Induction Drugs (Etomidate & Ketamine) (Exam II) Flashcards by Jeremy Steele

In general, thiobarbiturates are much more _____ soluble and have a greater _______ than oxybarbiturates.

What atom do thiobarbiturates have in lieu of an oxygen in the second position (like oxybarbiturates)?

Lipid; potency
Sulfur

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What is unique about Etomidate’s organic chemical structure?

It is the only carboxylated imidazole containing compound.

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Etomidate MOA

Same as prop, versed, Etoh,

directly opens Cl- channels to hyperpolarize cells

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When is etomidate water-soluble vs lipid-soluble?

H₂O-soluble at acidic pH.
Lipid-soluble at physiologic pH.

Weak base

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What percentage of etomidate is propylene glycol? What is the result of this?

35% propylene glycol resulting in pain on injection.

give lidocaine beforehand 1 or 2% only for smaller veins, the hand

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Which induction agent can be given without an IV? How is this?

Etomidate - can be given sub-lingual.

No hepatic first pass when given in oral mucosa

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Why does etomidate have a low incidence of myoclonus?

Trick Question. Etomidate has a high incidence of myoclonus, just like all other induction agents.

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What is the onset of etomidate?
How much of it is protein bound?
What protein does it bind to?

Onset: 1 minute
76% albumin bound

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What is etomidate’s Vd?
How does clearance compare to thiopental?
What is the result of this clearance?

Large Vd
5x faster clearance than thiopental resulting in a prompt awakening.

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What metabolizes etomidate?
What is the elimination profile?

CYP450’s (??) & hepatic microsomal enzymes plasma esterases and hydrolysis
Elimination ½ time = 2-5 hours with 85% via urine and 10 - 13% via bile.

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Peak effect table time

2.0 min
T 1/2 1.5 min ??

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What is the induction dosage range for etomidate?

0.2 - 0.4 mg/kg IV (book)
0.3 mg/kg IV (ppt)

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What is the best use for etomidate?

Induction for unstable cardiac patients.

especially with little to no cardiac reserve

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What needs to be used concurrently with etomidate when performing a laryngoscopy? Why?

Opioids, etomidate has no analgesic effects.

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What is Etomidate’s most common side effect?
How often does this occur?

Involuntary Myoclonic Movements ( 50 - 80 %) of administrations.

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How does Involuntary Myoclonic Movements occur when this induction drug is given?

Etomidate alters the balance of inhibitory and excitatory infuences on the thalamocortical tract

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How often do Involuntary Myoclonic Movements occur with the three drugs listed aside from etomidate?

Thiopental: 17%
Propofol: 6%
Methohexital: 13%

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What should be administered with etomidate to prevent involuntary myoclonic movements?

Fentanyl 1-2 μg/kg IV

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Etomidate has a dose dependent inhibition of the conversion of cholesterol to _________.
What does this mean clinically?

Cortisol (the response to stress)
Etomidate decreases SNS capability to respond to stress (longer vent times, hypotension, etc.)

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How long does adrenocortical suppression with etomidate last?
What two pathologies would cause you to hesitate before giving etomidate?

4-8 hours.
Sepsis & hemorrhage (any condition where you need an intact cortisol response).

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Compared to thiopental, etomidate will lower plasma concentrations of what substance?

See table slide 12

Cortisol

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What are etomidate’s effects on CBF & CMRO₂ ?
Why is this and what does it do?

Etomidate = ↓CBF & ↓CMRO₂ due to being a direct cerebral vasoconstrictor by 35% to 45%
Will also ↓ICP.

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CMRO₂ is couple with both CBF and _______.

CMRG (cerebral metabolic requirement of glucose)

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Effects on CV system with Etomidate

Decreased PAP

minimal changes with HR, SV, CO

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What is the EEG profile of etomidate?

- More excitatory than thiopental - May activate seizure foci - Augments SSEP amplitude.

Though etomidate is great for cardiac patients, what condition can result in significant hypotension if not treated prior to induction?

- Hypovolemia

Histamine release via etomidate is mediated through what?

- Trick question. **Etomidate does not release histamine**.

What is the pulmonary profile of etomidate?

- **No change in minute ventilation**. - Less respiratory depression than barbiturates - Rapid IV produces apnea - Stimulates CO₂ medullary centers

What type of drug is ketamine? What type of anesthesia does it produce? What two properties does it possess?

- Phenycyclidine derivative; NMDA receptor antagonist (PCP; "angel dust") - Dissociative anesthesia - Amnestic & intense **analgesia** properties

What signs and symptoms does dissociative anesthesia (ketamine) produce?

**"Zonked" state** - Non-communicative but awake - Hypertonus & purposeful movements - Eyes open but "no one's home".

What are ketamine's two greatest advantages over propofol or etomidate?

- No pain at injection (no propylene glycol) - **Profound analgesia** at sub-anesthetic doses.

What are the two greatest disadvantages of ketamine?

- Emergence delirium - Abuse potential

What is Benzethonium Chloride? What is it's relevance?

- Ketamine preservative that inhibits ACh receptors

Differentiate S(+)Ketamine vs R(-)Ketamine.

S-Ketamine (+) (left-handed isomer) is essentially better. - More intense analgesia - ↑metabolism & recovery - Less salivation - Lower emergence delirium

What benefits does a racemic ketamine mixture offer?

- Less fatigue & cognitive impairment - Inhibits catecholamine reuptake at nerve endings (like cocaine).

What is Ketamine's main mechanism of action?

- Non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors by inhibiting pre-synaptic release of **glutamate.**

What are Ketamine's secondary receptor sites?

- Weak GABA_A effects. - Opioid (μ, δ, and κ)

What is Ketamine's time of onset? (IV & IM) When would this drug be utilized IM?

- IV: 1 min - IM: 5 min (mostly for pediatric patients)

What is Ketamine's duration of action? What about its lipid solubility? What is the result of this?

- 10-20 min - Highly lipid soluble (5-10x greater than thiopental). - Results: **Brain** → non plasma bound → peripheral tissue.

What is the Vd and E½ time of ketamine?

- Vd = 3L/kg - E ½ = 2-3 hours

Name the pharmacokinetic profile of ketamine: - Clearance: - Metabolism: - Excretion:

- Clearance: high hepatic clearance (1L/min) - Metabolism: CYP450's. - Excretion: kidneys

What is the primary metabolite of ketamine and what its its significance?

Norketamine is metabolite (⅓ to 1/5) potency and prolongs analgesia).

In what patient population is ketamine tolerance most often seen?

Burn patients

What is the induction dose of ketamine IV? What if it is given intramuscularly? PO?

- 0.5 - 1.5 mg/kg IV - 4 - 8 mg/kg IM - 10 mg/kg PO

What is the maintenance dosing of ketamine?

- 0.2 - 0.5 mg/kg IV - 4 - 8 mg/kg IM

What is the subanesthetic/analgesic dose of ketamine?

- 0.2 - 0.5 mg/kg IV

What is the post-operative sedation and analgesia dosing for ketamine in pediatric cardiac surgery cases?

1-2 mg/kg/**hour**

What is the neuraxial epidural analgesia dosing of ketamine? What about intrathecal route?

- 30mg epidural - 5 - 50 mg in 3 mL of saline via intrathecal/spinal/subarachnoid

Ketamine is a potent sialagogue. What does this mean for your clinical practice?

- Manage excessive secretions during intubation & watch for coughing/laryngospasm.

What drug and dosing of said drug should be used to treat excessive salivary secretions from ketamine administration?

**Glycopyrrolate: 0.2mg**

You gave ketamine and the patient fell asleep within 30 seconds. If you gave no more doses when would you expect the patient to: - Wake up? - Be fully conscious? - Start remembering things?

- Wake up in 10-20 minutes - Full consciousness in 60 - 90 min - Amnestic effects should also wear off in 60 - 90 min.

What patient populations is ketamine best used for?

- Acutely hypovolemic patients - Asthmatics - Mental health patients

When would you do an IM induction of a patient?

- Uncooperative and difficult-to-manage mentally challenged patients. - IM Effective for pediatric pts

Though ketamine has many indications, when should it be avoided?

- Patients with **pulmonary HTN and ↑ICP**.

What are Ketamine's effects on ICP? Why?

- ↑ICP via ↑CBF by 60% - **Potent cerebral vasodilator**.

At what dosing will the ICP increasing effects of ketamine plateau?

- 2mg/kg IV

Due to ketamine's increased excitatory EEG activity, how much does seizure potential increase with administration?

Trick question. **No increase in seizure potential with ketamine**.

What does the cardiovascular profile of ketamine look like? How can this side effect profile be blunted?

- SNS stimulation ( ↑ in sBP, PAP, HR, CO, MRO2, etc.) - Blunted via pre-med with benzo's, volatiles, or nitrous. | See table

Say you just gave ketamine and you have an unexpected drop in systolic BP and CO. What happened? How do you treat it?

- Depleted catecholamine stores - **Treat with direct-acting SNS agents (ex. phenylephrine?? Epinepherine in lecture)** vs indirect (ex. ephedrine).

What is the Pulmonary profile of ketamine?

- No depression of ventilation with CO₂ response maintained. - ↑ salivary excretion - **Intact upper airway tone & reflexes**. - **Bronchodilator with no histamine release**.

What does emergence delirium present like with ketamine?

- Visual, auditory, proprioceptive illusions. Morbid & vivid dreams up to 24 hours.

What is the proposed physiologic mechanism of action for emergence delirium occurrence with ketamine?

Depression of inferior colliculus & medial geniculate nucleus.

What percentage of patients will develop ketamine induced emergence delirium? How can it be prevented?

- Psychedelic effects in **5 - 30%** of patients. - **Pre-med with midazolam & glycopyrrolate**. | Could also give clonidine and Dex

What "other systems" effects does ketamine have?

- **Non-depolarizing NMBs enhancement.** - **Succinylcholine prolongation via plasma cholinesterase inhibition.** - PLT aggregation inhibition

What are ketamine's most common drug interactions?

- Volatiles → hypotension - Non-depolarizing NMBs → enhancement - Succinylcholine → prolongation

Why does ketamine prolong succinylcholine's effects?

Ketamine is a plasma cholinesterase inhibitor.

Which induction agent has the highest analgesic properties?

- Ketamine

Why would ketamine be a decent induction drug for an OSA patient? Why not?

- Preservation of upper airway reflexes & ventilatory function. - Sialagogue, SNS activation

Why is Ketafol not a good mixture

Ketamine is a chiral compound and propofol is not --> unstable, pulonary embolism risk

What does the USP 797 state?

Sterile compounding can occur within 4 hours as long as aseptic technique is maintained

Induction Drugs (Etomidate & Ketamine) (Exam II) Flashcards

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