L1 - L7 Flashcards
3 Features of Childhood CNS Disorder
- arising from impaired brain development / functional deficits. child’s development is slowed
- often occurs as co-morbidities and lead to substance misues
- requires treating the mind (CBT) and brain (medicines)
ASD
- Neurodevelopment disorder
- Rett’s caused by MECP2 gene
- repetitive behaviour , communication deficit , poor social skills
- 70% have co-morbid conditions (anxiety depression, ADHD)
- if normal IQ with ASD they are likely to have increased visual and math ability
ASD Treatment
- risperadone only licensed in 5 - 17 yrs
- support of individual and family
- no meds for Core Autism
unless : children with aggression give Risperidone (anti-psychotic)
- 2mg/day up to 45kg –> 3.5mg/day >45kg
- only for children
ADHD Overview (neurodevelopmental)
- Pre Frontal cortex has defective inhibitory response.
Symptoms : inattention, hyperactivity, impulsivity
2/3 ADHD patients have co-morbidity
- tics , OCD , depression , substance misuse
Treatment
- methylphenidate
- used in children over 6yrs old
ADHD Diagnosing
- diagnosed by clinical interview and standardised reports
Symptoms :
- inattention / hyperactivity / impulsivity
- all 3 symptoms must be present in different settings (school, home)
- must present before 12 years old
Tourette’s Syndrome
- Tics - vocal and physical
- often associated with ADHD or OCD
underlying problem in basal ganglia which controls motor skills and behaviours
Treatment
- 1st line CBT therapy
- HRT fixes bad habits
- ERP exposes you to triggers in safe environment
- can use risperidone
OCD
- mild : <1hr / day
- moderate : 1-3hrs / day
- severe : >3hrs a day
Obsession: unwanted thoughts/urge that enters the mind repeatedly (anxiety)
Compulsion: repetitive behaviour to temporarily relieve unpleasant feelings brought by obsessive thought
Body Dysmorphic Disorder (BDD)
- Fears and anxiety about physical appearance
Treatment Same as OCD
- treat with SSRI’s (inc. serotonin levels)
1st line : sertraline in children with OCD
1st line : fluoxetine for children with BDD
OR children with OCD + depression
Eating Disorders
- anorexia nervosa , bulimia , binge eating
- also use CBT, interpersonal & dietary counselling
Anorexia Nervosa
- pathological need to keep weight low as possible
- caution with drugs because heart is weakened by emaciation
- SSRI’s commonly prescribed or (SGA’s)
Bulimia
- periods of binge eating and being deliberately sick or using laxatives
- Fluoxetine given at higher dose than depression
Neurodevelopmental Disorders
e.g. ASD & ADHD
- impairments in cognition, behaviour or communication from abnormal brain development
Emotional/Behavioural Disorders
- depression, anxiety, OCD, phobias, anorexia
internalising or externalising problems, usually as a consequence of stress
Psychotropic Drugs
- Antidepressants - SSRI’s , SNRI’s
- Antipsychotics - risperidone
- AEDs - lamotrigine , sodium val
- Psychostimulants - methylphenidate
Miscellaneous – [hypnotics, anxiolytics,
adrenergic agents]
Behavioural Therapies
- CBT (ERP, HRT)
CBT - identifying and modifying unwanted thought patterns/behaviours rather than symptoms
better than drug use: - no side effects
- tackles root problem
- no withdrawal symptoms like with drugs
- prevents dependency from drug use
Anti Psychotics
- 1st gen typical FGA’s
- causes ED, EPS (tremors, parkinons effects)
- arises from blocking D2 channels in nigro-strital pathway
- blocks Dopamine receptors in different pathways.
- to reduce nt for positive symptoms
- haloperidol , chlorpromazine
SGA Antipsychotics
- clozapine , risperidone ,
- less extra-pyramidal side effects because it doesnt fully block dopamine receptor
- most effective is clozapine (treatment-resistant schizo)
- more cardiotoxic + causes weight gain (metabolic Syndrome)
- effective for positive AND negative symptoms
Antipsychotic Monitoring Req’s
Weight - initial + every 3 months
U+E’s - baseline and annually
Blood Glucose - initial + every 3 months
Prolactin - if hyperprolactinaemia symptoms
ECG - if patient has cardia risk
ADHD Management Stages
- preschool , mild ADHD , Moderate/severe
Pre School Overactivity
- behaviour management from parents, teachers
Mild ADHD
- general behaviour management & ADHD-specific training
- no meds at this stage because it can cause long term damage
Moderate/Severe
- when symptoms impact learning, relationships, self esteem
- medicine used here for symptoms
ADHD Treatment
- 1st line CBT
- can use methylphenidate, dexamphetamine , atomoxetine , gaun
Drug Treatment
1st line - psychostimulants
- methylphenidate , then dexamphetamine
2nd line - Atomoxetine or Guanfacine
3rd line Clonodine
Methylphenidate + Dexamphetamine
- MoA
- psychostimulant meds
Methylphenidate
- blocks dopamine and NA transporters which degrade NA & Dopamine
- increases neuronal transmission
- regulates focus and emotion
Dexamphetamine
- stimulates dopamine release from pre-synaptic vesicle
- and blocks the reuptake transporter
Atomoxetine + Guanfacine
- non-stimulants
Atomoxetine
1. NA transporter inhibitor , A2 agonist.
2. stops NA being degraded
3. metabolised by CYP2D6 (hepatic)
Guanfacine
- sustained release is licensed (long time till therapeutic effect)
- has calming effect
Clonidine
- inhibits NA release by stimulating alpha2 adrenergic system
- unlicensed. 2-3x / day dosing
- major S/E BP drop
Tics Medication
AP’s - first and second gen
clonidine - but has s/e
- drowsiness , depression , major BP drop
Tics + Anxiety
- use SSRI’s
Co-morbid with ADHD
- atomoxetine non stimulant
- because stimulant drugs exacerbate tics
OCD Medication
mainly psychological treatment
- CBT
- antidepressants if severe
SSRI’s 1st
- sertraline 150mg daily
- clomipramine (ssri) 300mg daily
- used to treat delusions
Depression
- only treat children in severe cases
- discontinuation reduce by 25% weekly
mostly SSRI
1st line : sertraline 50mg/day
2nd - fluoxetine or citalopram
NOT paroxetine because of very short half life leads to dependence
NOT venlafaxine because of s/e
NOT TCA’s
Seizures Diagnosis
- Transient Seizure :
- due to abnormal or excessive activity
- affects 1/100
- Diagnosis :
- at least 2 unprovoked seizures >24hr apart
- one unprovoked seizure with 60% recurrence chance within 10yrs of original seizure
- diagnosis of epilepsy syndrome
Generalised Seizures Classes
- arising in both hemispheres engaging bilaterally
Atypical absence
– can’t respond , longer than 10 seconds
Typical Absent - altered awareness
Clonic – both arms jerking
Tonic – both arms go stiff
Atonic – going limp
Generalised Seizures
- status epilepticus
- results from failure of mechanisms for seizure termination
- failure of mechanisms responsible for abnormal seizure initiation
Focal Seizures
- one sided
- can also develop into secondary generalised seizures (bilateral convulsive)
Aura , Motor , Automatic , Awareness/Responsiveness
Acquired : accidents/injury or genetic
infectious : bacterial or viral encephalitis
Metabolic : GLUT1 deficiency leading to more glutamate in brain, more excitation
Genetic :
- SCN1a - codes for Na+ channels increasing excitability causing epilepsy
- called Dravets Syndrome
Seizure Sequence
- stage 1 - 3
Initiation - abnormal voltage-gated channel action
Synchronisation - abnormal receptor-operated channel action
Propagation - recruitment of neurons via anatomical connection
Treatment Strategies
- AED’s Action
- inhibition of voltage gated Na+ channels , reducing sodium can reduce excitability
- promotes inhibitory neurotransmitters (GABA)
- inhibition of voltage-gated Ca2+ channels to stop muscle contraction
AED Classes
- Na+ channel inhibition
- phenytoin , carbamazepine , oxcarbazepine
- lamotrigine ( 1 & 3 HVA Ca+ inhobition )
- dont fully block Na+ channels , they just prolong inactive period (refractory)
- enhance GABA action
- BZD’s - inc. frequency of GABAa channel opening
- Phenobarbital - inc. probability of GABAa channel opening
- Vigabatrin - inhibits GABA transaminase
–> they reduce nerve firing by Cl- influx into neuron to hyperpolarise
- Inhibit Ca2+ Voltage Channels
- ethosuximide - inhibits T-type Ca2+ channels (used for absence seizures)
- pregabalin - inhibits HVA Ca2+ and glutamate
- Gabapentin - inhibits HVA Ca2+ and NA+ channels
Seizures Treatment Guidelines
Generalised Seizures
- 1st line sodium valproate
- 2nd lamotrigine/topiramate
Focal Seizures
- 1st lamotrigine
- 2nd carbamazapine
Absence Seizures
- 1st ethosuximide
- 2nd sodium valproate/lamotrigine
Status Epilipticus
-1st midazolam (buccal) cuz BDZ’s have fast action
- 2nd lorazepam/diazepam
Anti Epileptic Drug Transport
- sodium valproate
- lamotrigine
- etho + midazolam
Sodium Valproate
- diffusion and carrier-mediated transport
- via monocarboxylate transporter
Lamotrigine
- carrier mediated transport
- via organic cation transporter (OCT1)
Neurological vs Psychiatric
- differences
Neurological - issues of the brain
- physical issue
- drug therapy is usually essential
- parkinsons , epilepsy , tumour , migraine
Psychiatric - issues of the mind
- disorders of mood, thought, behaviour
- psychological and drug treatment
- anxiety , depression , schizo
Enteric Coated Tablets
- polyvinyl actetate phthalate is coating
- dissolve in duodenum at higher pH
- sodium valproate
- cannot crush or chew tablets as drug could be released too early
Oro dispersible Tablets
- Co-beneldopa & lamotrigine
- tablet disintegrates in mouth in 1min in the saliva
- no difficulty swallowing
- more accurate dosing in kids
- can be dissolved in water before administration
Modified Release Tablets
- erosion controlled matrix (sinemet)
- diffusion control (ropinirole)
- Erosion Controlled Matrix (co-careldopa sinemet)
- drug dispersed in a wax matrix
- matrix breaks down over time and drug is released slowly while matrix breaks down
- Diffusion Control (ropinirole (ReQuip XL)(PD)
- drug dispersed in porous matrix formed of a water-insoluble polymer
- drug close to the surface dissolves
- rest of the drug diffuses slowly through the pores
Modified Release Tablet
- Erosion + Diffusion Controlled Matrix
- sodium valproate (Epilim Chrono, Epival CR)
- pramipexole ER (Mirapexin , PD)
- drug is dissolved and erodable matrix separates from drug
- over time the drug is released based on equilibrium changing once drug enters systemic uptake
Transdermal Administration
- requirements
- have low molecular weight <400
- aqueous solubility higher than 1mg/ml (to be removed by blood)
- moderately lipophilic (LogP 1-5)
- effective at low doses
- Co-Beneldopa given as pump
- Lorazepam given IM
Dopamine Peripheral S/E
comes from dopamine release before BBB
- stimulates vomiting centre in brain because its outside the BBB
- can cause schizophrenia
- increases excitability
Extended Release Tablets
-carbamazepine (Tegretol XR) (epilepsy)
- overcoat disintegrated releasing 22% of drug instantly
- water permeates into osmotic layer, expanding this layer and pushing drug out over the span of a morning
- release rate inc. into the afternoon. more drug pushed out from push compartment expanding
Headache Aetiology
- Pain stimuli activates nociceptors in skin, muscle, joints
- transmits signal from periphery nerves to brain - nociceptors in dura and pia.
- chemicals released from blood vessels near dura & pia activate nociceptors
= gives headaache
Headache Types
- Primary , Secondary
Primary - headache is main symptom
- stress/tension headache
- migraine
- cluster
Secondary - caused by something else
- symptom of something else
Primary Headache Types
- Tension , Migraine , Cluster
- migraine is neurological
Tension
- slow onset , bilateral , dull pain
- pain in posterior
Migraine (no aura)
- unilateral , lasts 4-72hr , pulsating , moderate/severe , nausea vomiting
Migraine (with aura)
- headache with 1 of following :
- visual, sensory, speech, motor, retinal
- REFER
Cluster
- severe pain, one sided, behind the eye
- lasts weeks or months
- swelling & runny nose
Primary Headache Treatment
- paracetamol (inhibits prostaglandins)
- Ibuprofen (COX inhibitor)
- buclizine ( anti histamine and anti emetic)
paracetamol - inhibits prostaglandins production in pain pathway
- activates descending serotoninergic pathway
Ibuprofen - acts on COX1/2 receptors inhibiting prostaglandin synthesis
Buclizine - anti-histamine and anti-emetic. sedating
General Headache Treatments
- triptans - selective 5-HT antagonist
- Pizotifen (serotonin , histamine & tryptamine)
- Propranolol (blocks B-adrenoreceptor)
Triptans - stimulates 5-HT1b in smooth muscle to cause cranial vasoconstriction
- sumatriptan
Pizotifen - reduces blood flow & alters pain threshhold
- POM
Propanolol - reduces blood flow by blocking Beta receptors
- rizatriptan + propranolol bad reaction
