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Y2 - BRS - Pharm > Pharmacology of Epilepsy > Flashcards

Pharmacology of Epilepsy Flashcards

1
Q

What are the 4 most common main drug classes prescribed for epilepsy / convulsions?

A
  1. Lamotrigine
  2. Sodium valproate
  3. Diazepam
  4. Levetiracetam
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2
Q

What is the primary mechanism of action for Lamotrigine?

A

Blocks voltage gated Na+ channels preventing Na+ influx

Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity

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3
Q

What is the drug target site for Lamotrigine?

A

Voltage gated Na+ channels

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4
Q

What are the main side effects for Lamotrigine?

A

Side effects:

Common: Rash, drowsiness

Less common but serious:

Steven-Johnson’s syndrome, suicidal thoughts

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5
Q

What is some extra information about Lamotrigine?

A

Introducing lamotrigine gradually is one of the keys to reducing the frequency and severity of allergic skin reactions

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6
Q

What is the primary mechanism of action for Sodium valproate?

A

Inhibition of GABA transaminase prevents the breakdown of GABA
This increases GABA concentrations directly in the synapse presynaptically and also indirectly prolongs GABA in the synapse due to the fact that extraneuronal metanolism of GABA is slowed which also slows GABA removal from the synapse

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7
Q

What is the drug target site for Sodium valproate?

A

GABA transaminase

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8
Q

What are the main side effects for Sodium valproate?

A

Side effects (MANY):

Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss

Serious:

hepatotoxicity, teratogenicity, pancreatitis

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9
Q

What is some extra information about Sodium valproate?

A

Broad CYP enzyme inhibitor - increases serum concentration of many co-administered drugs



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10
Q

What is the primary mechanism of action for Diazepam?

A

Increases choride ion influx in response to GABA binding at the GABA A receptor. Increased chloride ion influx associated with hyperpolarisation of excitatory neurones

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11
Q

What is the drug target site for Diazepam?

A

Benzodiazepine site on the GABA A receptor

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12
Q

What are the main side effects for Diazepam?

A

Side effects:

Common: Drowsiness, respiratory depression (if i.v. or at high dose)

Uncommon but serious:

Haemolytic anaemia, jaundice

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13
Q

What is some extra information about Diazepam?

A

Main reason that diazepam is not used for long term suppression of seizures is due to the development of tolerance

Diazepam is a Schedule 4 controlled drug - addiction prone individuals more likely to become dependent on diazepam

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14
Q

What is the primary mechanism of action for Levetiracetam?

A

Inhibition of the synaptic vesicle protein SV2A. It inhibits this protein and prevents vesicle exocytosis. A reduction in glutamate secretion is reduces glutamate excitotoxicity

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15
Q

What is the drug target site for Levetiracetam?

A

Synaptic vesicle protein SV2A

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16
Q

What are the main side effects for Levetiracetam?

A

Common:

dizziness, somnolence, fatigue and headache

17
Q

What is some extra information about Levetiracetam?

A

The metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system so it is favorable in terms of no drug–drug interactions

18
Q

What are the first three steps for pharmacology?

A

Identify the patient’s problem
Specify the therapeutic objective
Select a drug

19
Q

Essie = 21F referred to first seizure/urgent assessment neurology clinic from A&E after a single episode of collapse with jerking.

Was sitting and chatting on the sofa, and the next thing she remembers is feeling disorientated on the floor. Stressed lately, not much sleep. Essie’s boyfriend confirms Essie lost consciousness and started convulsing before she ‘came around’ a minute later. Essie makes strange quick jerk of her arms when she wakes up in the morning. 18 months ago – one minute she was putting her gym clothes on and next she was on the floor feeling confused.

A full physical examination is performed and Essie is sent for an EEG.

In A&E – Urea, electrolytes , calcium and glucose: All normal

General and neurological examinations were normal

What is the patient’s problem?

A

Epilepsy

Tonic clonic seizures
Myoclonic seizures

20
Q

What are the types of seizures?

A 
Absence
Focal
Generalised tonic-clonic
Myoclonic
Tonic or atonic
21
Q

What are the stages of tonic-clonic seizures?

A

Tonic stage: lose of consciousness, stiffening of the body

Clonic stage: Jerk

22
Q

What did the EEG show?

A

Interictal epileptiform discharge - risk of seizure recurrence

23
Q

What is the therapeutic objective for the patient?

A

Reduce severity of seizures
Reduce frequency of seizures
Prevent long term effects
Identify triggers (stress, lack of sleep etc.)
Educate patient
Friends and family should be educated on management of seizures

24
Q

What are the main goals of anti-epileptic drug treatment?

A

Eliminate seizures or reduce frequency
Evade the adverse effects associated with long term treatment

Aid patients in maintaining or restoring their usual psychical and vocational activities and in maintaining a normal lifestyle

25
Q

What drugs could be give to treat tonic-clonic seizures in women of child bearing age?

A

Lamotrigine or Carbemazepine

26
Q

What is the mechanism of action of Lamotrigine?

A

Blocks voltage gated Na+ channels preventing Na+ influx

Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity

27
Q

Why is sodium valproate not given to women of child bearing age?

A

Can cross placental barrier and cause physical birth defects or developmental uses

e.g. Neural tube defects
Decreased IQ

28
Q

Why might the OCP affect Lamotrigine concentration?

A

OCP may impact lamotrigine absorption so less gets into the blooding the first place

OCP may enhance metabolism so more is cleared from the blood

OCP may enhance excretion of Lamotrigine

29
Q

She begins taking the OCP, why might she be feeling more drowsy during the fourth week of her cycle?

A

During the fourth week of contraceptive cycle you stop taking the OCP

Therefore the concentration of the anti-epileptic while be twice as high in the fourth week as there is nothing reducing its concentration.

Increasing the side effects of Lamotrigine one of which is drowsiness

30
Q

What are the side effects of Lamotrigine?

A 
Dizziness
Diarrhoea
Loss of balance
Abnormal eye movements
Trouble speaking
Drowsiness
31
Q

What is the mechanism of action levetiracetam?

A

Inhibition of the synaptic vesicle protein SV2A

It inhibits this protein and prevents vesicle exocytosis

A reduction in glutamate secretion is reduces glutamate excitotoxicity

32
Q

What is the mechanism of action of Sodium Valproate?

A

Inhibition of GABA transaminase prevents the breakdown of GABA

This increases GABA concentrations directly in the synapse presynaptically and also indirectly prolongs GABA in the synapse due to the fact that extraneuronal metanolism of GABA is slowed which also slows GABA removal from the synapse

33
Q

What adjuvant therapy would you offer the patient?

How would administration differ in community or in hospital?

A

Benzodiazepines e.g. IV lorazepam

But continue usual therapy

In community take drug orally due to absence of trained staff to administer IV or rectally

34
Q

Essie - individuaalised treatment:

A

Oestrogens are generally thought of as seizure promoting and progesterone has been shown to be seizure inhibiting. Many women have an increased frequency of seizures during a particular phase of the ovulatory cycle e.g. day 10-13 (periovulatory estrogen peak)

If lamotrigine is effective and well tolerated by Essie, then the simplest solution will be to change her oral contraceptive to a long-term progesterone implant such as Implanon/Nexplanon

If Essie were to get pregnant later in life there is a chance her seizure frequency could increase. Lamotrigine dose may be reduced due to fears of harming the unborn child. In addition, pregnancy may lead to changes in liver metabolism. As a result, lamotrigine levels may decrease and be associated with increased seizures. Essie would need to have serum lamotrigine checked at the beginning of pregnancy and during the second and third trimester. Dose could then be adjusted as described.

Y2 - BRS - Pharm (9 decks)

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