epliepsy case Flashcards
1
Q
what is the normal physiology of sleep
A
Our bodies all require long periods of sleep in order to restore and rejuvenate, to grow muscle, repair tissue, and synthesize hormones. Memory is formed, and the brain is able to react to events of the previous day(s).
2
Q
what is meant by entrainment
A
Entrainment is the process by which an environmental rhythm, such as the light-dark cycle, regulates the period and phase relationship of a self-sustained oscillator.
3
Q
what is meant by circaidan (slave) oscillator
A
can drive a rhythmic output but requires other oscillators (known as pacemakers) for its entrainment and/or function. A slave oscillator can therefore be self-sustained but cannot operate properly independently of other oscillators.
4
Q
what is meant by A zeitgeber
A
is any external or environmental cue that entrains, or synchronizes, an organism’s biological rhythms to the Earth’s 24-hour light-dark cycle and 12-month cycle. Regular meal times and light are zeitgebers.
5
Q
describe the circadian rhythm
A
2am - deepest sleep 4-5am - lowest body temp 6-7am - sharp rise in BP 7-8am - secretion of melatonin stops 9am - high level of testosterone secretion (in males) 10am - high alertness 2-4pm - optimal coordination & reaction time 6-7pm - highest BP and body temp 9pm - melatonin secretion starts
6
Q
what disturbs the circadian rhythm
A
The circadian rhythm is disturbed by exposure to 450-500nm light at night or lack of light exposure in the morning.
7
Q
what regulates the body clock
A
Many areas of the body are involved in regulating the body’s clock. The primary mechanisms involve the timing of food consumption and the natural light-dark cycle. The following have roles in maintaining the circadian rhythms: cardiovascular tissue, liver, kidney, pancreas, gut, muscle and fat tissue.
8
Q
what is the Suprachiasmatic nucleus (SCN)
A
The SCN is the small area above the optic chiasm in the anteroventral region of the hypothalamus. It is the master body clock and regulates other circadian rhythms; it is a circadian pacemaker. The master clock in the SCN is composed bilaterally paired nuclei which contain 8,000–10,000 clock cells packed closely together. The SCN receives light information via the retino-hypothalamic tract (RHT).
9
Q
what is meant by the entrained SCN and what doe it do?
A
The entrained SCN coordinates the timing of slave oscillators in other areas of the brain (e.g. cortex) and peripheral organs (heart, liver), regulating brain homeostasis, peripheral metabolism (glucose homeostasis), vascular & peripheral regulation, and peripheral inflammation. The SCN also regulates amyloid plaque breakdown/ removal.
10
Q
what is the role of melatonin
A
Entrainment is mediated by melatonin, a naturally occurring hormone which induces sleep. It is released in response to low levels of light.
11
Q
how does melatonin induce sleep
A
Light is detected by the photoreceptors of the retina, including the rods and cones as well as photosensitive retinal ganglion cells (pRGCs), expressing the photopigment melanopsin. A signal is output to the SCN via the retino-hypothalamic tract (RHT), where it entrains an intracellular clock mechanism consisting of positive (BMAL1 and CLOCK) and negative (PER1/2 and CRY1/2) elements. The SCN projects excitatory information to the paraventricular nucleus (PVN). Long axons send nerve pulse to the preganglianic sympathetic neurons in the spinal cord. This modulates the activity of the superior cervical ganglia, projecting to the pineal gland and regulating melatonin secretion. The CLOCK genes operate on a negative feedback system; the under-lying principle of circadian clocks is successive gene activation in the form of a cycle: the initial activation of a gene is regulated by the last one in the sequence, making up an auto-regulatory feedback loop for which one cycle takes about 24-hours.
12
Q
what is meant by wakefulness
A
The neurotransmitters involved in maintaining wakefulness include acetylcholine, norepinephrine, serotonin, and histamine
The brain is kept ‘awake’ by the activity of the Ascending Reticular Formation. The ascending reticular formation projects to the thalamus and cerebral cortex. It exerts some control over which sensory signals reach the cerebrum and come to our conscious attention. For example, if a loud sound is heard during sleep, the signal is received as an auditory impulse. Reticular formation radiates to the cerebral cortex, resulting in waking. Lesions to this brain area leads to constant sleep.
13
Q
how are arousal signals stimulated
A
Cholinergic (ACh) cell groups in the upper pons – pedunculopontine (PPT) and laterodorsal tegmental nuclei (LDT) – and project through the thalamus and facilitate thalamocortical transmission of arousal signals.
14
Q
what is involved in the second pathway of arousal signals
A
A second pathway involves the hypothalamus and cortical centres. It facilitates processing of thalamocortical inputs from midbrain centres.
The following areas of the brain, and neurotransmitters are involved:
• Locus coeruleus, LC / noradrenergic
• Raphe / serotonergic
• Tuberomammillary nucleus, TMN / histaminergic
• Ventral periaqueductal grey matter, vPAG / dopaminergic
• Basal forebrain BF / GABA and ACh
• Lateral hypothalamus, LH / orexin – aka hypocretin – and melanin concentrating hormone
During sleep, the ventrolateral preoptic (VLPO) nucleus of the hypothalamus sends descending GABAergic inhibitory signals to the midbrain’s arousal centres, turning them off.
15
Q
list the steps during the sleep cycle
A
A complete cycle of sleep is 90-110 minutes and is divided into 5 stages.
•Stage 1 - Light sleep. Muscle activity slows with occasional twitching
•Stage 2 - Breathing and HR slows. Slight decrease in body temperature. ~50% of sleep is stage two
•Stage 3 - Deep sleep begins. Brain generates slow delta waves
Stage 4 - Very deep sleep. Rhythmic breathing with limited muscle activity. Delta waves are produced.
Stage 5 - Rapid eye movement (REM). Brainwaves speed up and dreaming occurs. There is an increase in HR and breathing is rapid and shallow. ~20% of sleep is REM sleep. The first sleep cycles have relatively short periods of REM and long periods of deep sleep but later in the night, REM periods lengthen, and deep sleep time decreases.
16
Q
what does EEG measure
A
Electroencephalography (EEG) is the measurement of electrical activity produced by the brain (cerebral cortex). It can be recorded from electrodes placed on the scalp.
17
Q
what does gamma waves measure during the sleep cycle
A
Gamma waves (40-100 Hz) are involved in higher processing tasks as well as cognitive functioning.
18
Q
what does the alpha waves measure during the sleep cycle
A
Alpha waves (9-14 Hz) bridge the gap between our conscious thinking and subconscious mind, promoting deep relaxation.
19
Q
what does the theta waves measure during the sleep cycle
A
Theta waves (4-8 Hz) are involved in daydreaming and stage 1 sleep.
20
Q
what does the delta waves measure during the sleep cycle
A
Delta waves (0-4 Hz) are the slowest recorded brain waves in human beings.
They are associated with the deepest levels of relaxation and restorative, healing sleep. They have also been found to be involved in unconscious bodily functions such as regulating heart beat and digestion; blood pressure, respiratory rate and basal metabolism is reduced by 10-30%. Less delta waves are produced as humans age.
Delta waves are produced in stages 3 and 4 (slow-wave sleep). During slow-wave sleep, the same neurons that are active during the day become re-active. Slow-wave sleep is implicated in memory consolidation. Long-term potentiation occurs in the synapses that are activated and are strengthened. In the elderly, stage 3-4 sleep is less commonly experienced, and there is increased cycling between stages and waking.
21
Q
describe how neuromodulators modulate neurone transmitters
A
Neuromodulates modulate neurotransmitters. When a neuron is active, it generates ATP.
ATP signalling can regulate both excitatory and inhibitory neurotransmission. ATP surges during the initial hours of sleep, displaying a significant positive correlation with the intensity of slow-wave activity in non-rapid eye movement (NREM) sleep.
Intracellularly, ATP is metabolized to ADP then to AMP, then to adenosine.
22
Q
what does the adenosinergic regaulation predominately mediate?
A
The adenosinergic regulation of sleep is predominantly mediated either via A1 inhibitory receptors (A1Rs). This activates purinergic receptors on glial cells, causing the release of low-levels of cytokines, such as TNF- and IL-ß1, and glutamate. They activate their own receptors, and can activate the transcription factor, NF-kB. This causes increased expression (insertion) of inhibitory A1 receptors on the post-synaptic neuron, altering the sensitivity of neurons. Thus, adenosine regulates either the amount of sleep or sleep homeostasis in multiple ways depending on the brain area and receptor subtype.
23
Q
how are sleep regulatory substances involved in the synaptic scaling
A
Sleep-regulatory substances are involved in synaptic scaling, which increases or decreases the efficiency of synaptic efficiency. Events or skills are remembered if they are novel or emotional, mediated by the brain itself. If the brain decides the event is not important, the synapse is depressed; if the brain decides something is worth remembering, synapses stay active (potentiated) or depressed.
24
Q
what is narcolepsy
A
Narcolepsy is a rare sleep disorder (0.02-0.06) characterised by excessive daytime sleepiness. It is possibly an autoimmune disorder caused by hypocretin deficiency.
25
how does wake promoting drugs work
Amphetamines, methylphenidate and modafinil all act on the dopamine (DA)-reuptake transporter in the vPAG. They directly prevent the reuptake of dopamine and noradrenaline. Increased synaptic dopamine activates the cerebral cortex to maintain wakefulness. WPDs also indirectly increase serotonin, glutamate, histamine and orexin levels & decrease the levels of GABA, through the hypothalamus & cortical pathway in the midbrain (see above).
Caffeine is an adenosine receptor antagonist, blocking the A1a receptor therefore reducing the inhibitory effects of adenosine.
26
what is meant by insomnia
Insomnia is a difficulty in initiating or maintaining sleep. In adolescence, insomnia is commonly a result of circadian rhythms maladjustment. It may be transient (e.g. jet lag), short-term (e.g. stress) or chronic (e.g. psychiatric illness). Insomnia has many causes: physical (pain); physiological (shift work, noise, caffeine); psychological (stress), psychiatric (depression) and iatrogenic (ß-blockers).
27
what are some of the side effects associated with insomnia
Too little sleep increases likelihood of developing a cold, worsen symptoms of inflammatory bowel disease/ acid reflux and deplete sex drive. Sleep deprivation is linked to visual disturbances, such as tunnel vision; the longer one is awake, the more likely they are to experience hallucinations. In addition, poor sleep can affect memory and learning, headaches and irritability.
Insomnia is linked to psychiatric disorders, such as anxiety and mood disorders.
Patients should be educated to have realistic sleep expectations and should be advised to find and treat the underlying cause of insomnia. This includes considering alcohol, drug and caffeine use. However, pharmacological interventions can be made.
28
what are hypnotics
Hypnotics induce sleep by modulating the effects of GABA at the GABAa receptor, causing sedation.
29
describe the MoA of benzodiazepines
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or causing the patient extreme distress.
Acting on GABAa chloride channels (on the gamma subunit), they induce Cl- conduction, inhibiting the AP. This enhances the action of the inhibitory neurotransmitter, GABA, causing sedation. BDZ induce and increase the duration of sleep.
Benzodiazepine-derivatives are not traditional BDZ but have BDZ activity.
30
name 2 Benzodiazepines (BDZ) and their dose strength
Diazepam 5–15 mg ON
| Temazepam 10–20 mg ON
31
what are the side effects associated with Benzodiazepines (BDZ)
BDZ depress REM and slow-wave sleep, so quality of sleep and memory formation is negatively affected. As a result, continuous use can cause amnesia, ataxia (movement disorders) and impaired memory/ cognition. In the elderly, hypnotic use is attributed to an increased risk of falls and confused state. Hypnotics should be used for a maximum of two weeks, so REM deprivation does not occur.
Paradoxical effects occur in < 1% of patients. It causes increased excitement, excessive talking, restlessness, agitation and aggression. If these occur, flumazenil, a competitive benzodiazepine antagonist at GABAa, can be given.
There are various factors which may predispose one to these effects, including:
Very young/ very old – varying pharmacokinetics
Alcoholism – effect on GABA
Psychiatric disorders
Genetic polymorphism affects response
32
what are the counselling points for someone who is on BDZ?
Patients should be advised not to drive, because the sedative effects of BDZs can impair concentration. As of 2015, “driving, attempting to drive, or being in charge of a vehicle, with certain specified controlled drugs in excess of specified limits” is an offence. One can be prosecuted unless the drugs was prescribed and there is no effect of impairment on driving.
Patients should be warned of the risks of dependence; it can occur within a 7-10 days and. If suspected, the patient should begin gradual withdrawal. Withdrawal symptoms include confusion, psychosis, convulsions or tremors.
Withdrawal syndrome occurs more rapidly for short acting DBZ; withdrawal may occur up to three weeks after abrupt withdrawal in longer-acting agents.
1. Transfer patient stepwise, one dose at a time over about a week, to an equivalent daily dose of diazepam preferably taken at night.
2. Reduce diazepam dose, usually by 1–2 mg every 2– 4 weeks. If uncomfortable withdrawal symptoms occur, maintain this dose until symptoms lessen.
3. Reduce diazepam dose further, if necessary, in smaller steps of 500 micrograms. Then stop completely.
4. For long-term patients, the period needed for complete withdrawal may vary from several months to a year or more.
33
name a Non-benzodiazepine hypnotics – Z-drugs drugs and describe how do they work
Zolpidem tartrate and zopiclone are non-benzodiazepine hypnotics (sometimes referred to as Z-drugs), but they act at the benzodiazepine receptor. They are not licensed for long-term use; dependence has been reported in a small number of patients. Both zolpidem tartrate and zopiclone have a short duration of action.
34
name a anti-cholinergic agent and describe how do they work
Diphenhydramine is an anti-histamine with anti-muscarinic activity (antagonist at H and M receptors). It crosses the blood-brain-barrier that blocking the arousing influence of central histamine causing drowsiness and promoting sleep. It may have effects on 5-HT1 receptor
CNS-acting dopamine antagonists (SGA antipsychotics) have a sedative action due to histamine receptor occupancy.
35
describe how barbiturates work
The intermediate-acting barbiturates should only be used in the treatment of severe intractable insomnia, in patients already taking barbiturates. They should be avoided in the elderly.
36
what are melatonin receptor agonists
A potential new treatment (still in clinical trials) involves enhancing the activity of melatonin.
37
explain why alcohol is a poor hypnotic
Alcohol depresses neuronal activity – it is an agonist at GABAa receptors and a antagonist at NMDA receptors (for electrical signals to pass, the NMDA receptor must be open and to remain open, glutamate and glycine must bind to the NMDA receptor – antagonist action prevents NMDA activation). Alcohol is a poor hypnotic because the diuretic action interferes with sleep during the latter part of the night. Alcohol also disturbs sleep patterns, and so can worsen sleep disorders. Using alcohol with hypnotics may cause respiratory depression due to CNS toxicity.
38
define epilepsy
Epilepsy is a neurological condition characterised by uncoordinated electrical activity of the brain. Recurrent epileptic seizures are unprovoked by any immediately identifiable cause.
Epilepsy affects ~65m worldwide, and there is a 5% lifetime risk of seizures.
39
what are the risks of developing epilepsy
The risk of developing epilepsy increases in age; this is due to stroke and neurodegeneration.
40
what is meant by an epileptic seizure
An epileptic seizure is abnormal electroactivity. Convulsions associated with epilepsy result from the repeated triggering of a neuronal circuit. The convulsions tend to last 1-2 minutes, and the seizure is followed by a postictal state (recovery, which may last minutes to hours).
41
list some of the causes of epilepsy
* Hypo/hyperglycaeimia
* Hypo/hypernatraemia
* Hypocalcaemia
* Hypomagneseamia
* Uraemia
* Drugs (phenothiazines, benzodiazepine withdrawal, antibiotics, antidepressants, EtOH, tramadol, antiepileptics, ciclosporin, cocaine, lithium, inteferons, barbiturates)
* Meningitis
* Encephalitis
* Head trauma
* Space Occupying Lesion
* Stroke / TIA
* Genetics (polygenetic)
* Epileptogenisis
42
what are the presentations of epilepsy
Syncope, where insufficient blood to the brain caused the patient to faint
Hyperventilation
Migraine
Panic attack
Pseudo seizure (non-epileptic attack), which is where a patient presents with a convulsion in the absence of abnormal electroactivity; it is thought to be a psychological issue
Transient global amnesia
Transient ischaemic attack
43
what is the prognosis of epilepsy
Remission is defined as achieving a 5-year seizure-free and 5-year medication-free period. Any subsequent seizure for any reason was considered a relapse. Complete remission at last contact was defined based on the date of last seizure and date seizure medications were completely stopped. Prognosis is highly dependent on the number of seizures experienced during the first 6 months of epilepsy; the higher the number of seizures, the less likely are the chances of remission.
Half of patients remit with 1 anti-epileptic drug (AED), 1/3 of the remainder remit with 2nd AED and ~ 10% of remainder remit with 3rd AED.
44
what are the two categorises of epilepsy
There are two broad categories of epilepsy: Generalised (global) and Partial (focal).
45
what is meant by generalised epilepsy
Generalised epilepsy affects the whole brain. The following types of epilepsy fall under this category:
•Absences (petit mal)
•Tonic-clonic (grand mal)
•Myoclonic (Juvenile myoclonic epilepsy)
•Tonic
•Akinetic – all muscle tone is lost, resulting in falls thus risk of head injury
46
what is meant by partial epilepsy
Partial epilepsy affects a local area of the brain. The following types of epilepsy fall under this category:
•Simple – consciousness is maintained, so the patient is aware of the seizure
•Complex – impaired awareness
•Secondary generalised (aka Focal to bilateral tonic-clonic seizures) – starts local, then becomes generalised
47
what age group is absence seizures most common and what is the cause of it
This type of seizure is most common in children aged 4-8. It is caused by a developmental abnormality.
48
what are the characteristics of an absence seizure
A typical absence seizure is characterised by a sudden loss of awareness, but the patient remains conscious. The seizure is sometimes associated with automatisms – repetitive, purposeless movements of the fingers, hands or mouth, such as some lip-smacking. There may also be eyelid flickering or fluttering.
49
how long does absence seizure last for?
Absence seizure usually lasts between 5 and 15 seconds and usually stops as suddenly as it starts; absences that last longer than 15 or 20 seconds or that have a lot of automatisms are called ‘atypical’ absences.
Absence seizures tend to happen more commonly when the child is bored, sitting quietly or when they are tired or unwell. They happen less often when the child is busy or focused on an activity that they enjoy.
50
how do you go about diagnosing absence seizures
The only diagnostic test for absence seizures is the EEG; a patient with absence epilepsy has similar electrical pattern of activity to a healthy patient during non-REM sleep. Atypical absence seizures are characterized by slow spike-and-wave paroxysms, classically 3 Hz.
51
what 3 things are considered to be the underlying mechanism of absence seizures
The thalamic relay neurons, reticular thalamic nucleus, and neocortical pyramidal cells form a circuit that sustains oscillatory burst firing and is regarded as the underlying mechanism of absence seizures.
52
how does the T- type calcium channels play a key role in the circuit that causes absence seizures
T-type calcium channels – CaV3 –play a key role in this circuit, as the pacemaker. It provides an inward, positive current into the neurone that brings the membrane up to a threshold of action potential firing.
53
describe how the T- type calcium channels plays a key role in the mechanism of absence seizures?
CaV3 are activated on at low voltages (similar to the resting membrane potential, -40mV). At low voltages, the activation gate can sense changes in voltage.
When the threshold for VgCa2+ is reached, channels open and there is an influx of Ca2+, resulting in depolarisation of the membrane.
This depolarisation causes the threshold for VgNa+ channels to be met; channels open and there is an influx of Na+, resulting in further depolarisation. VgNa+ channels are only open for a short time before closing.
At depolarised potentials, the threshold for opening VgK+ is met; channels open and there is an efflux of K+, causing hyperpolarisation of the membrane.
54
how does the concentration of calcium ions build up in the mechanism of absence seizure
With repeated APs, intracellular calcium concentration builds-up. Calcium can be cytotoxic leading to neuronal death, so cells have several mechanisms for removal. CaV3 has an inactivation gate which is sensitive to voltage and calcium concentration.
When calcium channels rise, calcium-dependent inactivation occurs; Ca2+ channels close, and no longer contributes to pacemaker neuronal firing. Gates will not reopen until the cell becomes hyperpolarised
. Calcium-activated potassium channels (KCN) are also present in the membrane. This conducts potassium from the inside to the outside, taking the cell to very hyperpolarised potentials, resetting CaV3 (voltage-sensitive).
55
name the 2 modes in which the thalamic neurone can fire
tonic and burst mode.
56
how does the thalamic neurone work in absence seizures
* When the thalamic neurone is firing in tonic-mode, information can be transmitted to the cortex, and one is conscious. The thalamic relay neuron receives inputs from other neurons via neurotransmitters, causing depolarisation of the cell & the threshold for VgNa+ is reached – without the need for a pacemaker. Because the membrane is depolarised, there is no Ca2+ entry to the cell. Therefore, there is no calcium-activated potassium channel activation and firing is constant.
* When the thalamic neurone is firing in burst-mode, information cannot be transmitted to the cortex, and one is unconscious. Burst firing is seen when the CaV3 channels are activated from a hyperpolarized state (KCN), allowing for low-threshold depolarization of neurons which creates bursts of action potentials through voltage-gated sodium channels.
57
how is the transition from tonic to burst firing implicated in absence seizures
The transition from tonic firing to burst firing is implicated in absence seizures. In absence epileptic patients, the thalamic neurones may prefer to fire in the burst-mode due to genetic variation of the Ca2+ channel, where the calcium or voltage sensitivity is disturbed.
The brain has ~ 100 billion neurons. Neurotransmitters include acetylcholine, dopamine, serotonin, glutamate and GABA.
Glutamate is the most abundant excitatory transmitter
58
what is TRet and TRel
```
TRet = thalamic reticular neuron
TRel = thalamic relay
```
59
how is GABA involved in absence seizures
GABA is the most abundant neurotransmitter and is inhibitory. The abundance of GABA means that the brain is in a highly suppressed state. There are two types of GABA receptor:
GABAa is ligand-gated receptor which conducts Cl- from outside-in (influx). The influx of negative ions hyperpolarises neurons, inhibiting neuronal firing.
GABAb is G-coupled protein receptor. It is inhibitory, reducing cAMP and activating K+ channels causing a movement inside-out. The efflux of positive ions hyperpolarises neurons, inhibiting neuronal firing.
60
describe how TRet signals to the relay neurone using GABA to contribute to absence seizures ?
TRet signals to the relay neuron, using GABA. It binds to GABAb, causing hyperpolarisation of the neuron, sending it into burst-mode firing; this may precipitate absence epilepsy, so we don’t want to activate GABAb receptors.
TRet can inhibit another TRet, using GABA. It binds to GABAa, causing chloride ion induction, therefore it is hyperpolarised and less likely to release GABA to the thalamic relay neuron. GABAb won’t be activated, therefore it will be polarised and fire in tonic mode.
61
what is another subcategory of generalise seizures
Tonic-clonic (aka grand-mal)
62
what is tonic-clonic seizures
• Tonic – loss of consciousness, muscle rigidity (which usually results in falls), sharp exhalation (results in loud cry)
• Clonic – limbs jerk quickly and rhythmically, control of bladder/ bowels may be lost, biting down (can result in injury to mouth/ tongue), and breathing is affected
These can last 1-2 mins and can cause coma.
63
what is generalised epilepsy with febrile seizure plus
Generalised Epilepsy with Febrile Seizures Plus (GEFS+) is where afflicted individuals can exhibit numerous epilepsy phenotypes. Known causative genes are the sodium channel α-subunit genes SCN1A, an associated β-subunit SCN1B.
64
how does SNC1A work
SNC1A is a loss of Loss of function and it work when An interneuron may be releasing inhibitory neurotransmitter, inhibiting glutamate, supressing activity. However, mutations may lead to loss of function of the sodium channel in the interneuron. The interneuron may play a role in releasing inhibitory neurotransmitters, therefore a loss of function limits or stops this release, resulting in the firing of glutamatergic neuron.
65
what is a SNC1B and how does it work
SNC1B – Gain of function mutations
SNC1B mutations can lead to over activity of sodium channels. Since sodium channels are excitatory, there will be an increase in likelihood to trigger an action potential, releasing glutamate and leading to overexcitability.
66
what is meant by a partial seizure
Generally caused by head trauma, intracranial bleed, stroke or a tumour – something which affects only a specific area of the brain.
67
what is meant by simple seizures
In simple seizures, people experiencing a simple partial seizure do not lose consciousness or awareness.
68
what are the different subcategories of simple seizures
motor
sensory
autonomic
psychic
69
what is a motor seizure
A motor seizure causes a person to lose control over muscle activity, usually in their arm, face, foot, or another part of their body. Due to the way motor nerves cross the brain, if a person loses control over the right side of their brain, it will cause problems on the left side of their body and vice-versa.
70
what is meant by a sensory seizure
Sensory seizures will cause changes to a person's hearing, vision, or sense of smell. This can cause hallucinations and difficulty hearing. Also, as in motor seizures, a seizure focus on the right side of the brain can cause numbness or tingling on the left side of the body.
71
what is meant by autonomic seizures
Autonomic seizures affect parts of the brain that deal with the functions of the body a person does not control with their thinking. Symptoms could include changes in heart rhythm, blood pressure, and bowel function.
72
what is meant by psychic seizures
A psychic seizure causes a person to experience sudden emotional changes, such as feelings of fear, anxiety, or even déjà vu.
73
what is meant by complex seizure ( temporal-lobe)
This is the most common form of focal epilepsy. There may be a mixture of different feelings, emotions, thoughts, and experiences, which may be familiar or completely foreign. In some cases, a series of old memories resurfaces. In others, the person may feel as if everything – including home and family – appears strange. Hallucinations of voices, music, people, smells, or tastes may occur. These features are called “auras” or “warnings.” They may last for just a few seconds or may continue as long as a minute or two. Experiences during temporal lobe seizures vary in intensity and quality. Sometimes the seizures are so mild that the person barely notices. In other cases, the person may be consumed with fright, intellectual fascination, or even pleasure. In complex epilepsy, consciousness may be lost and some patients may carry out automatisms that are associated with disruptions to normal behaviour: lip-smacking, chewing, grimacing, undressing, aimless activities. Progression to secondary generalised epilepsy is common.
74
define Status epilepticus
Defined as two or more sequential seizures without full recovery of consciousness between seizures, or more than 30 minutes of continuous seizure activity.
75
what should drs assess in status epilepticus
Physicians first should assess the patient's airway and oxygenation. If the airway is clear and intubation is not immediately required, blood pressure and pulse should be checked, and oxygen administered.
Isotonic saline infusion should be initiated. Because hypoglycaemia may precipitate status epilepticus and is quickly reversible, 50 mL of 50 percent glucose should be given immediately if hypoglycaemia is suspected.
76
what should be given to patients who have status epilepticus
1. Benzodiazepines
a. Lorazepam 2-4mg (at 2mg/ min) is first choice. It is less lipid-soluble than diazepam, with a distribution half-life of two to three hours thus has a longer duration; OR
b. Diazepam 5-10mg (at 5mg/ min)
2. Phenytoin - the main advantage of phenytoin is the lack of a sedating effect. However, a number of potentially serious adverse effects may occur. Arrhythmias and hypotension have been reported, particularly in patients older than 40 years
77
what are the different targets for treating epilepsy
Glutamate is the main excitatory neurotransmitter, and is a target for reducing activity of excitatory neurotransmission
1. Blocking VgCa2+
2. Blocking VgNa+
3. VgK+ activators
4. Blocking SVA2 (vesicular transport protein)
5. Blocking AMPA and NMDA receptors; AMPA and NMDA are the main types of ionotropic glutamate receptor mediating fast glutamatergic neurotransmission
78
why do we want to increase activity of GABAa receptors
GABA is the main inhibitory neurotransmitter, and is a target for increasing activity of inhibitory neurotransmission
79
what drugs are used for the treatment of tonic-clonic seizures
o Sodium valproate
o Carbamazepine
o Lamotrigine
80
what drugs are used for the treatment of absence seizures
o Sodium valproate
o Lamotrigine
o Ethosuximide
81
what drugs are used for the treatment of focal seizures
o Sodium valproate
o Carbamazepine
o Lamotrigine
o Levetiracetam
82
what drugs are used for the treatment of myoclonic seizures
o Sodium valproate
o Levetiracetam
o Topiramate
83
what drugs are used for the treatment of Status epilepticus
o Midazolam
o Diazepam
o Lorazepam
84
what is sodium valproate used for
Indicated for all forms of epilepsy.
Na+ channel blocker & reduces T-type Ca2+ channel current, preventing repetitive and sustained firing of an action potential.
1–2 g daily; therapeutic plasma conc of 30-100 μg/mL.
The rate of congenital malformations among babies born to mothers using valproate is about four times higher than the rate among babies born to epileptic mothers using other anti-seizure monotherapies.
To prevent major seizures, valproate should not be discontinued abruptly, as this can precipitate status epilepticus.
May cause hepatic/ renal failure and pancreatitis
85
what is Carbamazepine used for
Indicated for tonic-clonic & focal seizures.
Binds preferentially to VgNa+ channels in their inactive conformation – use dependent, preventing repetitive and sustained firing of an action potential.
0.8–1.2 g daily; therapeutic plasma conc of 4-12 µg/mL.
Not recommended for very young children. Toxicity can cause stupor, confusion, convulsions, respiratory depression
86
what is Ethosuximide used for
Indicated for absence epilepsy.
Blocks T-type VgCa+ channels (CAV3), preventing neurons from firing in burst mode.
1-1.5 g daily; therapeutic plasma conc of 40-100 µg/ml.
Can cause foetal harm when administered to a pregnant woman, especially in use with other anticonvulsants.
87
what is Lamotrigine used for
Indicated for tonic-clonic, absence & focal epilepsy.
Blocks various Ca2+ channels, including CaV3 and possibly reduces glutamate release.
100-200 mg daily.
88
what is Levetiracetam used for
Indicated for focal and myoclonic epilepsy.
Inhibits SVA2 protein on vesicles, prevents the fusion of vesicle to membrane & reduces glutamate release.
Causes a desire to sleep and may cause irritability.
89
what Is Topiramate used for
Indicated for myoclonic epilepsy.
Blocks AMPA receptors on post-synaptic membrane, preventing Na+ from entering cell thus preventing action potential. Also acts on GABAa receptors, increasing transmission of the inhibitory GABA neurotransmitter.
100–200 mg daily.
Affects memory and causes cognitive dysfunction.
90
what is Gabapentin/pregabalin used for
Bind to alpha-2 delta subunit on L-type VgCa2+ channels, increasing the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters.
91
what is Benzodiazepines used for
Midazolam, Diazepam & Lorazepam are indicated for status epilepticus.
Modulate GABAa Cl- channels, increase frequency of channel opening, increasing inhibitory effects of GABA. The cell will be hyperpolarised and less likely to release GABA to the thalamic relay neuron. GABAb won’t be activated, therefore it will be polarised and fire in tonic mode.
92
what is phenytoin used for
Phenytoin can be used for tonic-clonic, focal seizures & status epilepticus.
Causes a voltage-dependent block of VgNa+ channels on the neuronal cell membrane, promoting the efflux of sodium ions from neurons and stabilising the threshold against hyperexcitability.
For tonic-clonic seizures, loading dose of 3–4 mg/kg daily, then 200–500 mg daily
Therapeutic plasma concentration of 10-20 µg/L – narrow therapeutic index.
The most notable signs of toxicity associated with the intravenous use of this drug are cardiovascular collapse and/or CNS depression.
The rate of administration is very important; it should not exceed 50 mg per minute in adults, and 1 to 3 mg/kg/min
93
what are the common side effects of anti convulsants
* Gastrointestinal (nausea and vomiting, weight gain)
* Hyperammonaemia (nausea, vomiting, ataxia) – ammonia levels must be monitored
* Haemopoietic (leucopenia, thrombocytopaenia)
* CNS (suicidal ideation)
* Reduce fertility
* Increase risk of reproductive endocrine disorder & cause polycystic ovary syndrome
94
what does Ethosuximide, Lamotrigine & Levetiracetam cause
* DRESS: drug reaction with eosinophilia and systemic symptoms (hypersensitivity causing inflammation of organs and may be fatal)
* SJS: Stevens-Johnsons syndrome (complex immune-mediated hypersensitivity where flu-like symptoms and blistering rash are experienced)
95
what are the common interactions across all anti-convulsants
3A4 inhibitors (e.g. erythromycin) increase plasma levels & 3A4 inducers (e.g. phenytoin, rifampicin) decrease plasma levels.
Lithium may cause CNS toxicity.
Antipsychotics lower seizure threshold
96
what interaction is with carbamazepine
o Decrease plasma levels of corticosteroids, CCBs, warfarin, valproate, oral contraceptives (CYP3A4 inducer)
97
what interactions are associated with sodium valproate
o Drugs that elevate levels of glucuronosyltransferases (e.g. phenytoin, carbamazepine, rifampicin) may increase the metabolism of valproate
o Aspirin inhibits metabolism
o Carbapenem antibiotics cause significant reduction in plasma conc therefore loss of seizure control
o Valproate decreases efficacy of diazepam and phenytoin (by displacing from albumin binding sites and inhibiting metabolism)
98
describe the kinetics for phenytoin
Most drugs undergo first-order kinetics; when a constant proportion of the drug is eliminated per unit time. Rate of elimination is proportional to the amount of drug in the body. Phenytoin undergoes zero-order kinetics; it has a constant rate of elimination. If the dose is doubled, there is a disproportionate rise in serum-phenytoin.
Because phenytoin undergoes zero-order kinetics, rate of elimination = rate of administration.
99
what is Michaelis Menten Kinetics
rate of administration (maintenance dose )= (Vmax × Css ) / (Km + Css )
```
Vmax = max velocity of phenytoin clearance, which is 7mg/kg/day
Css = plasma concentration at steady state
Km = concentration at ½ Vmax – it is variable and depends on the person
```
If serum concentration (Css) is known, it can be substituted into the equation to calculate Km. From there, Km can be input to calculate the dose required to produce desired plasma concentration.
100
what does the orbit plot tell you
The y-axis represents Dose and Vm while the x-axis represents Km in the positive direction and Cpaverage in the negative direction.
After a dose of 256 mg/day and 333 mg/day the steady state Cpaverage values were measured to be 7 and 20 mg/L, respectively. These data are represented as the red and blue lines, respectively. These lines intercept at 400 which provide a value of Km and Vm of 4mg/L and 400 mg/day, respectively. If we were aiming for a Cpaverage value of 15 mg/L this point on the x-axis could be connected with the intersection of the red and blue lines by drawing the green line. The intersection of the green line with the y-axis provides the required dose of 316 mg/day. Various dose and expected Cpaverage could be estimated from the intersection of the red and blue lines.
101
how do you calculate the loading dose
Loading dose = Cp × Vd /F × S
```
Cp = desired peak concentration of drug
Vd = volume of distribution of drug in body
F = bioavailability
S = fraction of drug salt form which is active drug
```
102
why is rectal drug delivery used in anti epileptics
Most useful when the oral route is not available. This could be due to nausea, trauma, oesophageal stricture (where the patient can’t swallow), post-operative (effect of anaesthetic) or uncooperative (children, psychiatric patients, elderly – dementia, unconscious).
It is also used where drugs are not stable in the upper GIT, due to acid hydrolysis by enzymatic degradation, extensive first-pass metabolism or causing unwanted GI side effects.
It can be used to treat local conditions e.g. astringents to treat haemorrhoids, steroids to treat colitis, glycerine to treat laxatives.
103
what are some issues of rectal delivery for anti -epileptics
There is a strong aversion to rectal drug delivery in the UK, because there of patient acceptability and issues with absorption; absorption is slow & incomplete, with variations in the absorbed dose inter-subject (between patients) and intra-subject (between doses).
104
describe the anatomy of the rectum
The rectum is the last 1.5-2cm of the GI tract and is anatomically part of the colon. The rectum is divided into two parts: the ampulla is the main body of the rectum (80% of the volume) and the anal canal.
105
describe the 3 major folds in the rectum
The rectum is a hollow organ, which is usually empty as faecal matter is stored further up in the colon. It has a flat surface, with 3 major folds. There are also 3 veins that drain from the rectum:
Superior haemorrhoidal vein
- This vein drains to hepatic portal vein – drugs that are absorbed into the superior HV may undergo first-pass metabolism
* Middle haemorrhoidal vein
* Inferior haemorrhoidal vein
106
describe the physiology of the anal canal
The anal canal is squamous stratified epithelium and is primarily protective in nature; it is not good for absorption. The ampulla has similar epithelium to the rest of the GIT. It has simple columnar epithelium (80%), one cell layer, no villi but goblet cells to produce mucus so primarily absorptive in nature; it is good for absorption.
There is 300cm of rectal wall – not a huge surface area to facilitate absorption, but the epithelium of the ampulla is very thin, aiding absorption. The rectum secretes mucus (~3 mL) with a pH of 7.5, however it does not have a buffer capacity. As a result, a very acidic formulation will alter the pH of the rectum until clearance.
There is a high rate of motility, sufficient to spread most viscous molten bases over entire area.
107
what is the most common formulations for rectal delivery
These are the most common formulation for rectal delivery. Suppositories are shaped specifically so the pointed (but blunt) end is inserted and the tapered end is held during insertion. They are made by incorporating the fine powder of drug into melted base (usually triglyceride wax). The size of the mold is defined by volume of (usually fatty base) to give the final required weight. A ‘displacement’ calculation must be performed to find the volume of base displaced by added ingredient(s).
There are water-soluble bases available, however these are used for constipation (glycerin mixtures) only, because there is insufficient fluid in the rectum for dissolution so fluid may be drawn from the mucosa causing irritation.
Fat-soluble bases are more commonly used. Theobroma oil was previously used but is no longer employed due to polymorphic forms, poor mold-releasing properties, has low softening temperature, is chemically unstable and expensive. Now, adeps solidus (Witepsol) is used; it is a semi-synthetic mixture of triglycerides, meaning that its stability can be modified for optimum release
108
how do suppositories release the drug
Suppositories tend to melt at 30ºC, melting, spreading the drug which may dissolve in the rectal fluid. The drug can have a local affect or may diffuse across the rectal wall (transcellularly). If it is absorbed via the middle or inferior veins, it is systemically circulated. They must be water soluble to be available for absorption and lipid soluble to allow partitioning into the membrane. They should be small particles (50-100µg) to favour dissolution but prevent agglomeration.
109
what advise should be given to patients on administering suppositories
If necessary, empty bowels (and wash hands). Remove wrapping from suppository and either in a squatting position or lying down with one leg straight and the other bent, firmly push the suppository into the rectum far enough that it won’t slip out (and wash hands). Close legs and sit still for a few minutes, avoiding emptying bowels for at least one hour.
110
what are some of the issues relating to the dose in regard to suppositories
```
• Viscosity
o The higher the viscosity, the slower the rate of sedimentation so the suppository will be more homogenous
• Melting point of base
o Bases should melt at 30-35ºC
• Compatible
o Must be non-toxic
o Allows for wetting and release
```
111
how to calculate the displacement value
The displacement value can be defined as the volume of drug that displaces 1 gram of suppository base; e.g. lidocaine has a DV of 0.5; 0.5g of lidocaine displaces 1g of base.
The suppositories will be made using a 4g mold and each suppository will contain 10mg Lidocaine. You need to supply 55 suppositories. Given that the displacement value of Lidocaine in the oily base is 0.5, calculate how much base and active ingredient are required if a surplus of 5 suppositories are to be made.
112
how do Liquids - enemas formulations are used for the treatment for anti-epileptics
Liquids include solutions/ suspensions; they are usually aqueous but can be oily .
• High volume (~100 mL) – this volume is too large for the rectum, but the aim is to administer to the upper colon, to treat local conditions such as inflammatory bowel disease.
• Micro-enema (~3-5 mL) – this is ideal volume for rectal delivery. It is very useful for treating status epilepticus with diazepam where oral route is not available of when injection is not desirable.
Enemas are constituted of the active ingredient, vehicle and aids to solubility and stability. They do not usually contain preservatives because the GIT harbours many microorganisms anyway.
113
how are semi-solids produced
Drug is ground up and dispersed, generally in a paraffin base. These are applied outside of the anus or inside the rectum, as treatment for a local condition
114
why are buccal/ sublingual drug delivers used for the treatment of epilepsy
Buccal/sub-lingual delivery is useful since it avoids first-pass metabolism, provides a rapid onset of action (sublingual), controlled drug release (buccal) and avoids acid/ digestive enzymes in the lower GIT.
115
what are the issues associated with buccal/ sub-lingual drug delivery
The main problem with delivery via the oral cavity is patient acceptability, because of the taste or mouth-feel. The epithelium isn’t designed for absorption; there is only a small surface area. The best absorption is in the thinnest areas (sublingual). Molecules that are absorbed best are smaller, stable, potent, lipophilic (LogP 1.6-3.3, MW >600). Retention (duration of activity) is limited due to salivary washout, which removes the drug. Distribution within the oral cavity is limited by saliva; drug follows saliva, which pools in the lower part of the oral activity before being swallowed.
116
name the different formulations of buccal/ sub-lingual drug delivery
Midazolam buccal solution may be used but is unlicensed in the UK.
117
how does neurone pass signals to one another
the main form of communication between neurone occurs through the travelling wave electrical excitation called action potential. an action potential is the synchronising of opening and closing of ion channels.
when at res the inside of the neurone is slightly more negative than the outside.an action potential starts when voltage gated sodium channels ope allowing positively charged sodium ions to rush into the cell thus reversing the polarisation of the membrane.
membrane depolarisation leads to the opening of high voltage activated calcium channels which then allows calcium ions to enter the neurone therefore triggering glutamate from the vesicles into the synaptic cleft.
next glutamate binds to two types of receptors on the post-synaptic neurone
1) AMPA receptors that upon binding to glutamate, opens and permits entry of the sodium ions.
2) NMDA receptors that open and permit entry of calcium ions
in addition calcium may enter through low-voltage activated calcium channels also known as t-type calcium channels which open in response to small depolarisation at or below resting membrane potential
all the influx of positively charged ions, again leads to depolarisation and propagation of action potential. if there is too much glutamate around neurone, this can lead to hyper-excitability and seizures may result in seizures. this doesn't usually happen because there are also inhibitory neurone around that reduce excitable impulses. these inhibitory neurones release neurotransmitters GABA which binds to GABA-A receptors on the excitatory neurone. causes them to open and allow negatively charged chloride ions to enter in.
this causes an membrane potential to be more negative inside than outside and therefore limiting the neurones ability to respond to further stimulation. once GABA dissociates with GABA-A receptor, it becomes removed from the synaptic cleft by re-uptake through GABA-transporter- 1 and it is degraded by an enzyme GABA-T. too little glutamate can also cause hyper excitability in neurones which can also cause seizures
118
what is meant by a antiepileptics
used to prevent or control epilepsy commonly known as seizures.
119
what is a seizure
a seizure is a sudden burst of uncontrolled electrical activity in the brain that occurs when neutrons becomes excessively active.
120
how are seizures classified
generally classified into 2 major groups depending on where they begin in the brain.
FOCAL SEIZURE: affects initially one portion of the brain typically one hemisphere and may occur with or without impairment of awareness
GENERALISED SEIZURES: affects both sides of the brain at the same time and almost always causes loss of consciousness
121
how can seizures be viewed
seizures can be viewed as the result of an imbalance between inhibitory and excitatory processes in the brain that produce either too little inhibition or too much excitation.
122
what is the aim for anti epileptic drugs
the therapeutic intervention is simply to lower neural excitability and/or enhance neural inhibition.
123
describe how blocking voltage gated sodium channel will help epileptic patients?
one way is to prevent excessive firing of an action potential in neurones by blocking the voltage gated sodium channels. this reduces the amount of sodium from entering the neurone.
examples of these drugs includes Carbamazepine, Oxcarbazepine, Lamotrigine, phenytoin, topiramate, valproic acid and zonisamide
124
describe how blocking calcium channels will help epileptic patients?
it slows down hyper activity neurones by blocking calcium channels. works by inhibiting high voltage activated calcium channels.
examples of these drugs includes lamotrigine and topiramate and drugs that inhibit low voltage activated t-type calcium channels such as valproic acid and zonisamide
note- a lot of anti-epileptics drugs act on more than one target which can inhibit both calcium and sodium channels
topiramate has been shown to also inhibit excitatory neurotransmitters by blocking AMPA receptors
125
how does Gabapentin and pregabalin work as an anti epileptic drug?
they work by exerting their effects by interacting with high voltage activated calcium channels. however gabapentin and pregabalin bind to a subunit of the high voltage activated calcium channel called alpha-2-delta 1. because the presynaptic channels that contain this specific subunit of alpha-2-delta-1. this appears to modulate the release of excitatory neurotransmitters such as glutamate.
inhibition of alpha-2-delta-1 containing calcium channels by gabapentin and pregabalin is one of the main reasons for their anti epileptic effects
126
how does Levetiracetam work an an anti-epileptic?
it is an high voltage activated calcium channel blocker. works by binding to SV2A protein that is bound to the walls of the vesicles that contains glutamate. this binding impairs the synaptic release of glutamate and thus decrease in neural excitability.
FELBAMATE inhibits excitatory neurotransmission by blocking NMDA receptors.
127
what drugs act on the GABA system?
benzodiazepines and barbiturates which work by binding to GABA-A receptors therefore prolonging the opening of the channel and permitting greater influx of negatively charged chloride ions into the neurone
Tiagabine which is a selective inhibitor of the GABA transporter. it blocks the GABA reuptake therefore permitting more GABA to be available for receptor binding on the post synaptic neurone.
Vigabatrin which irreversibly inhibit GABA-amino transferas. the enzyme is responsible for catabolism of GABA therefore increasing concentration of GABA in the brain.
128
what are side effects associated with anti epileptics?
```
sedation, dizziness
visual field loss or double vision
cognitive problems
peripheral oedema
liver toxicity
```
129
what is the first line for seizures for generalised seizures:
First line: sodium valproate
| Second line: lamotrigine or carbamazepine
130
what is the first line for focal seizures?
First line: carbamazepine or lamotrigine
| Second line: sodium valproate or levetiracetam
131
what is meant by absence seizure
Absence seizures typically happen in children. The patient becomes blank, stares into space and then abruptly returns to normal. During the episode they are unaware of their surroundings and won’t res
132
what is the first line treatment is absence seizures?
First line: sodium valproate or ethosuximide
133
what is meant by atonic seizures?
Atonic seizures are also known as drop attacks. They are characterised by brief lapses in muscle tone. These don’t usually last more than 3 minutes. They typically begin in childhood. They may be indicative of Lennox-Gastaut syndrome
134
what is the treatment of atonic seizures?
First line: sodium valproate
| Second line: lamotrigine
135
what is meant by myoclonic seizures
Myoclonic seizures present as sudden brief muscle contractions, like a sudden “jump”. The patient usually remains awake during the episode. They occur in various forms of epilepsy but typically happen in children as part of juvenile myoclonic epilepsy.
136
what is the management of myoclonic seizures?
First line: sodium valproate
| Other options: lamotrigine, levetiracetam or topiramate
137
how to diagnose and investigate a seizure
An electroencephalogram (EEG) can show typical patterns in different forms of epilepsy and support the diagnosis. Perform an EEG after the second simple tonic-clonic seizure. Children are allowed one simple seizure before being investigated for epilepsy.
An MRI brain can be used to visualise the structure of the brain. It is used to diagnose structural problems that may be associated with seizures and other pathology such as tumours. It should be considered when:
The first seizure is in children under 2 years
Focal seizures
There is no response to first line anti-epileptic medications
Additional investigations can be considered to exclude other pathology that may cause seizures:
ECG to exclude problems in the heart.
Blood electrolytes including sodium, potassium, calcium and magnesium
Blood glucose for hypoglycaemia and diabetes
Blood cultures, urine cultures and lumbar puncture where sepsis, encephalitis or meningitis is suspected
138
what is the general advise for people who are epileptic
Patients and families presenting with seizures need to be given advice about safety precautions, recognising, managing and reporting further seizures. It is important to avoid situations where a seizure may put the child in danger, with advise to:
Take showers rather than baths
Be very cautious with swimming unless seizures are well controlled and they are closely supervised
Be cautious with heights
Be cautious with traffic
Be cautious with any heavy, hot or electrical equipment
Older teenagers with epilepsy will need to avoid driving unless they meet specific criteria regarding control of their epilepsy. These rules change frequently so it is always worth looking them up if advising patients.
139
describe the MoA sodium valproate
This is a first line option for most forms of epilepsy (except focal seizures). It works by increasing the activity of GABA, which has a relaxing effect on the brain. Notable side effects of sodium valproate include:
Teratogenic, so patients need careful advice about contraception
Liver damage and hepatitis
Hair loss
Tremor
There are a lot of warning about the teratogenic effects of sodium valproate and NICE updated their guidelines in 2018 to reflect this. It must be avoided in girls unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant
140
describe the side effects of Carbamazepine
This is first line for focal seizures. Notable side effects are:
Agranulocytosis
Aplastic anaemia
Induces the P450 system so there are many drug interactions
141
Phenytoin-side effects
Notable side effects:
```
Folate and vitamin D deficiency
Megaloblastic anaemia (folate deficiency)
Osteomalacia (vitamin D deficiency)
```
142
Ethosuximide- side effects
Notable side effects:
Night terrors
Rashes
143
Lamotrigine- side effects
Notable side effects:
Stevens-Johnson syndrome or DRESS syndrome. These are life threatening skin rashes.
Leukopenia
144
what is the management of seizures
Put the patient in a safe position (e.g. on a carpeted floor)
Place in the recovery position if possible
Put something soft under their head to protect against head injury
Remove obstacles that could lead to injury
Make a note of the time at the start and end of the seizure
Call an ambulance if lasting more than 5 minutes or this is their first seizure.
145
Management of status epileptics in the hospital
Secure the airway
Give high-concentration oxygen
Assess cardiac and respiratory function
Check blood glucose levels
Gain intravenous access (insert a cannula)
IV lorazepam, repeated after 10 minutes if the seizure continues
If the seizures persist the final step is an infusion of IV phenobarbital or phenytoin. At this point intubation and ventilation to secure the airway needs to be considered, along with transfer to the intensive care unit if appropriate.
146
what is the presentation for some who has epilepsy?
* Syncope, where insufficient blood to the brain caused the patient to faint
* Hyperventilation
* Migraine
* Panic attack
* Pseudo seizure (non-epileptic attack), which is where a patient presents with a convulsion in the absence of abnormal electroactivity; it is thought to be a psychological issue
* Transient global amnesia
* Transient ischaemic attack
147
what are some of the causes of epilepsy?
```
Hypo/hyperglycaeimia
• Hypo/hypernatraemia
• Hypocalcaemia
• Hypomagneseamia
• Uraemia
• Drugs (phenothiazines, benzodiazepine withdrawal, antibiotics, antidepressants, EtOH, tramadol, antiepileptics, ciclosporin, cocaine, lithium, inteferons, barbiturates)
• Meningitis
• Encephalitis
• Head trauma
• Space Occupying Lesion
• Stroke / TIA
• Genetics (polygenetic)
• Epileptogenisis
```
148
There are two broad categories of epilepsy: Generalised (global) and Partial (focal).
There are two broad categories of epilepsy: Generalised (global) and Partial (focal).
Generalised epilepsy affects the whole brain. The following types of epilepsy fall under this category:
• Absences (petit mal)
• Tonic-clonic (grand mal)
• Myoclonic (Juvenile myoclonic epilepsy)
• Tonic
• Akinetic – all muscle tone is lost, resulting in falls thus risk of head injury
Partial epilepsy affects a local area of the brain. The following types of epilepsy fall under this category:
• Simple – consciousness is maintained, so the patient is aware of the seizure
• Complex – impaired awareness
• Secondary generalised (aka Focal to bilateral tonic-clonic seizures) – starts local, then becomes generalised
