Exam 2 (Pt. 12) Flashcards
Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Cellular Metabolism
Reduced cellular energy metabolism causes increased release and decreased reuptake of glutamate, as well as increased extracellular K+ concentrations due to inhibition of the Na+-K+ ATPase.
Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Glutamate Effect
Glutamate Effect Neurons are strongly depolarized by glutamate stimulation of AMPA and kainate receptors and by exposure to the elevated K+ levels.
Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Prolonged Effect
Persistent glutamate activation of NMDA receptors with simultaneous membrane depolarization leads to a prolonged opening of NMDA receptor channels, permitting massive Ca2+ influx across the membrane.
Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Depolarization
Depolarization is also thought to cause additional Ca2+ entry into the cell through voltage-operated Ca2+ channels (VOCC).
Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Ca2+ Elevation
Elevated intracellular Ca2+ levels activate a variety of Ca2+-dependent processes, including specific proteases and endonucleases;
- phospholipase A2 (PLA2), which liberates arachidonic acid (AA) from membrane lipids
- nitric oxide synthase (NOS), which catalyzes the formation of nitric oxide (NO)
- ornithine decarboxylase (ODC), which mediates polyamine biosynthesis.
Ca2+ accumulation in mitochondria can also lead to severe damage to these organelles.
Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Diagram
GABA Synthesis - Reaction
The excitatory amino acid neurotransmitter is catalyzed by the enzyme, glutamate acid decarboxylase (GAD), to form the inhibitory amino acid neurotransmitter GABA.
GABA Synapse
The GABAergic synapse, illustrating the processes of -aminobutyric acid (GABA) synthesis and metabolism, neuronal and glial GABA uptake, and vesicular GABA uptake and release. Pre- and postsynaptic GABA receptors and sites of action of some GABAergic drugs are also shown. The table lists important GABAergic receptor agonists and antagonists.
The Interplay Between Neurons and Glia in GABA Metabolism
Glial cells play an important role in controlling the amount of GABA in neurons and in the extracellular space.
Schematic Models of the GABAA Receptor Complex
BDZ = Benzodiazepine
Full Agonists, Partial Agonists, Receptor Antagonists and Inverse Agonists
Inverse agonists acting on BDZ receptor can have anxiogenic effects (e.g., R015-4513) or even convulsive effects (certain beta-carbolines).
Therapeutic Uses of Sedative-Hypnotics and Anxiolytics
Barbiturates - Example
Barbiturates - Characteristic
Barbiturates - Absorption/Distribution
Barbiturates - CNS Action
Barbiturates - Respiratory/Cardiovascular/Autonomic Effect
Barbiturates - Caution/Side Effects
Barbiturates - Tolerance
Barbiturates - Physical Dependence
Barbiturates - Barbiturate Poisoning
Benzodiazepines - Example
Benzodiazepines - Characteristic
Benzodiazepines - Mechanism
Benzodiazepines - Absorption/Distribution
Benzodiazepines - Advantage
Benzodiazepines - Cocern
Non-Barbiturates/Non-Benzodiazepines - Example
Non-Barbiturates/Non-Benzodiazepines - Chloral Hydrate
Non-Barbiturates/Non-Benzodiazepines - Carbamates/Meprobamate
Non-Barbiturates/Non-Benzodiazepines - Buspirone
“Second Generation” Anxiolytic
Barbiturates: Duration of Action
Tolerance and Therapeutic Index - Representation
The images are theoretical dose-response curves for the barbiturate-induced desired effect (e.g., mood change or sedation) and lethal respiratory depression.
