What are anxiolytics?
What kind of effect do they have?
What effect does hypnotics have?
Encourage the onset and maintenance of a state of sleep
What kind of NT is GABA?
Neurons that secrete GABA are called...
How is GABA synthesized?
Via the decarboxylation of Glutamate
What enzyme catalyzes the decarboxylation of Glutamate?
GAD (glutamate decarboxylase)
GAD (glutamate decarboxylase) activity requires what cofactor?
Pyridoxal Phosphate PLP
Pyridoxal Phosphate PLP is generated from what vitamin?
PLP requires what for activation?
Deficiency of zinc of defect in PLP can cause....
What is GABAA modulated by?
What kind of receptors are GABAA?
Ligated-gated Cl- ion channels
What binds to GABAA receptors?
What is a GABAB agonist?
The major isoform of the GABAA receptor has what subunits?
Two α1 subunits
Two β2 subunits
One γ2 subunit
Where are the binding sites for GABA located?
Between α1 and β2
Where are the binding sites for BZs located?
Between α1 and γ2
Where is the binding site for Barbiturates located?
What do α1 subunits mediate?
What do α2 and α3 subunits mediate?
BZ anxiolytic action
What do α5 subunits mediate?
BZ Memory impairment
What effect do BZs have on GABA receptor?
Increases synaptic inhibition
What does increasing synaptic inhibition do?
How do BZ enhance GABAergic rec without directly activating the GABAA receptor?
Increase the frequency of Cl- channel openings
Enhance Cl- conductance
What are GABAA BZ site agonists?
What are GABAA agonists?
What is the function of GABAA agonists?
Enhance membrane hyperpolarization similar to BZs
GABAA agonists does not cause....
Muscle relaxant effect
What are BZ antagonists?
What is the function of Flumazenil?
Block BZ action
Block Zolpidem, Zaleplon, Eszopilone action
What doesn't Flumazenil block?
What are the inverse agonists of Flumazenil?
What is the function of the inverse agonists of Flumazenil? And what does it cause?
Causes anxiety and seizures
Graded dose-dependent depression of the CNS is seen with....
Older sedatives/ hypnotics such barbiturates have a....
Linear dose relationship
What does the linear dose relationship mean?
As the dose increases, CNS depression increases.
What is the MOA of barbiturates on GABAA and how does this occur?
Enhances membrane hyperpolarization by increasing the duration that the GABA-gated Cl- channels are opened
Compare the selectivity of barbiturates compared to BZs.
Barbiturates are less selective than BZs
Describe the absorption properties of BZs and Barbiturates.
Barbiturates and BZs are rapidly absorbed through which route of absorption (ROA)?
BZs are classified based on duration of action. Name the long-acting drugs and its duration.
BZs are classified based on duration of action. Name the medium-acting drugs and its duration.
BZs are classified based on duration of action. Name the short-acting drugs and its duration.
BZs are classified based on duration of action. Name the ultrashort-acting drugs and its duration.
What are the rapidly absorbed BZs?
How does elimination half-life of diazepam affect elderly patients?
In geriatric patients, elimination half-life is prolonged.
What side effects are associated with the frequent use of BZs? What drug causes this?
Rebound REM sleep; Triazolam and drugs with short duration of action
True/False: Newer drugs affect rebound REM.
What kind of drug is Clorazepate?
How does Clorazepate produces its effect following oral administration?
It converts to its active form (desmethyldiazepam/nordiazepam) by acid hydrolysis in the stomach.
What barrier do all sedative-hypnotics cross?
BBB and Placental barrier
Drugs with very short half lives for hypnotic effects may lead to....
Withdrawal symptoms between doses
What is Flumazenil?
A BZ competitive inhibitor with high affinity
What is the use of Flumazenil?
Reversing CNS depression effects of BZ OD
Helps recovery in anesthetic and diagnostic procedures
Explain the onset and DOA for Flumazenil.
Rapid onset and short half life
What is the half-life of Flumazenil?
List the adverse effects of Flumazenil.
What agents do not act through GABA-BZ mechanisms?
Explain the ROA and DOA of Ramelteon and Buspirone?
Rapidly absorbed orally
Undergoes extensive first-pass metabolism (2-5 hours)
What drug reduces the plasma levels of Ramelteon and its active metabolites?
What is the function of rifmapin?
What receptor(s) does Buspirone not interact with?
BZ sites and GABAA
True/False: Buspirone causes more psychomotor impairment than BZs.
False; Buspirone causes less psychomotor impairment than BZs and does not affect driving skills.
True/False: Unlike BZs, elderly do not appear to be more sensitive to buspirone
True/False: Buspirone is used in generalized anxiety states but less effective in panic disorders.