BZD, barbiturates and buspirone Flashcards by Chelsea Luedtke

What BZD is associated with procedural sedation and amnesia?

Midazoalm

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What BZD is associated with use for muscle relaxation?

Diazepam

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Which BZD is associated with use for drug and alcohol withdrawal symptoms?

Lorazepam

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What BZD effects are associated with developed tolerance with chronic use?

Anti-seizure and hypnotic effects

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Describe the tolerance to anti-anxiety effects of BZDs

Develops slowly or not at all

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Describe the physiological dependence to BZDs; psychological?

Relatively little; more common than physiological (tendency to continue use when not needed)

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What happens when someone discontinues using benzodiazepines after long-term use?

Symptom recurrence, rebound or withdrawal

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Recurrence definition (BZDs)

Return of symptoms that required therapy (common with BZDs, weeks-months long)

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Rebound definition (BZDs)

Symptoms are similar to before but with greater intensity (within hours or days of last dose)

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T/F: Rebound symptoms are greater with long-acting BZDs than with short-acting.

False (short-acting have greater rebounds)

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How is rebound intensity related to dose and duration of use (BZDs)

Proportionally

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Withdrawal general symptoms (BZDs)

General anxiety, sensory disturbances, flu-like

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Withdrawal autonomic sympathetic signs (BZDs)

Tachycardia/hypertension, tremors, abdominal distress, sweating

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Withdrawal symptoms following abrupt DC after long-term use (BZDs)

Seizures and delirium

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Explain how to discontinue BZDs

Switch to longer-acting drug (lorazepam, diazepam) and gradually taper dose by 10% per 1-2 weeks

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How can BZDs, specifically longer-acting ones, suppress abstinence symptoms from other CNS depressants like alcohol and barbiturates?

Cross-dependence

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Why should the use of BZDs be avoided in the elderly?

ADEs= confusion, anterograde amnesia are more common in elderly

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Paradoxical ADEs of BZDs (2)

Hyperactivity, aggression (esp. in pediatric population)

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BZD use in pregnancy

Chronic use is contraindicated (category D and X)

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Toxicity presenting signs (BZDs)

Severe drowsiness and ataxia, vital signs usually normal

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T/F: BZDs when taken orally do not cause fatal toxicity, but are potentially fatal when combined with alcohol or other CNS depressants.

True

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Treatment: BZD toxicity

Supportive care (technically could use flumazenil)

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Competitive antagonist at the BZD receptor sign on GABAa

Flumazenil (Romazicon)

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Flumazenil blocks the effects of ____, but does NOT reverse the effects of ___(4).

BZDs and non-benzo BZD agonists; barbiturates, ethanol, general anesthetics, or opioids

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Flumazenil administration, onset time, half-life

IV, 1-2 minutes, 1 hour (metabolized by liver)

2 uses of flumazenil:

Reverse sedation effect of BZDs after anesthesia, BZD overdose

T/F: Flumazenil is used to treat BZD overdose especially because it re-establishes the airway.

False- not a substitute for establishing airway-assisted ventilation

Boxed warning on flumazenil

Seizures (esp. in patients on long-term BZD therapy who have taken TCA)

ADEs= amnesia, agitation, dizziness, nausea, may precipitate withdrawal in dependency

Flumazenil (BZD receptor antagonist)

Phenobarbital and methohexital + CYP enzymes...

Strong inducers of CYP enzymes (multiple DDIs)

Onset of methohexital

Rapid (extremely lipid soluble)

What determines methohexital's DOA after a single dose? Plasma half-life?

Redistribution; hepatic metabolism

What determines phenobarbital's DOA? Plasma half-life?

Both determined by hepatic metabolism (less lipid soluble, so does not enter brain as rapidly)

Phenobarbital: % metabolized

75%

Phenobarbital: onset time

60 minutes

Phenobarbital: duration

10-12 h

Phenobarbital: lipid/water

T/F: Barbiturates have poor analgesic properties but DO relieve anxiety.

True

Main use and schedule of phenobarbital

Epileptic seizures (status epilepticus), CIV

Off-label use of phenobarbital

Treatment of alcohol and sedative/hypnotic withdrawal

Describe phenobarbital's use as a sedative/hypnotic

No longer recommended (overdose is deadly)

Uses of methohexital (2)

- Induction of general anesthesia | - procedural sedation

Tolerance to phenobarbital's ____ effects occurs, but NOT to its ___ or ____ effects.

Sedative-hypnotic; respiratory depression or anti-seizure

What causes the tolerance seen with phenobarbital use?

Increased metabolic clearance of the drug (CYP autoinduction)

Physical dependence on phenobarbital is a serious problem - what symptoms are seen 8-12 H after last dose?

Anxiety, tremors, restlessness, weakness, nausea, vomiting, insomnia

Physical dependence on phenobarbital is a serious problem - what symptoms are seen 2 days after last dose?

Increased sympathetic activity, delirium, seizures, death

How do you treat physical dependence to phenobarbital?

Supportive, switch to long-acting barbiturate and taper dose

T.I. Of barbiturates (phenobarbital)

ADEs= potentially fatal CNS/respiratory depression, hypotension, paradoxical stimulatory response (esp. in pediatrics), alkalinization of urine (enhances elimination)

Barbiturates (phenobarbital, methohexital)

MOA of busprione:

Unclear, partial agonist at 5-HT1a and 5-HT2 receptors

Does buspirone bind to any site on the GABAa receptors?

Use of buspirone

Generalized anxiety disorder (less effective for other anxiety disorders like social or panic)

ADEs of buspirone (4)

Dizziness, restlessness, tachycardia, palpitations (think CNS and CV)

What occurs upon abrupt discontinuation of buspirone?

Nothing- no rebound anxiety or withdrawal symptoms

Use of buspirone while pregnant

Safe during pregnancy (category B)

Use of buspirone while driving

Fine- does not affect motor skills

Does buspirone show any abuse potential?

No (not a controlled substance)

What is the main advantage of buspirone in treating anxiety?

No sedative/hypnotic or euphoric effects, NOT additive with other CNS depressants

What is the onset of buspirone?

3-4 weeks (until anti-anxiety effect becomes established)

T/F: Buspirone reverses withdrawal from other CNS depressants.

False

Buspirone anti-seizure effects

None

Buspirone muscle relaxant effects

None

Lipid solubility and ______ are directly proportional

onset of action

After a single dose, ______ of highly lipid soluble drugs i dependent on the rate of ______ out of the CNS into another compartment

duration of action | redistribution

Lipid solubility and ______ are inversely proportional

duration of action

When given chronically, duration of action is dependent on ______

hepatic elimination

How do AA and glucose readily cross the BBB?

L-amino acid transporter | GLUT1

The _____ is the primary drug target of CNS drugs

neuron

neurons are classified by what 3 things?

function location NT they release

Function of neurons are supported by what?

glial cells

Target selectivity in the CNS is based on what?

- different functions of the brain are mediated by release of specific NTs in discrete regions of brain by distinct groups of neurons - specific functions of the brain can be targeted by using drugs highly selective for the receptor subtypes

Major excitatory NT

glutamate

Where does glutamate act?

AMPA, KA, NMDA ion channels

major inhibitory NT

GABA

GABA A

Cl ion channels

GABA B

GPCRs

nicotinic and muscarinic NT

acetylcholine

4 amine NTs

Serotonin DA NE histamine

What NT is associated with Parkinson's?

What NT is implicated in virtually all CNS functions?

Serotonin

What NT modulates arousal and appetite?

Histamine

Where is MOA-A expressed?

GI tract liver CNS

1st pass metabolism of MOA-A

dietary tyramine

MAO-A inactivation of

Epi NE 5-Ht DA

MOA-A inhibitors are used to treat

depression

Where is MOA-B expressed?

platelets | CNS

MAO-B is selective inactivation of what?

MAO-B inhibitors are used to treat

Parkinson's

Major drug classes of CNS depressants

BZD Barbiturates Ethanol General anesthetics

Decreased responsiveness to external stimuli, but not asleep; anti-anxiety effect

sedation

also referred to as dissociative anesthesia

sedation

pharmacological definition of sleep-like state from which the individual can still be aroused

Hypnosis

unresponsive to external stimuli but responsive to pain

unconsciousness

state of unconsciousness where individual is unresponsive to external stimuli or pain, is paralyzed and amnestic

anesthesia

Non-selective CNS depressants

ethanol barbiturates general anesthetics

Selective CNS depressants

BZDs

How do CNS depressants bind?

allosteric agonists of GABA A

5 subunits of GABA-A

2alpha 2 beta gamma

Where is the GABA binding site?

between beta and alpha

Binding of GABA leads to what pore opening?

Where is the BZD binding site?

between alpha and gamma

alpha 1 subunit mediates what functions?

sedation amnesia ataxia

alpha 2,3 subunits mediates what functions?

anti-anxiety | muscle relaxing effects

alpha 5 subunits mediates what functions?

long-term memory and learning effects

Binding of BZDs locks the channel into a conformation that increases its affinity for GABA and increases the _____ of chloride channel opening

frequency

T/f BZDs will produce sedation and hypnosis given orally by themself

false

t/f barbiturates need the gamma subunit to bind

false

Barbiturates increase the ____ of chloride channel opening

duration

t/f at high doses, barbiturate binding can activate the receptor in the absence of GABA

true

BZD, barbiturates and buspirone Flashcards

(109 cards)