Week 9 - Chapter 24 Drugs for Epilepsy (Anti-epileptic drugs) Flashcards
Absence Seizures (Petit Mal)
Absence seizures are characterized by loss of consciousness for a brief time (10 to 30 seconds). Seizures usually involve mild, symmetric motor activity (eg, eye blinking) but may occur with no motor activity at all. The patient may experience hundreds of absence attacks a day. Absence seizures occur primarily in children and usually cease during the early teen years.
Antiepileptic Drugs
How do they work?
We have long known that AEDs can (1) suppress discharge of neurons within a seizure focus and (2) suppress propagation of seizure activity from the focus to other areas of the brain. However, until recently we didn’t know how these effects were achieved. It now appears that nearly all AEDs act through five basic mechanisms: suppression of sodium influx, suppression of calcium influx, promotion of potassium efflux, blockade of receptors for glutamate, and potentiation of gamma-aminobutyric acid (GABA).
Atonic Seizure
These seizures are characterized by sudden loss of muscle tone. If seizure activity is limited to the muscles of the neck, “head drop” occurs. However, if the muscles of the limbs and trunk are involved, a “drop attack” can occur, causing the patient to suddenly collapse. Atonic seizures occur mainly in children.
Breakthrough Seizure
Breakthrough seizures, inappropriate alterations in effective therapy, therapeutic complacency, and toxic side effects may result if the clinical considerations of efficacy and adverse effects are not given priority in adjustments to AED dosage.
Complex Partial Seizure
These seizures are characterized by impaired consciousness and lack of responsiveness. At seizure onset, the patient becomes motionless and stares with a fixed gaze. This state is followed by a period of automatism, in which the patient performs repetitive, purposeless movements, such as lip smacking or hand wringing. Seizures last 45 to 90 seconds.
Convulsion
- –In contrast to seizures, convulsion has a more limited meaning, applying only to abnormal motor phenomena, for example, the jerking movements that occur during a tonic-clonic attack. Accordingly, although all convulsions may be called seizures, it is not correct to call all seizures convulsions.
- –Convulsions, characterized by a period of muscle rigidity (tonic phase) followed by synchronous muscle jerks (clonic phase).
Epilepsy
The term epilepsy refers to a group of chronic neurologic disorders characterized by recurrent seizures, brought on by excessive excitability of neurons in the brain. Symptoms can range from brief periods of unconsciousness to violent convulsions. Patients may also experience problems with learning, memory, and mood, which can be just as troubling as their seizures.
Febrile Seizure
Fever-associated seizures are common among children ages 6 months to 5 years. Febrile seizures typically manifest as generalized tonic-clonic convulsions of short duration. Children who experience these seizures are not at high risk of developing epilepsy later in life.
Focus
Seizures are initiated by synchronous, high-frequency discharge from a group of hyperexcitable neurons, called a focus. A focus may result from several causes, including congenital defects, hypoxia at birth, head trauma, brain infection, stroke, cancer, and genetic disorders. Seizures occur when discharge from a focus spreads to other brain areas, thereby recruiting normal neurons to discharge abnormally. The overt manifestations of any particular seizure disorder depend on the location of the seizure focus and the neuronal connections to that focus. The connections to the focus determine the brain areas to which seizure activity can spread.
Gamma- aminobutyric acid (GABA)
Several AEDs potentiate the actions of GABA, an inhibitory neurotransmitter that is widely distributed throughout the brain. By augmenting the inhibitory influence of GABA, these drugs decrease neuronal excitability and thereby suppress seizure activity. Drugs increase the influence of GABA by several mechanisms. Benzodiazepines and barbiturates enhance the effects of GABA by mechanisms that involve direct binding to GABA receptors. Gabapentin promotes GABA release. Tiagabine inhibits GABA reuptake, and vigabatrin inhibits the enzyme that degrades GABA, and thereby increases GABA availability.
Generalized Seizures (6 types)
Generalized seizures may be convulsive or nonconvulsive. As a rule, they produce immediate loss of consciousness.
1) Tonic-Clonic Seizures
2) Absence Seizures (Petit Mal)
- loss of consciousness for a brief time (10 to 30 seconds), involve mild, symmetric motor activity (eg, eye blinking), may have hundreds a day, primarily in children to early teens
3) Atonic Seizures
- sudden loss of muscle tone (neck muscles = “head drop”, limbs/trunk = “drop attack” leading to collapse), occurs mainly in children
4) Myoclonic Seizures
5) Status Epilepticus
6) Febrile Seizures
- fever-associated, common among children 6 months to 5 years ,manifest as short generalized tonic-clonic convulsions, children who have this are not at high risk for developing epilepsy later in life
Gingival Hyperplasia
Gingival hyperplasia (excessive growth of gum tissue) is characterized by swelling, tenderness, and bleeding of the gums. In extreme cases, patients require gingivectomy (surgical removal of excess gum tissue). Gingival hyperplasia is seen in about 20% of patients who take phenytoin. Can risk be reduced? Yes. Evidence indicates that supplemental folic acid (0.5 mg/day) may prevent gum overgrowth. In addition, risk can be minimized by good oral hygiene, including dental flossing and gum massage. Patients should be taught these techniques and encouraged to practice them.
Hydantoin
Fetal hydantoin syndrome, characterized by growth deficiency, motor or mental deficiency, microcephaly, craniofacial distortion, positional deformities of the limbs, hypoplasia of the nails and fingers, and impaired neurodevelopment.
It’s a side affect of Phenytoin during pregnancy.
Lennox-Gastaut Syndrome (Mixed Seizures)
Lennox-Gastaut syndrome is a severe form of epilepsy that usually develops during the preschool years. The syndrome is characterized by developmental delay and a mixture of partial and generalized seizures. Seizure types include partial, atonic, tonic, generalized tonic-clonic, and atypical absence. 218In children with Lennox-Gastaut syndrome, seizures can be very difficult to manage.
Myoclonic Seizures
- sudden muscle contraction that lasts for just 1 second, may be limited to one limb (focal myoclonus) or entire body (massive myoclonus)
Postictal state
-a period of central nervous system (CNS) depression resulting from marked impairment of consciousness during Tonic-clonic seizures.
Secondarily Generalized Seizures
These seizures begin as simple or complex partial seizures, and then evolve into generalized tonic-clonic seizures. Consciousness is lost. These seizures last 1 to 2 minutes.
Seizure
Seizure is a general term that applies to all types of epileptic events and is not synonymous with convulsions.
Simple Partial Seizure
These seizures manifest with discrete symptoms that are determined by the brain region involved. Hence, the patient may experience discrete motor symptoms (eg, twitching thumb), sensory symptoms (eg, local numbness; auditory, visual, or olfactory hallucinations), autonomic symptoms (eg, nausea, flushing, salivation, urinary incontinence), or psychoillusory symptoms (eg, feelings of unreality, fear, or depression). Simple partial seizures are distinguished from complex partial seizures in that there is no loss of consciousness. These seizures persist for 20 to 60 seconds.
Sodium Channel
Neuronal action potentials are propagated by influx of sodium through sodium channels, which are gated pores in the cell membrane that control sodium entry. For sodium influx to occur, the channel must be in an activated state. Several AEDs, including phenytoin, carbamazepine, valproic acid, and lamotrigine, reversibly bind to sodium channels while they are in the inactivated state, and thereby prolong channel inactivation–> delaying return to the active state–>decrease the ability of neurons to fire at high frequency–>seizures are suppressed.
