Anticonvulsants for Pharmacology and Therapeutics Flashcards Preview

Y2 LCRS 1 - Pharmacology and Therapeutics - Laz > Anticonvulsants for Pharmacology and Therapeutics > Flashcards

Flashcards in Anticonvulsants for Pharmacology and Therapeutics Deck (27)
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1
Q

What is an epileptic seizure?

A

Manifestation of an abnormal or excessive synchronised discharge of a set of cerebral neurones

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

5
Q

What proportion of epilepsy is idiopathic?

A

70%

6
Q

What is a key characteristic of absence seizures?

A

3 Hz brain activity

7
Q

What are the possible harms that can be done to the patient by giving anti-epileptic drug therapy?

A
Psychosocial consequences (illness status etc.) 
Idiosynchratic and dose-related
8
Q

State some factors influencing the decision to treat.

A

Number of seizures at presentation
Seizure type and severity
Cause of seizure

9
Q

What are the main mechanisms of anti-epileptic drugs?

A

Enhancing GABA-mediated inhibition
Inhibiting glutamate-mediated excitation
Na+ channel blockade (blocking nerve conduction)
Calcium channel blockade

10
Q

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

A

Benzodiazepines

11
Q

Name two drugs that inhibit glutamate-mediated excitation.

A

Presynaptic – levatiracetam

Postsynaptic – parampanel

12
Q

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

A

Phenytoin
Carbamazepine
Lamotrigine

13
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

14
Q

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

A

SV2A

This is a protein found on the synaptic vesicle membrane

15
Q

What are the two main excitatory receptors?

A

AMPA and Kainate (Na+/Ca2+ channel)

NMDA

16
Q

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

A

Gabapentin

Pregabalin

17
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

18
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

19
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

20
Q

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

A

CYP4502C9 (mainly)

CYP2C19

21
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

22
Q

Describe the effects of important AEDs on hepatic enzymes.

A

Phenytoin and Carbamazepine – hepatic enzyme INDUCERS

Valproate – hepatic enzyme INHIBITORS

23
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

24
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

25
Q

State some drugs that induce carbamazepine metabolism.

A

Phenytoin

Phenobarbital

26
Q

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

A

Stevens-Johnsons Syndrome

Toxic Epidermal Necrosis

27
Q

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

A

HLA-B*1502