26 Sedative Hypnotics and Anti-anxiety Flashcards
What are of the brain regulates the heartbeat and other visceral functions and processes the emotion fear?
Amygdala
What are of the brain is needed for establishment of long-term memory in regions of the cerebral cortex?
Hippocampus
Drugs that reduce anxiety, exert calm are _, while drugs that produce drowsiness, encourage sleep are _
SedativesHypnotics
How can benzodiezapines be used to avoid producing sedation?
Low doses can relieve anxiety without sedation
What are the 2 examples of non-benzodiezapines that interact with benzodiezapine receptors?
ZolpidemZaleplon
What are the 4 examples of barbiturates provided?
PentobarbitalPhenobarbitalAmobarbitalThiopental
What class of drug is the preferred agent for use as a sedative hypnotic, anxiolytic, muscle relaxant and or anticonvulsant?
Benzodiezapines
True or false: Benzodiezapines can be used an anesthetics and analgesics at higher doses.
False. These drugs are neither anesthetics or analgesics
What is the receptor target of benzodiezapines? Where are these receptors targets located? What is the effect of receptor activation?
GABA-A receptorsLimbic systemGABA mimetic, enhance neuronal inhibition
When barbiturates and benzodiezapines bind GABA-A, what effect does that have on GABA activity?
Enhances GABA activity
When GABA binds the GABA-A receptor, what is the effect?
Increased chloride conduction, hyperpolarization of neuron
There were 2 examples of GABA antagonists provided. What were they? Which is competitive/non-competitive? What is the effect of their activity on the entire organism?
-Bicuculine - competitive-Picrotoxin - Non-competitive-Convulsions
There was a single example of an inverse agonist at the GABA-A receptor provided. -What is it? -Why is it relevant? -What is its mechanism? -Any therapeutic use?
-Beta-carbolines-Endogenous beta carbolines cause pathological anxiety-Reduces chloride conductance-No therapeutic use
What is the example of an antagonist that can block agonists at both the benzodiezapine activity at GABA-A receptors?
Flumenazil
How, mechanistically, do benzodiezapine enhance GABA conductance at the GABA-A receptor? What is their effect in the absence of GABA?
-Increase the FREQUENCY of channel opening in response to agonist-No effect in the absence of agonist
What are the 2 main CYP enzymes responsible for the metabolism of benzodiezapines?
CYP3A4CYP2C19
What is the active metabolite of diazepam? Alprazolam? Midazolam?
Diazepam - DesmethydiazepamAlprazolam and Midazolam - alpha hydroxy metabolites
Rank the following benzodiezapines in order of increasing half-life. Alprazolam, Diazepam, Lorazepam and Midazolam.
MidazolamAlprazolamLorazepamDiazepam
Of the following benzodiezapines, which is used as a preanesthetic medication? Anxiety? Insomnia? Muscle relaxant? Withdrawal?[Alprazolam, Diazepam, Lorazepam and Midazolam]
Preanesthetic - MidazolamInsomnia - Alprazolam, LorazepamAnxiety - Lorazepam, DiazepamMuscle relaxant - Diazepam, LorazepamWithdrawal - Diazepam
True or false, benzodiezapines have a high therapeutic index and overdose is not usually life threatening?
True, their major advantage over barbiturates
In addition to supporting BP and respiration, gastric lavage, how can you quickly reverse respiratory depression brought about by benzodiezapine overdose? How many treatments and why?
Flumenzil IVMultiple doses because flumenazil is short acting
True or false, while abuse potential for benzodiezapines is low, physical and psychological dependence may still occur
True
What are 2 ways by which withdrawal symptoms from benzodiezapines can be precipitated?
Stopping benzodiezapine useUse of antagonists
True or false: benzodiezapines induce a lot of CYP enzymes therefore can produce several drug interactions
False. They don’t induce a lot of CYP enzymes
What is the cause of a lot of the deaths associated with benzodiezapines use?
Mixing / co-ingesting with other CNS depressants (e.g alcohol)
Zolpidem and zaleplon act at what receptor? What is their effect at this receptor? What is the enzyme responsible for their metabolism? What is their main use?
-GABA-A receptor-Increase frequency of channel opening (more chloride)-CYP3A4-Induce sleep
Usually, zolpidem and zaleplon do not cause respiratory depression or cardiovascular depression. In what scenario is this not the case? (2)
IV administrationHeart failure patients (pt. with impaired cardiovascular function)
What are 3 major disadvantages of barbiturates over benzodiezapines?
- Respiratory depression- cardiovascular depression- Induction of CYP450 enzymes in liver (drug interactions)
What are the 3 main brain areas targeted by barbiturates? What receptor do they bind?
Pons, medulla and cortexGABA-A complex (Pons + medulla = reticular formation)
What is the mechanism by which barbiturates enhance chloride conductance by GABA-A receptor? What is their action in the absence of GABA?
Increase the open time (vs. frequency) of channelAt high doses, can open channel in absence of GABA
Arrange the following barbiturates in order of increasing halflife. Pentobarbital, thiopental, phenobarbital and amobarbital. What are they used for?
Thiopental - Anesthesia inductionAmobarbital - Preoperative sedationPento - Preoperative sedationPheno - Anticonvulsant
Drowsiness, confusion, diminished motor skills and impaired judgment. These are all side effects of _
Barbiturates
What are the 2 major contraindications of barbiturates?
PainPulmonary insufficiency
Barbiturates enhance the CNS depressive effects of 3 types of drugs. They are _
AntipsychoticsAntihistaminesEthanol
True or false, barbiturates have a high therapeutic index and overdose is not usually life threatening?
False. Only 10X hypnotic does is enough to cause life threatening respiratory depression, circulatory collapse, renal failure and pulmonary complications
How can you treat barbiturate poisoning? (2)
Support respiration and BPGastric lavage (activated charcoal, sorbitol)
What are 2 types of tolerance that occur with barbiturate use? How long does it take to occur?
-Metabolic (increased CYP metabolizing enzymes)-Pharmacodynamic (decreased CNS response)
True or false: Physical dependence and cross tolerance develops with continued use of barbiturates
True
What are 2 other non-benzodiazapine, non-barbiturate antianxiety drugs discussed? What are their target receptors and actions at these receptors?
Propranolol - Beta-adrenoreceptor blockerBuspirone - Partial 5HT-1A agonist
What enzyme metabolizes buspirone? How does it interact with alcohol? How long does it take to cause its effects? What is the risk of dependence developing?
CYP3A4No additive effects with ethanol1-3 weeks before effects are observedNo physical dependence develops
Sedation and amnesia for surgery, epilepsy and seizure, control of alcohol withdrawal, muscle relaxation, insomnia. These can all be treated by _ class of drugs.
Sedative hypnotics
Regardining benzodiazepines, what is the pharmacodynamic mechanism by which tolerance occurs? Does tolerance to benzos result in tolerance to other CNS depressants?
- Tolerance occurs by down regulation of CNS response - Cross tolerance occurs to other benzos and CNS depressants
True or false. anxiety, insomnia, irritability, bad dreams, tremors and anorexia are severe symptoms associated with benzodiazepine withdrawal.
False. These are considered mild symptoms
True or false. agitation, depression, panic, paranoia, muscle twitches and convulsions are considered mild symptoms of benzodiezapine withdrawal
False, these are considered severe symptoms
Why are barbiturates notorious for causing drug-drug interactions?
Barbiturates induce the activity and/or expression ofmany CYPs.
How are barbiturates metabolized (2 actions)? How are they excreted?
Dealkylated and glucuronidation Renal excretion
How are the following drugs related to barbiturates? Beta-blockers, Ca2+ channel blockers, corticosteroids,estrogens, phenothiazines, valproic acid and theophylline
Their metabolisms are all enhanced by barbiturates
Severe respiratory depression, coma, severe hypotension and hypothermia. These are all signs of _
Acute barbiturate toxicity
True or false: Anxiety, insomnia, dizziness and nausea are considered mild symptoms of barbiturate withdrawal?
True
True or False: vomiting, hyperthermia, tremors,delirium, convulsions and death are considered serious symptoms of barbiturate withdrawal
True
Does buspirone produce CNS depression? Does it produce rebound anxiety or withdrawal signs? What is it used to treat?
No NoAnxiety
