CNS PHA

CNS Pharmacology Notes

Organization of the CNS

  • Components: The Central Nervous System (CNS) includes the brain and spinal cord. It integrates sensory information and generates motor outputs necessary for interaction with the environment to enhance species survival.

  • Neurons: The human brain has approximately 100 billion interconnected neurons and supportive glial cells.

  • Neuron Arrangement: Neurons are organized into clusters called nuclei or layered structures such as the cerebellum or hippocampus.

  • Synaptic Connections: Connections between neurons form circuitry that regulates information flow through the CNS. The complexity of this circuitry exceeds that of the peripheral autonomic nervous system (ANS).

Neuronal Functioning

  • Information Transmission: In both CNS and peripheral systems, neurotransmitters are released and diffuse across a synaptic gap to bind specific receptors on postsynaptic neurons.

  • Electrical Activity: The recognition of neurotransmitters by postsynaptic receptors triggers intracellular changes. The CNS circuitry is significantly more complex than that of the ANS with a greater number of synapses.

  • Inhibitory Neurons: The CNS has extensive networks of constantly active inhibitory neurons that modulate neuronal transmission rates.

  • Neurotransmitter Types: The CNS employs over 10 neurotransmitters, while the ANS primarily utilizes acetylcholine (Ach) and norepinephrine (NA).

Anatomy of Neurons

  • Basic Structure: Neurons are excitable cells, consisting of a cell body (soma), dendrites (receive signals), and an axon (conducts signals).

  • Dendrites: Highly branched and function to integrate input from other neurons, transmitting this information to the cell body.

  • Axon: Carries output signals; typically, neurons have one axon which can branch to contact numerous targets.

  • Synapses: Axon terminals form synapses with other neurons where neurotransmitters are released.

  • Neuroglia Types: Include astrocytes (homeostasis), oligodendrocytes (myelin sheath), and microglia (immune defense).

Blood-Brain Barrier

  • Function: The blood-brain barrier (BBB) protects the CNS by preventing certain substances, including drugs, from entering.

  • Mechanism: Formed by tight junctions in capillary endothelial cells, requires drugs to be either highly hydrophobic or to utilize specific transport mechanisms.

  • Transport Examples: Nutrients such as glucose can cross via specific transporters, while precursor l-DOPA (for dopamine) can cross using an amino acid transporter, unlike dopamine itself.

  • Areas Lacking BBB: Circumventricular organs which include regions for sampling blood and secreting neurohormones lack a traditional BBB.

CNS Neurotransmission

  • Complexity: Chemical transmission within the CNS involves various mechanisms such as:

    • Excitatory postsynaptic potentials (EPSP)

    • Inhibitory postsynaptic potentials (IPSP)

    • Relay actions

    • Recurrent actions

    • Feed-forward effects

    • Auto effects

CNS Neurotransmitters

  • Pathway Diversity & Drug Selectivity: Different pathways employ different transmitters.

  • Neurotransmitter Groups: Include amino acids (e.g., glutamate, GABA), monoamines (e.g., dopamine, serotonin), and others such as neuropeptides.

Amino Acid Neurotransmitters

  • Glutamate:

    • Originates mainly from glucose and glutamine.

    • Function: Key excitatory neurotransmitter in the CNS present in high concentrations in synaptic vesicles.

    • Released via Ca