Exam 2 (Pt. 12)

Question 1

Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Cellular Metabolism

Answer 1

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.

Question 2

Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Glutamate Effect

Answer 2

Glutamate Effect Neurons are strongly depolarized by glutamate stimulation of AMPA and kainate receptors and by exposure to the elevated K+ levels.

Question 3

Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Prolonged Effect

Answer 3

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.

Question 4

Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Depolarization

Answer 4

Depolarization is also thought to cause additional Ca2+ entry into the cell through voltage-operated Ca2+ channels (VOCC).

Question 5

Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Ca²⁺ Elevation

Answer 5

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.

Question 6

Biochemical Processes Hypothesized to Underlie Ischemic Neuronal Injury and Death - Diagram

Answer 6

Question 7

GABA Synthesis - Reaction

Answer 7

The excitatory amino acid neurotransmitter is catalyzed by the enzyme, glutamate acid decarboxylase (GAD), to form the inhibitory amino acid neurotransmitter GABA.

Question 8

GABA Synapse

Answer 8

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.

Question 9

The Interplay Between Neurons and Glia in GABA Metabolism

Answer 9

Glial cells play an important role in controlling the amount of GABA in neurons and in the extracellular space.

Question 11

Schematic Models of the GABAA Receptor Complex

Answer 11

BDZ = Benzodiazepine

Question 12

Full Agonists, Partial Agonists, Receptor Antagonists and Inverse Agonists

Answer 12

Inverse agonists acting on BDZ receptor can have anxiogenic effects (e.g., R015-4513) or even convulsive effects (certain beta-carbolines).

Question 13

Therapeutic Uses of Sedative-Hypnotics and Anxiolytics

Answer 13

Question 15

Barbiturates - Example

Answer 15

Question 16

Barbiturates - Characteristic

Answer 16

Question 17

Barbiturates - Absorption/Distribution

Answer 17

Question 18

Barbiturates - CNS Action

Answer 18

Question 19

Barbiturates - Respiratory/Cardiovascular/Autonomic Effect

Answer 19

Question 20

Barbiturates - Caution/Side Effects

Answer 20

Question 21

Barbiturates - Tolerance

Answer 21

Question 22

Barbiturates - Physical Dependence

Answer 22

Question 23

Barbiturates - Barbiturate Poisoning

Answer 23

Question 24

Benzodiazepines - Example

Answer 24

Question 25

Benzodiazepines - Characteristic

Answer 25

Question 26

Benzodiazepines - Mechanism

Answer 26

Question 27

Benzodiazepines - Absorption/Distribution

Answer 27

Question 28

Benzodiazepines - Advantage

Answer 28

Question 29

Benzodiazepines - Cocern

Answer 29

Question 30

Non-Barbiturates/Non-Benzodiazepines - Example

Answer 30

Question 31

Non-Barbiturates/Non-Benzodiazepines - Chloral Hydrate

Answer 31

Question 32

Non-Barbiturates/Non-Benzodiazepines - Carbamates/Meprobamate

Answer 32

Question 33

Non-Barbiturates/Non-Benzodiazepines - Buspirone

Answer 33

"Second Generation" Anxiolytic

Question 34

Barbiturates: Duration of Action

Answer 34

Question 35

Tolerance and Therapeutic Index - Representation

Answer 35

The images are theoretical dose-response curves for the barbiturate-induced desired effect (e.g., mood change or sedation) and lethal respiratory depression.

Question 38

Localization of GABA Pathways - Technique

Answer 38

* Immunohistochemical localization of glutamic acid decarboxylase (GAD). * Immunohistochemical localization of GABA itself. * Histochemical localization of the GABA-destroying enzyme GABA aminotransferase. * Uptake of labeled GABA followed by autoradiography.

Question 42

Classification of Sedative-Hypnotics and Anxiolytics

Answer 42

* Barbiturates * Benzodiazepines * Non-Barbiturates/Non-Benzodiazepines