Sedative-Hypnotic Drugs

• Central Nervous System 


  composed of the brain and spinal cord and is responsible for integrating sensory information and generating motor and behavioral outcomes
• Neurons 


  are excitable cells that process and transmit information via electrochemical processes.
• Neuroglia / Glia


  are large number of non-neuronal support cells that serves several purposes in the CNS. You have your astrocytes, oligodendrocytes, and microglia.
• Blood-Brain Barrier 


  is a protective functional separation of the circulating blood from the extracellular fluid of the CNS that limits the penetration of other substances to the brain like drugs.
• General anesthetic and alcohol may not have specific action on membranes, but still demonstrates alteration in synaptic transmission
• Voltage-gated


  responds to the changes in the membrane potential of the cell. Mostly found on the initial part of the axon where they propagate the all-or-nothing fast AP to the nerve terminal
• Ligand-gated


  these are channels where NTs (like drugs or natural molecules) exert their effects by binding to their specific receptor targets
• Ligand-gated ion-channels


  NT directly binds and opens the channel and are responsible for fast synaptic transmission in the CNS pathway
• Metabotropic receptors


  these are GPCRs and NT binding do not directly open the channel, rather it produces 2° messengers to mediate intracellular signaling. Activation leads to modulation of voltage-gated channels.
• Membrane-delimited


  GPCR directly interacts with the voltage-gated channels
• Diffusible secondary messengers


  less direct modulation through enzymatic activation of 2° messengers
• When an excitatory pathway is stimulated, a small depolarization known as excitatory postsynaptic potential (EPSP) is created to due to increased cation permeability of the membrane
• When an inhibitory pathway is stimulated, hyperpolarization of the potential occurs referred to as inhibitory postsynaptic potential (IPSP) and is due to selective opening of Cl-channels.
• Ligand-gated ion channel (ionotropic) 


  type of channel:

  
• Voltage-gated


  type of channel:

  
• Membrane-delimited metabotropic ion channel


  type of ligand-gated ion channel:

  
• Diffusible second messenger metabotropic ion channel


  type of ligand-gated ion channel:

  
• Hierarchical systems


  pathways for sensory perception and motor control
• Non-specific/ Diffusive neuronal system


  includes many NTs and are located in discrete areas of the brain and responsible for modulating hierarchical systems. Acts mostly on metabotropic receptors which means the effects are mostly long-lasting.
• Glutamate

  • the major excitatory NT
  • it has effects on memory, learning, and stress response
• Gamma-aminobutyric acid (GABA)

  • the major inhibitory NT
• Serotonin/ 5-hydroxytryptamine (5-HT)

  • it has use in thought process and control of sensory transmission
  • it has effects on mood, wakefulness, and sleep
  • it also influences feeding behavior
• Dopamine (DA)

  • it has effects on motor control, behavioral control, and endocrine control centers of the CNS
• Norepinephrine (NE)

  • it has effects in arousal and mood
  • it also has effects of blood pressure regulation
• Acetylcholine (ACh)

  • it has use on memory and motor control
• Histamine (H)

  • it has effects on wakefulness especially on the central receptors
• Orexin

  • it has effects on energy homeostasis, sleep cycles, feeding behavior, and autonomic function
• Anxiety

  • increased levels of catecholamines (NE, DA, E)
• Mania

  • increased levels of NE and 5-HT
• Depression

  • decreased levels of NE and 5-HT (monoamine theory)
• Schizophrenia

  • increased levels of DA (dopamine hypothesis)
• Sedatives or Anxiolytics


  agent that reduces anxiety and exerts calming effect
• Hypnotics 


  agents that produces drowsiness and encourage the onset and maintenance of a state of sleep
• Generally, absorption of Sedative-Hypnotics depends on several factors, but the degree of lipophilicity plays a major role.
• Lipophilicity determines the rate a drug can enter the CNS and is responsible for its rapid onset of action.
• Sedative-Hypnotics can cross placental barrier and may contribute to depression of neonatal vital sign when taken predelivery period.
• Sedative-Hypnotics is also detectable in breast milk which may also cause depressant effect in the nursing infant.
• Benzodiazepines 


  Diazepam, Midazolam, and Lorazepam
• Barbiturates 


  Phenobarbital, Amobarbital, and Thiopental
• Newer Hypnotics 


  Zolpidem, Zaleplon, and Eszopiclone