Anticonvulsants for Pharmacology and Therapeutics Flashcards Preview

Y2 LCRS Pharm Fwong > Anticonvulsants for Pharmacology and Therapeutics > Flashcards

Flashcards in Anticonvulsants for Pharmacology and Therapeutics Deck (29)
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1
Q

What is a seizure?

A

Seizures are sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex ie UNCOORDINATED rapid firing of neurones in the brain (caused by INCREASE in EXcitatory neurotransmission or DECREASE in INhibitory neurotransmission)

2
Q

What is epilepsy?

A

A tendency to recurrent, unprovoked seizures

3
Q

What are the two main types of epilepsy?

A

Partial/Focal – the excess discharge is localised to one area of the brain
Generalised – the synchronised discharge affects all brain areas

4
Q

When are the two peaks in incidence of epilepsy and what are they usually caused by?

A

Young adults – where genetic predispositions begin to manifest
Later years – when patients start getting brain injuries e.g. stroke can cause seizures after the stroke due to brain damage

5
Q

What proportion of epilepsy is idiopathic?

A

70%

6
Q

What are absence seizures

A

brief staring episodes with behavioural arrest (NO JERKY MOVEMENTS etc. its essentially just someone going into a ‘quiet state’ staring at something)

7
Q

Describe the sequence of events in tonic clonic seizures

A
loss of consciousness
muscle stiffening (hence tonic)
jerking/twitching (hence clonic)
deep sleep 
wakes up (this seizure is what most people see in films etc)
8
Q

What are the main mechanisms of anti-epileptic drugs?

A

Inhibit Glutamate mediated excitation

  • VGSC inhibitor
  • VGCC inhibitor
  • SV2A inhibitor (synaptic vesicle protein)
  • glutamate receptor antagonist

Enhancing GABA mediated inhibition

  • benzodiazepines (Positive Allosteric Modulators)
  • GABA transaminase inhibitors (stop GABA breakdown)
9
Q

Give an example of a group of drugs that enhance GABA-mediated inhibition.

A

Benzodiazepines

10
Q

Name two drugs that inhibit glutamate-mediated excitation.

A

Presynaptic – levatiracetam

Postsynaptic – parampanel

11
Q

Name three drugs that exert their effect as AEDs by blocking action potentials (Na+ channel blockade).

A

Phenytoin
Carbamazepine
Lamotrigine

12
Q

What is the main mechanism of current anti-epileptic drugs?

A

Sodium channel blockade
It causes use-dependency blockade meaning that it only blocks the nerve conduction when the neurones are firing excessively (i.e. during a seizure) and so the drugs inhibit seizures without affecting normal cognitive function

13
Q

What does Levatiracetam bind to in order to inhibit glutamate release?

A

SV2A

This is a protein found on the synaptic vesicle membrane

14
Q

What are the two main excitatory receptors?

A

AMPA and Kainate (Na+/Ca2+ channel)

NMDA

15
Q

Name two important drugs that block the presynaptic calcium channel, hence preventing neurotransmitter exocytosis.

A

Gabapentin

Pregabalin

16
Q

Describe the difference in terms of the old and new anti-epileptics in terms of efficacy and pharmacokinetics.

A

The new ones are no more effective than the old ones at preventing seizures but they have better pharmacokinetics and are better tolerated

17
Q

What are the main principles of AED therapy?

A

Discuss risks and benefits with the patient
One AED where possible
Therapeutic drug monitoring is of little use
Never withdraw drugs suddenly (could cause status epilepticus)
Make one change at a time
Consider drug interactions

18
Q

Why is drug monitoring of little use with most AEDs? What is the exception?

A

Because of the blood-brain barrier, the amount of drug in the blood has little relationship with the amount in the brain
Exception – phenytoin

19
Q

What are the two main enzymes that are responsible for metabolizing phenytoin?

A

CYP4502C9 (mainly)

CYP2C19

20
Q

Describe the enzyme kinetics of phenytoin.

A

They are saturable
So once the enzymes get saturated, there is a large increase in plasma concentration of the drug for every small increase in dose

21
Q

Describe the effects of important AEDs on hepatic enzymes.

A

Phenytoin and Carbamazepine – hepatic enzyme INDUCERS

Valproate – hepatic enzyme INHIBITORS

22
Q

List some drugs that affect phenytoin metabolism/availability.

A

Amiodarone and isoniazid INHIBIT phenytoin metabolism
Aspirin displaces phenytoin from plasma protein binding thus increasing the amount of free phenytoin
Valproate displaces phenytoin from plasma protein binding and it INHIBITS phenytoin metabolism
Generally speaking, avoid using valproate and phenytoin together

23
Q

List some of the effects of phenytoin on other drugs.

A

Warfarin – increased metabolism of warfarin
Increased clearance of lamotrigine, corticosteroids, cyclosporin
Decreased effectiveness of the oral contraceptive pill

24
Q

State some drugs that induce carbamazepine metabolism.

A

Phenytoin

Phenobarbital

25
Q

What are the two most severe forms of allergic reaction to AEDs?

A

Stevens-Johnsons Syndrome

Toxic Epidermal Necrosis

26
Q

What polymorphism confers increased risk of getting these severe allergic reactions?

A

HLA-B*1502

27
Q

Tonic and atonic seizures definition?

A

Tonic/atonic seizures: sudden muscle stiffening (tonic)/sudden loss of muscle control (atonic)

(basically tonic clonic seizure but just the muscle elements)

28
Q

What do you call seizures that are ‘briefer’ versions of tonic seizures?

A

Myoclonic seizures: sudden, brief muscle contractions. Similar to tonic seizures but shorter time period

29
Q

What is the most severe type of seizure

A

status epilepticus

> 5 min of continuous seizure activity. Can manifest as any one of the 4 mentioned above. This is the most severe type