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PR3153 > IC4 Anti-epileptic & Anti-migraine medications > Flashcards

IC4 Anti-epileptic & Anti-migraine medications Flashcards

1
Q

How is signal transduced within a neuron?

A

Electrically

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2
Q

How is signal transduced between neurons?

A

Biochemically

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3
Q

What is the function of astrocytes?

A

Astrocytes provide:
1. Trophic support - a variety of chemical signals that neurons need to continue living

  1. Electrolyte balance
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4
Q

What are the function of oligodendrocytes and Schwann cells?

A

They both produce myelin sheath.

Oligodendrocytes - CNS
Schwann cells - PNS

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5
Q

What is the voltage when a neuron is at resting membrane potential (RMP)?

A

-70mV

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6
Q

Describe the process of a neuron transducing an electrical signal within itself.

A

At rest, the neuron has a RMP of -70mV.

When it is triggered by a signal, neuron depolarises to -50mV. This triggers the opening of the voltage gated Na+ channel..

Once the neuron reaches +50mV, the Na+ channels closes and the voltage gated K+ channels open. This leads to an efflux of K+

https://encrypted-tbn2.gstatic.com/images?q=tbn:ANd9GcQ0bznpEDa3IU07WyHGs_UPxbm29ZGPWFIDTLSYKL6X6HG3MssY

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7
Q

Describe the process of a neuron transducing an biochemical signal across to another neuron.

A

Vesicles containing neurotransmitters are anchored away from the presynaptic membrane by Ca2+ sensitive vesicle membrane protein (VAMPs).

When action potential reaches terminal, voltage gated Ca2+ channels open. This leads to an influx of Ca2+.

The Ca2+ acts on the VAMPs to release the vesicles and facilitate fusion of the vesicle with the presynaptic membrane, leading to exocytosis.

Neurotransmitters present in the synaptic cleft proceeds to activate the postsynaptic receptors.

Signal transmission is then inhibited via feedback inhibition by catalytic enzymes and/or reuptake transporters.

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8
Q

What are the 4 types of neurotransmitters?

A
  1. Glutamate
  2. GABA
  3. Acetylcholine
  4. Dopamine
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9
Q

What is the function of glutamate?

A

Glutamate is the major transmitter in excitory synapses.

Presynaptic neuron releases glutamate, which directly correlates w postsynaptic depolarisation.

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10
Q

What is the function of GABA?

A

GABA is the major transmitter in inhibitory synapses.
Presynaptic neuron releases GABA which inversely correlates with postsynaptic inhibitory potential.

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11
Q

What is a seizure?

A

It is a paroxysmal event due to an abnormal hypersynchronous discharge from a mass of CNS neurons.

A seizure occurs when there is excessive synchronous depolarization, usually starting from defined region before spreading to other regions.

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12
Q

Can epilepsy be cured?

A

No, epilepsy is not a curable disease. It can only be treated and maintained.

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13
Q

What are the 3 broad types of seizures?

A
  1. Generalized seizures
  2. Partial seizures
  3. Status epilepticus

https://www.cdc.gov/epilepsy/about/types-of-seizures.htm

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14
Q

What are the 4 types of generalized seizures?

A
  1. Tonic Clonic (aka Grand mal)
  2. Absence (aka petit mal)
  3. Myoclonic - Short jerking in parts of the body.
  4. Atonic - Muscles in the body relax.

https://www.cdc.gov/epilepsy/about/types-of-seizures.htm

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15
Q

What are the 2 types of partial seizures?

A
  1. Simple partial seizure (consciousness not impaired)
  2. Complex partial seizure (consciousness impaired)
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16
Q

What do we use to measure if a patient is having a seizure?

A

Electroencephalogram (EEG)

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17
Q

Describe what happens to a person when he/she is undergoing tonic-clonic seizures?

A

Tonic-clonic seizures, also called grand mal seizures, can make a person:

  1. Cry out.
  2. Lose consciousness.
  3. Fall to the ground.
  4. Have muscle jerks or spasms.

The person may feel tired after a tonic-clonic seizure.

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18
Q

Describe what happens to a person when he/she is undergoing absence seizures?

A

Absence seizures (aka petit mal seizures), can cause rapid blinking or a few seconds of staring into space.

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19
Q

What is the general MOA of antiepileptics?

A
  1. To decrease membrane excitability via altering Na+ & Ca2+ conductance during action potential
  2. Enhance effects of GABA.
    GABA allow Cl- influx into the cell, causing membrane potential to become negative.
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20
Q

What are the 3 first-line antiepileptics?

A
  1. Phenytoin
  2. Carbamazepine
  3. Sodium valproate

Other antiepileptics:
4. Benzodiazepine
5. Barbiturates
6. Levetiracetam
7. Lamotrigine
8. Topiramate

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21
Q

What is phenytoin’s MOA?

A

It is a Na+ channel blocker.

Note: It has a narrow therapeutic index of 40-100µM

22
Q

What type of seizures can Phenytoin be used for?

A

It can be used in all types of seizures, except absence seizures.

23
Q

Can phenytoin be used in pregnant women?

A

No, phenytoin is teratogenic.

It should not be given to pregnant patients or women of reproductive age

24
Q

What is carbamazepine’s MOA?

A

It is a Na+ channel blocker.

25
Q

What type of seizures can carbamazepine be used for?

A

It can be used for all types of seizures, except absence seizures.

26
Q

What do we have to do before we use carbamazepine?

A

We have to conduct pharmacogenetics testing for HLA-B*1502 before using carbamazepine.

Those positive for HLA-B*1502 are at greater risk of SJS & TEN.

27
Q

Which race experiences greater risk of SJS and TEN associated with carbamazepine use?

A

Asians

28
Q

What is Valproate’s MOA?

A

It is both a Na+ and Ca2+ channel blocker.

It also inhibits the enzyme that metabolises GABA, leading to increased GABA.

29
Q

What type of seizures can Valproate be used for?

A

All seizure types.
(Including absence seizures)

Note: Phenytoin and Carbamazepine are only Na+ channel blockers. Both cannot be used in absence seizure.

However, Valproate is both a Na + and Ca2+ & is able to be used for absence seizure.

Could Ca2+ blockade be essential in management of absence seizure?

30
Q

Is Valproate highly protein bound or poorly protein bound??

A

Highly protein bound

31
Q

What are the some of the general ADRs associated with antiepileptics use?
(State Dose-related ADRs)

A
  1. Drowsiness
  2. Confusion
  3. Nausea
    4.Uncontrolled eye movement
  4. Loss of coordination
  5. Slurred speech
  6. Coma
32
Q

What are some of the general ADRs associated with antiepileptics use?
(State non-dose-related ADRs)

A
  1. Acne
  2. Hirsutism
  3. Swollen & overgrown gums
  4. Folate deficiency
  5. Hypersensitivity rxn
33
Q

What is the MOA of benzodiazepines?

A

Benzodiazepines enhances the inhibitory effects of GABA.

They have an addictive effect, which makes them dangerous to use.

E.g Diazepams

34
Q

Which benzodiazepines are intermediate acting and long acting?

  1. Clonazepam
  2. Lorazepam
  3. Diazepam
A

Clonazepam and lorazepam are intermediate acting.

Diazepam is long acting.

35
Q

What is the main ADR of benzodiazepines?

What can we use to reverse the ADR of benzodiazepines?

A

The main ADR of benzodiazepines is respiratory depression, especially if used concurrently w alcohol.

Treatment agent of benzodiazepine ADR:
- flumazenil - a benzodiazepine antagonist

36
Q

What is the MOA of barbiturates?

A

They enhance GABA effect as well, but at a different site from benzodiazepines.

37
Q

Can flumazenil be used to reverse barbiturate toxicity?

A

No, flumazenil is not effective in barbiturate overdose.

Flumazenil is the reversal agent for benzodiazepines.

Barbiturates are worse than diazepam, where they have higher chance of causing tolerance & dependence.

Barbiturates are in fact so dangerous that we do not use it often anymore. It can induce coma.

38
Q

How is levetiracetam used in practice?

A

It is primary used as an adjunctive therapy for:

  1. Tonic-clonic seizures (generalized seizure)
  2. Myoclonic seizures (generalized seizure)
  3. Partial seizures

It can also be used as monotherapy for onset partial seizures in newly diagnosed epilepsy patient.

39
Q

How is lamotrigine used in practice?

A

Lamotrigine can be used as adjunctive or monotherapy for generalized seizures & partial seizures.

This includes absence seizures.

Important: Lamotrigine can also be used for Lennox-Gastaut Syndrome - (a type of childhood epilepsy)

40
Q

What is the most dangerous ADR of levetiracetam and lamotrigine that we must monitor for?

A

Agranulocytosis

41
Q

How is topiramate used in practice?

A

Topiramate is used as monotherapy of tonic-clonic seizures and partial seizures.

It can also be used for Lennox-Gastaut Syndrome - (a type of childhood epilepsy)

42
Q

What is the drug strategy approach in treating a patient w antiepileptics?

A
  1. Drug treatment should be individualised.
  2. Pt should be commenced on monotherapy initially. If it is unsuccessful or pt develops ADR, monotherapy w another drug should be tried.
43
Q

What are the reasons to conduct testing of antiepileptic drug levels?

A
  1. For pt with refractory epilepsy, testing will allow us to assess the pt’s compliance to the drug treatment
  2. Allows us to assess symptoms that pt face and attribute to possible antiepileptic drug toxicity
  3. Allows us to titrate phenytoin’s dose
    - phenytoin has high variability and a narrow therapeutic index, we must monitor carefully
44
Q

What is the MOA that cause a headache or migraine?

A

Vasodilation of intracranial extracerebral blood vessels.

This leads to the activation of the trigeminal nerves, causing the release of vasoactive neuropeptides which trigger neurogenic inflammation.

45
Q

What are the 5 medications we can use for headache and migraine?

A

The 5 medications we can use are:
1. Cafergot
2. Sumatriptan
3. Erenumab
4. Paracetamol
5. NSAIDs

We only use cafergot, sumatriptan and erenumab when pt is refractive to paracetamol and NSAIDs.

46
Q

What is Cafergot used for?

A

It is used as acute treatment for migraine attacks.

47
Q

What is the MOA of cafergot?

A

It causes vasoconstriction of the intracranial extracerebral blood vessels, via the stimulation of a-adrenergic, 5-HTb & 5-HTd receptors.

48
Q

What is the DDI associated w cafergot?

A

Cafergot should not be used with CYP3A4 inhibitors.

It can result in ergot toxicity.

Cafergot also should not be used w other vasoconstrictor agents - e.g sumatriptan & other 5HT1 antagonist.

49
Q

What is sumatriptan used for?

A

It is used as acute treatment of migraine.

50
Q

What is the MOA of sumatriptan?

A

It is a selective vascular serotonin (5-HT1d) receptor antagonist.

It inhibits trigeminal activity.

51
Q

What is Erenumab used for?

A

Erenumab is used as prophylaxis of migraine in adults w at least 4 migraine days per month.

52
Q

What is the MOA of erenumab?

A

Erenumab is a calcitonin gene-related peptide (CGRP) inhibitor.
It blocks CGRP receptors.

CGRP are nociceptive neuropeptides that can trigger migraine like headaches.

PR3153 (18 decks)

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