General neuronal physiology

• Nerve cells have a low threshold for excitation and the

stimulus may be electrical, chemical, or mechanical.
• The conduction depends on the net movement of
ions, Na+, Cl-, K+ and Ca++ through their respective
channels.
Neurotransmitter at synaptic junctions facilitate the
transmission of the action potential.
• GABA is the main inhibitory neurotransmitter in the
CNS. GABA increase Cl- influx into the neuron causing
A

hyperpolarisation.
• An action potential is generated when
stimulus to a nerve fiber reaches threshold.
Seizures
 Definition of a seizure
• Seizures are the manifestation of periods of
uncontrolled, rapid, synchronized firing of
groups of neurons, sometimes in localised
areas (partial seizures) and sometimes in
widespread areas in both hemispheres
(generalised seizures).
Pathophysiology
The following mechanisms may
coexist in different combinations to
cause partial and generalised
seizures.
1. Defective activation gamma-
aminobutyric acid (GABA)
neurons.
2. Decreased inhibition
3. Transient calcium current
mediated oscillations in the
resting membrane potential of
thalamic relay neurons.
 Drugs that prolong the inactivated
state of Voltage gated Na+ channels
• Voltage gated Na+ channels are important for the
propagation of the action potential.
• The channels have 3 states: the active, Inactive and
resting states.
• These drug act by blocking the transition of the
inactive Na+ channels to the resting state thereby
reducing the propagation of the action potential thus
reducing the frequency of seizures.
Examples include:
• Carbamazepine
• Phenytoin
• Valproic acid
 Drugs that act at GABAminergic synapses

-Drugs that enhance GABA action either by

• enhancing the activation of GABAA receptors (e.g. phenobarbital
and benzodiazepines),
• inhibiting the enzyme GABA transaminase (e.g. Vigabatrin)
• inhibiting GABA uptake (e.g. Tiagabine)
These mechanisms facilitate the GABA-mediated opening of Cl-
channels which hyperpolarizes the neurons and increases the
threshold of stimulation for the neuron thereby leading to the
inhibition of excitatory transmission in the neurons.
Further due to the decrease in the membrane potential, the
voltage-gated sodium channels will hardly be activated; in this
manner, GABA enhancers also indirectly inhibit voltage-gated
sodium channel function.
Drugs that block voltage gated calcium channels
• Calcium is required for neurotransmitter release at
the synaptic junction.
• Calcium ions entry into the post synaptic neuron
causes depolarization of its membrane potential. This
reduces the threshold for stimulation.
• These calcium channels are more concentrated in the
thalamic relay neurons.
• These drugs block the release of excitatory
neurotransmitter, glutamate thereby halting the
transmission of the action potential in thalamic
neurons.
Examples include:
• Ethosuximide
• Valproic acid