10. Anticonvulsants, antiepileptics

Question 1

What are Anticonvulsants, antiepileptics drugs?

Answer 1

Medications used to treat epilepsy and they are divided into two main categories:
1. Long-term treatment of epilepsy
They are used regularly to prevent seizures over time
2. Management of status epilepticus
They are emergency treatments for a severe, continuous seizure or a series of seizures without recovery between them, This will need immediate medical attention

There are three line of defense treatment

Question 2

Name the line defense treatment for epilepsy

Answer 2

First-line treatment = Benzodiazepines
Second-line treatment = Antiepileptic drugs like levetiracetam
Third-line treatment = Propofol, pentobarbital (Typically administered in an intensive care setting with close monitoring)

Question 3

Long-term treatment of epilepsy,
Active substances

Answer 3

• Phenobarbital
• Primidone – Human medicine
• Potassium bromide
• Levetiracetam
• Imepitoin
• Gabapentin

Question 4

Management of status epilepticus, Active substances

Answer 4

• Benzodiazepines:
  Diazepam, Midazolam
• Propofol
• Pentobarbital

Question 5

Long-term treatment of epilepsy,
Indication

Answer 5

1. If a seizure lasts longer than 5 minutes = it’s called a status epilepticus
2. When multiple seizures occur within 3-6 months
3. When postictal (after seizure) symptoms occur for longer than 24 hours or 3 seizures
4. Confirmed lesions in the brain, or after a head injury

Question 6

Phenobarbital, effectiveness

Answer 6

Works in 60-90% of the cases and can work both alone and in combination. Phenobarbital controls seizures at low doses, between levels that cause sedation and sleepiness

Question 7

Phenobarbital, pharmacokinetics

Answer 7

Absorption: Has a good oral absorption. Can be given IV, but this takes 10-20 minutes to work ⭢ usually in emergencies like status epilepticus
Metabolism: Mainly broken down by the liver. Phenobarbital produces reactive oxygen species (ROS) which contributes to liver damage over time ⭢ important to consider in animals with liver disease
Phenobarbital can increase its own breakdime obe time by activating enzymes, meaning that the body needs a higher dose later to maintain the effect ⭢ Does not happen in Fe

Phenobarbital has a long half-life, between 37-73 hours, and it will stay in the body for a longer time.
It takes about 4-6 times the half-life to reach a steady level in the blood, approx. 2-3 weeks. Do not change the dose before this time.

Question 8

Phenobarbital, Monitoring

Answer 8

Blood levels should be checked 1 hour before the next dose, this will help determine if dose adjustments are necessary

Question 9

Phenobarbital, side effects

Answer 9

• Sedation, ataxia
• Polyuria, polydipsia
• Elevated liver enzymes
• Idiosyncratic reactions
• Hepatotoxicity
• Pancreatitis

Question 10

Potassium bromide, effectiveness

Question 11

Potassium bromide, advantages

Answer 11

• It is not metabolised by the liver, so it is non-hepatotoxic
• It has a long duration of action, usually, SID (once per day) is enough

Question 12

Potassium bromide, side effects

Answer 12

• Toxic to cats !!
• It can cause vomiting, especially if given with food.
• Can give ataxia and sedation

Question 13

Potassium bromide, pharmacokinetics

Answer 13

Has a long half-life and stays in the body for a longer time. Usually, SID (once per day) is enough, but vomiting can cause a problem.
We must monitor the blood plasma levels to make sure the dose is safe and effective

Question 14

Levetiracetam, effectiveness

Answer 14

Is good for patients not responding to phenobarbital, especially when used as a combination partner

Question 15

Levetiracetam, Advantages

Answer 15

Minimal side effects, slight metabolism in the liver and is excreted by the kidneys
Has a short half-life

Question 16

Levetiracetam, disadvantages

Answer 16

High dose: 20 mg/kg 3-4 times per day
If it is given by IV, we have to increase the dose, because levetiracetam interacts with the CYP450 enzyme, which will speed up the metabolism and reduce the concentration in the body. So the dose is increased to compensate for the increased metabolism.

Question 17

Impeitoin, effectiveness

Answer 17

Imepitoin enhances the effect of GABA receptors, which is a natural calming receptor.
Imepitoin is as effective as phenobarbital, even in combination

Question 18

Impeitoin, Advantages

Answer 18

It has minimal side effects (increased hunger, sedation
Short half-life, so the drug reaches its full effect quickly.
It works pretty much the same way, even with liver or kidney problems.

Question 19

What can cause status epilepticus?

Answer 19

1. Epilepsy
2. Poisoning: Certain toxins can cause seizures, such as pesticides, snail bait, insecticides
3. Low blood sugar: Can occur in young animals, animals with diabetes and animals that have ingested xylitol (artificial sweetener)

Question 20

Benzodiazepines, mechanism of action

Answer 20

Benzodiazepines affect the GABA receptors. Normally, the GABA receptors are a neurotransmitter that inhibits the activity of nerve cells in the central nervous system.
Benzodiazepines facilitate or amplify the GABA’s inhibitory effect, which is done by potentially causing a structural change in the GABA receptor complex.
This structural change leads to the opening of chloride ion channels.
The benzodiazepines bind to BZD receptors (Benzodiazepine receptors), which are found throughout the CNS and in muscles.
This binding opens the GABA-gated chloride channels, leading to hyperpolarisation, which makes it harder for a nerve cell to fire, resulting in CNS and muscle depression

Question 21

Benzodiazepines, administration

Answer 21

Both diazepam and midazolam can be given intranasallay, while diazepam can also be given rectally.