Benzodiazepines Flashcards by Shirica Shaw

Whats the difference between a sedative and a hypnotic?

sedative: induces calm or sleep

hypnotic: induces hypnosis or sleep

both share similarities with anesthesia

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What does sedative/hypnotics inhibit?

Thalmic & mid brain RAS
CNS

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T/F: some people will have awareness under general anesthesia

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What is a good range for BIS monitoring to be between? What does it mean when they are within this range? Below this range?

40 - 60

Within: Probably will have no recall

Below: Too deep

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What are the 4 components of BIS monitors? And what do they tell us?

SQI (signal quality index)
EMG: tell us if the patient is about to move. You shouldn’t have EMG movement if patient is paralyzed.
EEG
SR (suppression ratio): how much of time within the last few minutes has the BIS # been 0
you should never have a number for this

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How do synergistic anesthetics affect the BIS number?

Decreases it

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How does ketamine affect the BIS number?

Increases it

Ketamine is a sympathomimetic and stimulates the CNS and causes the brain to be more active while being in an anesthetic state

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How does beta blockers affect the BIS number?

Decreases it

Peripheral nervous system is stimulated so CNS like it’s more suppressed

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When taking drugs that may artificially manipulate the BIS number, we are more interested in _________

trends

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What are the pharmacological effects of benzodiazepines?

SAAAS

Sedation
Anxiolytics
Anterograde amnesia
Anticonvulsant
Spinal-cord mediated skeletal muscle relaxation

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Anterograde amnesia in benzos lasts ______ than sedative effects

longer

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What are reasons that we give benzodiazepines over barbiturates?

Less risk for increased tolerance
Less risk for abuse
Fewer serious side effects
Don’t induce hepatic microsomal enzymes

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All benzos are structurally & chemically ______

similar

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The antagonist for benzos is considered __________. What does this mean?

Nonspecific

This means if given, will affect any benzos that have been taken

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What is the antagonist for benzos? (reversal agent)

Flumazenil/Romazicon

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Midazolam is most commonly used in ________. Why?

Pre/Periop

Quick onset, shorter half time, and prompt recovery

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What is the MOA of benzos?

Facilitates action of GABA, which is a main inhibitory neurotransmitter in the CNS, at GABA_A receptors which are located in lipid bilayers.

This allows the receptor to open and Cl- to hyperpolarize the postsynaptic membrane –> more resistant to depolarization

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Where do benzos bind on the GABA-A receptor?

Alpha1-gamma
Alpha2-gamma

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What is the difference between the Alpha 1 and Alpha 2 subunit?

Alpha1: most abundant type
-sedative, amnestic, anticonvulsant
-cerebral cortex, cerebellar cortex, thalamus

Alpha2: anxiolytic, skeletal muscle
-hippocampus, amygdala

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What are other things that bind to GABA-A receptor binding sites? Why does this matter?

Barbiturates
Etomidate
Propofol
Alcohol
Volatiles

Synergistics increase risk for overdose & tolerance

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All benzos have a ______ lipid solubility & ______ protein bound

high

highly

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How do benzos affect your EEG?

Decreased alpha activity

Some can produce isoelectric state

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Which benzo does not produce in isoelectric state in EEGs?

Versed/Midazolam

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What things cause synergistic affects with benzos?

Barbiturates
Etomidate
Propofol
Alcohol
Volatiles
Opioids
Alpha-2 agonists
Injected anesthetics

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Benzos ______ platelet aggregation by doing what?

inhibit preventing the conformational change in the platelet membrane to be able to grab on to each other

Midazolam is made with a _______ ring. How does this effect the pharmacokinetics?

Imidazole -Stabilize the structure -Allows rapid metabolism

Which is more potent Midazolam/Versed or Diazepam/Valium? Why?

Midazolam (2-3x) Greater affinity for receptor

What is a consideration that we need to have for Midazolam?

Since it causes amnesia for several hours, family needs to be present to sign postop paperwork and to drive home

Describe how pH and solubility of midazolam (versed) work.

In the bottle: **Imidazole ring is open** -pH is < 3.5 & protonated form -water soluble -stabilzed When you put in normal blood pH: **ring closes** -pH >4.0 & unprotonated form -lipid soluble -able to have rapid onset

Pharmacokinetics: Midazolam Onset; Peak; DOA; Half time; Vd; enzymes

Onset: 1-2mins Peak: 5 mins DOA: short Half time: 2 hours **Doubled in elderly, hepatic flow, enzyme activity** Vd: 1-1.5 L/kg (large) **Larger in morbidly obese; smaller in elderly with less fat** Enzymes: CYP450; CYP3A4

What happens during metabolism to midazolam?

Active & inactive metabolites active metabolite: 1-hydroxymidazolam

What drugs cause inhibition of CYP450? What are these?

Cimetidine Antifungals Fentanyl Erythromycin Calcium channel blockers **Drug interactions to midazolam and diazepam**

Clearance for Midazolam (versed) is _____ faster than lorazepam (Ativan) and _____ faster than diazepam (Valium).

5x 10x

How does Midazolam/versed and diazepam/valium both affect CMRO₂ and CBF?

They both decreased depending on the dose The more you give the more they are decreased

T/F: Midazolam is a potent anticonvulsant in status epilepticus

What effect does Midazolam have on vasomotor response to CO₂?

It preserves it It doesn't affect how blood vessels respond to CO2. Blood vessels will still dilate if CO2 is increased and vice versa.

Why is Midazolam (versed) good for induction with neuro patients?

It causes no change in ICP

How does Midazolam effect pulmonary? What are concerns we should have with this?

It is dose dependent -decreases hypoxic drive -increases depression with COPD (& other respiratory disorders) -depresses swallowing reflex -decreases upper airway activity **-transient apnea, if rapid IV w/ opioids** ** risk for aspiration**

How does Midazolam (versed) effect the CVS?

Dose dependent HR: increases BP: decreases CO: unchanged SVR: decreases

T/F: Midazolam inhibits BP/HR response to intubation

Dose: Midazolam (child/sedation)

0.25 - 0.5 mg/kg PO **peak 20-30 mins**

Dose: Midazolam (adults/sedation)

1 - 5 mg IV **elderly require decreased doses**

Dose: Midazolam (Induction)

0.1 - 0.2 mg/kg IV over 30-60 secs Give opioid 1st: 1-3 mins beforehand Fentanyl 50-100 mcq

Dosing: Midazolam (maintenance)

Uncommon, but can be used

T/F: Midazolam is associated with N/V an emergence excitement

F Your patient will not try to fight you when they wake up

Dosing: Midazolam (versed) (Postop sedation)

1 - 7 mg/hr IV **Markedly delayed awakening dt active metabolites accumulation**

What are the reason reasons why we don't like to use Midazolam (versed) as a drip?

Active metabolites accumulation Immune/ T cell affects Overall, not good for a long-term

Diazepam is soluble in ______ and insoluble in ______

lipids water

Which has a longer DOA, midazolam (versed) or diazepam (Valium)?

diazepam

What is added to diazepam (Valium) to make is soluble in water and less painful upon injection?

Propylene glycol **Also has a soybean formula thats less painful but more expensive**

Pharmacokinetics: Diazepam (Valium) Onset; Peak; DOA; Half time; Vd; enzymes

Onset: 1- 5 mins Peak: DOA: longer than midazolam Half time: 20 - 40 hours Vd: 1-1.5 L/kg (large) **Larger in woman than men** enzymes: CYP450/**CYP3A**

Diazepam dissociates _______ from GABA-A receptors than lorazepam. What does this cause?

faster shorter DOA

What are the active metabolites to diazepam? How do they affect the body?

Desmethyldiazepam (48-96 hrs) Oxazepam **both are nearly as potent as diazepam** **return of drowsiness 6 to 8 hours**

Dose: Diazepam (Valium) (anticonvulsant/other?)

0.1 mg/kg IV other: DTs, lidocaine toxicity related seizures

T/F: diazepam can produce isoelectric on EEG

What are the pulmonary affects that diazepam has?

-minimal effects on ventilation Slight decrease tidal volume -affects exaggerated with synergistic drugs or existing respiratory disorders

What can reverse respiratory depressant effects?

Surgical stimulation

How does diazepam affect the CVS?

HR: none BP: minimal decrease CO: minimal decrease SVR: minimal decrease **significant BP changes can occur with synergistic drugs**

T/F: adding nitrous can significantly lower the BP while giving diazepam due to synergistic effects

Why is diazepam (Valium) great for cardiac surgery induction?

Minimal reduces/changes in hemodynamics

Which benzo decreases tonic effect on spinal neuron? What effect does this have?

Diazepam This decreases skeletal muscle tone --> muscle relaxant effect **they gave me for back pain**

Dosing: Diazepam (Valium) (Induction)

0.5 - 1.0 mg/kg IV Decrease dose by 25 - 50% -elderly -liver disease -presence of opioids

Which benzo is more potent?

Lorazepam/Ativan

Lorazepam resembles _________ which is a metabolite of __________. What type of extra atom does it have?

oxazepam Diazepam Chloride

Lorazepam (Ativan) is soluble in _______ & insoluble in_______

Lipids Water

What do you add to lorazepam/Ativan to make it soluble in water?

Polyethylene glycol

Pharmacokinetics: lorazepam (Ativan) Onset; Peak; DOA; Half time; Vd; enzymes

Onset: slower than midazolam or diazepam dt lower lipid solubility Peak: 20 -30 mins with 1-4mg IV DOA: Half time: 14 hours Vd: enzymes:

Why is Ativan good for patients with liver disease or patients just with not a good liver?

Lorazepam/Ativan is not entirely dependent on hepatic enzymes. They can directly conjugate to inactivate metabolites.

Why is lorazepam (Ativan) the better choice for a benzo for a long term drip?

-cost-efficient -conjugated to inactive metabolites -can directly conjugate without hepatic enzymes

T/F: if your patient is actively fighting, you, lorazepam is a great choice

F Slower onset of action and longer peak effect

Describe the organ effects in lorazepam

Similar to other benzos

Dosing: lorazepam (single dose)

1 - 4 mg IV

Flumazenil/Romazicon is a _________ antagonist with a _____ affinity for the Benzo receptor

Competitive High

How is Flumazenil/Romazicon metabolized?

The hepatic enzyme, **hepatic esterase**, into inactive metabolites

Dosing: Flumazenil/Romazicon

--0.2 mg IV initial dose 0.1 mg subsequent doses until consciousness or **1 mg total** Sedation: 0.3 - 0.6 mg Abolished therapeutic dose: 0.5 - 1.0 mg

What happens if you give 1 mg of Flumazenil/Romazicon and nothing changes?

They have something else in their system, then benzos. Move on to other antagonist/reversal agents

What is the DOA of Flumazenil/Romazicon?

30 - 60 mins

What are the side effects of Flumazenil/Romazicon?

No side effects other than reversing benzos Ex) think! Could be taking these benzos for seizures or DTs. Those pathos can become present.

Benzodiazepines Flashcards

Test 1