Letcure 24 - Epilepsy And Antiepileptics Flashcards

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1
Q

What is the main excitatory neurotransmitter?

A

Glutamate

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2
Q

What is the main receptor which the excitatory neurotransmitter glutamate acts at?

A

NMDA receptor

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3
Q

What is the main inhibitory neurotransmitter in the brain?

A

GABA

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4
Q

What are the receptors which the main inhibitory neurotransmitter GABA acts on in the brain?

A

GABA alpha and beta receptors

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5
Q

What happens when glutamate binds to NMDA receptors?

A

Influx of Na+ and Ca2+ leading to depolarisation

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6
Q

What happens when GABA binds to a GABA receptor?

A

Cl- influx
Causes membrane hyperpolarisation reducing firing

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7
Q

What are seizures?

A

Clinical manifestation of abnormal excessive excitation and synchronisation of a group of neurones within the brain (is sudden and temporary)

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8
Q

What causes seizures?

A

Loss of inhibitory signalling
Unchecked excitatory signalling
Post tetanic potentiation

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9
Q

What are non epileptic seizures called?

A

Dissociative seizures

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10
Q

What are some causes of dissociative (non epileptic seizures)?

A

Drugs
CNS infection
Alcohol
Hypoglycaemia
Pyrexia

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11
Q

What are some causes of non epileptic seizures in kids?

A

Febrile convulsions
Breath-holding attacks
Night terrors
Stereotyped ritualistic behaviour

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12
Q

What is an epileptic seizure?

A

A transient occurrence of signs and or symptoms due to abnormal excessive or synchronous neuronal activity in the brain

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13
Q

What is epilepsy?

A

A disorder of the brain characterised by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition

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14
Q

What are the risk factors for epilepsy?

A

Premature
Complicated febrile seizure (can be linked to whooping cough)
Genetic conditions (tuberous Sclerosis, neuorfibromatosis)
Head trauma, infection, tumour
Cererbrovascular disease
Dementia and Neurodegenerative disorders

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15
Q

What is epilepsy simplified?

A

Tendency toward recurrent seizures unprovoked by a systemic or neurological insult

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16
Q

What is an epilepsy syndrome?

A

A condition that is not epilepsy but causes epilepsy like condition

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17
Q

What is an epilepsy syndrome?

A

GLUT 1 deficiency

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18
Q

How do we diagnose epilepsy?

A

Urgent referral following first suspected seizure
Assess risk of second seizure
First aid and saftey. Guidance
Detailed Hx

EEG
Neuroimgaing

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19
Q

What neuroimaging is first line for diagnosing epilepsy?

A

MRI

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20
Q

What are the 2 types of seizures that can be seen in epilepsy?

A

Focal seizures
Generalised seizures

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21
Q

What are focal seizures?

A

Seizures that often have focal impaired awareness

So remain conscious but unaware of what’s happening

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22
Q

What is a tonic-clonic seizure?

A

Where there’s violent jerking

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23
Q

Why do you have to give IV fluids when having tonic-clinic seizures?

A

Hyperhidrosis occurs (excess sweating)

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24
Q

What are the 2 main types of seizure?

A

Focal onset
Generalised onset

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25
Q

What are the types of focal onset seizures?

A

Aware, impaired awareness

Can be motor onset and nonmotor onset

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26
Q

What are the types of generalised onset seizures?

A

Motor seizures (tonic-cloning)

Non motor (absence)

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27
Q

What are the 3 main types of seizures?

A

Generalised seizures
Absence seizures
Focal seizure

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28
Q

What is prodrome?

A

Early signs or symptoms a seizure may be coming hours to days before

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29
Q

What is aura?

A

A warning,focal awareness seizure leading to secondary generalised

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30
Q

What is the meaning of ictal?

A

During a seizure

31
Q

What is interictal?

A

Between seizures in reference t EEG

32
Q

What is post ictal?

A

Begins as seizure subsides last minutes to hours

Confusion, lack of consciousness, fatigue, headache, anxiety, frustration, embarrassment, muscle aching or pain

33
Q

What is sudden unexplained death in epilepsy?

A

Sudden Death that occurs in patients with epilepsy that not linked to seizures

34
Q

What is the mechanism of action of carbamazepine?

A

Blockage of Na+ channels leading to reduced Ca2+ influx leading to reduced glutamate release (excitatory)

35
Q

What is carbamazepine used to treat?

A

Epilepsy
Trigeminal neuralgia

36
Q

What are the adverse drug reactions of Carbamazepine?

A

Dizziness
Skin rash (Steven Johnson syndrome)
Eosinophilia
Leukopenia
Hyponatraemia

37
Q

What are the contraindications to carbamazepine?

A

Teratogenic (neural tube defects)
Bone marrow depression
AV conduction issues
HLA-B 1502 allele

38
Q

What are the drug-drug interactions of carbamazepine?

A

Is a CYP3A4 inducer (dec effect of COCP) and inc Warfarin metabolism (reduced effect of warfarin)

CYP3A4 inhibitors affect it: clarithryomycin, diltiazem increasing the concentration of carbamazepine

It induces its own metabolism reducing its half life needed a dose increased

39
Q

What is the mechanism of action of phenytoin?

A

Blocks Na+ channels, preventing Ca2+ influx and reducing glutamate release

exactly the Same as carbamazepine

40
Q

What is phenytoin used for?

A

2nd line in status epilepticus

41
Q

Why is dosing with phenytoin very important?

A

Has zero order elimination kinetics so rate of elimination is constant
Therapeutic window is narrow and small change in dose can drastically change plasma conc

42
Q

What are the adverse reactions of phenytoin?

A

Lots
Dizziness
Skin rash (Steven Johnson syndrome)
Visual disturbance
Gingival hyperplasia
Arrhythmia

43
Q

What are the contraindications to phenytoin?

A

Is teratogenic often cuasing facial and digital defects
Acute porphyria’s
Bone marrow depression

44
Q

What are the drug drug interactions phenytoin?

A

Is a CYP inducer so decreases the plasma conc of drugs like COCP, Abx and other antiepileptics

45
Q

What is the mechanism of action of sodium valproate?

A

Multiple sites including Na+ channels
Increases GABA synthesis and transcription of channel coding genes

46
Q

What is sodium valproate used for?

A

Epilepsy

47
Q

What are the adverse effects of sodium valproate?

A

Hepatotoxicity
Appetite stimulant
Alopecia
Thrombocytopenia

48
Q

What are the contraindications of sodium valproate?

A

Teratogenic (causes major malformation in pregancy)
Avoided in pregnancy unless pregnancy programme in place

49
Q

What are the drug drug interactions of sodium valproate?

A

It increases the conc of Lamotrigine, phenytoin and sodium valproate
Hepatotoxicity

50
Q

Why do you need a family planing pregancy prevention programme for women’s taking Anti epileptics?

A

Teratogenic

51
Q

What anti epileptic drug should only ever be given in women of child bearing age if a pregnancy prevention programme is in place/

A

Sodium valproate

52
Q

What is the pregancy prevention programme?

A

At least one highly effective contraception method or two complimentary forms including barrier method

53
Q

What is the method of action of lamotrigine?

A

Na+and Ca2+ channel blocker selectively blocking neurones

Selective for dendrites of pyramidal neurones

54
Q

What are the adverse effects of lamotrigine?

A

Aggression
Agitation
Hypersensitivity

55
Q

What are the contraindications of lamotrigine?

A

Phase 2 metabolism makes it have a long half life

56
Q

What are the drug-drug interactions of lamotrigine?

A

Sodium valproate increases conc of lamotrigine
Phenytoin and oral contraceptives decreases conc of lamotrigine

57
Q

What is the mechanism of action of levetiracetam?

A

Inhibts synaptic vesicle protein 2A so decreases synchronised burst firing without affecting neuronal excitability

58
Q

What is levetiracetam used for?

A

Focal seizures including secondary generalisation

Safer options for PREGNANCY

59
Q

What are the adverse effects of levetiracetam?

A

Anxiety
Drowsiness
Dizziness

All common to all anti epileptics

60
Q

What are the contraindications to levetiracetam?

A

QT prolonging risk factors

61
Q

What are the drug drug interactions of levetiracetam?

A

CNS depressants which is the same with other anti epileptics

62
Q

How do you decide to initiate and titrate doses of antiepileptics?

A

Start at low dose and mono therapy is desirable
Aim to be seizure free balanced with acceptable side efffect profile

63
Q

What are the benzodiazepine drugs?

A

Diazepam
Lorazepam
Midazolam

64
Q

What is the mechanism of action of the benzodiazepines?
(Diazepam, lorazepam and midazolam)

A

Bind to Allosteric site at GABA receptors enchancing hte activity of GABA to hyperpolarising membranes via Cl- influx

65
Q

How does the duration of action of midazolam differ to diazepam?

A

Midazolam = short acting
Diazepam = longer acting

66
Q

Which benzodiazepine is best in hepatic dysfunction?

A

Lorazepam

67
Q

What are the adverse effects of benzodiazepines?

A

Ataxia
Depression
Drowsiness
Hypotension
Muscle weakness
Sleep disorders

68
Q

What are the contraindications of benzodiazepines?

A

Cause resp depression at high doses

69
Q

What are the drug-drug interactions of benzodiazepines?

A

Other CNS depressants

70
Q

What is the first line drug in convulsive status epilepticus?

A

IV lorazepam

Buccal midazolam if cant get a line in
Or per rectal diazepam

71
Q

What is convulsive status epilepticus?

A

Epileptic seizure lasting 5 minutes or more or multiple seizures without recovery in between

A MEDICAL EMERGENCY

72
Q

What is the steps of treatment for status epilepticus?

A

Benzodiazepine first line (IV LORAZEPAM)
Immediately prepare 2nd dose of benzodiazepine
Give 2nd dose after 5-10mins
If that doesn’t work give 2nd line levetiracetam, phenytoin or sodium valproate
If doesn’t work give a different second line agent to what you gave
If doesn’t work then give barbiturates or general anaesthesia

Always get help. And treat metabolic derangement like glucose and electrolytes

73
Q

What is important when prescribing antiepileptics?

A

Always stick to the same specific brand or generics cuz they may differ slightly
Specific brand and generic may be same but there may be differences between generics