Wk 32 - Epilepsy 4

Question 1

When should initiation of pharmacological treatment occur?

Answer 1

• After confirmed diagnosis of epilepsy + after 2nd seizure
• Recommended by specialist
• After consultation w/ patient + fam

Question 2

How do you initiate AED monotherapy?

Answer 2

• Use 1st line
• Low dose
• Gradually inc til seizure stops
• Adjust drug dose to minimal effective AED dosage/optimal maintenance dosage
• Monitor AED response: freq, discharge + adverse effects

Question 3

What to do when seizure remains uncontrolled w/ maximum tolerated dose of 1st line drug?

Answer 3

• Review diagnosis, underlying aetiology + compliance
• Start low dose of another 1st line drug
• Inc dosage til seizure stops
• Gradual tapering off + w/drawal of 1st drug

Question 4

What are the advantages of monotherapy?

Answer 4

• High efficacy
• Better tolerated than multi drug therapy
• Easy management
• Simple
• No interactions
• Cost-effective

Question 5

When should polytherapy be used?

Answer 5

Continued seizures despite, 1st, 2nd + 3rd monotherapy w/ max tolerated dose

Question 6

How should you initiate polytherapy?

Answer 6

• Establish optimal dose of baseline AED
• Add drug w/ diff./Multi mechanisms
• Titrate new AED slowly
• Red dose of baseline AED
• Replace less effective drug
• Add 3rd drug if seizure control = sub-optimal

Question 7

Outline ways to improve methods of compliance

Answer 7

• Adequate + clear info about AED treatment
• Drug therapy: monotherapy
• Aid-memoire: drug wallet + remainders
• Reinforce at clinic follow up visits

Question 8

Drug interactions are likely due to what?

Answer 8

• Polytherapy
• Narrow therapeutic window
• AED induction/inhibition of major hepatic drug metabolising enzyme

Question 9

What does hepatic metabolising enzyme inducers lead to + give examples

Answer 9

• Production of: Cytochrome P450 enzyme, GT + epoxidase hydrolase
• Leads to rapid clearance of substrate drugs
• Leads to build up of active/toxic metabolites
• Major inducers: CBZ, PHY, phenobarbital + primidone

Question 10

What does polytherapy with major inducers lead to?

Answer 10

• Inc metabolic clearance

- Red serum levels of LTG (>50%), valproic acid (75%) + tiagabine

Question 11

What does co-administration of major inducers w/ warfarin lead to?

Answer 11

• Inc metabolic clearance + red serum level of warfarin

- Dec prothrombin time + red anticoag - inc warfarin dose

Question 12

What does co-administration of major inducers w/ oral contraceptives lead to?

Answer 12

• Inc metabolic clearance + red serum level of ethinyl estradiol + progesterone
• Inc synthesis of SHBG -> inc estradiol binding -> dec serum level of unbound, bioactive estradiol
• Contraceptive failure + mid-cycle breakthrough bleeding

Question 13

What does co-administration of oral contraceptives w/ lamotrigine lead to?

Answer 13

• Inc metabolic clearance + red serum of lamotrigine by 50%

- Inc breakthrough seizure

Question 14

What does hepatic metabolising enzyme inhibition lead to + give examples

Answer 14

• Production: Cytochrome P450 enzyme, GT + epoxidase hydrolase
• Leads to red clearance of substrate drugs
• Leads to inc serum level + risk of toxicity
• Major inhibitors: SVP, stiripentol + felbamate

Question 15

What does polytherapy with major inhibitors lead to?

Answer 15

• Red metabolic clearance

- Inc serum level of LTG (inc neurotoxicity) + phenobarbital (50%)

Question 16

Why consider discontinuation?

Answer 16

• Limit exposure to ST + LT adverse effects: cognitive dec, osteoporosis + teratogenic effects
• Avoid masking effect of AEDs on spontaneous seizure remission

Question 17

Outline how to withdraw from AEDs

Answer 17

• Managed by specialist
• One drug at a time
• Slow taper (2-3 months)
• Slow taper w/ barbiturates + benzodiazepines (>6 months)
• Slow initial taper + rapid final taper w/ phenytoin
• Reverse last dose red if seizure occurs