Antiepileptics Flashcards

1
Q

What is epilepsy?

A

A chronic disorder characterized by recurrent seizures (abnormal discharges of neurons in the brain)

Primary epilepsy

Secondary epilepsy: febrile seizures in young children with high fevers and infection, anoxia and after alcohol withdrawal

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2
Q

What are complex partial seizures?

A

Consciousness is not lost but impaired, associated with temporal lobe

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3
Q

What is status epilepticus?

A

Epilepsy which cannot be stopped, medical emergency where you have to administer IV benzodiazepines

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4
Q

What are the actions of antiepileptics?

A

Decreases membrane excitability to cause neurons to fire less frequently

Enhance effects of GABA inhibitory neurotransmitter effects on ligand gated chloride channels

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5
Q

What drugs are used for tonic clonic (grand mal) and partial seizures?

A

Phenobarbitone

Phenytoin

Carbamazepin

Valproate

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6
Q

How does phenytoin work?

A

Increases CNS GABA

Decreases membrane excitability by inhibiting sodium and calcium channels activation to stop action potential generation, reducing speed and effectiveness of sodium channels, stopping the neuron from sending repeated messages

Also increases refractory period via K+ current

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7
Q

How does carbamazepine work?

A

Increases CNS GABA

Decreases membrane excitability by inhibiting sodium and calcium channels activation to stop action potential generation, reducing speed and effectiveness of sodium channels, stopping the neuron from sending repeated messages

Also increases refractory period via K+ current

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8
Q

How does phenobarbitone work?

A

Binds to GABA receptor channel complex, potentiating GABA effects

At low doses, potentiates GABA by increasing frequency of channel opening induced by GABA

At high doses, independent of GABA and causes prolonged channel opening and death

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9
Q

How does valproate work?

A

Increases GABA by preventing its breakdown, inhibiting GABA-transaminase

Hyperpolarizes membrane potential by increasing K+ influx, thus reducing excitability of neurons

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10
Q

Absorption of phenytoin?

A

Oral: slow but complete

IM: unpredictable

IV: used in status epilepticus, immediate

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11
Q

Metabolism of phenytoin?

A

Hydroxylation and conjugation in the liver

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12
Q

Elimination of phenytoin?

A

First order in normal therapeutic range

When above therapeutic range, becomes zero order kinetics where elimination rate plateaus, can result in accumulation and toxicity

Therefore doesn’t go into steady state concentration

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13
Q

PK of phenobarbitone and carbamazepine?

A

Hepatic enzyme inducers, increasing metabolism of drugs and may result in other drug concentrations dropping below MEC

T1/2 shortens with repeated doses

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14
Q

PK of valproate?

A

Highly bound to plasma protein to displace other anti-epileptics like diazepam

Inhibits other anti-epileptic drug metabolism

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15
Q

What is carbamazepine used for?

A

Trigeminal neuralgia
Seizures
Mood disorders

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16
Q

Adverse effects of phenytoin?

A

Dose dependent systemic effects, may cause gum hypertrophy, hirsutism, with overdose can cause convulsions, cerebellar lesion (diplopia, cant walk properly), vestibular lesion (loss of balance) and folate Vit D deficiency

Can result in idiosyncratic hypersensitivity, lupus-like skin, bone marrow issues and liver necrosis

Can be teratogenic in pregnant patients, esp 1st trimester, can cause deformities in fetus

17
Q

Adverse effects of phenobarbitone?

A

Sedation
Drowsiness
Ataxia
Diplopia
Behavioral disturbances like hyperactivity
Loss of concentration
Depression

18
Q

Adverse effects of carbamazepine?

A

Dose dependent GI upset, diplopia, nystagmus, drowsiness, folate Vit D def, antidiuresis

Overdose can cause ataxia, confusion, behavioural disturbances

Hypersensitivity causing bone marrow issues, rashes, SLE, stevens johnson, lymphadenopathy, hepatitis

Teratogenic in animals