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Drugs and the Brain > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

What does convulsion mean?

A

Muscles contract and relax in a rapid cycle

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2
Q

What is a seizure?

A

Paroxysmal (attack) events that may involve motor, sensory systems or are related to consciousness: brain involvement

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3
Q

What is Epilepsy?

A

A set of disorders that have recurrent, (unprokoved) seizures

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4
Q

What are disorder components involved in epilepsy?

A
  • Muscle rigidity
  • Convulsions
  • Psychic (changes in sensory perception, anxiety or deja vu)
  • Loss of consciousness
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5
Q

In what age groups is epilepsy most common?

A

Children and elderly

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6
Q

What percentage of people have epilepsy at a singular given time?

A

0.5-1% of the population

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7
Q

What percentage of the population will experience epilepsy in thier lifetime?

A

5%

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8
Q

What factors increase the risk of epilepsy in old age?

A
  • Causes to brain structure via….
  • Stroke
  • Dementia
  • Tumours
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9
Q

What is a Myoclonic (myoclonus) seizure?

A

Involuntary twitching of muscle or muscle group

Can occur in everyday life such as hiccups or jolts when we fall asleep

Does not normally have a rhythm

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10
Q

What is a clonic (clonus) seizure?

A

Rhythmic muscle contractions

Normally involve large movements

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11
Q

What is a tonic seizure?

A

A phase in which there is sustained muscle contraction (initial rigidity)

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12
Q

What is an atonic seizure?

A

Loss of muscle tone

Usually a brief loss of consciousness

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13
Q

What is a common name for an atonic seizure?

A

Drop seizure

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14
Q

What is an absence seizure?

A

A short lapse in consciousness

Doesn’t have a motor component

Normally has rapid recovery

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15
Q

What is an Ictal seizure?

A

Anything pertaining to a seizure

Sometimes this term can also be used for strokes

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16
Q

What are the three first ILAE system seizure classes?

A
  • Focal onset
  • Generalised onset
  • Unknown onset
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17
Q

In the focal onset category of the ILAE system, what are the following elements of a seizure?

A
  • Aware/ impaired awareness
  • Motor onset/ Non-motor onset
  • Focal/ bilateral tonic-clonic
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18
Q

In the Generalised onset and unknown categories of the ILAE system, what are the following elements of a seizure?

A
  • Motor (tonic-clonic/ other motor)
  • Non motor (absence)
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19
Q

What are the two groups of seizure categorisation for the old system (most common)?

A
  • Partial: simple/complex
  • Generalised: grand mal (tonic-clonic)/petit mal (absence)
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20
Q

What are the four epilepsy syndromes as disclosed by the ILAE system?

A
  • Focal
  • Generalised
  • Combined generalised and focal
  • Unknown
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21
Q

What are five electroclinical ways of classifying epilepsy?

A
  • Neonatal
  • Infancy
  • Childhood
  • Adolescence/Adult
  • Not age related
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22
Q

How can we classify epilepsy based on brain areas, give examples (3)?

A
  • EEG can identify the particular brain region involved
  • This may be included in the naming:
  • ADNFLE (autosomal dominant nocturnal frontal lobe epilepsy)
  • Temporal lobe epilepsy
  • Occipital lobe epilepsy
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23
Q

What is a focus?

A
  • A group of neuronns generating high frequency acitivity
  • The initial problem stems from this focal area
  • There may be a single focus, or multiple foci
  • Can spread
  • Symptoms depend on the areas of the brian involved
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24
Q

What are four possible causes of a focus?

A
  • Paroxysmal depolarizing shift (neurons undergo periodic changes in the resting membrane potential)
  • Synchronization of activity (generation of the high frequency activity)
  • Remodelling (of synaptic connectivity and neuronal loss because of seizures may feed in and worsen it)
  • Kindling
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25
Q

What is Kindling?

A

An animal model where an animal is given a repeated low level stimulation to a particualr brain region

Makes this area more sensitive and then a small stimulation can cause seizures

Eventually, spontaneous seizures occur

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26
Q

What are the triggers of epilepsy?

A
  • Most occur spontaneously
  • Stress can increase frequency
  • Some have particular triggers:
  • Photosensitive (most common, still only 3% of epileptic patients)
  • Reading
  • Music
  • Hot water
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27
Q

What are four ways of diagnosing epilepsy?

A
  • Electroencephalography (scalp recordings)

-Video EEG (can be combined with video recording to correlate with the change in consciousness or motor activity)

  • CT/MRI scans (to see underlying causes)
  • PET scans (are there regions of the brain that function differently)
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28
Q

What are three main animal models that are used as a model of human disease?

A
  • Genetic models
  • Chemically induced models
  • Electrically induced models
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29
Q

What is the aetiological classification of epilepsy?

A
  • Direct genetic inheritance
  • structural/metabolic such as brain trauma which predisposes a person to epilepsy
  • Unknown causes
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30
Q

What percentage of epilepsy is thought to be of genetic origin?

A

40%

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31
Q

How do genetic epilepsies occur?

A
  • Due to mutations in ion channels and receptors
  • “channelopathies”
  • May cause more epilepsies than identified by inheritance patterns
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32
Q

What proteins are most likely to be involved in genetic epilepsies?

A
  • GABAA receptors
  • neuronal nAChR
  • VS channels
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33
Q

What is autosomal dominant nocturnal frontal lobe epilepsy?

A
  • “Channelopathy”
  • Seizures happen at night during sleep
  • Frequently misdiagnosed as nightmares
  • Linked to mutations in neuronsal nAChR alpha and beta subunits (important in regulation of other CNS neurotransmitters)
  • Causes the receptors to change sensitivity to ACh and desensitization altered
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34
Q

What is Hyperekplexia?

A
  • “Channelopathy” NOT an epilepsy
  • Startle syndrome
  • EEG generally normal
  • Mutations in proteins associated with glycinergic transmission in the spinal cord such as:
  • Glycine receptor subunits
  • Glycine transporters
  • Cytoskeletal proteins
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35
Q

What are the legal driving implications of having epilepsy?

A
  • Driving licence removed after a seizure

Unless

  • Seizure free for one year
  • Three years of seizures only at night
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36
Q

What are four social implications of Epilepsy?

A
  • Employment may be difficult for people with severe epliepsy
  • Pregnancy may be difficult
  • Some people with epilepsy feel a sense of shame (stigma
  • There is still a fear of epilepsy in society
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37
Q

What is a tonic-clonic seizure’s classification name?

A

Grand Mal

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38
Q

What type of seizure is regarded as the ‘classic’ epileptic seizure?

A

Tonic-clonic

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39
Q

What are the three stages of a tonic-clonic seizure?

A
  • (prodromal phase (20%))
  • Aura
  • Tonic phase
  • Clonic phase
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40
Q

What is the aura phase of a tonic-clonic seizure?

A
  • Altered sensory perception and psychic symptoms such as deja vu, anxiety and hallucinations
  • May be a valuable warning that they are about to have a seizure
  • Is a form of seizure activity- type of focal seizure with maintained consciousness
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41
Q

What is the tonic phase of a tonic-clonic seizure?

A

The patients will lose consciousness and their muscles will become rigid, they may make strange sounds during this part of the seizure

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42
Q

What is the clonic phase of a tonic-clonic seizure?

A

The seizure will progress into convulsions and the patient may suffer from incontinence. This phase can last several minutes

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43
Q

What is the prodromal phase of the tonic-clonic seizure?

A
  • Only happens in 20% of epileptic patients
  • A sensation which starts hours or days before the seizure which can serve as a further warning sign
  • This is not a form of epileptic acitvity
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44
Q

What are absence seizure’s classification name?

A

Petit Mal

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45
Q

What age group are absence seizures most common in?

A

Children

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46
Q

What is an absence seizure?

A
  • Involve a siggen, brief lapse in consciousness
  • Have very rapid recovery
  • Can happen frequently during the day
  • Some people have a brief motor component (more subtle than a proper motor seizure)
  • Usually the person has no memory of what has happened.
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47
Q

What is Juvenile Myoclonic Epilepsy?

A
  • Very common type of epilepsy (10% of all epilepsies)
  • Frequently inherited
  • Myoclonic jerks of the arms or legs
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48
Q

What percentage of people with JME experience a myoclonic component?

A
  • 17%
  • In other cases, the person will also experience tonic-clonic seizures or absence seizures
49
Q

What are the triggers for JME?

A
  • Sleep deprivation
  • Fatigue
  • Alcohol consumption
50
Q

What are the four mutations associated with JME?

A
  • GABAAR alpha subunit
  • GABAAR delta subunit
  • EFHC1 (role unknown but associated with calcium channels)
  • CACNB4 (calcium channel beta subunit)
51
Q

What is a Gelastic seizure?

A
  • A ‘laughing seizure’
  • There is also a dacrystic seizure type (‘crying seizure’)
52
Q

What is Status Epilepticus?

A
  • Single epileptic seizures that lasts longer than five minutes
  • Or repeated seizures within 5 minutes of each other
  • It can involve all types of generalised seizure
53
Q

What is the fatality rate for status epilepticus?

A

20% of people who have status epilepticus will die within 30 days of the seizure

Others will be left with a permanent disability due to brain damage and oxygen deficiency

54
Q

What is often the cause of status epilepticus?

A
  • Underlying medical reason
  • Stroke
  • brain tumour
  • Head injury
55
Q

What drug type is used to treat status epilepticus and give examples

A
  • benzodiazepines
  • Lorazepam
  • Midazolam
  • Diazepan
56
Q

If status epilepticus cannot be bought under control what can be used to stop it?

A
  • General anaesthetics

such as

  • Barbiturates
  • Propofol
57
Q

How do doctors choose which anti-epileptic drug to prescribe?

A
  • Some work better than other for particular types of epilepsy
  • Some will make certain kinds of epilepsy worse
  • NICE guidelines
  • Simplified guidance in BNF
58
Q

What are the 3 main targets for anti-convulsants?

A
  • Calcium channel inhibition
  • GABAergic potentiation (receptor potentiation, uptake inhibition, metabolism inhibition)
  • Sodium channel inhibition
59
Q

What drug is phenytoin structurally related to?

A

Barbiturates

60
Q

What is phenytoin’s trade name?

61
Q

What does Phenytoin do?

A
  • Stabalises voltage- gated sodium channels in inactivated state
  • Effective against tonic-clonic and partial seizures (can worsen absence and myoclonic seizures)
62
Q

What are some side-effects of phenytoin?

A
  • Teratogenic
  • Risk of lupus
  • Cerebeller atrophy (changes in brain structure)
  • Acne, hirsuitism (extra hair growth)
  • Gingival overgrowth (gum growth)
63
Q

What is a major issue with Phenytoin’s pharmacokinetics?

A
  • Different people’s plasma levels react in different ways to changes in the dose
  • Once the dose gets to a certain amount, the plasma levels no longer increase proportionally
  • There is a small therapeutic range which is hard to keep individuals in
64
Q

What does Carbamazepine do?

A

-Blocks voltage-gated sodium channels

  • Secondary action of GABAA receptors
  • First line treatment for focal seizures, useful in tonic-clonic
  • Also used as a mood stabalizer and neuropathic pain treatment
65
Q

What are two related drugs to carbamazepine?

A
  • Oxycarbazepine
  • Eslicarbazepine

(have better side-effect profiles)

66
Q

What enzyme is carbamazepine metabolised by?

67
Q

Why is the fact that carbamazepine metabolised by CYP3A4 a problem?

A
  • Takes a while to reach a steady plateu because carbamazepine auto-induces the enzyme (when patient takes more drug, means more enzyme is produced)
  • Interaction with grapefruit juice
  • Because of induction of CYP, there are many interactions as this enzyme metabolises a range of drugs (auto-induction means other drugs will be metabolised quickly and there will be competition between these and carbamezapine).
68
Q

What are some side-effects of carbamazepine?

A
  • Tetratogenic
  • Risk of lupus
  • Worsens JME and absence seizures
  • Cognitive problems and mood changes
69
Q

What is Lamorigine?

A
  • Sodium channel blocker
  • First line treatment for tonic-clonic seizures
  • Second line for absence
  • Can exacerbate myoclonic seizures at higher doses
  • Also used to treat bipolar disorder
70
Q

What are the side-effects of Lamotrigine?

A
  • Sedation
  • Sleep disturbances
  • Rash
  • Binds to eye pigment
  • Steven Johnson’s disease
71
Q

How can we effect the GABAergic presynaptic terminal in order to treat epilepsy?

A
  • Have the GAT1 GABA transmitter on the presynaptic nerve terminals
  • If inhibit this, we will boost GABA in the synapse
  • This increases inhibition
  • Combats epilepsies excitatory effects
72
Q

How can we effect the GABAergic post-synaptic terminal to treat epilepsy?

A
  • If we potentiate the GABAA receptor in the post-synaptic membrane
  • More inhibitory actions occur such as chloride flux
  • Combats epilepsies excitatory effects
73
Q

How can we effect the GABAergic reuptake in order to treat epilepsy?

A
  • The enzyme GABA transaminase is an enzyme in the astrocyte (recycles GABA) and the presynaptic nerve terminal
  • This enzyme metabolises GABA
  • If we inhibit this enzyme, we will cause more GABA in the cleft and therefore boost inhibition
  • This combats the excitatory effect of epilepsy
74
Q

What do Benzodiazepines do?

A

Potentiate the actions of GABAA receptors by binding to the allosteric site

74
Q

What are 3 benzodiazepines?

A
  • Clobazam
  • Clonazepam
  • Diazepam
75
Q

What is Clobazam used for?

A
  • Adjunct medication for epilepsy
  • Also treats anxiety
76
Q

What is Clonazepam used for?

A
  • Refractory epilepsy
  • Also acts on calcium channels
  • Can only be prescribed by specialists in special circumstances
77
Q

What is Diazepam used for?

A
  • Status epilepticus
  • Only used for serious epilepsies as can become tolerant very quickly
78
Q

What are the side-effects of the benzodiazepines?

A
  • Sedation
  • Tolerance/dependance
  • Seizures on withdrawal
79
Q

What is a similar acting class of drugs to the benzodiazepines?

A
  • Barbiturates
  • Similar action but worse side effects
  • Listed in BNF but mostly prescribed by specialists
  • Allosteric potentiates GABAAR
  • Directly acts on the GABAAR so it is easy to overdose
80
Q

What is Tiagabine?

A
  • GAT1 inhibitor (transporter inhibitor)
  • Adjuvant medication
  • Partial seizures (focal seizures)
  • Panic attacks
  • Neuropathic pain
81
Q

What is Tiagabine’s trade name?

82
Q

What are the side-effects of tiagabine?

A
  • Sedation
  • Dizziness
  • Paraesthesias (pins and needles)
  • Provokes seizures in non-epileptic patients
  • When overdose: amnesia and confusion also
83
Q

What is Vigabatrin?

A
  • Irreversible GABA transaminase inhibitor
  • Adjuvant medication
  • Addictions
  • Panic attacks
84
Q

What is vigabatrin’s trade name?

85
Q

Why can vigabatrin be taken only once a day?

A
  • Has a short plasma half life

but

  • This doesn’t matter becasue it is irreversible, if take once a day, will have actions as it covalently modifies the enzyme
  • So will have a continued effect once it has been metabolised
86
Q

What are the side-effects of vigabatrin?

A
  • Visual disturbances
  • Depression
  • Psychosis
  • Sedation
  • Teratogenic actions
87
Q

What are the three forms of Sodium valproate?

A
  • Sodium valproate
  • Valproic acid
  • Mixture: valproate semisodium

(no difference in the actions of these drug formations)

88
Q

What is sodium valproate?

A
  • First line treatment for a range of epilepsies
  • Also used in bipolar disorder and migraine’s
89
Q

What are the potential mechanisms for sodium valproate (4)?

A
  • GABA transaminase inhibitor (most likely)
  • Enhances post-synaptic GABA function
  • Inhibits sodium channels
  • Inhibits calcium channels
90
Q

What are sodium valproate’s trade names?

A
  • Epilim
  • Depakote
91
Q

What are the side-effects of valproate?

A
  • Liver toxicity (can be sudden onset)
  • Teratogenic (folic acid antagonist)
  • ASD
  • Cleft palate
  • Limb defects
  • Cognitive changes and brain structure changes with long term use (could be reversible when the drug is withdrawn)
92
Q

What are the characteristic facial structures of foetal valproate syndrome?

A
  • High forehead
  • Flat nasal bridge
  • Broad base of nose
  • Shallow philtrum
  • Long upper lip
93
Q

What are gabapentin and pregabalin trade names?

A
  • Neurontin
  • Lyrica
93
Q

What are the two main Gabapentinoids?

A
  • Gabapentin
  • Pregabalin
94
Q

How do gabapentin and pregabalin act?

A
  • Bind to a alpha2delta subunit of a neuronal calcium channel
  • Has a physiological role with the natural ligands leucine and isoleucine
  • Normally, when one amino acid is bound, the calcium channel complex is transported to the cell surface
  • If a gabapentinoid binds , the channel is retained in the cell and is broken down, reducing the calcium channels on the cell surface
95
Q

What does pregabalin increase the levels of?

96
Q

What are gabapentin and pregabalin used for?

A
  • Adjunct medication for focal seizures
  • Pregabalin also as a monotherapy and for anxiety
  • Used for neuropathic pain
97
Q

What are the side-effects of gabapentin and pregabalin?

A
  • Sedation
  • Diziness
  • Suicidal thoughts
  • Abuse potential
  • Seizures upon withdrawal
98
Q

What are the gabapentinoids street drug names?

A
  • Gabbies
  • Johnnies
  • Budweisers
99
Q

Where is there a particular problem with gabapentinoids as a street drug?

A
  • Prisons- double the rate of prescriptions here
  • 19/96- 20% of prescrptions were not in the possesion of the person who was prescribed them
  • Can be fatal when combined with methadone (problem when prescribed for withdrawal in prisons)
100
Q

What class are the gabapentinoids?

A

Class C controlled substance under schedule 3

101
Q

What is Ethosuximide?

A
  • Blocks T type calcium channels
  • First choice drug for absence seizures (can exacerbate other types of epilepsy)
  • Lacks the liver toxicity seen with valproate
102
Q

What are the side-effects of ethosuximide?

A
  • Sedation
  • Nausea
  • Mood changes
103
Q

What seizures is Leviteracetam (Keppra) used to treat?

A
  • Focal
  • Myoclonic
  • Tonic-clonic
104
Q

What is the mechanism of leviteracetam?

A
  • Bit of a mystery
  • Likely inhibits presynaptic calcium channels
  • or binds to SV2A which is a protein involved in the release of neurotransmitter
  • inhibiting this and the channels will cause the same overall effect of a reduce in neurotransmitter release
105
Q

What are the side-effects of leviteracetam?

A
  • Depression
  • Agitation
  • Aggression
  • Suidide ideation
  • Psychosis (rare)
  • Stevens-Johnson syndrome (v. rare)
106
Q

What drugs is Stevens-Johnson syndrome seen with?

A
  • Lamotrigine
  • Phenytoin
  • Valproate
  • Oxcarbazepine
  • Ethosuximide
  • Carbamazepine
107
Q

What are the two forms of Stevens-Johnson syndrome?

A
  • Skin blisters, peeling and lesions around the mouth
  • Toxic epidermal necrolysis which is where the top layer of the skin comes off and looks like burn damage
108
Q

What is topiramate used for?

A
  • Adjunct treatment for focal seizures and tonic-clonic seizures
  • Migraines
  • Bipolar disorder
  • Alcoholism
109
Q

What are the side-effects of topiramate?

A
  • Sedation
  • Cognitive problems
  • Psychiatric
  • Teratogenic
110
Q

What is the ketogenic diet used for?

A
  • The 30% of epileptic patients where antiepileptic drugs do not work
111
Q

What is the ketogenic diet?

A
  • An extreme version of the Atkins diet
  • Very high in fat
  • Very low in carbohydrates
  • Controlled protein
112
Q

What percentage of children will see an improvement in symptoms when on the ketogenic diet?

A
  • 50% of children will see a significant decrease in the number of seizures
  • Some even become seizure free
113
Q

What is a hemispherectomy and what is it used to treat?

A

-Treats Rasmussen’s encephalitis which is an inflammatory condition that results in frequent and severe seizures

  • The removal of one hemisphere of the brain occurs
114
Q

What is a corpus callosotomy and what is it used to treat?

A
  • Treats intractable epilepsy
  • Severs the corpus callosum
  • This prevents seizures from spreading to the other hemisphere
  • Can have adverse effects such as cognitive impairment, language difficulty and hand syndrome (hand has a mind of its own)
115
Q

What are optogenetics?

A
  • Use light gated channels or pumps to modify the behaviour of neurons
  • Can be used for the treatment of epilepsy in the future
116
Q

What are DREADDs?

A
  • Designer receptors exclusively activated by designer drugs
  • An engineered form of receptor is introduced into the target cells
  • This receptor is mutated so it no longer responds to its nornal endogenous ligand, but only the synthetic drug
  • A possible future method for treating epilepsy

Drugs and the Brain (9 decks)

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