People and illness Week 1 Flashcards
1
Q
What is growth?
A
A programmed sequence of development that is reversed towards the end of life
2
Q
Describe how the brain changes as it grows in utero:
A
- initially to gyral/sulcal pattern
- 26 weeks -> very immature (danger if born premature)
- some neuroblasts remain undifferentiated for plasticity
- term brain formed by 40 weeks
3
Q
What 3 overlapping processes are involved in developments of the cerebral cortex?
A
1) Neuroblast proliferation where the cells divide
2) Migration of immature neurons from ventricular zone to cortical plate
3) Organisation into 6 layered cortex and connections form throughout the brain
4
Q
What is holoprosencephaly?
A
Prosencephalon fails to develop into two halfs
5
Q
What is lissencephaly?
A
Smooth brain with lack of gyri and sulci as neural crest cells fail to migrate
6
Q
What are congenital causes of neurodisability?
A
- genes
- chromosomes
- intrauterine infections
- prematurity
7
Q
What are environmental causes of neurodisability?
A
- toxins (cocaine)
- FAS (foetal alcohol syndrome)
- infection (rubella)
- anti-epileptic drugs
- general anaesthetics
8
Q
What is focal cortical dysplasia?
A
- where there is poorly differentiated grey matter, areas of FCD is the brain are common in children/adults with epilepsy
9
Q
What is periventricular leukomalacia?
A
- type of white matter necrosis that can occur as a result of ischemia during premature birth or from hypotension during a caesarean section
10
Q
Describe non-accidental brain injuries:
A
- classed as “shaken baby syndrome”
- triad of symptoms that some medical professionals use to infer child abuse:
- > subdural haematoma
- > retinal haemorrhage
- > encephalopathy
11
Q
What is neuroplasticity?
A
- the brains ability to grow and change and reorganise new connections throughout life
- after a brain injury you may need more brain volume to carry out a simple function -> the brain can reorganise and some neural cells can change their function
12
Q
What is the Kennard principle?
A
There is a linear relationship between the age you are when you have a brain injury and the outcome expectancy (i.e. the older you are the worse you recover)
13
Q
What are some of the relationships between eduction attainment and upbringing?
A
- children with quiet homes and how have a predictable routine tend to do better at school
- children with confusion/unpredictable home life tend to withdraw from challenge
- family chaos = poor early reading level and poor sleep cycles
- maternal IQ is most predictive of a child’s IQ
14
Q
Why is attachment important for child development?
A
- rely and thrive on family
- needed for mother-child relationships
15
Q
What effects can neglect/deprivation have on child development?
A
- children raised in institutions are at increased risk for many social and behavioural problems
- as the age of entry into foster care increases, the IQ of the child is reduced
16
Q
What NORMAL social/cognitive/behavioural changes occur during adolescence?
A
- starts around 9-12 years (earlier for girls and older for boys)
- brain changes continue into 20’s
- metabolic changes
- rapid period of physical growth
- new sex drives
- identity
- relationships develop
- intimacy
- emotional regulation
- social skills
- risk taking
- peacock displays
- remained attachments to parents and family as well as growing friend groups
- become more independent
- gain strong peer identification
- committed
- develop morals
17
Q
What brain changes occur in adolescence?
A
- decreased grey matter volume after adolescence
- major prefrontal cortex changes (initially there is increased neuronal growth in the prefrontal cortex but then synaptic pruning occurs for fine tuning and strengthening of important connections)
- limbic system changes (is hypersensitive during adolescence)
18
Q
Define normal adolescence:
A
- transition from child to adult
- WHO = 10-19 years
- ends when an adult has an accepted behaviour and identity
19
Q
What changes occur in behaviour during adolescence:
A
- more exploratory behaviour: smoking, violence, risk taking
- relationship interests and sexual identity
- maturation
- later on reduction in risk-taking tendancies
20
Q
What factors increase risk taking tendency?
A
- low socioeconomic status
- peer pressure
- lack of parental monitoring
- lack of future ambition
21
Q
What factors decrease risk taking tendency?
A
- close trusting parental relationships
- good self-esteem
- good future ambition
22
Q
What is the prefrontal area of the brain involved in?
A
High level cognitive functioning:
- decision making
- planning
- inhibiting inappropriate behaviour
- self-awareness
- social interaction
- understanding other people
- stops us taking excessive risks, but is still developing in adolescence
23
Q
What is the function of the limbic system?
A
- involved in emotion and reward processing
- in adolescence it is hypersensitive to the reward feeling and ‘rush’ of risk taking
24
Q
What makes up the limbic system?
A
- cingulate gyrus (medial part of cerebral cortex)
- temporal lobe
- amygdala
- nucleus accumbens
- hippocampus
25
What hormonal changes occur in adolescence?
- noradrenaline, dopamine and serotonin changes
| - sex hormone changes
26
What is the function of dopamine?
pleasure, reward, motivation, drive
27
What is the function of noradrenaline?
alertness, concentration, energy
28
What is the function of serotonin?
emotion, memory, obsession and compulsion
29
Define ADHD and its aetiology:
- attention deficit hyperactivity disorder
- group of behavioural symptoms that include inattentiveness, hyperactivity and impulsiveness
- various genetic and environmental factors are thought to cause the disorder
30
What genetic factors can predispose to ADHD?
- no single gene identified by various susceptibility gene mutations
- > dopamine receptor D4 (causes impulsivity and overactivity)
- > dopamine receptor transporter genes
- > serotonin transporter genes
- > serotonin receptor gene
- 3-4 males to every 1 female
- genes can increase/decrease the impact an environment has
31
What environmental factors can predispose to ADHD?
- maternal smoking
- alcohol consumption
- heroin use in pregnancy
- epilepsy
- foetal hypoxia
- brain injury
- dietary factors (additives, E-numbers)
- disruptive family life and being in care
32
What are signs/symptoms of ADHD?
- inattention and lack of persistence in activities that require concentration
- impulsivity (running across road without checking)
- excessive activity
- restless and fidgety
- poor peer relationships
- social disinhibition
- talking excessively and using inner voice
33
What co-morbidities are associated with ADHD?
- sleep disorders
- OCD
- learning disabilities
- co-ordination disorders
- anxiety
- social and communication difficulties
- below average IQ
34
What brain changes are seen on a fMRI in ADHD?
- smaller volume frontal and parietal cortexes
- smaller basal ganglia
- deficits in the fronto-striatal network
35
How do you diagnose ADHD using ICD10?
1 - symptoms apparent before the age of 7 in a child
2 - behaviours are excessive for the child's age
3 - evidence of behaviours in 1+ environment
4 - symptoms worsen in the afternoon
3 principle features:
- inattentiveness
- impulsivity
- excessive activity
36
How do you diagnose ADHD?
- history
- questionnaires (SNAP-4 = 18Q for parents and teachers and rate answers 0-3 / Conner's parent rating scale)
- PMH -> birth, trauma
- observe in school and at home
- develop a formulation: look for predisposing and perpetuating factors
37
How can ADHD be treated non-pharmacologically?
1) psychostimulants
2) non-stimulants
3) supplementary therapy
38
How can ADHD be treated non-pharmacologically?
- manage the environment (remove stimuli, avoid long quiet situations)
- behaviour training programmes
- reward programmes
- praise children for short periods they are calm and well behaved
- praise parents too
- routine and reinforcements with rewards
- specialised school teaching
- regular reassessments
39
Describe common psychostimulants, how they work and some common side effects:
DEXAMFETAMINE
- increases dopamine release from presynaptic terminal
- prevents dopamine re-uptake by blocking the transporter protein
- very potent, careful prescribing (abuse)
ELVANSE (lisdexamfetamine) = pro drug converted to dexamfetamine that has more sustained release effect
METHYLPHENIDATE
- sustained release tablet taken in morning with 'immediate' release top ups
- only has 1 action acting on dopamine transporter preventing re-uptake
- have side effects of growth retardation, anorexia, BP/HR irregularities, headaches
- may cause anxiety, suicidal tendencies
- can develop tolerance with long term use
40
Describe common non-stimulant drugs, how they work and some common side effects:
ATOMOXETINE
- noradrenaline reuptake inhibitor
- enhances NA transmission in the PFC
- binds to NA transporter in the synapse to stop NA being reuptaken into the presynaptic terminal so it remains in the synapse and has potentiated action
- takes 6 weeks to work so beneficial if dose missed
- GOOD for depression and anxiety
- side effects of nausea, vomiting, insomnia, hepatic impairment
41
Describe common supplementary drugs, how they work and some common side effects:
- NA antagonists = CLONIDINE/GUANFACINE
- guanfacine is substrate for CYP enzyme so avoid enzyme inducers
- can cause sedation/dizziness
- anti-depressants (MAOI, SSRI) - increase the amount of monoamines in the synapses
- dopaminergic drugs (MODAFINOL)
- weak psychostimulants that decreases GABA and increase glutamate
- side effects of dry mouth, GI upset and tachycardia
42
What is CAMHS and its role?
- child and adolescent mental health services
- umbrella term for all the services involved in working with children and adolescents with emotional and behavioural difficulties
- many MDT's involved (psychiatrists, social workers, nurses, support workers, OT's, psychotherapists, psychologists)
- treat many mental health disorders like schizophrenia, anxiety, anorexia etc.
- works with and supports entire family
43
What are the risks for an ADHD child later in life:
- 20% cases progress into adulthood
- difficulty holding down job
- delayed writing and reading
- poor academic attainment
- relationship issues
- 4x increased risk of dying in RTA
- 3x increased risk of illegitimate child
- 10% prisoners have ADHD
44
How is dopamine synthesised?
tyrosine -(tyrosine hydroxylase)-> dopa -(dopa decarboxylase)-> dopamine
45
How is NA synthesised from dopamine?
dopamine -(dopamine Beta hydroxylase)-> NA
46
How is NA converted to A?
NA -(PNMT)-> A
PNMT = phenylethanolamine-N-methyltransferase
47
Describe the two main arousal changes that can occur in the brain in ADHD:
- hypoarousal
| - hyperarousal
48
Describe hypoarousal in ADHD:
- brain under-active (low dopamine and NA firing)
- does not react enough to stimuli
- to improve this type of ADHD you must increase the signal to noise detection ratio
- even though this seems counter-intuitive as you are giving someone a stimulant who already is stimulated, you are stimulating certain under-active brain areas
49
Describe hyperarousal in ADHD:
- too much arousal and XS dopamine and noradrenaline firing
- the signal to noise detection ratio is deteriorated (so a small signal results in a large response)
- to treat this you have to desensitise post-synaptic NA/dopamine receptors to down-regulate neuronal activity to return NA/dopamine neurons to normal phasic firing
50
What are the three legal classes of drugs?
1) GSL: general sales list
2) P: pharmacy
3) POM: prescription only medication
51
What is pharmacokinetics?
What your body does to a drug (what happens to the drug from ingestion to secretion)
52
What is pharmacodynamics?
What the drug does to your body (how a drug actually exerts its effect and any side effects it may have)
53
What is bioavailability and why is it important?
- F = the fraction of the administered drug that reaches the systemic circulation
- it can be affected by other factors like:
- > drug factors
- > absorption and 1st pass metabolism
- > grapefruit juice (increase F)
- > phenytoin (reduce F)
54
What is volume of distribution?
- volume into which a drug must be uniformly distributed to produce the desired blood concentration
55
What is the relationship between VOD and half life?
- drugs with high VOD have a much longer half life and are harder to excrete therefore takes longer time for toxic side effects to pass
56
What is clearance?
The volume of plasma cleared of drug per unit time
57
How can poor renal function affect clearance?
- can impair clearance, so less dosing of drug required (less top ups needed as drug remains in body for longer time)
58
What is the relationship between clearance and half life?
When clearance is halves, the half life is doubled
59
What is half life and how is it calculated?
- half life = time taken for serum plasma concentration to decrease by half
- loading doses often used for drugs with a long half life
- t(.5) = -0.693 x V/Cl
60
How much active drug will be left in your body after 4-5 half lives?
3-6% of the active drug
61
Describe linear pharmacokinetics in terms of concentration and dose:
As you double the dose you double the concentration = they are proportional
62
Describe non-linear pharmacokinetics in terms of concentration and dose:
When you give a dose of a drug and then the resulting drug is not proportional to the dose
- as the dose gradually increases, the concentration suddenly peaks
63
Name a non-linear drug:
There are very few but one is PHENYTOIN
64
What can changing drug route of administration do?
Can alter bioavailability as oral drugs have much lower F than IV drugs
65
How do you calculate loading dose?
Target concentration (mg/L) x V(L/kg)
| the L's cancel out
66
Describe 6 different types of receptor proteins:
1 - regulatory protein that changes activity of cellular enzymes
2 - enzyme linked receptor that can be inhibited or activated by drugs
3 - transport proteins (ATPases)
4 - structural proteins that form cell parts
5 - ion channel linked
6 - nuclear (gene) linked
67
What is affinity?
The attractiveness of a drug and receptor - the propensity of a drug to bind to its receptor
68
What is efficacy?
= intrinsic activity
| - the ability of a bound drug to change the receptor and cause an effect
69
What is potency?
The strength of a drug
| - a drug which is more potent is not necessarily clinically superior
70
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Describe the following in terms of affinity and efficacy:
1 - agonist
2 - antagonist
3 - full agonist
4 - partial agonist
```
1 - affinity and efficacy
2 - affinity but not efficacy
3 - has affinity and maximal efficacy
4 - has affinity but less than maximal efficacy
71
How does a competitive agonist work?
Competes with agonist for receptor and can be overcome as agonist concentration increases
72
How does a non-competitive agonist work?
Changes shape of receptor so that normal agonist cannot bind, cannot be overcome
73
What is therapeutic index and how can you calculate it?
TI = TD or LD / ED
74
What is LD?
lethal dose = the dose at which a drug is lethal for 50% of the population
75
What is TD?
toxic dose = the amount of substance taken that is expected to produce a toxic dose
76
What is ED?
effective dose = the dose that produces the desired effect
77
Is high TI good or bad?
The higher the TI the better the drug, but their use has to be monitored carefully
78
What two factors increase dosing interval?
Hepatic disease and renal disease
79
What condition reduces dosing interval?
CF - it increases drug metabolism and clearance and so reduces the dosing interval, overall more drug is needed
80
What drugs should be avoided in renal disease?
NSAID's and metformin
81
What drugs should be reduced in dose in renal disease?
Digoxin, antibiotics phenytoin and LMWH
