EXAM #3: SEDATIVES Flashcards
What is the definition of CNS depression?
Decreased neuronal excitability
What are CNS depressants generally used to treat?
1) Anxiety states
2) Sleep disorders
List the categories of selective CNS depressants.
Benzodiazepines
Barbiturates
Ethanol
List the categories of non-selective/ general CNS depressants.
Antihistamines
Opoid analgesics
What is the effect of sedative anxiolytics?
Exertion of a calming effect and relief of anxiety
What is the effect of hyponotics?
Production of drowsiness
What are the graded dose-dependent effects of the sedative hypnotics?
1) Sedation
2) Sleep
3) Anesthesia
4) Coma
5) Respiratory depression/ death
What is a linear slope sedative-hypnotic? Non-linear? Which is safer?
Linear= higher dose leads to increased dose-dependent effects
Non-linear= plateau in dose-dependent effects*
Non-linear are SAFER
What are the indications for sedative-hypnotics (6)?
1) Anxiety
2) Insomnia
3) Amnesia
4) Seizures
5) Ethanol withdrawal
6) Muscle relaxation
What suffix is associated with the benzodiazepines?
- “zepam”
- “zolam”
What are the three main pathways of benzodiazepine metabolism?
1) Inactive water-soluble glucuronides
2) Weakly active short-lived metabolites
3) Long-lived and active metabolites
What benzodiazepines undergo metabolism to inactive water-soluble glucuronides? What is the half-life/ duration of action?
Lorazepam
Oxazepam
Short acting
What benzodiazepines undergo metabolism to weakly active, short-lived metabolites? What is the half-life/ duration of action?
Alprazolam
Triazolam
Intermediate-acting
What role does age play in the metabolism of benzodiazepines?
Hepatic processing SLOWS in the elderly and INCREASES the half-life
What is the general mechanism of action of the benzodiazepines?
- Bind GABA-A ion channel (Cl-) at specific binding site increasing opening of GABA channels
- Increased Cl- enters the neuron and is INHIBITORY/ causes HYPERPOLARZIATION
What is Alpha-1 GABA agonism associated with?
Sedation
Anti-seizure
Anterograde amnesia
What is Alpha 2,3,5 GABA agonism associated with?
Anxiolysis
What are the adverse effects of the benzodiazepines?
1) Respiratory depressant
2) Anterograde amnesia
3) Tolerance
4) Dependence
5) Withdrawal
What increases the adverse effects of benzodiazepines?
Use with other CNS depressant
What drug is strongly associated with anterograde amnesia and is used as a date-rape drug?
Flunitrazepam i.e. Rohypnol/ roofies
What drugs when combined with benzodiazepines will cause additive CNS depression?
Ethanol Opoids Anti-consulsants Phenothiazine Anti-histamines Tricyclic antidepressants
What is the common name for flumazenil? Why is this drug important?
Romazicon
Can reverse the adverse effects of benzodiazepine overdose*
What is the mechanism of action of Flumazenil?
Competitive inhibitor of benzodiazepines
What are the “z-drug” benzodiazepine related drugs?
Newer sedative agents used to treat insomnia
What is the mechanism of action of z-drugs?
Agonism of benzodiazepine receptors on GABA-A receptors
What are the clinical uses for Barbiturates?
1) Anesthesia
2) Sedative/hypnotic
3) Anticonvulsant
4) Medically induced coma
What is the important clinical difference between benzodiazepines and barbiturates?
Barbiturates follow a linear slope and are much less safe
What is the mechanism of action of barbiturates? How does this differ from the benzodiazepines?
Barbiturates= increased the duration GABA channel opening
Benzodiazepines increase the frequency of GABA channel opening
What is the mechanism of action of Ramelteon?
Melatonin receptor agonist
What is the clinical use of Ramelteon?
Insomnia– especially for people that have difficulty falling asleep
What is the mechanism of action of Buspirone?
Partial agonist of 5-HT1a receptors (autoreceptors)
- Decreases 5-HT release
- Decreases neuronal excitability
What is unique about Buspirone?
NON-SEDATING anxiolytic (long-term/ maintenance)
- Less psychomotor impairment
- Does NOT affect driving skills
Where are 5-HT1a receptors located?
Located on the pre-synaptic terminal and INHIBIT release of the NT from the pre-synaptic membrane
What is classification 5-HT1a receptors?
Autoreceptors
What Beta-Blocker is used to treat anxiety?
Propranolol
What facets of anxiety is propranolol treating?
Somatic manifestations of anxiety
What antihistamines have a mild sedative effect?
Hydroxyzine
Diphenhydramine
What is the oldest ad most commonly used anxiolytic?
Ethanol
