Term
| what percent of the US population have at some time been treated with drugs for anxiety? |
|
Definition
|
|
Term
| what are the symptoms of anxiety? |
|
Definition
1. verbal complaint of anxiety
2. somatic and autonomic effects
3. interference with normal productive activities
4. phobic anxiety |
|
|
Term
| what are the somatic and autonomic effects of anxiety? |
|
Definition
| restlessness, agitation, tachycardia, increased sweating, choking, GI disorders |
|
|
Term
| what is the most frequent symptom of anxiety? |
|
Definition
|
|
Term
| what is a panic disorder? |
|
Definition
| unbearable fear with marked somatic symptoms |
|
|
Term
| effect of sedative drugs (3)? |
|
Definition
1. decrease activity
2. moderate excitement
3. calm the recipient |
|
|
Term
| when are sedative drugs used? |
|
Definition
| prior to general anesthesia |
|
|
Term
| effects of drugs for insomnia? |
|
Definition
1. produce drowsiness
2. facilitate onset and maintenance of sleep resembling natural sleep and from which the recipient can be easily aroused |
|
|
Term
| what is the major class of drugs used for treatment of anxiety and insomnia? |
|
Definition
|
|
Term
| benzodiazepines have high potency for what disorders? |
|
Definition
| anxiety, sedation, and insomnia |
|
|
Term
| are benzodiazepines fatal when used alone? |
|
Definition
NO
alone they do not cause sufficient CNS depression for surgical anesthesia or fatal intoxication |
|
|
Term
| benzodiazepines effect on non-selective CNS depressants? |
|
Definition
can intensify the effect
alone do not cause sufficient CNS depression to produce surgical anesthesia nor fatal intoxication |
|
|
Term
| what property of benzodiazepines treatment has resulted in their displacing older treatments of insomnia and anxiety? |
|
Definition
| the safety of treatment with benzodiazepines |
|
|
Term
| all effects of benzodiazepines result from action on what? |
|
Definition
|
|
Term
| do benzodiazepines act as non-selective CNS depressants? |
|
Definition
|
|
Term
| mechanism of action of benzodiazepines? |
|
Definition
act by specifically augmenting the action of GABA at GABAa receptors in the CNS
produces and increased chloride conductance due to increased frequency of opening of the chloride channels |
|
|
Term
| benzodiazepines work at what receptor? |
|
Definition
| GABAa receptors in the CNS |
|
|
Term
| how do benzodiazepines produce increased chloride conductance? |
|
Definition
| increase frequency of opening of Cl channels |
|
|
Term
| what GABA receptors are affected by benzodiazepines? |
|
Definition
GABAa in the CNS
GABAb and most GABAa in peripheral neurons are not affected |
|
|
Term
| what actions are not affected by benzodiazepines? |
|
Definition
GABAb receptor actions - reduction of Ca currents and increased K permeability
most GABAa in peripheral neurons |
|
|
Term
| effect of GABA and benzodiazepines binding to receptor-Cl channel complex? |
|
Definition
bind to independent sites
each increases the affinity of the sites for the other |
|
|
Term
| do benzodiazepines directly open Cl channels? |
|
Definition
NO
act allosterically to increase the affinity of the receptors for GABA |
|
|
Term
| how do benzodiazepines enhance the action of GABA? |
|
Definition
due to increase in the number of channels that are opened by a given concentration of GABA
*done by increased the FREQUENCY of opening (not due to increase in channel conductance or open time) |
|
|
Term
| what type of receptor is GABAa? |
|
Definition
|
|
Term
| composition of GABAa receptor? |
|
Definition
| several subunits (alpha, beta, gamma) surrounding a central channel |
|
|
Term
| what characteristic of the GABAa channel gives drugs their different specificities? |
|
Definition
| the various subtypes of the main subunits |
|
|
Term
| how does the GABAa gated ion channel differ in different neurons? |
|
Definition
| different subunits and subtypes make up the channel |
|
|
Term
| what subunits makes up the benzodiazepines receptor? |
|
Definition
| alpha, beta, and gamma subunits |
|
|
Term
| different subtypes of GABAa receptors give rise to distinct types of benzodiazepines receptors which differ in what? |
|
Definition
| pharmacological properties and distribution in the brain |
|
|
Term
| structure of benzodiazepines? |
|
Definition
| benzene ring fused to a 7-membered diazepine ring (1,4 position) that contains a 5-aryl substituent |
|
|
Term
how many benzodiazepines have been synthesized?
how many have been tested in clinical trials?
how many are in clinical use? |
|
Definition
|
|
Term
| what is important about slight changes in structure of benzodiazepines? |
|
Definition
| very little difference can lead to very different specificity at the GABA receptor and change the function of a drug |
|
|
Term
| benzodiazepines in clinical use have qualitatively ____ effects, but show quantitative _____ in pharmacological response |
|
Definition
similar; differences
this has led to different therapeutic uses for different drugs in this class of compounds |
|
|
Term
| therapeutic uses of benzodiazepines (6)? |
|
Definition
1. insomnia
2. reduction of anxiety and aggression
3. preoperative sedation
4. muscle relaxants in muscle spasm and spasticity
5. anticonvulsant
6. alcohol withdrawal |
|
|
Term
| how do benzodiazepines treat insomnia? |
|
Definition
1. time to onset of sleep (sleep latency) is decreased
2. first 2 stages of sleep are prolonged
3. stages 3 and 4 (deep sleep) and REM sleep are shortened |
|
|
Term
| how do benzodiazepines affect time to onset of sleep (sleep onset)? |
|
Definition
|
|
Term
| how do benzodiazepines effect the first 2 stages of sleep? |
|
Definition
|
|
Term
| how do benzodiazepines effect stages 3/4 (deep sleep) and REM sleep? |
|
Definition
|
|
Term
| which benzodiazepine is used in preoperative sedation? |
|
Definition
|
|
Term
| why is midazolam used in preoperative sedation? |
|
Definition
| it is the most rapidly inactivated |
|
|
Term
| what benzodiazepine appears to have more anticonvulsant action relative to its other effects? |
|
Definition
|
|
Term
| therapeutic uses of clonazepam? |
|
Definition
seizure disorders
adjunctive treatment in acute mania and some movement disorders |
|
|
Term
| what is the problem with using clonazepam as an anticonvulsant? |
|
Definition
| tolerance develops to the anticonvulsant effects |
|
|
Term
|
Definition
|
|
Term
| onset of action of clonazepam |
|
Definition
|
|
Term
| benzodiazepines for anxiety (7)? |
|
Definition
1. clonazepam
2. clorazepate
3. diazepam
4. chlordiazepoxide
5. alprazolam
6. lorazepam
7. oxazepam |
|
|
Term
| benzodiazepine used for seizure disorders and in adjunctive treatment for acute mania and some movement disorders? |
|
Definition
|
|
Term
| what benzodiazepines are converted to the active metabolite nordiazepam (3)? |
|
Definition
1. chlorazepate
2. diazepam
3. chlordiazepoxide |
|
|
Term
| what makes benzodiazepines used for anxiety long acting? |
|
Definition
| they are converted to the metabolite nordiazepam |
|
|
Term
| what benzodiazepine is used in the management of alcohol withdrawal? |
|
Definition
chlordiazepoxide
clorazepate |
|
|
Term
| what benzodiazepines can be used for status epilepticus? |
|
Definition
|
|
Term
| what benzodiazepine is used for skeletal muscle relaxation? |
|
Definition
|
|
Term
| what benzodiazepines are used in anesthetic pre-medication (3)? |
|
Definition
1. diazepam
2. chlordiazepoxide
3. lorazepam |
|
|
Term
| what benzodiazepine is used for treating agoraphobia? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| withdrawal symptoms may be especially severe with which benzodiazepine? |
|
Definition
|
|
Term
| what benzodiazepines for anxiety are intermediate acting? |
|
Definition
1. alprazolam
2. lorazepam |
|
|
Term
| metabolism of lorazepam and oxazepam? |
|
Definition
| metabolized solely by conjugation |
|
|
Term
| what 2 benzodiazepines are metabolized solely by conjugation? |
|
Definition
|
|
Term
| benzodiazepines used for insomnia (5)? |
|
Definition
1. flurazepam
2. quazepam
3. temazepam
4. estazolam
5. triazolam |
|
|
Term
| what is a problem with chronic use of flurazepam and quazepam? |
|
Definition
| active metabolites accumulate with chronic use |
|
|
Term
|
Definition
mainly by conjugation
conjugate is not active - why duration is intermediate rather than long |
|
|
Term
| which benzodiazepine may cause disturbing daytime side effects? |
|
Definition
triazolam
taken off the market in some countries |
|
|
Term
|
Definition
| short - rapidly inactivated |
|
|
Term
| what benzodiazepine is used for pre-anesthetic intraoperative medication? |
|
Definition
|
|
Term
| what benzodiazepine has the shortest duration? |
|
Definition
| midazolam - rapidly inactivated |
|
|
Term
| rate of metabolism of benzodiazepines? |
|
Definition
metabolized at variable rates
some demethylated metabolites are pharmacologically active and have long half-lives (those converted to nordiazepam) |
|
|
Term
| are benzodiazepines active orally? |
|
Definition
YES
differ mainly in DURATION of action |
|
|
Term
| intermediate acting benzodiazepines are metabolized to _______ and used mainly for what? |
|
Definition
inactive compounds
insomnia
estazolam, temazepam; half life = 3-10 hr |
|
|
Term
| long acting benzodiazepines are converted to ____ and are used mainly for what? |
|
Definition
nordiazepam - long-lasting active metabolite
anxiety
diazepam, chlordiazepoxide, clorazepate |
|
|
Term
| what gives certain benzodiazepines their long duration of action? |
|
Definition
| they are converted to nordiazepam which has a long duration |
|
|
Term
| what happens after cessation of diazepam (and other long acting benzodiazepines)? |
|
Definition
| slow decline due to metabolite nordiazepam |
|
|
Term
| benzodiazepines distribution in the body? |
|
Definition
| bind strongly to plasma protein |
|
|
Term
| how are benzodiazepines excreted? |
|
Definition
| as glucuronide conjugates in the urine directly or after demethylyation and/or hydroxylation |
|
|
Term
| do benzodiazepines have inducing effect on hepatic microsomal cytochrome oxidases? |
|
Definition
|
|
Term
| adverse side effects of benzodiazepines? |
|
Definition
1. drowsiness, confusion, amnesia, impaired motor coordination
2. long-lasting hangover effects due to long-lasting active metabolites
3. development of dependence
4. resp depression in presence of other CNS depressants
5. toxic effects from acute overdose |
|
|
Term
| drowsiness, confusion, amnesia, and impaired motor coordination as adverse side effects of benzodiazepines come from what? |
|
Definition
| long term use which leads to gradual accumulation in the body due to high lipid solubility |
|
|
Term
| why does long term use of benzodiazepines lead to adverse side effects? |
|
Definition
| due to gradual accumulation in the body due to high lipid solubility |
|
|
Term
| what are the long-lasting hangover effects of benzodiazepines due to? |
|
Definition
| long-lasting active metabolites |
|
|
Term
| can benzodiazepines become drugs of abuse? |
|
Definition
YES
due to development of dependence |
|
|
Term
| can toxicity result from overdose of benzodiazepines? |
|
Definition
YES
much less dangerous than older drugs used for anxiety and insomnia |
|
|
Term
| are benzodiazepines life threatening when given alone? |
|
Definition
|
|
Term
| how can benzodiazepines cause severe, even life-threatening resp depression? |
|
Definition
| in the presence of other CNS depressants, particularly ethanol |
|
|
Term
| what adverse effect of benzodiazepines can be seen in the presence of ethanol? |
|
Definition
| severe, even life-threatening resp depression |
|
|
Term
| treatment for benzodiazepines overdose? |
|
Definition
flumazenil
benzodiazepine antagonist |
|
|
Term
|
Definition
| benzodiazepine antagonist used for OD treatment |
|
|
Term
| flumazenil mechanism of action? |
|
Definition
acts as a competitive antagonist of benzodiazepines
binds at the benzodiazepine binding site --> has no effect itself --> prevents the binding of benzodiazepines |
|
|
Term
| does flumazenil have effect itself? |
|
Definition
NO
prevents the binding of benzodiazepines by binding to the benzodiazepines binding site
competitive antagonist |
|
|
Term
|
Definition
| treatment of benzodiazepine overdose |
|
|
Term
| what type of drugs are zolpidem and zaleplon? |
|
Definition
benzodiazepine related drugs
don't have the benzodiazepine structure but have similar mechanism of action |
|
|
Term
| zolpidem and zaleplon mechanism of action? |
|
Definition
bind to same site on the GABAa receptor chloride ion channel complex as the benzodiazepines
do not have benzodiazepine structure but mechanism of action is similar to that of benzodiazepines |
|
|
Term
| tolerance and dependence for zolpidem and zaleplon? |
|
Definition
|
|
Term
| what rarely develops with use of zolpidem and zaleplon? |
|
Definition
|
|
Term
| use of zolpidem and zaleplon? |
|
Definition
| potent activity for sedation and insomnia |
|
|
Term
| how do zolpidem and zaleplon work for treatment of insomnia? |
|
Definition
| decrease time to onset of sleep (sleep latency) with little effect on sleep stages |
|
|
Term
| what are zolpidem and zaleplon of little use for treating? |
|
Definition
|
|
Term
| side effects of zolpidem and zaleplon? |
|
Definition
incidence of side effects is low
infrequently produces residual daytime sedation or amnesia
large overdoses do not produce severe resp depression unless other agents are also ingested |
|
|
Term
| do large overdoses of zolpidem and zaleplon produce severe resp depression? |
|
Definition
not unless other agents (like ethanol) are also ingested
similar to benzodiazepines |
|
|
Term
| administration of zolpidem and zaleplon? |
|
Definition
|
|
Term
| metabolism of zolpidem and zaleplon |
|
Definition
| rapidly metabolized in the liver to inactive products - mostly by aldehyde oxidase and to a lesser extent by CYP3A4 |
|
|
Term
| zolpidem and zaleplon are metabolized in the liver by what? |
|
Definition
mostly aldehyde oxidase
to a lesser extent CYP3A4 |
|
|
Term
| elimination of zolpidem and zaleplon? |
|
Definition
| rapidly eliminated in urine |
|
|
Term
|
Definition
2 hours
very short acting |
|
|
Term
|
Definition
|
|
Term
| where does eszopiclone act? |
|
Definition
|
|
Term
| what benzodiazepine related drug is used for treatment of chronic insomnia? |
|
Definition
|
|
Term
|
Definition
| treatment of chronic insomnia |
|
|
Term
| metabolism of eszopiclone? |
|
Definition
|
|
Term
| half life of eszopiclone? |
|
Definition
about 6 hours
longer than zolpidem and zaleplon |
|
|
Term
a patient with hepatic insufficiency is admitted with severe alcohol withdrawal.
which of the following benzodiazepines would be the most appropriate treatment?
a. lorazepam
b. alprazolam
c. chlordiazepoxide
d. diazepam
e. clonazepam |
|
Definition
c. chlordiazepoxide
only benzodiazepine used primarily for alcohol withdrawal |
|
|
Term
| what is the only benzodiazepine used primarily for alcohol withdrawal? |
|
Definition
|
|
Term
| what was the major class of drugs for sedation and insomnia until the introduction of the benzodiazepines in the 1960s? |
|
Definition
barbiturates
only some are still in use |
|
|
Term
| what type of drug are barbiturates? |
|
Definition
non-selective CNS depressants
produce all degrees of CNS depression ranging from mild sedation to general anesthesia |
|
|
Term
| effects of high doses of barbiturates? |
|
Definition
| cause unconsciousness and eventually death from resp and CV depression |
|
|
Term
| mechanism of action of barbiturates? |
|
Definition
enhance the binding of GABA to GABAa receptors
less specific than benzodiazepines |
|
|
Term
| barbiturates and benzodiazepines binding to ____ sites on the GABA receptor/chloride channel complex |
|
Definition
|
|
Term
| what subunits of the GABAa receptor are requires for barbiturate action? |
|
Definition
| only alpha and beta (not gamma) |
|
|
Term
| what subunits of the GABAa receptor are required for benzodiazepine action? |
|
Definition
|
|
Term
| how do barbiturates and benzodiazepines result in different action? |
|
Definition
| because they bind to different places on the GABAa receptor |
|
|
Term
| barbiturates effect on the binding of benzodiazepines? |
|
Definition
| barbiturates promote (rather than displace) the binding of benzodiazepines |
|
|
Term
| how do barbiturates increase GAAB chloride currents? |
|
Definition
| by prolonging the time which the channels are open |
|
|
Term
| how does barbiturates action on GABA induce chloride channels different from benzodiazepines? |
|
Definition
barbiturates - prolong TIME which the channels are open
benzodiazepines - increase FREQUENCY of opening |
|
|
Term
| barbiturates are derivative of what? |
|
Definition
|
|
Term
| does barbituric acid have CNS depressant activity? |
|
Definition
|
|
Term
| what substituent on barbituric acid gives barbiturates activity for sedation and insomnia? |
|
Definition
| alkyl or aryl substituents at position 5 |
|
|
Term
| how do thiobarbiturates differ from barbiturates? |
|
Definition
| a sulfur is at position 2 of barbituric acid rather than an oxygen |
|
|
Term
| what does the substitution of S at position 2 of thiobarbiturates do to the characteristics of the drug? |
|
Definition
| makes them more lipid soluble than the corresponding oxybarbiturates |
|
|
Term
| what barbiturates are given IV for the induction and maintenance of anesthesia? |
|
Definition
1. methohexital
2. thiopental |
|
|
Term
| therapeutic uses of methohexital? |
|
Definition
| induction and maintenance of anesthesia |
|
|
Term
| administration of methohexital? |
|
Definition
|
|
Term
| what barbiturate is used for seizure disorders, status epilepticus, and daytime sedation? |
|
Definition
|
|
Term
| therapeutic uses of phenobarbital? |
|
Definition
1. seizure disorders
2. status epilepticus
3. daytime sedation |
|
|
Term
| therapeutic uses of thiopental? |
|
Definition
| induction and/or maintenance of anesthesia |
|
|
Term
| administration of thiopental? |
|
Definition
|
|
Term
| why are thiopental and methohexital used as IV anesthetic agents? |
|
Definition
| high lipid solubility allows them to rapidly cross the BBB --> producing a rapid onset of action |
|
|
Term
| what barbiturate is used as an anticonvulsant in the treatment of epilepsy? |
|
Definition
|
|
Term
| a side effect of barbiturates is the development of a high degree of what? |
|
Definition
tolerance and dependence
benzodiazepines - lead to dependence, NOT tolerance |
|
|
Term
| side effect of barbiturates in the liver? |
|
Definition
| strongly induce hepatic cytochrome P450 and conjugating enzymes |
|
|
Term
| what is the result of barbiturates inducing hepatic cytochrome P450 and conjugating enzymes? |
|
Definition
| increases the rate of metabolic degradation of other drugs |
|
|
Term
| what other drugs are especially susceptible to metabolic degradation by induced cytochrome P450s from barbiturates use? |
|
Definition
|
|
Term
| what are residual after effects of barbiturates use? |
|
Definition
| impairment of judgment and motor skills |
|
|
Term
| what increased CNS depressant effect of barbiturates? |
|
Definition
1. ethanol
2. antihistamines
3. MAOIs |
|
|
Term
| when is there a danger of overdose with barbiturates? |
|
Definition
| if they are given alone or particularly with other drugs |
|
|
Term
| how do barbiturates precipitate attacks of acute porphyria in susceptible individuals? |
|
Definition
| due to induction of the mitochondrial enzyme, delta-aminolevulinic acid synthetase which is involved in the biosynthesis of porphyria |
|
|
Term
A patient comes to your office complaining of being very nervous and having trouble sleeping. She says that she recently lost her mother and her death marks when these problems started. You decide to prescribe Valium for her on a short-term basis. Valium is a benzodiazepine and binds to a receptor that is involved in the movement of which of the following ions?
a. sodium ions
b. chloride ions
c. phosphate ions
d. potassium ions
e. ammonium ions |
|
Definition
|
|
Term
| mechanism of action for buspirone? |
|
Definition
high affinity for 5HT1A receptors in the brain
partial agonist |
|
|
Term
| what type of drug is buspirone? |
|
Definition
|
|
Term
|
Definition
| potent activity for anxiety |
|
|
Term
| what is buspirone not effective for? |
|
Definition
| severe anxiety with panic attacks |
|
|
Term
| onset of action of buspirone? |
|
Definition
| takes days or weeks of treatment to produce effect |
|
|
Term
| side effects of buspirone? |
|
Definition
1. does NOT cause sedation or motor incoordination
2. no withdrawal effects
3. main side effects are nausea, dizziness, headache
4. does NOT produce tolerance or dependence |
|
|
Term
| does buspirone produce tolerance and dependence? |
|
Definition
|
|
Term
| what type of drug is propranolol? |
|
Definition
| B-adrenoreceptor antagonist |
|
|
Term
|
Definition
| used for some forms of anxiety, particularly where physical symptoms such as sweating, tremor, and tachycardia are prominent |
|
|
Term
| mechanism of action of propranolol? |
|
Definition
| block peripheral sympathetic responses rather than having a central effect |
|
|
Term
| what drug is often used to reduce stage fright? |
|
Definition
|
|
Term
| side effect of propranolol? |
|
Definition
|
|
Term
| what drug is used occasionally for people who don't respond to benzodiazepines? |
|
Definition
|
|
Term
| properties of meprobamate? |
|
Definition
similar to benzodiazepines
higher potential for abuse and less selective effect |
|
|
Term
| meprobamate produces what? |
|
Definition
non-selective depression of CNS but does not produce anesthesia
enhances analgesic effects of other drugs |
|
|
Term
| overdose of meprobamate can cause what? |
|
Definition
| severe or even fatal resp depression, hypotension, shock, and heart failure |
|
|
Term
| what drug was previously used extensively for treatment of anxiety until it was replaced by benzodiazepines? |
|
Definition
|
|
Term
| where does ramelteon act? |
|
Definition
| at melatonin receptors MT1 and MT2 |
|
|
Term
| how does ramelteon potency compare to melatonin? |
|
Definition
| ramelteon is 10 times more potent |
|
|
Term
|
Definition
|
|
Term
|
Definition
| treating problems with sleep onset |
|
|
Term
| what is the newest insomnia drug FDA approved in 2005? |
|
Definition
|
|
Term
| what is an OTC antihistamine with sedative activity? |
|
Definition
|
|
Term
| what is diphenylhydramine? |
|
Definition
| an OTC antihistamine with sedative activity |
|
|
Term
| diphenylhydramine is sometimes used to treat? |
|
Definition
|
|
Term
| what people is diphenylhydramine particularly useful for? |
|
Definition
|
|
Term
| what are 3 non-GABA receptor drugs for anxiety? |
|
Definition
1. buspirone
2. propranolol
3. meprobamate |
|
|
Term
| what 3 non-GABA receptor drugs are used for treating insomnia? |
|
Definition
1. ramelteon
2. diphenylhydramine
3. chloral hydrate |
|
|
Term
| what is chloral hydrate occasionally used to treat? |
|
Definition
insomnia
doesn't act at GABA receptor |
|
|
Term
| what drug is a non-selective CNS depressant that may have effect in insomnia and anxiety treatment but is clinically of limited value? |
|
Definition
|
|
Term
A 70 year old woman with chronic lung disease and dementia is brought to the ER after having ingest 50 5-mg Valium (diazepam) tablets. She is cyanotic and comatose, and her respiration is rapidly deteriorating. Which is the most appropriate treatment after you assure that her respiration is supported?
a. Zolpidem
b. Phenobarbital
c. Ethanol
d. Flumazenil
e. Flurazepam |
|
Definition
d. Flumazenil
antagonist at GABA receptor for benzodiazepine |
|
|
Term
A patient complains that he is not able to get to sleep at night and asks you to prescribe a sleeping pill. He says he doesn’t want benzodiazepine because in the past he has had bad reactions from them. Which of the following would you prescribe?
a. Phenobarbital
b. Triazolam
c. Buspirone
d. Ramelteon
e. Meprobamate |
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Definition
d. Ramelteon
only drug that isn't a benzodiazepine that is used to treat insomnia |
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