Sedatives , Hypnotics, Anxiolytics Flashcards
What is a sedative drug
A drug that decreases activity moderate excitement and calms
What is a hypnotic drug
A drug that produces drowsiness facilitates I’m sets and maintenance of the state of sleep resembling natural sleep from which the recipients can be aroused easily
Two phases of sleep
Non-rapid movement sleep
Rapid eye movement sleep
How many stages of nonrapid eye movement sleep there is
4
In healthy sleep do you go fast into the first REM sleep Or do you first experience four stages of nonrapid eye movement sleep
Experience first four stages of nonrapid eye movement sleep
What part of the brain controls the nonrapid eye movement sleep
The basal forebrain
Area surrounding solitary Tracts in Medullal
Dorsal Raph’s nucleus
Decrease of that hormone reduces sleep
Serotonin
Destruction of this part of the brain that contains lots of serotonergic bodies reduces sleep
Dorsal raphe
What cells turns on the rapid eye movement sleep
cholinergics cells
Pontine gigantocellular celld
Hormone responsible for alertness and its decrease promote sleepiness
Dopamin
Mira chemicals involved in wakefulness
Acetylcholine noradrenaline histamine Substance p , CRF
What is insomnia
Complaints of difficulty falling asleep
difficulty maintaining sleep
experiencing non restorative sleep
When is insomnia considered chronic
One last more than one month
E What is anxiety
Vague in present emotion experienced in anticipation of some future misfortune
State of apprehension and certainty of fear
Is anxiety always a medical condition
No it’s actually a normal adaptive function
What is anxiety disorders
Extreme of normal anxiety which occur in this regulation of six of system when there is apprehension even though there shouldn’t be
Types of anxiety disorders
Généralised anxiety disorder Panic disorder Phobias PTSD Ocd
What is generalized anxiety disorder
Excessive uncontrollable irrational worry
What is panic disorder
Unexpected repeated episodes of intense fear with physical reaction
What is phobia
Persistent fear of an object or situation
What is OCD
Repetitive unwanted obsession or compulsive act
Anxiety etiology
Genetic neurotransmitter abnormalities - serotonin noradrenaline gabba HPA DYSREGULATION social factors personality factors
What body mechanism is responsible for the action of sedative hypnotics
Central nervous system depression
Can you go over the state of hypnosis with new sedative hypnotic drugs as easily as it was with older sedative hypnotic drugs
No , much harder Requires very large doses
What is considered an ideal anxiolytic drug
Calm patients without causing daytime sedation
No physical or psychological
What is an ideal hypnotic drug
Patience fall asleep quickly
Sleep has sufficient quality and duration
What are the class of drug considered sedative hypnotic drugs
Benzodiazepines Barbiturates Nonbenzodiazepine benzodiazepine receptor agonist Sedative antihistamines Melatonin receptor agonist Herbals Miscellaneous drug
The use of barbiturate is now confined to two specific uses ,what are they
Epilepsy
anesthesia
Examples of non-benzodiazepine benzodiazepine receptor agonist
Zaleplon
zopiclone
Eszopiclone
zolpidem
Examples of melatonin receptor agonist
Ramelteon
Example of sedative antihistamines
Diphenhydramine
Hydroxyzine
Promethazine
Examples of herbals
Valerian
Examples of miscellaneous drugs
Chloral hydrate
Meprobamate
Methaqualone
What substituent is necessary at the 7 position in the heterocyclic structure coupled to the benzene ring in benzodiazepines for sedative hypnotic activity to occur
A halogen or nitro group
What special structures do you find in triazolam and alprazolam which are benzodiazepines
Triazole ring at position one and two
Administration modes of benzodiazepine
Oral
Which Benzodiazepine have extremely rapid absorption
Triazolam
Diazepam
Clorazepate
What factor plays major role in determining rate at which a particular benzodiazepine will enter the central nervous system
The Lipids solubility profile
Can sedative hypnotics cross placental barrier during pregnancy
Yes
Can you find sedative hypnotics in breast milk
Yes
What is the metabolism of benzodiazepine
Hepatic - Microsomal oxidation with the alkylation and aliphatic hydroxylation
Conjugation with glucuronide
Metabolism of alprazolam and triazolam
Alfa hydroxylation. And then form inactive glucuronides
Are the effects of alprazolam and trialozam long lived or short lived
Short lived
How are benzodiazepine excreted
Through urine
The changes in renal function have it marked effect on elimination of parent benzodiazepine
No
In which type of disease do you see increased time of elimination
In old patients with severe liver disease
Which type of drugs when taken for a long term can cause increased hepatic microsomal activity of the enzyme
Barbiturates
Do benzodiazepine change hepatic drug metabolizing enzyme activity with continuous use
No
Where do benzodiazepine bind on GABA receptor
Between alpha 1 and gamma 2
Why do zolpidem zaleplon and eszopiclone buying bind more selectively to GABA receptors
Only interact with subunit containing alpha 1 subunit
Which part of the central nervous system do benzodiazepine potentiates GABA inhibition
Spinal cord hypothalamus hippocampus substantial nigra cerebellar cortex cerebral cortex
Do benzodiazepines substitute or enhance gaba effects
Enhance rather than substitute
What are the action at the organ level of benzodiazepine
Sedation
Hypnosis
anticonvulsants
muscle relaxation
What are the clinical uses of benzodiazepine
Anxiety states insomnia skeletal muscle relaxation premedication in anesthesia status epilepticus acute seizures Antero grade amnesia alcohol and sedative hypnotic withdrawal
What are the adverse effects of benzodiazepine
Toxic effects from overdosage
Unwanted effect wiith normal therapeutic use
Tolerance
dependence
What are the side effects with therapeutic use in benzodiazepine used
Drowsiness
confusion
amnesia
impaired coordination
Is chlordiazepoxide also known as Librium a long or short acting benzodiazepines
Long
What is Librium mostly used for
Anxiety disorders
anesthetic premedication
alcohol withdrawal management
muscle relaxation
Is clonazepam also known as clonopin a long acting or short acting benzodiazepine
Long acting
When do you use clonazepam
Seizure disorders
adjunctive treatment in acute mania
movement disorders like Tourette syndrome
Can clonazepam lead to tolerance in seizures disorders treatment
Yes
Is Diazepam known as Valium a long or a short acting benzodiazepine
Long acting
What are the main uses of diazepam
Anxiety disorders
seizures disorders like status epilepticus
anesthetic premedication
skeletal muscle relaxation
Is flurazepam a long acting or short acting benzodiazepine
How long acting
In which case is flurazepam used
Insomnia
anxiety disorders
Alprazolam is long shorts or medium acting benzodiazepine
Medium acting
Are withdrawal symptoms severe in alprazolam use
Yes
When do you use alprazolam
Anxiety disorders
depressio
Nitrazepam is a long short or medium acting benzodiaze
Medium
When do you mostly use nitrazepam
Anxiety disorders
insomnia
lorazepam a short long or medium acting benzodiazepine
Short acting
Usage of lorazepam
Anxiety disorders
insomnia
preanesthetic medication
Oxazepam short long or medium acting benzodiazepines
Short
Use of oxazepam
Anxiety disorders
insomnia
Is temazepam a short long or medium acting benzodiazepine
Short
Use of temazepam
Insomnia
anxiety disorders
Is midazolam a short medium long or ultra short acting benzodiazepine
Ultrashort
Main uses of midazolam
Anxiety disorders
insomnia
preanesthetic medication
Triazolam is a short ultrashort long or medium acting
Ultrashort
Usage of triazolam
Insomnia
Is clorazepate prodrug or active
Prodrug
Use of clorazepate
Anxiety disorders seizures disorders
Metabolism of clorazepate
Form nordazepam by decarboxylation
What is an example of a specific benzodiazepine antagonists
Flumazenil
Mode of administration of flumazenil
Iv
What is the primary use of flumazenil
Management of benzodiazepine overdose
Reversal of sedative effect produced by benzodiazepine
Is there a psychological and physical dependence with barbiturates
Yes
Examples of barbiturates
Phenobarbital Secobarbital Thiopental Methohexital Pentobarbital Amobarbital
What does action of barbiturates
Increase duration of gabba gated chloride channel openings
Can act like gabba mimetic at high concentration and activate directly chloride channels
The barbiturate binds on the same site as benzodiazepine on GABA receptor
No
What is the reason why barbiturates seem to have full surgical anesthesia ability and pronounced central depressants affect compared to benzodiazepine
Because of multiplicity of site of action
Where is barbiturate absorbed
Small intestine
stomach
Because weakly acidic
Is lipid profile important for central nervous system entry of barbiturates
Yes
Which type of barbiturate are very lipid soluble and have a high entry and Rapid onset of action
Thiobarbiturates
How are barbiturates cleared
Metabolized to more water soluble metabolites with conversion to alcohols and then conversion to glucuronides
How are barbiturates excreted
By kidneys
What method can be used to increase rate of elimination of barbiturates by kidneys
alkalinization of urine
C clinical uses of barbiturates
Epilepsy
insomnia
general anesthesia
Adverse effects of barbiturates
Dizziness lightheadedness sedation headache nausea abdominal pain Tolerance dependence cardiovascular depression respiratory depression
What is an example of a non-benzodiazepine benzodiazepine receptor agonist
Zolpidem
Zaleplon
Can flumazenil antagonize zolpidem
Yes
Action an organ of zolpidem
Minimal Muscle relaxation
minimal anticonvulsant effect
Does zolpidem have a Rapids aonset of action
Yes
Which case can you have respiratory depression with zolpidem
If you take ethanol
Metabolism of zolpidem
Oxidation and hydroxylation by liver
Half life of zolpidem
1.5 hours to 3.5
should you reduce the dosage of zolpidem in patients with hepatic dysfunction surgery patient and patient taking cimetidine
Yes
Elimination half-life of Zaleplon
One hour
Metabolism of zaleplon
Hepatic aldehyde oxidase and CYP3A4 in liver
Which direction inhibits metabolism of zaleplon
Cimetidine
What is the effect of zaleplon on sleep
Decrease sleep latency
no effect on sleep time or architecture
Do you have rebound insomnia in zaleplon usage
Yes
What is an example of a melatonin receptor agonist
Ramelteon
Which receptor Ramelteon act
MT1
MT2
Who should use Ramelteon
Patient will have difficulty falling asleep
What is the goal of melatonin receptors
Maintain circadian rhythms
Metabolism of Ramelteon
CYP1A2
Cyp2c9
Which drug should you not give with Ramelteon
Cyp1a2 Ciprofloxacin Fluvoxamine Tacrine zileuton Fluconazole (cyp2c9)
Is there dependence or abuse with Ramelteon
Yes
Should you pay attention in patients with liver dysfunction when administering Ramelteon
Yes
Adverse effects of Ramelteon
‘Dizziness
somnolence
fatigue
Endocrine changes
What is the function of histamine
Circadian pattern of release to activate neuron in day and silence them at night
Act on H1 receptors in cortex and reticular activating system for arousal and wakefulness
Examples of antihistamine
Diphenhydramine
Chlorpheniramine
Hydroxyzine
Promethazine
What is believed to be the mechanism of action of valerian which is an herbal remedy
May be involved in increasing concentration of gabba
First line drugs for generalized anxiety disorders
Duloxetine Escitalopram Imipramine PAroxetine Sertraline Venlafaxine
Secondly drugs for generalized anxiety disorders
Benzodiazepines
Busipirone
Buspirone
Imipramine
First line drugs for panic disorders
SSRIs
venlafaxine
Social anxiety disorder first line drugs
Escitalopram Fluvoxamine Paroxetine sertraline venlafaxine
Post traumatic stress disorder first line drugs
SSRI
First example of a class of anxiolytic agents
Buspirone
What is the mechanism of action of Buspirone
Serotonin receptor partial agonist
Inhibits activity of nor adrenergic nucleus Ceruleus neurons and interfere with arousal reaction
Who is more effective buspirone or benzodiazepines for treatment of general anxiety
They are both equally effective
Does Buspirone has sedative effect
No
Can you call uses of Buspirone
Generalized anxiety disorder
Anxiety with depression
Adverse effects of Buspirone
Dizziness
lightheadedness
headache
increased but blood pressure when taken with MAO inhibitors
can increase plasma levels of haloperidol
Abuse dependence and withdrawal symptoms
