Benzodiazepines Flashcards
Test 1
Whats the difference between a sedative and a hypnotic?
sedative: induces calm or sleep
hypnotic: induces hypnosis or sleep
both share similarities with anesthesia
What does sedative/hypnotics inhibit?
Thalmic & mid brain RAS
CNS
T/F: some people will have awareness under general anesthesia
T
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
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
How do synergistic anesthetics affect the BIS number?
Decreases it
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
How does beta blockers affect the BIS number?
Decreases it
Peripheral nervous system is stimulated so CNS like it’s more suppressed
When taking drugs that may artificially manipulate the BIS number, we are more interested in _________
trends
What are the pharmacological effects of benzodiazepines?
SAAAS
Sedation
Anxiolytics
Anterograde amnesia
Anticonvulsant
Spinal-cord mediated skeletal muscle relaxation
Anterograde amnesia in benzos lasts ______ than sedative effects
longer
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
All benzos are structurally & chemically ______
similar
The antagonist for benzos is considered __________. What does this mean?
Nonspecific
This means if given, will affect any benzos that have been taken
What is the antagonist for benzos? (reversal agent)
Flumazenil/Romazicon
Midazolam is most commonly used in ________. Why?
Pre/Periop
Quick onset, shorter half time, and prompt recovery
What is the MOA of benzos?
Facilitates action of GABA, which is a main inhibitory neurotransmitter in the CNS, at GABAA receptors which are located in lipid bilayers.
This allows the receptor to open and Cl- to hyperpolarize the postsynaptic membrane –> more resistant to depolarization
Where do benzos bind on the GABA-A receptor?
Alpha1-gamma
Alpha2-gamma
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
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
All benzos have a ______ lipid solubility & ______ protein bound
high
highly
How do benzos affect your EEG?
Decreased alpha activity
Some can produce isoelectric state
Which benzo does not produce in isoelectric state in EEGs?
Versed/Midazolam
What things cause synergistic affects with benzos?
- Barbiturates
- Etomidate
- Propofol
- Alcohol
- Volatiles
- Opioids
- Alpha-2 agonists
- Injected anesthetics
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
T
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
F
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
T
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
F
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.
