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284 Cards in this Set
- Front
- Back
Sedatives cause.....
Also considered ____ agents Not intended for the use for.... |
Calmness and relaxations;
anxiolytic/antianxiety; the stress and tension of every day living |
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Hypnotics produce _____ therefore it is automatically a ____ Agent.
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sleep; sedative
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What are the 4 stages of sleep?
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0=awake; 1= onset of sleep; 2= slight sleep; 4= REM sleep
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How much time is spent in light sleep/stage 2?
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50%
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How much time is spent in REM sleep?
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25%
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Most all drugs in the sedative-hypnotic class of drugs can cause....
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physical and psychological dependence
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Barbiturate sedative/hypnotics are induces of _______ which can cause.......
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P450 system;
numerous drug interactions |
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Barbiturate sedatives-hypnotics are _____ depressants.
Low doses are _____, higher doses are ______ and highest doses are ______. No longer considered appropriate for treatment of _____ or ______. Have a ______ therapeutic index All barbiturates exhibit _______ activity. |
CNS;
sedative; hypnotic; anesthetic; anxiety or insomnia; low/narrow; anticonvulsant |
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What is an ADR of large doses of barbiturates?
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prolonged CNS depression
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Chronic use of barbiturates can cause ____, ____ and risk of _____.
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tolerance, dependence, withdrawal syndrome
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What are the two components of tolerance?
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enzyme induction; adaptive CNS changes
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Barbiturates have a very high potential for ______ and ______ which can occur in as little as ___________
_______ syndrome can be experience and can be severe/fatal. Sx include ____ and _____ |
physical and psych dependence; 1-3 months;
Abstinence; convulsions and delirium |
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Abstinence syndrome is associated with which class of drugs?
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Barbiturate sedative/hypnotics
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An overdose of barbiturates results in depression of the _____ and ____ control centers in the brain resulting in......
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medullary respiratory and CV control centers; fatality due to respiratory failure
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Barbiturates have an additive/synergistic CNS depression when mixed with....
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other depressants including alcohol
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Estazolam, Triazolam and Flurazepam are all drugs of the __________ class
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benzodiazepine hypnotic
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Benzodiazepine Hypnotic agents are indicated for ______ characterized by _____, _______ or _______
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insomnia; difficulty in falling asleep, frequent nocturnal awakening, or early morning awakening
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Benzo Hypnotics work by....
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potentiating (increasing) transmission involving pathways using GABA as an inhibitory NT
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There are two subtypes of the GABA-A receptor: BZ1 and BZ2.
BZ1 receptor stimulation results in ______ and ______ |
sleep onset and cycle regulation
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All GABA-A BZ1 receptors become activated nonspecifically by ______ which accounts for......
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benzos; the wide range of a cation of BZs (sedation, hypnosis, anti anxiety, anticonvulsant, muscle relaxant)
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Which three benzo drugs can activate only one of the BZ binding sites?
This may account for their relatively selective ______ action and lack of ____ and _____ effects. |
zolpidem, zalepon, eszopiclone;
hypnotic; anticonvulsant; muscle relaxant |
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Barbiturates bind to specific receptors that are _____ from BZ receptors which results in _____ CNS depressant activity compared to BZs
Have _____ activity at higher concentrations and inhibit ......... |
distant; greater
GABAmimetic; excitatory CNS NTs (glutamate) |
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What is the effect of BZs on sleep patterns?
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increase total sleep time
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BZs decrease time spent in sleep stage ___ and ____ and also decrease the number of ____ during the night.
They also increase stage _______. BZs delay the onset of ____ and _____ is diminished. BZ hypnotics are very successful initially but.... |
0, 1; awakenings;
2; REM; dreaming; tolerance develops |
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Short-Medium acting BZs are best to achieve ___ onset with duration lasting through the night but having no _____ the next day.
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rapid; 'hangover'
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Triazolam is a ____ acting BZ and is preferable in the _____ but may result in......
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short; elderly; early morning awakening
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Estazolam is a _____ acting BZ
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intermediate
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Flurazepam is a _____ acting BZ that has a long _________
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long; half-life
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Increased daytime anxiety after 10 days of continuous use was experience in pts taking _______ and this is thought to be due to......
Also experienced _____ which is considered to be a class effect of BZs |
Triazolam; development of tolerance and 'interdose withdrawal'
anterograde amnesia |
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Pts can develop _______ while taking BZs and withdrawal symptoms following abrupt d/c can occur including ____, _____ or _____ if severe.
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physical dependence;
muscle cramps, tremors, convulsions |
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Rebound insomnia can occur in pts taking BZs when the drug is ______. Duration of sleep and quality also becomes ________ than before treatment.
May occur after abrupt d/c of _____ but is less likely to occur in _____ agents. |
withdrawn; worse; triazolam;
longer-acting agents |
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BZs have additive/synergistic effects with other _________
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CNS depressants
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Zolpidem and Zaleplon are _______ Drugs used in the short term treatment of ______ and is generally limited to ___-___ days.
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nonbarb/nonbz sed/hypnotic; insomnia; 7-10
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Zolpidem ER, eszopiclone, ramelteon are ______ Drugs indicated for the treatment of ________
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nonbarb/nonbz sed/hypnotic; insomnia
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Chloral hydrate is a ______ drug that is rapidly absorbed and metabolized to _________ (active metabolite)
_____, ____ and ____ may develop after several weeks of continued administration. Sudden withdrawal may cause ____, ____ and ______ |
nonbarb/nonbz sed/hypnotic; trichloroethanol;
tolerance, physical, psych dependence; seizures, hallucinations, delirium; |
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Chloral Hydrate has synergistic effects with ____ because they ___________ each other's metabolism and both have CNS _____ effects
Also have additive/synergistic effects with other CNS ______ |
alcohol; competitively inhibit; depressant;
depressants |
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Zolpidem is a ______ Drug that is a BZ receptor _____ which preferentially interacts with the ____ subtype.
Exerts ____ effects at doses which have no anxiolytic, anticonvulsant, or muscle relaxant effects Also decreases stage ___ of the sleep cycle, increases _______ and _______ |
nonbarb/nonbz sed/hypnotic; agonist; BZ1;
hypnotic; 1; total sleep time; sleep duration |
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Zolpidem therapy is limited to ____-____ days.
Potential for dependence, tolerance or rebound insomnia upon d/c appears ______ Does additive/synergistic interactions with other CNS _______ |
7-10;
minimal; depressants |
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Zolpidem ER (Ambien) is the first and only ____ sleep medication that promotes _____ and _______ with no significant decrease in __________.
Not limited to _____ treatment. |
ER; falling asleep; maintaining sleep; next day performance;
short-term |
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Zaleplon is a ____ receptor agonist.
Functions to shorten the time to _____ but does not significantly increase _____ or reduce the number of _____ Administer immediately at ___ or up to 4 hours prior to the ___________ when _______ occurs. Can be dosed in the middle of the night without...... Has synergistic/additive CNS ______ effects. |
BZ1;
sleep onset; sleep duration; awakenings; bedtime; anticipated; difficulty falling asleep; residual sedation and next morning memory impairment; depressants |
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Eszopiclone is the active S-isomer of the hypnotic _____ which is a ____ receptor agonist.
Has a lower ____ and ____ potential and improved all components of ________ Less likely to cause residual ____ and ____ compared to BZs Not limited to _____ use. |
zopiclone; BZ1;
dependence; abuse potential; insomnia; daytime psychomotor and memory impairment; short term |
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Ramelteon is a _____________ drug and specifically stimulates _____ receptors which results in...
Indicated for use in adults for tx of ____ characterized by difficulty with _____. Not limited to _____ use. No evidence of ___, ________, ____, or _____ |
selective melatonin receptor agonist; MT1; sleepiness;
insomnia; sleep onset;short term; abuse potential, dependence, rebound insomnia, withdrawal effects/next day residual effects |
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BZ anxiolytics have what 5 shared pharm actions?
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hypnotic, anxiolytic, anticonvulsant, muscle relaxant, amnesiac
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What are the three advantages of BZ anxiolytics compared to other anxiolytics?
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rapid onset,high therapeutic index, relatively few ADR
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What are 3 disadvantages to BZ anxiolytics?
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tolerance, impaired psychomotor performance, dependence
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What is the first line of treatment for generalized anxiety disorder?
Second line? When would BZs be used? |
antidepressants;
buspirone; for acute relief or if sx warrant |
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Stress related anxiety is.....
What is the DOC for reducing symptoms, especially insomnia and restlessness? |
anxiety that occurs as a result of a major life stressful event
BZs |
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What is the DOC for panic disorder? What is important to tell pts when they begin these drugs?
What are the second line drugs? _______ is very effective quickly (within days) |
SSRIs; they will require 203 weeks for sx improvement;
BZs; alprazolam |
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What are the DOC for treatment of PTSD?
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SSRIs
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Alcohol withdrawal syndrome symptoms can include ________, ___________ which occurs usually 48-72 hours after d/c, _____. _______. _____. _____ and _______
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tonic-clonic seizures, delirium tremens; hyperthermia, tachycardia, HTN, delirium, hallucinations
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What is the DOC for treatment for alcohol withdrawal syndrome?
Which two longer acting drugs are the best to use? This is because these drugs have active metabolites which _____ and provide _______ as the parent BZs are _____ resulting in fewer....... Which two shorter acting drugs may be better to use in elderly pts or those with hepatic dz? This is because they do not undergo _________ |
BZs;
chlordiazepoxide; diazepam; accumulate; continued activity; tapered; rebound effects/withdrawal seizures lorazepam, oxazepam; hepatic metabolism |
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Diazepam is indicated for use as a ____, _____ and _____
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muscle relaxant, anticonvulsant, preop medication
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Lorazepam is indicated as a ____ medication to produce ____ and ____. Can also be used in treatment of ______
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preanesthetic; sedation; amnesia;
status epilepticus |
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Alprazolam is used for the treatment of ______ with or without _______
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panic disorder; agoraphobia
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Chlordizepoxide is used for the treatment of ________
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acute alcohol withdrawal syndrome
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All of the pharmacological effects of benzodiazepines are mediated through interactions with the _______ complex.
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GABA receptor;
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GABA-A Receptors are ____ channels that when activated by GABA they .......
This causes what to occur? |
ligand-gated;
open and allow chloride ion influx; cell hyper polarizes which decreases/interrupts the synaptic and neuronal transmission |
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The GABA-A receptor contains how many binding sites for BZs?
What do BZs act as? |
at least 3;
allosteric modulators of GABA activity |
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When BZ binds to its receptor on the GABA-A receptor, the frequency of chloride channel opening is ______, GABA activity is _____ and the pharm actions of BZs are produced (_______, ______ and ______)
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increased; enhanced; hypnotic; anticonvulsant; muscle relaxant
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Potentiate means:
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facilitates
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BZs potentiate the effects of GABA (facilitates _________) by binding to the specific BZ receptor binding sites on the ___ subunit of the GABA receptor complex.
BZs are _____ of GABA and not GABA _______. In the absence of GABA, BZs have..... |
inhibitory GABAergic neurotransmission;
alpha; allosteric modulators; agonists; no pharm actions |
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In the spinal cord, BZs cause...
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muscle relaxation
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In the brain stem, BZs cause...
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anticonvulsant properties
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In the cerebellum, BZs cause....
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ataxia and sedation at doses beyond those needed for anxiolytic effects
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In the limbic and cortical areas, BZs cause....
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anxiolytic and amnesic effects
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BZs have a ____ margin of safety between the therapeutic and toxic doses.
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wide
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Which two BZs are absorbed poorly due to precipitation in muscle causing slow erratic absorption?
This causes peak levels to be _____ and take _____ to reach compared to oral dosing. |
Diazepam; chlordiazepoxide;
lower; longer; |
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What is a common active metabolites of BZs, including diazepam?
This metabolite is formed via a ______ reaction. Accumulation of substance can occur in chronic dosing and cause.... |
destheyldiazepam;
oxidation; oversedation and ataxia |
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Which two BZs are metabolized to inactive compounds and have a relatively short duration of action?
When may these be preferred for use? |
oxazepam; lorazepam;
in the elderly or those with hepatic disease |
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BZs can have physical dependence with withdrawal symptoms occurring after several _____ of treatment.
What three factors favor withdrawal symptoms? |
weeks;
Use of short-ating agents, regular use for >3 month, abrupt d/c |
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What are the characteristics of withdrawal syndrome associated with BZ dependence?
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muscle cramps, tremor, tonic-clonic seizures
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What are some expected ADRs associated with BZ use (due to high therapeutic index)?
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CNS depression (sedation, ataxia, lethargy, impaired psychomotor performance, depression)
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Overdoses of BZs have only a mild effect on _________ but may be fatal when taken with _____.
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respiration; alcohol
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BZs have additive/synergistic effects with other _______ causing severe ______
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CNS depressants; ataxia
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Buspirone is a ______ drug that is indicated for the management of ________ or short term relief of _____________
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non-BZ anxiolytic; anxiety disorders; symptoms of anxiety;
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The net effect of buspirone is to decrease _____ activity in states of ________.
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serotonergic; serotonin excess
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Buspirone is a ______ for serotonin at ____ receptors and an _______ in the presence of serotonin.
Is a full agonist at _________ receptors and _______'s serotonin release. |
partial agonist; postsyn; antagonist;
5HT1A presynaptic; inhibits |
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Buspirone does not bind ______ receptors nor does it affect ______ transmission.
Has no ____ or ____ effects and lacks prominent _____ effects of other anxiolytics. Does not exhibit cross-tolerance with ____ and ______. |
BZ; GABAergic;
anticonvulsant; msucle relaxant; sedative; BZs and other sedatives/hypnotics |
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Optimal results of buspirone use require ________.
No withdrawal syndrome or other significant ADR was reported upon abrupt d/c after _______ |
3-4 weeks;
1 year of tx |
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Buspirone ADR: affinity for ____ receptors might cause symptoms of blockade. These were NOT observed during clinical trials
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dopamine
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Concomitant administration of _________ is contraindicated when using Buspirone.
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MAOIs
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Inhibitors of ________ can cause elevation of busprione concentrations causing excessive _____ or _______
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CYP3A4 isozyme (P450); drowsiness or dizziness
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Flumazenil is a _______ drug.
Acts as a ______________. Does not antagonize the effects of ____, _____ or ____ and does not reverse the actions of _____. |
BZ antagonist;
BZ receptor competitive antagonist; ethanol, barbiturates, or general anesthetics; opioids |
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Flumazenil Is indicated for the complete or partial reversal of the _____ effects of BZs in cases where ....(3).....
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sedative;
general anesthesia has been induced/maintained with BZs; sedation has been produced with BZ for dx and tx studies; management of BZ overdose (as an adjunct to supportive measures) |
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When using Flumazenil, there is a risk of ____ due to the reversal of BZ effects in high risk populations (what are the three populations?)
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seizures;
those undergoing concurrent sed-hypnotic withdrawal, those with TCA poisoning, and those with physical dependence to BZs |
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Imipramine is a.....
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TCA
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Amitriptyline is a....
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TCA
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Nortryptilline is a.....
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TCA
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Clomipramine is a......
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TCA
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Phenelzine is a....
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MAOI
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Trazodone is a ......
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atypical antidepressant
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Buproprion is a.....
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atypical antidepressant
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Fluoxetine is a.....
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SSRI
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Paroxetine is a....
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SSRI
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Sertraline is a....
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SSRI
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Citalopram is a....
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SSRI
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Venlafaxine is a .....
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dual-mechanism antidepressant
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Duloxetine is a....
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dual mechanism antidepressant
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Nefazodone and Mirtazapine are....
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'other' third generation antidepressants
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Which antidepressant categories are first gen drugs?
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TCAs and MAOIs
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Which antidepressant categories are second gen drugs?
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atypical antidepressants
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Which antidepressant categories are third gen drugs?
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SSRIs, dual mecahnism and others
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When treating depression, which drug class is tried first due to its efficacy, tolerability and once daily dosing?
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SSRIs
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What are some potential side effects that can be experienced with depression and therapy?
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GI (N/V)
CNS stimulation/activation (agitation, restlessness, insomnia, anxiety) Sexual dysfunction (Delayed arousal, anorgasmia, impotence) Sedation Weight gain Withdrawal syndrome Anticholinergic effects (dry mouth, constipation) Arrhythmias Orthostatic hypotension, hypertensive crisis Serotonin syndrome |
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What is the black boxed warning associated with SSRI use in pts up to age 24?
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increased suicidal tendencies
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What are the advantages of adding another antidepressant to a current treatment instead of switching the type?
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avoids risk of withdrawal sx's, maintains any benefit of first drug, diff MOA may counteract side effects
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What is the most common antidepressant combination?
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SSRI plus bupropion
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MAOI combinations can lead to what two conditions?
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hypertensive crisis and serotonin syndrome
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Venlafaxine/SSRI combo has caused _______ due to........
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spontaneous bleeding; platelet serotonin release and inhibition of platelet aggregation
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What is the most common augmenting agent (non-antidepressant)? What does it improve?
What are the second-line augmenting agents? |
buspirone; SSRI-induced sexual dysfunction;
atypical antipsychotics |
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TCAs block the reuptake of ____, ____ or both from the synaptic cleft back into the _____ nerve terminal.
How long is required for antidepressant effects, even though blockade of reuptake occurs immediately? What other receptors do TCAs also block (3)? |
NE, 5HT; presynaptic;
2-4 weeks; histamine 1, muscarinic, and alpha 1 adrenergic receptors |
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TCAs have a ____ therapeutic window.
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narrow
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Anticholinergic actions include: (6)
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dry mouth, constipation, urinary retention, mydriasis, blurred vision, tachycardia
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Which TCA has the highest anticholinergic actions?
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amitryptilline
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What three cardiovascular ADRs can be experience with TCAs?
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orthostatic hypotension, conduction abnormalities, tachycardia
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Orthostatic hypotension caused by TCA use is due to _____ blockade. Highest rate seen with _________
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alpha1 blockade;
amitryptiline |
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What conduction abnormalities can occur with the use of TCAs?
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EKG abnormalities, altered intraventricular conduction, may cause AV block (in pts with preexisting conduction defects)
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The conduction abnormalities that may be experienced with TCAs is highest with ______.
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amitryptiline
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Tachycardia experienced with use of TCAs is caused by a combination of ____________ and _________
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reflex response to orthostatic hypotension; anticholinergic effects
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What CNS ADR can be experienced with TCAs?
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sedation
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What are some symptoms of overdose of TCAs?
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slurred speech, confusion, tachycardia, hypotension, resp distress, QT prolognation, seizures
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What is a common side effect experienced with antidepressant treatment?
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weight gain
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Use of TCAs and Clonidine together is contraindicated due to reports of.....
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hypertensive crisis (mechanism unknown)
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TCAs potentiate the actions of which two types of drugs?
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antimuscarinics and CNS depressants
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MAOIs with concurrent use of TCAs may cause severe ____ toxicity (consequences=(3)).
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CNS; hyperpyrexia, seizures, coma
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Want to avoid concurrent use of TCAs with class IA antiarrhythmics which predispose a pt to....
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conduction disturbances
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When dosing TCAs, want to start at the ____ end of the dose range and give the total daily dose divided up. You can then increase the dose to obtain maximal effects as long as ......
The total daily dose may be given as a single dose at _______ after the initial period of use. do not d/c abruptly because.... |
low; side effects are tolerated;
bedtime it may cause withdrawal syndrome of 'cholinergic rebound' |
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Clomipramine is indicated only for the treatment of ____
Has strong ___ and ___ actions, can cause __________ (aka "_______". Want to take with food to prevent _______. Can cause _________ |
OCD;
anticholinergic; sedative; orthostatic hypertension (first dose syncope); N/V; sexual dysfunction |
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Trazodone functions by inhibiting the reuptake of ______.
Want to give at bedtime due to its strong _____ Effect. Advantages include a decreased incidence of ____ and ____ side effects and it is less toxic in______. Common ADR= _____/_____ Associated with a rare incidence of _____. DI: Potentiates _______ drugs. Useful in severe ____ Secondary to depression |
serotonin;
sedative; anticholinergic, antihistaminergic; overdose; sedation/drowsiness; priapism; CNS depressant; insomnia |
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Bupropion may be considered a prodrug with an active metabolite that is a strong reuptake inhibitor of ____.
It lowers ______ threshold and an immediate-release dosage form is rarely used since it is associated with a higher frequency of ______ |
NE;
seizure; seizure |
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Major pharmacological action of SSRIs is a ____ and ____ inhibition of ____ reuptake.
Are the DOCs in treating ____, _____ and _____. Have largely replaced ____ for initiation and maintenance of therapy. |
selective; potent; serotonin;
depression, OCD, panic disorder; TCAs |
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SSRIs have minimal effects on _____, _____ or ____ receptors.
Have a ____ therapeutic index. Withdrawal symptoms (____.____ and _____) may occur especially after chronic use of high doses |
muscarinic, adrenergic, or histaminergic;
high; anxiety, dizziness, nausea |
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SSRIs work to increase serotonin levels at the synaptic cleft which results in .......
The time course of this process correlates with the onset of...... |
the serotonin autoreceptors to down regulate and become desensitized;
therapeutic actions |
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Withdrawal syndrome is more significant with ___-acting SSRIs.
This is attributed to the ______ of 5HT receptors during tx. FLUSH symptoms= NOTE *Appearance of withdrawal syndrome may be greatly delayed after SSRI is d/c * |
shorter;
downregulation; Flu-like sx, Lightheadedness, Uneasiness (anxiety), Sleep disturbances (insomnia), Headache |
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How can you treat sexual dysfunction caused by SSRI treatment?
|
decreasing dose of SSRI or switching to another antidepressant of a diff class (bupropion)
|
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What two pathways are altered by SSRIs that can cause sexual dysfunction?
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Mesolimbic and Descending pathways from BS to SC
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In the mesolimbic pathway, SSRIs increase the ____ levels which results in stimulation of _____ Receptors. This disinhibits serotonergic pathways innervating the mesolimbic _____ system. By doing this, SSRIs _____ the dopamine system and results in which sexual dysfunction symptoms (2)?
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serotonin; 5HT2; dopamine; oppose; decreased libido, anorgasmia
|
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SSRI-induced disinhibition of the descending serotonergic pathways (from the brainstem to the SC) increases ____ release which inhibits sexual function (_______, _______).
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Serotonin; impotence, ejaculatory failure
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Bupropion is a reuptake inhibitor of both _____ (potent) and ____ (Weaker). Have been reports of several reversals of SSRI-induced _________, _________ and _______
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NE; dopamine; impotence, decreased libido, delayed orgasm
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Cyproheptadine is a _______ drug commonly used for _______ that also acts as a __________ agent. By blocking this receptor, it may reverse the SSRI-induced ________ in both genders and ________
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antihistamine; pruritis; serotonin-receptor blocking; impotence; impaired ejaculation
|
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Buspirone has demonstrated improvement of SSRI-indcued ________ and _______
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anorgasmia and decreased libido
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Exrapyramidal symptoms (_____) that may be experienced with SSRI use are due to an excess of ____ and a decreased ____ Activity
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tremors; serotonin; DA activity
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Which SSRI drug has the highest incidence of weight gain?
|
paroxetine
|
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SSRIs block serotonin reuptake into platelets and depletes platelet 5HT which results in ......
3x increase risk of ____ bleeding |
inhibition of coagulation;
GI |
|
Concurrent use of MAOIs and SSRIs is contraindicated due to the prevalence of _________
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serotonin syndrome
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SSRIs inhibit which metabolism system? specifically _____.
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P450; 2D6
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What the symptoms of serotonin syndrome?
|
rigidity, diaphoresis and hyperthermia
|
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Which drug is the prototype SSRI?
|
fluoxetine
|
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Fluoxetine is indicated for the acute and maintenance treatment of ____, ____, _____ and _____
Can also be used for ________ |
Major depressive disorder, OCD, bulimia nervosa, panic disorder;
PMDD |
|
What are some ADR of Fluoxetine? (3)
|
CNS stimulation (nervousness, anxiety, agitation, insomnia); GI disturbances, Increased risk of GI bleeding
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Fluoxetine has serious interactions with MAOIs so need to wait _____ weeks after d/c before starting the MAOI
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5
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Fluoxetine inhibits ____ and ___ isozymes of the P450 system
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2D6, 3A4
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When using Fluoxetine with Dextromethorphan the pt can experience ___________
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hallucinations
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Fluoxetine and Warfarin can increase bleeding ________
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diathesis (susceptibility to bleeding)
|
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Paroxetine is indicated for ________, _____, _______, _____ and ____
Is a potent inhibitor of the _____ isozyme of the P450 system. Paxil CR is a combined delayed release and extended release tablet, with a purpose to decrease _____ and ________ |
Major depressive disorder, OCD, panic disorder, GAD, PTSD;
2D6; nausea; other GI disturbances |
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Which drug has the highest sedative activity of SSRIs and the most significant risk of DIs?
|
fluvoxamine
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Which SSRI has possibly the lease potential for DIs?
|
citalopram
|
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Up to 70% of pts with panic disorder also fulfill the dx criteria for ____.
_______ has an approved indication for this treatment. |
major depressive disorder;
alprazolam |
|
What are the advantages of using an SSRI in treatment of panic disorder?
|
little to no abuse potential; very low-no incidence of orthostatic hypotension, anticholinergic side effects or sedation
|
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Which SSRI has the most CNS stimulating ability?
|
fluoxetine
|
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What are the disadvantages of using an SSRI in the treatment of panic disorder?
|
CNS stimulating side effects , DIs due to the inhibition of P450 system, and sexual dysfunction
|
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In the treatment of panic disorder, _______ have been found efficacious but the onset of action may be quite _____. The current view is that these drugs may be the DOC for panic disorder with ________
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SSRIs; slow; concurrent depression
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Serotonin syndrome most often occurs in patients taking two or more drugs that......
Usually involves ____, ____ and ____. Excessive stimulation of the ____ and ____ receptor subtypes are responsible for most of the symptoms. |
increase serotonin levels by different mechanisms.
MAOIs, SSRIs, TCAs 5HT1a and 5HT2a |
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What is the triad of serotonin syndrome?
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altered mental status, autonomic hyperactivity and neuromuscular abnormalities
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Mental status changes associated with serotonin syndrome can inlude...
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agitation, confusion, delirium
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Autonomic changes associated with serotonin syndrome can include....
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N, fever, diaphoresis, HTN, tachycardia, tachypnea
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NM changes associated with serotonin syndrome can include....
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rigidity, myoclonus (rhythmic muscular contractions), hyperreflexia, shivering, tremor, hyperthermia
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Drugs that can cause serotonin syndrome include:
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L-tryptophan, MAOIs (with another drug), amphetamines, cocaine, TCAs, SSRIs,meperidine, dextromethorphan, buspirone, triptans
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L-tryptophan can cause serotonin syndrome because it functions to....
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increase 5HT synthesis
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Most cases of serotonin syndrome caused by MAOIs were used concurrently with _____, ____, _____ a ____ or _____
MAOIs function to decrease... |
meperidine, tryptophan, dextromethorphan, TCA, SSRI
5HT metabolism |
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MAOI-SSRI combination may produce a serotonin syndrome lasting for ______ after d/c due to....
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weeks;
SSRIs long-half life and MAOIs long DOA |
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Amphetamines and cocaine cause serotonin syndrome by increasing....
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5HT release
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Some TCAs, SSRIs, meperidine and dextromethorphan all function to inhibit....
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5HT reuptake
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Buspirone and triptans can cause serotonin syndrome because they are....
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specific 5HT agonists
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Venlafaxine is a potent reuptake inhibitor of....
Has minimal effects on _____, ____ or _____ receptors Weakly inhibits _______ (much less potent that SSRIs) and has serious reaction with _____ (_____, _____, _____ and ____) |
both NE and 5HT;
cholinergic; adrenergic; or histaminic receptors; P450 system; MAOIs, hyperthermia, rigidity, myoclonus, seizures |
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Duloxetine is a potent reuptake inhibitor of....
Has low affinity for ____, ____, ____ and ____ receptors. Indicated for ______ and _____ Moderately inhibits ____ so concurrent use with ____ is not recommended and concurrent use with _____ is contraindicated. |
NE and 5HT (SNRI)
dopaminergic, adrenergic, cholinergic, and histaminic; major depressive disorder, GAD 2D6; thioridazine; MAOIs |
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Mirtazapine blocks the central presynaptic ____ receptors and results in an increased release of .......
It selectively enhances neurotransmission over ____ receptors. It also blocks several postsynaptic ____ receptor subtypes (___,___ and ___). These subtypes are responsible for ______ and _____ ADRs so by blocking them, they are avoided. Has minimal to no effects on the reuptake of..... Blocks ____ receptors resulting in potent _____. |
alpha-2; NE and 5HT;
5HT1; 5HT; 2A, 2C, 3; GI Adverse reactions and sexual dysfunction; NE or 5HT; histamine H1; sedation |
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What are two ADRs associated with Mirtazapine?
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sedation and increased appetite/weight gain due to blockage of 5HT3 receptors
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Mirtazapine has _____ sedative/psychomotor effects with some drugs and has _____ interactions but doesn't appear to inhibit metabolism of any other drugs.
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additive; MAOI
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MAOIs function by blocking the enzyme _____ and preventing the metabolic degradation of ________ to increase concentrations at the synaptic cleft.
Onset of action is _____ days for maximal inhibition but therapeutic effects take _____ weeks. Long DOA is due to ___________ and 1 week or longer is required to resynthesize the enzyme after rate drug is d/c |
MAO; biogenic amines (NE, DA, 5HT)
2-3; 2-3; irreversible inhibition of MAO |
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Indications for MAOIs include: (3)
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atypical depression, phobic anxiety syndromes, lack of response to other antidepressants (refractory depression)
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What are some ADRs of MAOIs?
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orthostatic hypotension, tachycardia, palpitations, sexual dysfunction
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What are some symptoms of MAOI overdose?
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hyperpyrexia, HTN, agitation, hallucinations, seizures
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MAO normally metabolizes ____ in the GIT which is found in some foods. With the MAO inhibited by MAOIs, this is not digested and is absorbed and can cause release of massive amounts of ____ from ___________
This can result in _____ and other signs of adrenergic stimulation such as..... Treatment= |
tyramine; NE; adrenergic nerve terminals;
HTN crisis; acute elevation of BP, tachycardia, agitation, headache, sweating, pallor, stroke; alpha blockers (phentolamine) |
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What is the first line DOC for the treatment of mania in Bipolar 1 disorder?
What are some alternatives? |
Lithium or divalproex sodium;
AAPs and carbamazepine |
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When a pt is in Euphoric mania, what is the DOC? what is the alternative?
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lithium; divalproex sodium
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When a pt is in Dysphoric mania, what is the DOC? what is the alternative?
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Divalproex sodium; lithium
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What is the FDA approved maintenance therapy for bipolar 1 disorder? What is the alternative?
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lithium; lamotrigine and some AAPs
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What is the DOC for treating rapid cycling bipolar disorder?
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divalproex
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What is the 1st line DOC for treating bipolar depression?
What is the second line? |
lithium;
olanzapine/fluoxetine (symbyax) |
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Lithium has a ____ therapeutic index which requires _____.
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narrow; monitoring
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What are some side effects of therapeutic doses of lithium?
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GI distress, polyuria/dipsia and fine tremor of the hands
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What are some side effects of chronic treatment with lithium?
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Nephrogenic Diabetes insipidus, hypothyroidism, wt gain, edema
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When using lithium, need to be cautious to avoid ____ because it can cause....
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dehydration; lithium retention and toxicity
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Moderate toxicity effects of lithium present as....
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coarse tremor, muscle twitches, slurred speech, unsteady gait and ataxia
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Increased sodium intake decreases renal _____ of lithium while reduced sodium intake ______ lithium serum levels.
Pts on a sodium restricted diet or diuretics are at risk for.... |
reabsorption; increases;
lithium toxicity |
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Serum lithium concentrations are increased by ______ and ____ due to sodium _____ as well as ____ which cause volume depletion and lowers GFR resulting in......
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thiazide diuretics; NSAIDs; depletion; ACEIs; reduced lithium excretion
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Carbamazepine and antipsychotics may cause neurotoxicity within _____ lithium levels
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normal
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What is a contraindication for lithium treatment?
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serious renal disease with unpredictable variations
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What are some long term adverse effects of divalproex sodium?
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tremor, thrombocytopenia
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What is a more serious side effect of divalproex sodium therapy?
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hepatotoxicity
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What are the most common adverse effects of divalproex sodium treatment
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GI disturbances (lessened with food) and sedation
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Extended release carbamazepine is indicated for _____ or _____ episodes associated with bipolar disorder.
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acute manic; mixed
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What are the most common ADRs for carbamazepine?
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sedation, dizziness, rash, GI disturbances
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What are some hematological ADR effects of carbamazepine?
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leukopenia
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Carbamazepine can induce ____ and ____ conditions
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SIADH and hyponatremia
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Carbamazepine induces the _____ system and also auto induces its own_________
Can cause neurotoxicity when combined with _____ even when plasma levels of both are in therapeutic range. Symptoms include...... |
P450 system; metabolism;
lithium; confusion, weakness, coarse tremor, lethargy, hyperreflexia, ataxia |
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Antipsychotic therapy for schizophrenia should be directed towards the _________type.
First generation agents are effective in treating _______ but much less at treating _____ (may even worsen them) |
dominant;
positive symptoms; negative symptoms |
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Atypical antipsychotic are antagonists at _____ and ____ receptor types.
Clozapine like antipsychotics have low ____ antagonism and high _____ antagonism Non-clozapine like antipsychotics are relatively specific for ____ receptors in the _____ pathway. Have moderate to high ____ antagonism. Have high ____ antagonism. |
DA; 5HT;
D2; 5HT2A; D2; mesolimbic; D2; 5HT2A |
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The blockade of 5HT2A by non-clozapine like antipsychotic drugs causes ____ release in the _____ pathway (lessens _____ symptoms and some ___ symptoms)
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DA; nigrostriatal; extrapyramidal; negative
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Aripiprazole has partial ____ and _____ properties at D2 receptors.
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agonist and antagonist
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Typical antipsychotic agents are used in the treatment of _______ (_______ and ____).
Major targets are the ____ symptoms. Can also be used as an _____ |
psychoses (schizophrenia; paranoia);
positive; antiemetics |
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Which drugs are tended to be used more of the typical antipsychotic drugs?
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high potency drugs (haloperidol and fluphenazine)
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Typical antipsychotic agents have erratic and incomplete bioavailibility when taking ______ preparations so want to use.....for rapid initiation of treatment
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oral; parenteral formsMO
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What is the MOA of typical antipsychotic drugs?
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block dopamine receptors (D3 receptor subtype)
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What are the 4 central dopaminergic pathways?
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mesolimbic, mesocortical, nigrostriatal, tuberinfundibular
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What causes the positive symptoms of schizophrenia?
How do you treat this? |
overactivity of dopaminergic neurons in the mesolimbic pathway and limbic system;
blockade of DA receptors |
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What causes the negative symptoms and cognitive deficiency symptoms of schizophrenia?
What happens if you block DA receptors in this area? |
decreased dopaminergic activity in the mesocortical pathway;
may worsen negative symptoms |
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Interruption of the dopaminergic transmission in the nigrostriatal pathway causes.....
Neuroleptic blockade here causes.... |
parkinsons disease;
pseudo-Parkinsonism |
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The DA in the tuberinfundibular pathway functions to...
Blockade of this results in... |
inhibit prolactin secretion;
hyperprolactinemia |
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Binding of antipsychotic drugs to D2 is strongly correlated with both ______ and ________
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antipsychotic action; toxicity (Extrapyramidal symptoms)
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Blocking the mesocortical pathway (with DA already deficient) causes:
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worsened negative symptoms
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Blocking the DA in the nigrostriatal pathway causes:
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Extrapyramidal symptoms
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Blocking the DA in the tuberinfundibular pathway causes:
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hyperprolactinemia
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Extrapyramidal symptoms are seen in Haloperidol _____Than in Chlorpromazine.
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more
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What are some extrapyramidal symptoms that may be seen with antipsychotics?
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acute dystonias, akathisias, pseudo-Parkinsonism
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How do you treat acute dystonias (EPS) associated with typical antipsychotics?
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prophylactic use of anticholinergic (1st gen antihistamine with anticholinergic properties preferable)
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How do you treat akathisias (EPS) associated with typical antipsychotics?
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beta blocker or BZs
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How do you treat pseudo-parkinsonism (EPS) associated with typical antipsychotics?
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anticholinergics
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What are some ADRs associated with typical antipsychotics?
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EPS, tardive dyskinesias, sedation, anticholinergic effects, orthostatic hypotension, others (photosensitivity, poikilothermia, hyperprolactinemia, thioridazine)
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Akathisias is=
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unpleasant sensitization of inner restlessness with the inability to sit still
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Tardive Dyskinesias is caused by...
Is... |
the long-term blockade of D2 receptors which causes up-regulation and supersensitivity of D2 receptors;
a late developing EPS syndrome of abnormal choreoathetoid movements |
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Tardive dyskinesias are very serious, potentially ______ and very resistant to _______.
Characterized by..... |
irreversible; drug treatment;
involuntary movements and abnormal facial movements |
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Which two typical antipsychotic drugs cause more sedation than haloperidol and what causes it?
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chlorpromazine; thioridazine;
blockade of central H1 receptors |
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Which two drugs cause more anticholinergic effects/sedation than haloperidol?
This is because of the blockade of ________ receptors and also results in a ______ and ______ |
chlorpromazine; thioridzine;
peripheral muscarinic; dry mouth; constipation |
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Which two drugs cause more cases of orthostatic hypotension than haloperidol?
What causes this? |
chlorpromazine; thioridizine;
blockade of alpha 1 receptors |
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Which typical antipsychotic has the highest incidence of photosensitivity?
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chlorpromazine
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Which typical antipsychotic prolongs the QT interval?
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thioridazine
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What are the 4 typical antipsychotic drugs?
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chlorpromazine, thioridazine, haloperidol, prochlorperazine
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Chlorpromazine is indicated for ....(5).....
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psychotic disorders, control N/V, tx of acute intermittent porphyria, adjunct in tx of tetanus, relief of intractable hiccups
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Thioridazine has a black boxed warning because of.....
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QT prolongation
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Haloperidol is a ____ potency agent with very strong ________ symptoms. Has the highest incidences of ____ and ____
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high; extrapyramidal symptoms; EPS, TD
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Prochlorperazine is used for ______. Is not used as an antipsychotic due to its.....
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antiemetic; strong extrapyramidal symptoms
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Atypical antipsychotic drugs are referred to as atypical because....
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therapeutic efficacy can be achieved without significant extrapyramidal symptoms
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Atypical antipsychotic drugs are antagonists at _____ and ____ receptors but more more selective for ________ receptors.
5HT activity at 5HT2 receptors decreases the _____ levels which contributes to the negative symptoms experienced. By blocking the 5HT2 receptors, _______ is able to increase leading to relief from negative symptoms. |
5HT2 and D2 (central);
limbic-specifc D2 receptors dopamine; dopamine |
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Atypical antipsychotic agents usually display ______cognitive fxn in schizo's where as typical agents generally have a negative effect on cognitive fxn.
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improved;
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Atypical antipsychotic drugs are effective in the treatment of many schizo pts who are....
Also effective against the _____ symptoms |
resistant to typical antipsychotic drugs
negative |
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Atypical antipsychotic agents improve ________, significantly reduce _________symptoms, leaves unchanged or minimally elevates ________ and has a decreased or absent propensity to produce _____.
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cognitive function; both positive and negative symptoms; prolactin levels; EPS's
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Clozapine has two separate interactions=
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central and peripheral
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Clozapine (in regard to central receptor interactions) is a relatively weak antagonist at ____ receptors which is the site of action of most other antipsychotics. Results in little to no ____ stimulation.
Also have a strong blockade of ______ receptors which modulates DA release; may account for minimal risk of _____ and a lower risk of ____ compared to typicals. |
D2; prolactin;
5HT2; EPS; TD |
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What are the three receptors blocked by Clozapine in the periphery?
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alpha1, histamine 1, msucarinic
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Clozapine causes an alpha1 blockade which results in=
Histamine 1 blockade results in= Msucarinic blockade results in= |
orthostatic hypotension;
sedations; anticholinergic effects |
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Clozapine is indicated in psychotic pts who have....
tx with clozapine is limited to... |
tried and failed 2 other antispychotic classes of drugs (either failed tx or couldnt tolerate adverse effects);
resistant pts |
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Clozapine has a black boxed warning for: (5)
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agranulocytosis, potent anticholinergic effects (constipation), sedation, metabolic effects (wt gain, DM, dyslipidemias) and QT prolongation
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Risperidone is a....
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atypical antipsych
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Clozapine is a....
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atypical antipsych
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Olanzapine is a....
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atypical antipsych
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Ziprasidone is a...
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atypical antipsych
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Aripiprazole is a...
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atypical antipsych
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Paliperidone is a...
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atypical antipsych
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Iloperidone is a...
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atypical antipsych
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Asenapine is a...
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atypical antipsych
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Lurasidone is a....
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atypical antipsych
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Risperidone is indicated for...
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the management of schizo; NOT restricted to resistant pts
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Risperidone is the first drug approved for the tx of irritability in children and adolescents with ______
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autism
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Risperidone is the 1st _______ atypical drug.
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long-acting injection
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Risperidone has a lower incidence of ______ compared to clozapine, lower incidence of dose-dependent _______ than clozapine, has incidence of _____________ and has no reported incidences of ________
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seizurs; EPS; QT interval prolongation; agranulocytosis
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Risperidone has a strong affinity for ____ and ____ receptors where it is a potent _____
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5HT2 and D2; antagonist
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The Potent 5HT antagonism actions of Risperidone accounts for the relatively low incidence of _____ Despite strong D2 antagonism (comparable to ______). Incidence of EPS is ______with clozapine
The D2 antagonism does result in a dose-related increase in _________ |
EPS; haloperidol; lower;
prolactin secretion |
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Olanzapine has similar receptor binding and activity as _______
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clozapine
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Indications for olanzapine include management of _____ and as a mono therapy or adjunct therapy for short-term treatment of ______ or ______ associated with __________disorder
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schizophrenia; acute manic, mixed episodes; bipolar 1 disorder
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Olanzapine treatment is not restricted to...
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resistant pts
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What ADRs have not been demonstrated with Olanzapine?
Olanzapine has significant ______ effects including.... |
leukopenia or agranulocytosis;
metabolic; high risk of DM, dyslipidemia, high amount of wt gain |
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Ziprasidone is indicated for the treatment of....
Has the least amount of associated __________. Is a 2nd line agent due to the_____________ that occurs to a greater extent than for any other antipsychotic drug except for _________ |
both positive and negative symptoms of schizophrenia;
metabolic syndrome; QT prolongation; thioridazine |
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Aripiprazole is a partial agonist at ______ receptors. Is an antagonist when ______ is present and an agonist when .....
ADR include: |
D2; excess DA is present; DA is deficient;
prolongs QT interval |
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Paliperidone is the active metabolite of _______.
ADR includes ....... Want to avoid concurrent use of other drugs which..... |
risperidone;
prolongation of QT; prolong QT interval |
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Iloperidone has been associated with ______ and not _______
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prolonged QT interval; wt gain
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Asenapine has been associated with ______ so you need to avoid use of concurrent agents which also _______ and in pts with ....
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prolonged QT interval; prolongate the QT interval; risk factors for prolonged QT intervals
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Lurasidone did not report any _________
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Qt prolongation
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Neuroleptic malignant syndrome is characterized by what 4 things?
Most commonly seen with _______ and ______. Thought to be due to...... Treatment: |
rigidity, hyperthermia, tachycardia, sweating;
haloperidol, fluphenazine; excessive blockade of postmen DA receptors causing a severe DA depletion and a severe extrapyramidal syndrome muscle rigidity= IV dantrolene |
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atypical antipsychotic drug therapy is associated with _______, ________, _______ and ________
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impaired glc metabolism; exacerbation of existing DM I and II, new onset DM II and diabetic ketoacidosis
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Atypical antipsychotics may cause ____, ___, and ______ increasing the risk for _______
Which drug was associated with a greater weight gain and metabolic abnormalities? Which drug was associated with improvement in most metabolic states and showed the least amount of metabolic syndrome? |
weight gain, DM, dyslipidemias; developing metabolic syndrome;
olanzapine; ziprasidone |
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To minimize weight gain and metabolic effects when using atypical antipsychotics, which do you want to use? which do you want to avoid?
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aripiprazole, ziprasidone;
olanzapine, clozapine, quitiapine |
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Which atypical antipsychotic drugs should you avoid if you want to minimized QT prolongation?
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ziprasidone, iloperidone, paliperidone
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