L16: Epilepsy Flashcards
what are the types of epilepsy?
- Generalized seizure (grand mal)
- Generalized (petit mal)
- Partial seizure
- Status epilepticus
What is a generalized seizure (grand mal)?
- Sustained contracture of the musculature
- Cessation of respiration and defecation
- Consciousness reappears after several minutes
What is a generalized seizure (petit mal)?
- Not associated with motor function
- Characterized by a loss of attention for some seconds
What is a partial seizure?
- Involves muscle spasms in some of the limbs or on one side of the body
- Spreads from one location to the other
What is status epilepticus?
- Occurs when a generalized seizure continues for 30 minutes or more
- Poses a medical emergency
What does EEG stand for and what does it record?
- EEG stands for Electroencephalogram
- records the voltage change by the activity of many nerve axons and synapses in the brain
What are some causes of abnormal EEG patterns?
- Brain injury caused by stroke or traumatic injury, epileptic focus (cyto-excitable scar tissue through which activity can be initiated)
- Infection which can also provide an epileptic focus
- Tumors
- Autoimmune disease, leading to localized encephalitis and epileptic focus
- Idiopathic - no obvious pathology
What is kindling in the context of epilepsy?
- refers to repetitive chemical/electrical stimulation of brain that can lead to the development of epileptic focus or seizures
How do anti-epileptic drugs limit the excitability of neurons?
- Anti-epileptic drugs increase inhibitory synaptic input by stimulating GABA
- they enhance GABAa receptors (i.e. Cl- channels)
- BDZs, barbiturates, valproic acid, and potassium bromide are examples of drugs that act on GABAa receptors to increase inhibitory effects.
How do benzodiazepines enhance the action of GABA?
- BZDs bind to the α subunit of GABAa receptors, which ↑ affinity of GABA for its binding site
- they nhance the inward flow of Cl- when GABA binds to the receptor, leading to ↑ inhibitory effects.
What are the effects of benzodiazepines on GABA receptors?
- BZDs = non-selective for alpha subunits, but their activation of the alpha1 subunit has sedative effects.
- also have anxiolytic effects by activating the alpha2 subunit.
- knockouts of the alpha5 subunit can improve cognitive function.
What other substances can enhance GABA action?
- Neurosteroids & ethanol can enhance GABA action by modulating GABA receptors
- Picrotoxin promotes seizures by blocking Cl- conductance pore, ↓ GABA’s inhibitory effects.
- Br- enhances inhibition by being more permeable through GABAa receptors than Cl-
What type of receptors are GABAb receptors, and how do they function?
- G protein-coupled receptors (Gi).
- function: inhibit the production of cAMP & have modulatory effects on neuronal excitability
What are some drugs used for tonic-clonic, partial, and temporal lobe seizures that enhance GABA actions?
- Diazepam
- Midazolam
- Phenobarbital
- Vigabatrin
- Tiagabine
- Lamotrigine
Describe how the drugs used for tonic-clonic, partial, and temporal lobe seizures that enhance GABA actions work
Diazepam:
- both sedative and anticonvulsant, enhancing GABA actions.
Midazolam:
- 2-3x more potent than diazepam
- administered intravenously (iv)
Phenobarbital:
- barbiturate
- works even when GABA is not present & it enhances GABA actions
Vigabatrin:
- Inhibits GABA aminotransferase,
- leading to ↑ GABA levels in the synapse.
Tiagabine:
- Inhibits GABA uptake
- ↑ availability of GABA in the synapse.
Lamotrigine
- a use-dependent drug that blocks Na+ channels
- but it is not used in pregnant women due to safety concerns
