 2 to 8 times
- Environmental factors, e.g.:
- Low birth weight or preterm birth
- Exposure to cigarettes or alcohol during pregnancy
NEURONAL CIRCUITS
Dysfunction of several systems involving neurotransmitters, especially NA and DA
8
Q
COMORBIDITIES ADHD
A
Nearly 70% of children with the condition are reported to have another psychiatric disorder Examples : • Behavioural disorders • Anxiety • Depressive disorder • Tourette’s syndrome
9
Q
NON-PHARMACOLOGICAL TREATMENT
A
§ Interventions at school • Environnement, organisation, routine, educational help § Psychosocial interventions • Individual psychotherapy • Behavioural psychotherapy • Sports activities • Family therapy • Respite measures
10
Q
THERAPEUTIC ARSENAL ADHD
A
PSYCHOSTIMULANTS
q Methylphenidate
q Amphetamines-based
NON PSYCHOSTIMULANTS q Atomoxetine q Alpha2-adrenergic agonists q Bupropion q Tricyclic antidepressants q Antipsychotics
11
Q
NON PSYCHOSTIMULANTS onset
A
Slower onset of action than psychostimulants (2 weeks)
12
Q
METHYLPHENIDATE types
A
RitalinTM Short: BID-TID
ConcertaTM Long
BiphentinTM Long
FoquestTM Very long
13
Q
METHYLPHENIDATE MECHANISM OF ACTION
A
Inhibition of DA and NA recapture
14
Q
Why treat hyperactivity with a stimulant?
A
- Inattention is often the main problem
* Treating inattention (FOCUS) indirectly treats other symptoms
15
Q
CONCERTATM release system
A
OROS RELEASE SYSTEM
• Part of the active ingredient (22%) is released for rapid action < 1 hour
• The rest of the drug (78%) frees itself through an orifice for about 12 hours
16
Q
BIPHENTINTM release system
A
BIPHASIC RELEASE
• The capsule contains short- and long-acting granule
17
Q
FOQUEST release system
A
MLRTM TECHNOLOGY (IN GRANULES)
• Multi-layered release
• Capsule made up of multi-layered release
• 1st layer : immediate-release methylphenidate
• Other layers: act by delaying the release of the drug
18
Q
ADVERSE EFFECTS METHYLPHENIDATE
A
o ↓ appetite and weight loss o Gastrointestinal pain o Irritability o Sleep disorders o Headache o Worsening tics o ↑ heart rate and blood pressure o Long-term growth delay o Risk of abuse : risk with longacting formulations • Dose-dependent • Especially at the beginning of treatment
19
Q
AMPHETAMINES types
A
Dextroamphetamine short Amphetamine salts (Adderall) XR long Lisdexamfetamine Vyvanse long
20
Q
ADDERALL XR release system
A
CAPSULE CONTAINING 2 TYPES OF GRANULES IN EQUAL PARTS
• Immediate release granules (effect lasts 4 to 6 hours)
• Controlled-release granules (effect lasts 12 hours)
21
Q
VYVANSETM pharmacokinetic
A
INACTIVE PRO-DRUG
• Enzymatic reaction releases dextroamphetamine (active molecule)
22
Q
ADVERSE EFFECTS stimulants
A
o Decreased appetite (+) and weight loss o Gastrointestinal pain o Irritability o Sleep disorders (+) o Headache o Worsening tics o ↑ heart rate and blood pressure o Long-term growth delay o Risk of abuse : (+) vs methyphenidate • Dose-dependent • Especially at the beginning of treatment
23
Q
ATOMOXETINE duration
A
long straterra
24
Q
MECHANISM OF ACTION ATOMOXETINE
A
Inhibition of NA recapture
25
ADVERSE EFFECTS ATOMOXETINE
* Céphalées
* Douleurs abdominales
* Vomissements
* Augmentation de la tension artérielle
* Augmentation de la fréquence cardiaque
* Très faible potentiel d’abus
* Ne cause pas d’aggravation des tics
* Peu d’insomnie
26
ALPHA2-ADRENERGIC AGONISTS
Clonidine CatapresTM intermediate adjuvant only
Extended-release
Guanfacine Intuniv XRTM long
27
MECHANISM OF ACTION Guanfacine
selective alpha2A receptor agonist
28
MECHANISM OF ACTION Clonidine
non-selective alpha2 receptor agonist
29
Guanfacine used for
Used as an adjuvant with psychostimulants in complex cases or for tics or aggression comorbidities
30
SIDE EFFECTS ALPHA2-ADRENERGIC AGONISTS
```
• Headache
• Hypotension
• Drowsiness
• Xerostomy
• Bradycardia (rare)
Gradually taper to avoid the rebound hypertensive effect
```
31
TRICYCLIC ANTIDEPRESSANTS ADHD
Inhibition of NA recapture
• Sometimes used in patients with other comorbidities, including anxiety disorders, tics and depression
• Imipramine, desipramine, nortriptyline
• Lower doses than in depression
• Profile of adverse events limits their use
32
ANTIPSYCHOTICS ADHD
* Limited evidence
* Risperidone may decrease symptoms of hyperactivity and impulsivity
* Little effect on symptoms of inattention
* Negative impact on learning and cognition
33
Short-acting pros and cons
```
PROS: • PRN Use
• Supplemental doses
• Little anorexia and insomnia
Cons: • Administration BID
• Loss of effect in the
evening
• Dependence
```
34
Intermédiaire pros and cons
```
PROS: • Administration DIE
• Less anorexia and insomnia than
long-acting
• Less dependency than short-acting
CONS: • Loss of effect in the
evening
```
35
Long-acting pros and cons
```
PROS • Administration DIE
• Evening effect
• Little dependency
CONS • Morning action time
• Insomnia, anorexia at
dinner
```
36
Atomoxetine
| Bupropion pros and cons
```
Pros
• Administration DIE
• Duration of 24 hours and + if missed
dose
• Possible association with
psychostimulants
• No dependency
• No tics
Cons
• Delay of action : 2 weeks
• Less effective than
stimulants
• Drug interactions (CYP2D6)
```
37
Guanfacine pros and cons
```
Pros: • Administration DIE
• Duration of 24 hours and if dose
missed
• Possible association with
psychostimulants
• Little dependency
• Decrease in insomnia and tics
associated with psychostimulants
Cons: • Delay of action : 2 weeks
• Less effective than stimulants
```
38
At least ??? of patients respond to psychostimulants
60- and 70%
39
CHOOSING A DRUG ADHD
① Long-acting psychostimulants based on methylphénidate or amphetamines
Preschool-age :
- Methylphenidate if failure to non-pharmacological measures
School-aged children and teenagers :
- Non-pharmacological measures + psychostimulant
② Short/intermediate-acting psychostimulants, atomoxetine (StratteraTM) or extended-release guanfacine (Intuniv XRTM)
③ Others
• Bupropion, clonidine, imipramine, modafinil, atypical
antipsychotics
40
COMBINAISON? ADHD
Same molecule
• Combine a long action time (e.g. ConcertaTM) with a short action time (e.g. Ritalin SRTM) to cover certain moments of the day
Different molecules
• Only guanfacin XR is approved by Health Canada in adjuvant treatment for psychostimulants (not for adults)
• Other combinations sometimes used in practice: atomoxetine and psychostimulants
• Attention to additive effects (e.g. increase in BP/HR)
41
BIPOLAR DISORDER and ADHD
* Manic Phase: mood Stabilizers
| * If ADHD treatment is added: bupropion, atomoxetine, guanfacine
42
TOURETTE’S DISORDER and ADHD
* Psychostimulants or atomoxetine
| * If tics worsen: add clonidine or change to a non-psychostimulant
43
FOLLOW UP PSYCHOSTIMULANTS
1 week
44
FOLLOW UP NON-PSYCHOSTIMULANTS
* Longer onset of action
| * Wait at least 2 weeks
45
KEY PARAMETERS FOLLOW UP
* Weight
* Size
* Heart rate
* Blood pressure
* Appetite
* Sleep
46
WILL MY CHILD BE DEPENDANT TO DRUGS IF HE TAKES
| PSYCHOSTIMULANTS?
* ADHD (not exposure to psychostimulants) increases the risk of substance abuse and addiction
* A well-treated ADHD could reduce the risk of other substance use
* If there is a risk of substance abuse, choose a non-psychostimulant
47
BIPOLAR DISORDER – MANIC EPISODE
abilify
48
BIPOLAR DISORDER – DEP EPISODE
latuda
49
DEPRESSION
* Support, psychoeducation, implication of school/family
* If no response after a 2 – 3 months : psychotherapy or pharmacotherapy
* Fluoxetine is often a first-line choice
* Other SSRI : citalopram, escitalopram, sertraline, fluvoxamine
* More side effects with paroxetine
50
MOOD STABILIZERS
* No anticonvulsivant indicated in the treatment of BP in pediatrics
* Studies with : carbamazepine, oxcarbazepine, valproate, lamotrigine, topiramate
* Valproate and lamotrigine are often used
* Lithium recommended by CANMAT in first-line treatment
51
INSOMNIA
* Priorise non pharmacological interventions
* Antihistaminics
* Melatonine
