Central Nervous System Drugs Flashcards
What is Central Nervous System (CNS)
- consist of brain and spinal cord, which act as integrating and command centers of the nervous system. The human brain contains about 100 billion interconnected neurons surrounded by various supporting glial cells. Throughout the CNS, neurons are either clustered into groups called nuclei or are present in layered structures such as the cerebellum or hippocampus.
Drugs acting in CNS
- These include medications used to treat a wide range of neurologic and psychiatric conditions as well as drugs that relieve pain, suppress nausea, and reduce fever, among other symptoms. In addition, many CNS-acting drugs are used without prescription to increase the sense of well-being.
Neurons
- cells that process and transmit information via an electrochemical process. There are many types of neurons in the CNS, and they are classified in multiple ways:
> by function
> by location
> by the neurotransmitter they release.
The typical neuron, however, possesses a cell body (or soma) and specialized processes called dendrites and axons.
The process
Dendrites, receive and integrate the input from other neurons and conduct this information to the cell body.
The axon, carries the output signal of a neuron from the cell body, sometimes over long distances. The axon terminal makes contact with other neurons at specialized junctions called synapses where neurotransmitter chemicals are released that interact with receptors on other neurons.
Neuroglia
- there are a large number of nonneuronal support cells, called glia, that perform a variety of essential functions in the CNS.
> Astrocytes are the most abundant cell in the brain and play homeostatic support roles, including providing metabolic nutrients to neurons and maintaining extracellular ion concentrations.
Oligodendrocytes are cells that wrap around the axons of projection neurons in the CNS forming the myelin sheath, the myelin sheath created by the oligodendrocytes insulates the axons and increases the speed of signal propagation.
Microglia are specialized macrophages derived from the bone marrow that settle in the CNS and are the major immune defense system in the brain.
Blood-brain Barrier
- is a protective functional separation of the circulating blood from the extracellular fluid of the CNS that limits the penetration of substances, including drugs. This separation is accomplished by the presence of tight junctions between the capillary endothelial cells as well as a surrounding layer of astrocyte end-feet.
Two classes of receptor
- The first class is referred to as ligand-gated channels, or ionotropic receptors. These receptors consist of multiple subunits, and binding of the neurotransmitter ligand directly opens the channel, which is an integral part of the receptor complex.
- The second class of neurotransmitter receptor is referred to as metabotropic receptors. The binding of neurotransmitter to this type of receptor does not result in the direct gating of a channel.
What is synapse?
- communication between neurons in the CNS occurs through chemical synapses in the majority of cases. An action potential propagating down the axon of the presynaptic neuron enters the synaptic terminal and activates voltage-sensitive calcium channels in the membrane of the terminal. There is two types of pathways;
Excitatory postsynaptic potential (EPSP)
- This potential is due to the excitatory transmitter acting on an ionotropic receptor, causing an increase in cation permeability. When a sufficient number of excitatory synapses are activated, the excitatory postsynaptic potential depolarizes the postsynaptic cell to threshold, and an all-or-none action potential is generated.
Inhibitory postsynaptic potential (IPSP)
- When an inhibitory pathway is stimulated, the postsynaptic membrane is hyperpolarized owing to the selective opening of chloride channels. The opening of the chloride channel during the inhibitory postsynaptic potential makes the neuron “leaky” so that changes in membrane potential are more difficult to achieve.
Cellular organization of the brain: Hierarchical Systems
- include all the pathways directly involved in sensory perception and motor control. These pathways are generally clearly delineated, being composed of large myelinated fibers that can often conduct action potentials at a rate of more than 50 m/s.
In sensory systems, the information is processed sequentially by successive integrations at each relay nucleus on its way to the cortex.
Two types of cells within each nucleus
- relay or projection neurons and local circuit neurons
> The projection neurons form the interconnecting pathways that transmit signals over long distances. Neuron are excitatory
> Local circuit neurons are typically smaller than projection neurons, and their axons arborize in the immediate vicinity of the cell body. Neurons are inhibitory
Cellular organization of the brain: Nonspecific or Diffuse Neuronal Systems
- Neuronal systems containing many of the other neurotransmitters, including the monoamines and acetylcholine, differ in fundamental ways from the hierarchical systems. These neurotransmitters are produced by only a limited number of neurons whose cell bodies are located in small discrete nuclei, often in the brain stem.
What is Central Neurotransmitters?
- Because drug selectivity is based on the fact that different pathways use different transmitters, a primary goal of neuroscience has been to identify the neurotransmitters in CNS pathways. The following criteria were established for transmitter identification:
Transmitter Identification
- Localization: A suspected transmitter must reside in the presynaptic terminal of the pathway of interest.
- Release: A suspected transmitter must be released from a neuron in response to neuronal activity and in a calcium-dependent manner.
- Synaptic Mimicry: Application of the candidate substance should produce a response that mimics the action of the transmitter released by nerve stimulation, and application of a selective antagonist should block the response.
