Pharmacology 2011- Anticonvulsants

Front 1

What are the 3 possible mechanisms of anticonvulsants?

Back 1

1. Increase inhibitory neurotransmitters (ex. GABA)

2. Decrease excitatory neurotransmitters (less common)

3. Alter electrolyte conductance

Front 2

What are the goals of treatment with anticonvulsants?

Back 2

1. Treat underlying disease
2. Decrease seizure frequency
3. Minimal side effects
4. Maintain serum drug levels

Front 3

What anticonvulsants are GABA Agonists (inc flow of Chloride into cell)?

Back 3

* Phenobarbital
* Diazepam
* Clonazepam
* Clorazepate

Front 4

What is a seizure?

Back 4

Abnormal electrical activity in CNS; complete depolarization of entire CNS/brain

Front 5

What is Epilepsy?

Back 5

disease condition where patient suffers from multiple seizure over time

Front 6

What is the goal for the treatment of seizures?

Back 6

* Treat underlying disease first (is a pathologic process causing the seizures?)

*Decrease seizure frequency (control measure, not a cure) (if idiopathic seizures)

* Minimize the side effects of drug administration (i.e. CNS depression)

* Maintain serum drug levels

Front 7

What is classified an anticonvulsant drug?

Back 7

drug action that suppresses seizure activity without producing unconsciousness

Front 8

What is the 4 possible MOAs of anticonvulsants?

Back 8

1. Can act by increasing inhibitory NT (i.e. GABA)

2. Decreasing excitatory NTs (i.e. Glutamate)

3. Altering electrolyte conduction (i.e. K+ influx/efflux),

4. A combination thereof

Front 9

What is th most widely-used anticonvulsant drug in small animal medicine?

Back 9

Phenobarbital (barbiturate)

Front 10

What drug has the fastest effect on seizures?

Back 10

Diazepam

Front 11

What is the MOA of Phenobarbital?

Back 11

******Potentiates effect of inhibitory GABA and alters electrolyte conductance

• Binds to GABA binding site thus increasing GABA binding which leads to increased Cl- influx = raises seizure threshold

* Also see decrease influx of Ca2+ into nerve cells which leads to decreased release of excitatory NT

Front 12

What are the side effects of Phenobarbital?

Back 12

Sedation, polyphagia, PU/PD, mild behavior changes, lethargy, ataxia, liver disease, blood disorders, affected thyroid hormones, and accelerated corticosteroid metabolism

Front 13

Where is Phenobarbital metabolized?

Back 13

Liver

Front 14

What is the MOA of the anticonvulsant Primidone?

Back 14

potentiates GABA inhibitory action

Front 15

What are some side effects of Primidone?

Back 15

* Same as with phenobarbitol, but usually with higher incidence of liver damage

* Rarely used today; not recommended for use in cats

Front 16

What is Primidone metabolized into?

Back 16

phenobarbitol

Front 17

What is the MOA of the anticonvulsant Phenytoin?

Back 17

***Alters electrolyte conduction

• Blocks influx of Na+ which stabilizes excitable tissue

• Decreases Ca2+ influx which decreases release of NT

Front 18

What species is Phenytoin commonly used in?

Back 18

Horses

not recommended for dogs/cats

Front 19

What side effects can be seen in horses given Phenytoin?

Back 19

recumbency, excitement, sedation

Front 20

Which drug is used for acute seizures?

Back 20

Diazepam (benzodiazepine)

Front 21

What is MOA of Diazepam?

Back 21

Potentiates inhibitory NT (GABA) and alters electrolyte conductance

* Same mechanism, but different binding site, as barbiturates

Front 22

What are the possible side effects of Diazepam?

Back 22

• Patients may experience tachyphylaxis (become refractory to chronic treatment) because feedback decrease in receptor synthesis or decrease in GABA synthesis

* hepatic toxicosis in cats

Front 23

What type of drug is Clonazepam?

Back 23

benzodiazepine

Front 24

What is the MOA of Clonazepam?

Back 24

Potentiates inhibitory action of GABA (similar to Diazepem, but more potent)

Front 25

What type of elimination does Clonazepam go through?

Back 25

undergoes zero-order elimination (half-life increases as dosage increases)

Front 26

Which drug Clonazepam or Diazepam has the lower risk of hepatic toxicity in cats?

Back 26

Clonazepam

Front 27

What type of drug is Clorazepate?

Back 27

benzodiazepine

Front 28

What is the MOA of Clorazepate?

Back 28

similar to diazepam (bind to GABA site and augment GABA inhibitory action)

Front 29

What drus is used as alternative to Diazepam in cats?

Back 29

Clorazepate

Front 30

What anticonvulsant is usually the last resort drug?

Back 30

***Felbamate

* Used for chronic treatment: in dogs that are refractory to other anticonvulsant drugs; more expensive, so it’s a last resort

Front 31

What is the MOA of Felbamate?

Back 31

Antagonist at N-methyl-D-aspartate (NMDA) receptor-ionophore complex which blocks effects of the excitatory NMDA

* Increases seizure threshold, and decreases seizure spread

Front 32

What is the MOA of Gabapentin?

Back 32

blocks calcium-dependent channels which reduces NT release from presynaptic neurons

Front 33

Under what cases is Gabapentin used?

Back 33

Chronic treatment of seizures: used in dogs and cats when other drugs aren’t effective or have been too toxic; more expensive

Front 34

What anticonvulsant is preferred in dogs for treatment of refractory epilepsy?

Back 34

Levetiracetam (MOA is unknown)

Front 35

What is Zonisamide used for?

Back 35

Chronic treatment of seizures

Front 36

What is the MOA for Zonisamide?

Back 36

It blocks Na+ and calcium channels (T-type) which blocks Na+ influx whichsuppresses neuronal activity

Front 37

What side effects are seen with Zonisamide?

Back 37

transient sedation, ataxia, vomiting

Front 38

What is Potassium Bromide used for?

Back 38

Chronic treatment of seizures

Front 39

What is the MOA for Potassium Bromide ?

Back 39

stabilizes neuronal cell membranes by interfering with Cl- transport across membrane

Front 40

What side effects are seen with Potassium Bromide ?

Back 40

• Formulated as a salt, so it can cause GI upset

• Dogs: polyphagia, behavior changes; bromide toxicosis at high doses (CNS depression, weakness, ataxia, decreased proprioception, joint stiffness in rear limbs), sedation, pruritis

• Cats: respiratory signs (due to airway inflammation, not allergic reaction)

Front 41

Where is potassium bromide eliminated?

Back 41

eliminated in kidneys; able to co-administer with phenobarbitol

Front 42

Which drug has the longer half life- Potassium Bromide or Phenobarbitol?

Back 42

Potassium Bromide has longer half-life (14-21d) compared to phenobarbitol (56-102 hrs)