3 - PKPD of anticonvulsants (VPA, carbamazepine, phenytoin) Flashcards
List common antiepileptics studied in this PK lecture
- phenobarbital
- valprioc acid
- carbamazepine
- phenytoin
Define seizures
when the nerves in the brain fire spontaneously, causing (most commonly) muscle spasms and loss of consciousness
Causes of seizures
- idiopathic
- brain damage
- diseases
- low glc, Ca, Mg, or Na
- alcohol withdrawal
List and describe 4 types of generalized seizures (bilateral disorder)
- Tonic clonic (grand mal): stiffening of limbs (tonic) followed by erking (clonic phase)
- Myoclonic: brief, rapid contractions*
- Absence (petit mal): lapses of awareness, staring
- Atonic (drop attacks): abrupt loss of muscle tone, head drop, loss of posture, sudden collapse*
- very resistant to drug therapy
Describe characteristics of seizure disorders
- lasting only a minute or two
- most are not life-threatening
- repeated seizures w/o regaining consciousness in btw, or seizure episodes >5 mins is status epilepticus
Anticonvulsant drugs can be given one of two ways
- Prophylactically to prevent seizures (eg: after subarachnoid or intracranial hemorrhage, or after traumatic brain injury)
- Actively for a recent seizure - for instance after a single tonic-clonic seizure, status epilepticus, or non-convulsive status
Define status epilepticus (SE)
unrelenting seizures for a duration of >5 mins! The most severe, life-threatening form of seizure activity
Define non-convulsive status epilepticus (NCSE)
a condition in which electrographic seizure activity is prolonged and results in nonconvulsive clinical sx (simply appears unconscious)
Common etiologies for status epilepticus
- 25% anticonvulsant withdrawal [this one has best response to tx!]
- 25% alcohol-related
- 9% drug toxicity
- 8% CNS infection
1st line therapy for status epilepticus?
60% of all pts respond to phenytoin +/- diazepam (or lorazepam) as first-line
If a status-epilepticus pt doesn’t respond to the 1st line tx, what can we add on?
Some pts require the addition of phenobarbital to phenytoin +/- diazepam
Which seizure pts should NOT use phenytoin or phenobarbital? What can they use instead?
pheny or phenobarb. NOT recommended in alcohol-withdrawal seizures! These pts respond better to benzodiazepines (ie diazepam or lorazepam)
Who are the worst responders to tx?
- anoxic injury (total oxygen depletion)
- drug toxicity
- CNS infection
- metabolic abnormalities
Workup of seizure disorders
- Characterize the seizure type
- Clinical investigations targeting the cause are conducted
- Most appropriate tx is selected
- often 1st single seizures don’t require long-term tx (ie if acute)
- Treat only those with recurrent seizures, those presenting with status epilepticus, or those with a structural predisposition
Therapeutics of seizure disorders
a) certain seizure-types respond better to some agents than others
b) dosing involves some titration to find the right dose to control the seizures, but with minimal side effects
c) some do well on one agent, while others may require several agents to control the disorder
