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284 Cards in this Set

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Sedatives cause.....

Also considered ____ agents

Not intended for the use for....
Calmness and relaxations;

anxiolytic/antianxiety;

the stress and tension of every day living
Hypnotics produce _____ therefore it is automatically a ____ Agent.
sleep; sedative
What are the 4 stages of sleep?
0=awake; 1= onset of sleep; 2= slight sleep; 4= REM sleep
How much time is spent in light sleep/stage 2?
50%
How much time is spent in REM sleep?
25%
Most all drugs in the sedative-hypnotic class of drugs can cause....
physical and psychological dependence
Barbiturate sedative/hypnotics are induces of _______ which can cause.......
P450 system;

numerous drug interactions
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
What is an ADR of large doses of barbiturates?
prolonged CNS depression
Chronic use of barbiturates can cause ____, ____ and risk of _____.
tolerance, dependence, withdrawal syndrome
What are the two components of tolerance?
enzyme induction; adaptive CNS changes
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
Abstinence syndrome is associated with which class of drugs?
Barbiturate sedative/hypnotics
An overdose of barbiturates results in depression of the _____ and ____ control centers in the brain resulting in......
medullary respiratory and CV control centers; fatality due to respiratory failure
Barbiturates have an additive/synergistic CNS depression when mixed with....
other depressants including alcohol
Estazolam, Triazolam and Flurazepam are all drugs of the __________ class
benzodiazepine hypnotic
Benzodiazepine Hypnotic agents are indicated for ______ characterized by _____, _______ or _______
insomnia; difficulty in falling asleep, frequent nocturnal awakening, or early morning awakening
Benzo Hypnotics work by....
potentiating (increasing) transmission involving pathways using GABA as an inhibitory NT
There are two subtypes of the GABA-A receptor: BZ1 and BZ2.
BZ1 receptor stimulation results in ______ and ______
sleep onset and cycle regulation
All GABA-A BZ1 receptors become activated nonspecifically by ______ which accounts for......
benzos; the wide range of a cation of BZs (sedation, hypnosis, anti anxiety, anticonvulsant, muscle relaxant)
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
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)
What is the effect of BZs on sleep patterns?
increase total sleep time
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
Short-Medium acting BZs are best to achieve ___ onset with duration lasting through the night but having no _____ the next day.
rapid; 'hangover'
Triazolam is a ____ acting BZ and is preferable in the _____ but may result in......
short; elderly; early morning awakening
Estazolam is a _____ acting BZ
intermediate
Flurazepam is a _____ acting BZ that has a long _________
long; half-life
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
Pts can develop _______ while taking BZs and withdrawal symptoms following abrupt d/c can occur including ____, _____ or _____ if severe.
physical dependence;

muscle cramps, tremors, convulsions
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
BZs have additive/synergistic effects with other _________
CNS depressants
Zolpidem and Zaleplon are _______ Drugs used in the short term treatment of ______ and is generally limited to ___-___ days.
nonbarb/nonbz sed/hypnotic; insomnia; 7-10
Zolpidem ER, eszopiclone, ramelteon are ______ Drugs indicated for the treatment of ________
nonbarb/nonbz sed/hypnotic; insomnia
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;
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
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
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
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
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
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
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
BZ anxiolytics have what 5 shared pharm actions?
hypnotic, anxiolytic, anticonvulsant, muscle relaxant, amnesiac
What are the three advantages of BZ anxiolytics compared to other anxiolytics?
rapid onset,high therapeutic index, relatively few ADR
What are 3 disadvantages to BZ anxiolytics?
tolerance, impaired psychomotor performance, dependence
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
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
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
What are the DOC for treatment of PTSD?
SSRIs
Alcohol withdrawal syndrome symptoms can include ________, ___________ which occurs usually 48-72 hours after d/c, _____. _______. _____. _____ and _______
tonic-clonic seizures, delirium tremens; hyperthermia, tachycardia, HTN, delirium, hallucinations
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
Diazepam is indicated for use as a ____, _____ and _____
muscle relaxant, anticonvulsant, preop medication
Lorazepam is indicated as a ____ medication to produce ____ and ____. Can also be used in treatment of ______
preanesthetic; sedation; amnesia;

status epilepticus
Alprazolam is used for the treatment of ______ with or without _______
panic disorder; agoraphobia
Chlordizepoxide is used for the treatment of ________
acute alcohol withdrawal syndrome
All of the pharmacological effects of benzodiazepines are mediated through interactions with the _______ complex.
GABA receptor;
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
The GABA-A receptor contains how many binding sites for BZs?

What do BZs act as?
at least 3;

allosteric modulators of GABA activity
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 ______)
increased; enhanced; hypnotic; anticonvulsant; muscle relaxant
Potentiate means:
facilitates
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
In the spinal cord, BZs cause...
muscle relaxation
In the brain stem, BZs cause...
anticonvulsant properties
In the cerebellum, BZs cause....
ataxia and sedation at doses beyond those needed for anxiolytic effects
In the limbic and cortical areas, BZs cause....
anxiolytic and amnesic effects
BZs have a ____ margin of safety between the therapeutic and toxic doses.
wide
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;
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
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
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
What are the characteristics of withdrawal syndrome associated with BZ dependence?
muscle cramps, tremor, tonic-clonic seizures
What are some expected ADRs associated with BZ use (due to high therapeutic index)?
CNS depression (sedation, ataxia, lethargy, impaired psychomotor performance, depression)
Overdoses of BZs have only a mild effect on _________ but may be fatal when taken with _____.
respiration; alcohol
BZs have additive/synergistic effects with other _______ causing severe ______
CNS depressants; ataxia
Buspirone is a ______ drug that is indicated for the management of ________ or short term relief of _____________
non-BZ anxiolytic; anxiety disorders; symptoms of anxiety;
The net effect of buspirone is to decrease _____ activity in states of ________.
serotonergic; serotonin excess
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
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
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
Buspirone ADR: affinity for ____ receptors might cause symptoms of blockade. These were NOT observed during clinical trials
dopamine
Concomitant administration of _________ is contraindicated when using Buspirone.
MAOIs
Inhibitors of ________ can cause elevation of busprione concentrations causing excessive _____ or _______
CYP3A4 isozyme (P450); drowsiness or dizziness
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
Flumazenil Is indicated for the complete or partial reversal of the _____ effects of BZs in cases where ....(3).....
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)
When using Flumazenil, there is a risk of ____ due to the reversal of BZ effects in high risk populations (what are the three populations?)
seizures;

those undergoing concurrent sed-hypnotic withdrawal, those with TCA poisoning, and those with physical dependence to BZs
Imipramine is a.....
TCA
Amitriptyline is a....
TCA
Nortryptilline is a.....
TCA
Clomipramine is a......
TCA
Phenelzine is a....
MAOI
Trazodone is a ......
atypical antidepressant
Buproprion is a.....
atypical antidepressant
Fluoxetine is a.....
SSRI
Paroxetine is a....
SSRI
Sertraline is a....
SSRI
Citalopram is a....
SSRI
Venlafaxine is a .....
dual-mechanism antidepressant
Duloxetine is a....
dual mechanism antidepressant
Nefazodone and Mirtazapine are....
'other' third generation antidepressants
Which antidepressant categories are first gen drugs?
TCAs and MAOIs
Which antidepressant categories are second gen drugs?
atypical antidepressants
Which antidepressant categories are third gen drugs?
SSRIs, dual mecahnism and others
When treating depression, which drug class is tried first due to its efficacy, tolerability and once daily dosing?
SSRIs
What are some potential side effects that can be experienced with depression and therapy?
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
What is the black boxed warning associated with SSRI use in pts up to age 24?
increased suicidal tendencies
What are the advantages of adding another antidepressant to a current treatment instead of switching the type?
avoids risk of withdrawal sx's, maintains any benefit of first drug, diff MOA may counteract side effects
What is the most common antidepressant combination?
SSRI plus bupropion
MAOI combinations can lead to what two conditions?
hypertensive crisis and serotonin syndrome
Venlafaxine/SSRI combo has caused _______ due to........
spontaneous bleeding; platelet serotonin release and inhibition of platelet aggregation
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
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
TCAs have a ____ therapeutic window.
narrow
Anticholinergic actions include: (6)
dry mouth, constipation, urinary retention, mydriasis, blurred vision, tachycardia
Which TCA has the highest anticholinergic actions?
amitryptilline
What three cardiovascular ADRs can be experience with TCAs?
orthostatic hypotension, conduction abnormalities, tachycardia
Orthostatic hypotension caused by TCA use is due to _____ blockade. Highest rate seen with _________
alpha1 blockade;

amitryptiline
What conduction abnormalities can occur with the use of TCAs?
EKG abnormalities, altered intraventricular conduction, may cause AV block (in pts with preexisting conduction defects)
The conduction abnormalities that may be experienced with TCAs is highest with ______.
amitryptiline
Tachycardia experienced with use of TCAs is caused by a combination of ____________ and _________
reflex response to orthostatic hypotension; anticholinergic effects
What CNS ADR can be experienced with TCAs?
sedation
What are some symptoms of overdose of TCAs?
slurred speech, confusion, tachycardia, hypotension, resp distress, QT prolognation, seizures
What is a common side effect experienced with antidepressant treatment?
weight gain
Use of TCAs and Clonidine together is contraindicated due to reports of.....
hypertensive crisis (mechanism unknown)
TCAs potentiate the actions of which two types of drugs?
antimuscarinics and CNS depressants
MAOIs with concurrent use of TCAs may cause severe ____ toxicity (consequences=(3)).
CNS; hyperpyrexia, seizures, coma
Want to avoid concurrent use of TCAs with class IA antiarrhythmics which predispose a pt to....
conduction disturbances
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'
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
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
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
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
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
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
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
How can you treat sexual dysfunction caused by SSRI treatment?
decreasing dose of SSRI or switching to another antidepressant of a diff class (bupropion)
What two pathways are altered by SSRIs that can cause sexual dysfunction?
Mesolimbic and Descending pathways from BS to SC
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)?
serotonin; 5HT2; dopamine; oppose; decreased libido, anorgasmia
SSRI-induced disinhibition of the descending serotonergic pathways (from the brainstem to the SC) increases ____ release which inhibits sexual function (_______, _______).
Serotonin; impotence, ejaculatory failure
Bupropion is a reuptake inhibitor of both _____ (potent) and ____ (Weaker). Have been reports of several reversals of SSRI-induced _________, _________ and _______
NE; dopamine; impotence, decreased libido, delayed orgasm
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 ________
antihistamine; pruritis; serotonin-receptor blocking; impotence; impaired ejaculation
Buspirone has demonstrated improvement of SSRI-indcued ________ and _______
anorgasmia and decreased libido
Exrapyramidal symptoms (_____) that may be experienced with SSRI use are due to an excess of ____ and a decreased ____ Activity
tremors; serotonin; DA activity
Which SSRI drug has the highest incidence of weight gain?
paroxetine
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 _________
serotonin syndrome
SSRIs inhibit which metabolism system? specifically _____.
P450; 2D6
What the symptoms of serotonin syndrome?
rigidity, diaphoresis and hyperthermia
Which drug is the prototype SSRI?
fluoxetine
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
Fluoxetine has serious interactions with MAOIs so need to wait _____ weeks after d/c before starting the MAOI
5
Fluoxetine inhibits ____ and ___ isozymes of the P450 system
2D6, 3A4
When using Fluoxetine with Dextromethorphan the pt can experience ___________
hallucinations
Fluoxetine and Warfarin can increase bleeding ________
diathesis (susceptibility to bleeding)
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
Which drug has the highest sedative activity of SSRIs and the most significant risk of DIs?
fluvoxamine
Which SSRI has possibly the lease potential for DIs?
citalopram
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
Which SSRI has the most CNS stimulating ability?
fluoxetine
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
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 ________
SSRIs; slow; concurrent depression
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
What is the triad of serotonin syndrome?
altered mental status, autonomic hyperactivity and neuromuscular abnormalities
Mental status changes associated with serotonin syndrome can inlude...
agitation, confusion, delirium
Autonomic changes associated with serotonin syndrome can include....
N, fever, diaphoresis, HTN, tachycardia, tachypnea
NM changes associated with serotonin syndrome can include....
rigidity, myoclonus (rhythmic muscular contractions), hyperreflexia, shivering, tremor, hyperthermia
Drugs that can cause serotonin syndrome include:
L-tryptophan, MAOIs (with another drug), amphetamines, cocaine, TCAs, SSRIs,meperidine, dextromethorphan, buspirone, triptans
L-tryptophan can cause serotonin syndrome because it functions to....
increase 5HT synthesis
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
MAOI-SSRI combination may produce a serotonin syndrome lasting for ______ after d/c due to....
weeks;

SSRIs long-half life and MAOIs long DOA
Amphetamines and cocaine cause serotonin syndrome by increasing....
5HT release
Some TCAs, SSRIs, meperidine and dextromethorphan all function to inhibit....
5HT reuptake
Buspirone and triptans can cause serotonin syndrome because they are....
specific 5HT agonists
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
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
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
What are two ADRs associated with Mirtazapine?
sedation and increased appetite/weight gain due to blockage of 5HT3 receptors
Mirtazapine has _____ sedative/psychomotor effects with some drugs and has _____ interactions but doesn't appear to inhibit metabolism of any other drugs.
additive; MAOI
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
Indications for MAOIs include: (3)
atypical depression, phobic anxiety syndromes, lack of response to other antidepressants (refractory depression)
What are some ADRs of MAOIs?
orthostatic hypotension, tachycardia, palpitations, sexual dysfunction
What are some symptoms of MAOI overdose?
hyperpyrexia, HTN, agitation, hallucinations, seizures
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)
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
When a pt is in Euphoric mania, what is the DOC? what is the alternative?
lithium; divalproex sodium
When a pt is in Dysphoric mania, what is the DOC? what is the alternative?
Divalproex sodium; lithium
What is the FDA approved maintenance therapy for bipolar 1 disorder? What is the alternative?
lithium; lamotrigine and some AAPs
What is the DOC for treating rapid cycling bipolar disorder?
divalproex
What is the 1st line DOC for treating bipolar depression?

What is the second line?
lithium;

olanzapine/fluoxetine (symbyax)
Lithium has a ____ therapeutic index which requires _____.
narrow; monitoring
What are some side effects of therapeutic doses of lithium?
GI distress, polyuria/dipsia and fine tremor of the hands
What are some side effects of chronic treatment with lithium?
Nephrogenic Diabetes insipidus, hypothyroidism, wt gain, edema
When using lithium, need to be cautious to avoid ____ because it can cause....
dehydration; lithium retention and toxicity
Moderate toxicity effects of lithium present as....
coarse tremor, muscle twitches, slurred speech, unsteady gait and ataxia
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
Serum lithium concentrations are increased by ______ and ____ due to sodium _____ as well as ____ which cause volume depletion and lowers GFR resulting in......
thiazide diuretics; NSAIDs; depletion; ACEIs; reduced lithium excretion
Carbamazepine and antipsychotics may cause neurotoxicity within _____ lithium levels
normal
What is a contraindication for lithium treatment?
serious renal disease with unpredictable variations
What are some long term adverse effects of divalproex sodium?
tremor, thrombocytopenia
What is a more serious side effect of divalproex sodium therapy?
hepatotoxicity
What are the most common adverse effects of divalproex sodium treatment
GI disturbances (lessened with food) and sedation
Extended release carbamazepine is indicated for _____ or _____ episodes associated with bipolar disorder.
acute manic; mixed
What are the most common ADRs for carbamazepine?
sedation, dizziness, rash, GI disturbances
What are some hematological ADR effects of carbamazepine?
leukopenia
Carbamazepine can induce ____ and ____ conditions
SIADH and hyponatremia
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
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
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
The blockade of 5HT2A by non-clozapine like antipsychotic drugs causes ____ release in the _____ pathway (lessens _____ symptoms and some ___ symptoms)
DA; nigrostriatal; extrapyramidal; negative
Aripiprazole has partial ____ and _____ properties at D2 receptors.
agonist and antagonist
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
Which drugs are tended to be used more of the typical antipsychotic drugs?
high potency drugs (haloperidol and fluphenazine)
Typical antipsychotic agents have erratic and incomplete bioavailibility when taking ______ preparations so want to use.....for rapid initiation of treatment
oral; parenteral formsMO
What is the MOA of typical antipsychotic drugs?
block dopamine receptors (D3 receptor subtype)
What are the 4 central dopaminergic pathways?
mesolimbic, mesocortical, nigrostriatal, tuberinfundibular
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
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
Interruption of the dopaminergic transmission in the nigrostriatal pathway causes.....

Neuroleptic blockade here causes....
parkinsons disease;

pseudo-Parkinsonism
The DA in the tuberinfundibular pathway functions to...

Blockade of this results in...
inhibit prolactin secretion;

hyperprolactinemia
Binding of antipsychotic drugs to D2 is strongly correlated with both ______ and ________
antipsychotic action; toxicity (Extrapyramidal symptoms)
Blocking the mesocortical pathway (with DA already deficient) causes:
worsened negative symptoms
Blocking the DA in the nigrostriatal pathway causes:
Extrapyramidal symptoms
Blocking the DA in the tuberinfundibular pathway causes:
hyperprolactinemia
Extrapyramidal symptoms are seen in Haloperidol _____Than in Chlorpromazine.
more
What are some extrapyramidal symptoms that may be seen with antipsychotics?
acute dystonias, akathisias, pseudo-Parkinsonism
How do you treat acute dystonias (EPS) associated with typical antipsychotics?
prophylactic use of anticholinergic (1st gen antihistamine with anticholinergic properties preferable)
How do you treat akathisias (EPS) associated with typical antipsychotics?
beta blocker or BZs
How do you treat pseudo-parkinsonism (EPS) associated with typical antipsychotics?
anticholinergics
What are some ADRs associated with typical antipsychotics?
EPS, tardive dyskinesias, sedation, anticholinergic effects, orthostatic hypotension, others (photosensitivity, poikilothermia, hyperprolactinemia, thioridazine)
Akathisias is=
unpleasant sensitization of inner restlessness with the inability to sit still
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
Tardive dyskinesias are very serious, potentially ______ and very resistant to _______.

Characterized by.....
irreversible; drug treatment;

involuntary movements and abnormal facial movements
Which two typical antipsychotic drugs cause more sedation than haloperidol and what causes it?
chlorpromazine; thioridazine;

blockade of central H1 receptors
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
Which two drugs cause more cases of orthostatic hypotension than haloperidol?

What causes this?
chlorpromazine; thioridizine;

blockade of alpha 1 receptors
Which typical antipsychotic has the highest incidence of photosensitivity?
chlorpromazine
Which typical antipsychotic prolongs the QT interval?
thioridazine
What are the 4 typical antipsychotic drugs?
chlorpromazine, thioridazine, haloperidol, prochlorperazine
Chlorpromazine is indicated for ....(5).....
psychotic disorders, control N/V, tx of acute intermittent porphyria, adjunct in tx of tetanus, relief of intractable hiccups
Thioridazine has a black boxed warning because of.....
QT prolongation
Haloperidol is a ____ potency agent with very strong ________ symptoms. Has the highest incidences of ____ and ____
high; extrapyramidal symptoms; EPS, TD
Prochlorperazine is used for ______. Is not used as an antipsychotic due to its.....
antiemetic; strong extrapyramidal symptoms
Atypical antipsychotic drugs are referred to as atypical because....
therapeutic efficacy can be achieved without significant extrapyramidal symptoms
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
Atypical antipsychotic agents usually display ______cognitive fxn in schizo's where as typical agents generally have a negative effect on cognitive fxn.
improved;
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
Atypical antipsychotic agents improve ________, significantly reduce _________symptoms, leaves unchanged or minimally elevates ________ and has a decreased or absent propensity to produce _____.
cognitive function; both positive and negative symptoms; prolactin levels; EPS's
Clozapine has two separate interactions=
central and peripheral
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
What are the three receptors blocked by Clozapine in the periphery?
alpha1, histamine 1, msucarinic
Clozapine causes an alpha1 blockade which results in=

Histamine 1 blockade results in=

Msucarinic blockade results in=
orthostatic hypotension;

sedations;

anticholinergic effects
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
Clozapine has a black boxed warning for: (5)
agranulocytosis, potent anticholinergic effects (constipation), sedation, metabolic effects (wt gain, DM, dyslipidemias) and QT prolongation
Risperidone is a....
atypical antipsych
Clozapine is a....
atypical antipsych
Olanzapine is a....
atypical antipsych
Ziprasidone is a...
atypical antipsych
Aripiprazole is a...
atypical antipsych
Paliperidone is a...
atypical antipsych
Iloperidone is a...
atypical antipsych
Asenapine is a...
atypical antipsych
Lurasidone is a....
atypical antipsych
Risperidone is indicated for...
the management of schizo; NOT restricted to resistant pts
Risperidone is the first drug approved for the tx of irritability in children and adolescents with ______
autism
Risperidone is the 1st _______ atypical drug.
long-acting injection
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 ________
seizurs; EPS; QT interval prolongation; agranulocytosis
Risperidone has a strong affinity for ____ and ____ receptors where it is a potent _____
5HT2 and D2; antagonist
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
Olanzapine has similar receptor binding and activity as _______
clozapine
Indications for olanzapine include management of _____ and as a mono therapy or adjunct therapy for short-term treatment of ______ or ______ associated with __________disorder
schizophrenia; acute manic, mixed episodes; bipolar 1 disorder
Olanzapine treatment is not restricted to...
resistant pts
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
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
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
Paliperidone is the active metabolite of _______.

ADR includes .......

Want to avoid concurrent use of other drugs which.....
risperidone;

prolongation of QT;

prolong QT interval
Iloperidone has been associated with ______ and not _______
prolonged QT interval; wt gain
Asenapine has been associated with ______ so you need to avoid use of concurrent agents which also _______ and in pts with ....
prolonged QT interval; prolongate the QT interval; risk factors for prolonged QT intervals
Lurasidone did not report any _________
Qt prolongation
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
atypical antipsychotic drug therapy is associated with _______, ________, _______ and ________
impaired glc metabolism; exacerbation of existing DM I and II, new onset DM II and diabetic ketoacidosis
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
To minimize weight gain and metabolic effects when using atypical antipsychotics, which do you want to use? which do you want to avoid?
aripiprazole, ziprasidone;

olanzapine, clozapine, quitiapine
Which atypical antipsychotic drugs should you avoid if you want to minimized QT prolongation?
ziprasidone, iloperidone, paliperidone