PHA 6575 Lecture 12 (GABA)

GABA-A

drugs that inhibit _________ receptors produce seizures in animals

Mutations

__________ in GABA-A receptor subunits that impair activation are associated with inherited human epilepsy

True

T/F: GABA-A receptors activation may enhance bronchodilation because they are located on airway epithelium

K and Ca

GABA-B interacts with GPCRs, which leads to dissociation of beta-gamma subunit to directly activate ______ channels and inhibit the opening of voltage-gated ______ channels

Adenylyl Cyclase

GABA-B leads to suppression of _________

Inhibitory Postsynaptic Potentials

increased K efflux in GABA-B receptor leads to slow, long-lasting _______

Presynaptic Neurotransmitter Release

reduced calcium influx may account of GABA-B autoreceptors to inhibit ____________

Tetanus Toxin

inhibits GABA and glycine release; convulsant

Tiagabine

inhibits GAT-1 in neurons and glial cells; anticonvulsant

True

T/F: tiagabine increases both synaptic and extrasynaptic GABA concentrations and is non-specific agonist for both ionotropic and metabotropic GABA receptors

Picrotoxin

non-competitive inhibitor of GABA-A receptor that blocks the ion pore

Epileptic Convulsions

all GABA-A antagonists induce __________ and are only used for research

Beta-Carbolines

inverse BZP agonist that can elicit anxiogenic effects and convulsions

Alprazolam (Xanax), Clonazepam (Klonopin), Diazepam (Valium), and Lorazepam (Ativan)

BZP agonists

Flumazenil (Romazocon)

BZP antagonist

Vigabatrin

inhibits GABA transaminase; anticonvulsant

Muscimol

GABA-A receptor agonist; mimics psychosis

Bicuculline

competitive antagonist of GABA-A; convulsant

Benzodiazepines

potentiate GABA binding; anticonvulsant, anxiolytic

Barbiturates

increase GABA efficacy, weak agonist; anticonvulsant, anesthetic

Baclofen

GABA-B receptor agonist; muscle relaxant

Zolpidem (Ambien)

nonbenzodiazepine hypnotic drug

Sedation

reduction of anxiety

Addiction

the state of response to a drug whereby the drug taker feels compelled to use the drug and suffers anxiety when separated from it

Anesthesia

loss of consciousness associated with absence of response to pain

Amnesia

a deficit in or loss of memory

Anxiolytic

a drug that reduces anxiety, a sedative

Dependence

the state of response to a drug whereby removal of the drug evokes the unpleasant, possibly life-threatening symptoms, often opposite of the drug effects

Hypnosis

induction of sleep

REM Sleep

the phase of sleep associated with rapid eye movement; most dreaming takes place during this sleep and is the deepest level of sleep

NREM Sleep

stage 2, non-rapid eye movement; light sleep that normally comprises approximately half of the sleeping time

Tolerance

reduction in drug effect requiring an increase in dosage to maintain the same response

Ataxia

lack of coordination of muscle movements

Seizure

rapid depolarizing CNS neurons that repeatedly fire action potentials

Sedative, Hypnotic, Muscle Relaxant, Amnestic, and Anxiolytic

BZPs have ___________ effects

Low

when GABA is in low concentrations, BZPs increase the frequency of channel openings

High

when GABA is in high concentrations, BZPs slow receptor deactivation to lead to net increase of Chloride influx

False

T/F: BZPs activate native GABA-A receptors in the absence of GABA

Left

BZPs shift the dose response curve to the ________ because they increase potency

Insomnia and Brain Disorders

Zolpidem is used for __________ and _________

Alcohols and Sedative Hypnotics

co-administration of BZPs with ________ decreases the margin of safety

Spinal Cord

BZPs reduce skeletal muscle spasticity by enhancing inhibitory interneurons in the ___________

Medullary Depression

in patients with pulmonary or cardiovascular disease, BZPs can lead to respiratory or cardiovascular depression due to __________

Sedated

patients who have suffered stroke or head trauma may be ________ when administered BZPs

Diazepam (Valium)

BZP used for anxiety, muscle relaxation, general anesthetic, and alcohol withdrawal and is long-acting

True

T/F: high doses of BZPs rarely cause death unless administered with other drugs

Amnesia, Arrhythmias, CNS Depression, Drug Dependence, and Hypotension

adverse effects of BZPs

Flumazenil

BZPs overdose can be reversed with ______ (competitive BZP antagonist)

Withdrawal Symptoms

administration of flumazenil in a patient with BZP dependence will result in severe _____________

Reduction

the number of receptors can be increased by a sustained __________ in NT release or by the long-term administration of a receptor antagonist

NT Reuptake Blockade

the number of receptors can be decreased by a sustained ________ or by long-term administration of receptor agonist

Phenobarbital

BBT agonist: Luminal

Thiopental

BBT agonist: Pentothal

Amobarbital

BBT agonist: Amytal

Pentobarbital

BBT agonist: Nembutal

Secobarbital and Methohexital

two BBT agonists

Thiopental, Pentobarbital, and Methohexital

anesthetics BBTs that act as both GABA-A agonists and enhancers of GABA-A responses

Anticonvulsant BBT

phenobarbital produces less agonism on native GABA-A receptors and is an _________

False

T/F: BBTs bind to the binding site of GABA-A receptors

Duration

BBTs work by enhancing efficacy of GABA by increasing the ________ that the Cl channel is open

BBTs

do BBTs or BZPs have a greater GABA-enhancing ability?

Hypnosis, Coma, Respiratory Depression, and Death

adverse effects from overdoses of BBTs

AMPA Receptors

BBTs affect excitatory neurotransmission by decreasing ________ by glutamate and reducing membrane depolarization

General Anesthesia

thiopental, methohexital, and pentobarbital induce ________

CYP3A4, 3A5, and 3A7

BBTs are metabolized by ___________

Low

do BBTs have a high or low TI?

Brain, Muscle, and Fat

a BBT's duration of action is determined by the rapidity with which it is redistributed from the _________ to other vascular compartments, particularly ______ and ________

Linear

BBTs exhibit a __________ dose-response effect

High and Low

BZPs are __________ potency and _______ efficacy

Low and High

BBTs are ________ potency and _______ efficacy

True

T/F: baclofen is the only compound clinically used to target GABA-B receptors

Ethanol

acts as an anxiolytic and sedative by causing CNS depression and targets both GABA-A and glutamate receptors

Increases and Decreases

ethanol _________ GABA-A mediated Cl influx and __________ excitatory effects of glutamate at NMDA receptors

Synergistically

ethanol acts ________ with other sedatives, hypnotics, antidepressants, anxiolytics, anticonvulsants, and opioids

Gamma-Hydroxybutyric Acid (GHB)

GABA isomer used as a sedative and treatment for narcolepsy

Flunitrazepam (Rohypnol)

fast acting BZP that can cause amnesia and prevent recall of events and are typically known as "date-rape" drugs due to amnesia effects