General Approach to GAD Treatment - plan depends on (3 factors) - considerations when initiating drug therapy (3 factors)

- develop patient specific treatment plan; psychotherapy and drug therapy Plan depends on: - severity and chronicity of symptoms - medication history - comorbid medical and psychiatric conditions Considerations when initiating drug therapy: - anticipated adverse effects - history of prior response in the patient or a family member - patient preference and compliance

Flumazenil - even at very high doses rarely fatal - with severe toxicity, respiratory depression can be complicated by aspiration of gastric contents Treatment: - ensure patient airway, maintenance of plasma volume, renal output, and cardiac function

- competitive antagonist; binds same site as BZ but does nothing - approved for use in reversing CNS depressant after BZ overdose - requires repeated administration

- rapid onset of action - a relatively high therapeutic index and availability of flumazenil for treatment of overdose - low risk of drug-drug interactions based on liver enzyme induction - minimal effects on cardiovascular and autonomic functions

- risk of dependence - depression of CNS functions - amnesic effects

Sedative-Hypnotic Agents Flashcards by Andrea Fontanetta

Sedative

anxiolytic; anti-anxiety

- indicated for patients experiencing symptoms severe enough to produce functional disability

How well did you know this?

Not at all

Perfectly

Hypnotic

promotes sleep

- requires more pronounced CNS depression (reduce excitability of CNS)

How well did you know this?

Not at all

Perfectly

Pharmacologic Therapy of GAD

Shore Term
– reduce severity and duration of anxiety symptoms
Long Term
– remission with minimal or no anxiety symptoms
– no functional impairment
– increased quality of life

How well did you know this?

Not at all

Perfectly

General Approach to GAD Treatment

plan depends on (3 factors)
considerations when initiating drug therapy (3 factors)

develop patient specific treatment plan; psychotherapy and drug therapy

Plan depends on:

severity and chronicity of symptoms
medication history
comorbid medical and psychiatric conditions

Considerations when initiating drug therapy:

anticipated adverse effects
history of prior response in the patient or a family member
patient preference and compliance

How well did you know this?

Not at all

Perfectly

Short-Term Pharmacotherapy for Acute Anxiety States

Benzodiazepines (BZ)
- biggest class for ACUTE anxiety treatment
- v. good acute, v. bad long term; v. high risk of dependency
*** act fast, long duration***
(rapid time to peak blood levels; long half-life)

How well did you know this?

Not at all

Perfectly

Alprazolam (Xanax)

BZs

How well did you know this?

Not at all

Perfectly

Max time usage for BZ

Max 2-4 weeks (due to risk of physical and mental dependency)

How well did you know this?

Not at all

Perfectly

Chlordiazepoxide (Librium)

BZs

How well did you know this?

Not at all

Perfectly

Clonazepam (Klonopin)

BZs

How well did you know this?

Not at all

Perfectly

Diazepam (Valium)

BZs

How well did you know this?

Not at all

Perfectly

Lorazepam (Ativan)

BZs

How well did you know this?

Not at all

Perfectly

Oxazepam (Serax)

BZs

How well did you know this?

Not at all

Perfectly

Benzodiazepine Mechanism

BZs bind to GABA receptor in neuronal membranes
– does NOT bind where GABA binds, binds elsewhere and improves GABA function
BZs increase the frequency of GABA-gated channel opening events
– GABA firing = inhibition of CNS
underlies a “GABAergic” mechanism of action, that results in inhibition at all levels of the neuraxis

How well did you know this?

Not at all

Perfectly

BZs Clinical Toxicity/Adverse Effects

can lead to drowsiness, impaired judgement, and diminished motor skills; intensified by alcohol
can cause significant dose-related anterograde amnesia, and can impair ability to learn new information
at high doses, toxicity can present as lethargy, exhaustion, or as gross symptoms of ethanol intoxication

How well did you know this?

Not at all

Perfectly

Prolonged use of BZs

- withdrawal symptoms due to abrupt cessation

can lead to tolerance, psychologic and physiologic dependence

CLASS IV controlled drugs

Withdrawal symptoms:

increased anxiety
insomnia
CNS excitability that may progress to convulsions

How well did you know this?

Not at all

Perfectly

BZ OD

- treatment

Flumazenil

even at very high doses rarely fatal
with severe toxicity, respiratory depression can be complicated by aspiration of gastric contents

Treatment:
- ensure patient airway, maintenance of plasma volume, renal output, and cardiac function

How well did you know this?

Not at all

Perfectly

Flumazenil

competitive antagonist; binds same site as BZ but does nothing
approved for use in reversing CNS depressant after BZ overdose
requires repeated administration

How well did you know this?

Not at all

Perfectly

Advantages of BZ

rapid onset of action
a relatively high therapeutic index and availability of flumazenil for treatment of overdose
low risk of drug-drug interactions based on liver enzyme induction
minimal effects on cardiovascular and autonomic functions

How well did you know this?

Not at all

Perfectly

Disadvantages of BZ

risk of dependence
depression of CNS functions
amnesic effects

How well did you know this?

Not at all

Perfectly

First-Line Drugs Long-term GAD

Newer Antidepressants

SSRIs
SNRIs

How well did you know this?

Not at all

Perfectly

Escitalopram

SSRI

How well did you know this?

Not at all

Perfectly

Paroxetine (Paxil)

SSRI

How well did you know this?

Not at all

Perfectly

Sertraline

Study These Flashcards

SSRI

Duloxetine

Study These Flashcards

SNRI

Venlafaxine XR (Effexor XR)

SNRI

SSRI

Selective Serotonin Reuptake Inhibitors

SNRI

Serotonin-Norepinephrine Reuptake Inhibitors

Long-Term Treatment GAD Second Line

- TCA - Anxiolytic - Anticonvulsant

TCA

Tricyclic Antidepressant

Mechanism of Action for Antidepressants for Anxiety | not GABA

- block manifestations of anxiety by increasing amount of serotonin available to interact with postsynaptic 5-HT(1A) receptors ***Calming-sedative effect*** - downregulates 5-HT(2) receptors which cause anxiety

Response time for antidepressants

2-4 weeks+

Buspirone

- Anxiolytic (anxiety only; doesn't help with depression) - second-line treatment GAD - does NOT interact with GABAergic systems - takes 2+ weeks to take effect *** NOT good for acute anxiety treatment***

Pregabalin

- Anticonvulsant - second-line treatment GAD - increases GABA synthesis and release - DOES NOT BIND TO GABA RECEPTORS - produces effects similar to BZs and anti-depressants - controlled substance; dependence risk (V) (less than BZs) - is GABAergic

Imipramine

- TCA - second line treatment GAD - acts like SNRI - higher toxicity and adverse effect rates than newer antidepressants

***Imipramine Side-effects***

- antihistamine (sedation/somnolence) - anticholinergic (dry mouth; constipation; burred/double vision/ tachycardia) - antiadrenergic (orthostatic hypotension/BP dips) - risk of serious toxicity (including seizures, rapid heart rate, and cardiac arrest) with high doses

Hypnotics

- drugs used for treatment of insomnia | - SHORT t1/2: want to be able to get up in the morning

GABAergic Hypnotics

- Benzodiazepines (higher doses than used for anxiety) | - Non-Benzodiazepines hypnotics (also bind to GABA receptors)

Triazolam (Halcion)

BZ Hypnotic

Temazepam (Restoril)

BZ Hypnotic

Estazolam (ProSom)

BZ Hypnotic

Flurazepam (Dalmane)

BZ Hypnotic

Quazepam (Doral)

BZ Hypnotic

Zaleplon

Non-BZ Hypnotic | - help fall asleep DOESNT help KEEP asleep

Zolpidem (Ambion)

Non-BZ Hypnotic | - helps fall asleep & stay asleep

Eszopiclone

Non-BZ Hypnotic | - helps fall asleep & stay asleep

Newer Non-GABAergic Hypnotics

- Melatonin (MT) Receptor Agonists | - Orexin (OX) Receptor Antagonist

Ramelteon

Melatonin (MT) Receptor Antagonist

Tasimelteon

Melatonin (MT) Receptor Antagonist

Suvorexant (Belsomra)

Orexin (OX) Receptor Antagonist

Goals of Treatment for Hypnotics

- correct underlying sleep complaint - consolidate sleep (fall asleep and stay asleep) - improve daytime functioning (can wake up and function) - avoid adverse effects from drug therapies *** Drug therapy should be used in the LOWEST possible dose for the SHORTEST possible period of time ***

BZ as Hypnotic Agents

- decreases number of awakenings - higher dose than used for GAD - after prolonged use, can result in withdrawal and increased insomnia

Non-BZ Hypnotics

- bind to same site on GAGA receptor as BZs; exhibit similar effects - all decrease time to persistent sleep - rapid onset of activity, short half lives, few amnesic effects - schedule IV controlled substance: SHORT TERM USE ONLY

All Non-BZ Hypnotics Increase Total Sleep Time EXCEPT

Zaleplon | - helps fall asleep, does not help stay asleep

MT Receptor Agonists

- Ramelteon & Tasimelteon - act as agonists at MT1 and MT2 receptors - NO GABAergic effects in the CNS - no risk of dependency - promote sleep

Tasimelteon is uniquely approved for:

non-24 hour sleep-wake disorder

Orein (OX) Receptor Antagonist

- BLOCKER of WAKE receptor - acts as antagonist at OX1 and OX2 receptors in the brain, with non GABAergic CNS effects - BLOCKS WAKEFULNESS - schedule IV controlled substance - "sleep-driving" behavior and amnesic effects

Sedative-Hypnotic Agents Flashcards

(56 cards)