Grimm Anti-Convulsants

Front 1

Definition of Primary Seizure

Back 1

idiopathic

Front 2

Definition of Secondary Seizure

Back 2

that occurs due to an underlying disease (i.e. renal, liver, CNS)

Front 3

Definition of Epilepsy

Back 3

recurring seizures

Front 4

Definition of Status epilepticus

Back 4

series of tonic-clonic seizures without return to consciousness

Front 5

Definition of Syncope

Back 5

sudden loss of consciousness and is due to a loss of blood flow to brain…NOT A TYPE OF SEIZURE

Front 6

Phenobarbital has a long half-life relative to its dosing interval (35-75 hr. and 12 hr. respectively). Explain the significance of this with respect to the peak and trough concentration observed. Compare to a drug w/ a short half life relative to dosing interval like diazepam.

Back 6

-Due to phenobarbitals long half-life relative to the dosing interval there are not wide fluctuations in plasma concentrations of the drug.
-Unlike a drug like diazepam (w/ high peaks and troughs), Phenobarbital stays steady w/ very tiny peaks and troughs

Front 7

How long must Phenobarbital or KBr be administered before plasma drug concentrations reach steady state?

Back 7

Phenobarbital:
-Half-life elimination is 35-75 hours (dog)
-Reaches steady state in 5-7 half-lives
-Total time = 2-3 weeks to reach steady state

KBr:
-Half-life elimination is roughly 24 days
-Reaches steady state in 4-6 months

**This is why a loading dose can be given of either drug, therefore you don’t need to wait the long time to reach the steady state**

Front 8

When contemplating TDM of Phenobarbital, when would you sample if you wanted to measure peak drug concentration, trough drug concentration, during an acute manifestation of toxicity, and for a periodic recheck of the serum drug concentration?

Back 8

-Therapeutic Drug Monitoring (TDM) should be sampled 4-6 hours since last dose given to determine peak, trough, or toxicity.
-TDM should not be done until 2-3 weeks after initiation of therapy (samples can be taken early, steady state may not have been reached yet)

Front 9

Describe the treatment for accidental overdosage of Phenobarbital.

Back 9

-Sodium bicarbonate to alkalinize the urine.
-Alkalinzation promotes ionization and reduces diffusability of drug
-Respiratory support when toxicity is severe enough to depress respiration
-Activated charcoal enhances body clearance

Front 10

List the common side effects seen when initiating Phenobarbital therapy

Back 10

-Polyphagia
-Polydipsia
-Polyuria (due to inhibition of ADH action or release)
-Fatigue
-Listlessness
-Hepatotoxicity
-Increases in ALP and transaminase
-Hepatic hypoxia causes non-specific liver enzymes to increase following a seizures

Front 11

Describe the metabolic fate of primidone in the dog, and justify the use of Phenobarbital TDM to guide therapy

Back 11

-Primidone (in vivo) is metabolized to Phenobarbital
-For TDM, you measure Phenobarbital since these levels accurately reflect the anticonvulsant and toxic effects of primidone

Front 12

Explain why phenytoin is not a very useful anticonvulsant for dogs

Back 12

Phenytoin toxicity in dogs appears in two forms:
1.Dose dependent chronic hepatitis can progress to cirrhosis and appear to be reversible following drug discontinuation
2.Dose dependent intrahepatic cholestatis is accompanied by poor prognosis

Front 13

List the common manifestations of bromide adverse reactions.

Back 13

-Ataxia
-Grogginess
-Sedation
-Skin reactions (in animals w/ pre-existing skin conditions)
-Vomitting
-Intermittent cough
-Radiographic changes associated w/ disease in small airways (cats)

Front 14

What is the treatment of choice for status epilepticus? What route(s) of administration would you choose and why?

Back 14

Treatment of choice for status epilepticus:
-Diazepam (benzodiazepines)
Route of administration:
-IV or rectally (preferred by Erin)
-Not good orally due to low bioavailability

Front 15

Why is diazepam ineffective for the long-term control of generalized seizures in dogs?

Back 15

-Tolerance to anticonvulsant activity can develop quickly, therefore long term control is not good

Front 16

List the commonly available forms of bromide.

Back 16

-Sodium
-Potassium (KBr is the most commonly used)**
-Ammonia salts

Front 17

What is the emergency treatment for overdose of bromide?

Back 17

Sodium chloride

Front 18

What is the approximate half life of bromide?

Back 18

24 days

Front 19

5. Phenobarbital is a potent inducer of hepatic microsomal enzymes. Describe how enzyme induction will affect Phenobarbital concentrations, endogenous hormone concentrations, and the potential effectiveness and toxicity of prodrugs that require the liver for metabolism.

Back 19

Phenobarb concentrations:
- there will be increased clearance of the drug b/c it undergoes hepatic metabolism
Endongenous hormone concentrations:
-T4 levels decrease due to increased hepatic inactivation
-Estrogen, androgens, progesterones, and adrenocortical steroids are hydroxylated more rapidly
Phenobarb related increases in liver enzyme activity may affect other drugs by:
-Increasing the rate of biotransformation leading to therapeutic failure
-Increasing the rate of conversion of prodrugs to active compounds enhancing toxicity***
-Increasing the rate of formation of toxic metabolites increasing toxicity
-Increasing production of carcinogenic compounds by the liver increasing the risk of neoplasia