Sedative-Hypnotics Flashcards
What are the sedatives that target GABA-A receptors?
- Benzodiazepines
- Non-benzodiazepine Agonists
- Barbiturates
- Ethanol
GABA-A Receptors
Ionotropic receptors that cause Cl- channels to open leading to inhibitory synaptic potentials
GABA-B Receptors
Metabotropic G-protein linked receptors that act on presynaptic terminals and regulate the release of GABA or other NTs
What is the most abundant GABA-A configuration?
2-alpha
2-beta
1-gamma
What is the binding site on GABA-A for GABA?
Alpha/beta interface - normally 2 sites
What is the binding site on GABA-A for benzodiazepines, imidazopyridines and pyrrolopyrazines?
Alpha/gamma interface
What are the BZ1 selective class of drugs?
Non-benzodiazepines
- Imidazopyridines
- Pyrrolopyrazines
Benzodiazepine MOA
Binding of the drug acts as a positive allosteric regulator that increases GABA affinity for GABA-A receptor and increases the frequency of Cl- channel opening - more inhibitory signal
Where do the barbiturates bind?
Bind to parts of GABA-A separate from BZ sites and lead to increased DURATION of Cl- channel opening rather than frequency
What suffices are indicative of benzodiazepines?
- AM
- PAM
- LAM
What are the indications for benzodiazepines?
- Anxiety
- Sleep disorders
- Anticonvulsant
- Treatment for EtOH withdrawal
What are the contraindications of benzodiazepines?
Significant pulmonary illness or CNS depression
Benzodiazepines are highly _______.
Protein-bound
What happens to the half life of diazepam as the age of patients increases?
It will increase due to the decreased hepatic function
What are the benzodiazepines that go directly to phase II metabolism in the liver?
LOT
Lorazepam
Oxazepam
Temazepam
What are the benzodiazepines with the shortest half lives?
LOT
Lorazepam
Oxazepam
Temazepam
Benzodiazepine SE
- Amnesia
- Confusion
- Dizziness
- Allergic Reaction
- Tolerance
- Dependence
What is the tolerance that is developed to benzodiazepines?
Tolerance is only developed to the sedative effects, NOT the anti-anxiety effects
What are the imidazopyridines?
Zolpidem
Zaleplon
What are the pyrrolpyrazines?
Eszopiclone
Non-benzodiazepine MOA
Bind selectively to BZ1 and positively modulates GABA-A action
Non-benzodiazepine SE
- Similar to benzodiazepines
- Sleep-driving/eating
- Anterograde amnesia
Which of the non-benzodiazepines has the longest half life?
Eszopiclone
What are the barbituates?
Penobarbital
Methohexital
Thiopental
-AL suffix
Barbituate MOA
Binds to GABA-A at distinct regions from BZ1/2 and increase duration of Cl- channel opening - at high doses they can directly open Cl- channels
What are the short acting barbiturates?
Thiopental and Mexihexital
What are the long acting barbiturates?
Phenobarbital
Barbituate SE
- Respiratory Depressant
- Death from OD
- Withdrawal
- Tolerance due to CYP450 induction
Ramelteon MOA
Melatonin agonist that binds MT1 and 2 receptors with higher affinity that melatonin - no BZ binding
Ramelteon SE
- Headache
- Fatigue
- Dizziness
What is a major advantage of ramelteon?
No physical dependence or withdrawal symptoms
Do benzodiazepines cure insomnia?
No, they will only resolve the symptoms for as long as they are taken.
Valeriana officinalis - Herbal MOA
Mediate GABA release and inhibit its breakdown - can be used to treat insomnia for up to 4 weeks
Chamomile - Herbal MOA
Benzodiazepine agonist
Passion Flower - Herbal MOA
Benzodiazepine partial agonist
Buspirone MOA
5-HT1A partial agonist
Buspirone SE
- Headaches
- Dizziness
- Sedation
Buspirone Contraindications
DO NOT USE alongside a MAO-I
Buspirone Indications
- Major depression
- Anxiety disorders
What are advantages of buspirone over benzodiazepines?
- NO risk of dependence
- NO sexual dysfunction
Sedative (Anxiolytic)
Reduces anxiety and exerts a calming effect
Hypnotic
Produces drowsiness and facilitates the onset and maintenance of sleep
Where is GABA synthesized?
Nucleus Accumbens
Which GABA receptors do all sedatives act on?
GABA-A
What drug classes does BZ1 bind?
- Benzodiazepines
- Imidazopyridines
- Pyrrolopyrazines
What drug classes does BZ2 bind?
- Benzodiazepines
Flumazenil MOA
Competitive antagonist of BZ1 and 2 site and blocks the actions of drugs that act at these sites
Benzodiazepine Indications
Anxiety, Insomnia, Anesthesia, Alcohol Withdrawal, Seizures
What are the benzodiazepines with long half lives?
- Chlordiazepoxide
- Diazepam
- Flurazepam
What is the metabolism of zaleplon inhibited by?
Cimetidine
