IV sedatives Flashcards
1
Q
What are some examples of general anesthetics that potentiate GABA_A receptors?
A
Propofol, barbiturates.
2
Q
Name three inhaled anesthetics that enhance GABA_A receptor activity.
A
Isoflurane, desflurane, sevoflurane.
3
Q
Which classes of drugs that potentiate GABA_A receptors are used as anxiolytics and sedatives?
A
Benzodiazepines, neurosteroids.
4
Q
List four antiseizure medications that work by potentiating GABA_A receptors.
A
Barbiturates, benzodiazepines, lorecazole, ganaxolone, topiramate.
5
Q
What are some insomnia medications that act on GABA_A receptors?
A
Benzodiazepines, zolpidem (Ambien), eszopiclone.
6
Q
Which medications that enhance GABA_A receptor activity are used for alcohol withdrawal treatment?
A
Benzodiazepines, clonidine.
7
Q
What type of receptor is the GABA_B receptor?
A
Metabotropic.
8
Q
How does the GABA_B receptor exert its inhibitory effects?
A
Through modulation of potassium (K⁺) and calcium (Ca²⁺) channels.
9
Q
What kind of receptor signaling does the GABA_B receptor use?
A
G-protein-coupled receptor (GPCR) signaling.
10
Q
How does activation of the GABA_B receptor affect neuronal activity?
A
It leads to slow, prolonged inhibitory effects.
11
Q
What is an example of a drug that acts on GABA_B receptors?
A
Baclofen.
12
Q
What is baclofen used for?
A
Muscle relaxation.
13
Q
A
14
Q
How do general anesthetics affect GABA_A receptor activity?
A
They enhance GABA_A receptor activity.
15
Q
What are the effects of GABA_A potentiation by general anesthetics?
A
Increased neuronal inhibition, sedation, hypnosis, and loss of consciousness.
16
Q
How do general anesthetics influence neuronal excitability?
A
They reduce neuronal excitability.
17
Q
How does GABA_A receptor activation inhibit neuronal activity?
A
Through fast inhibition via Cl⁻ influx.
18
Q
What type of inhibition is mediated by GABA_B receptors?
A
Slow inhibition via GPCR modulation.
19
Q
Which receptor is primarily associated with anesthesia effects?
A
GABA_A receptor.
20
Q
What is an example of a drug that acts on GABA_B receptors?
A
Baclofen.
21
Q
What type of receptor does propofol act on?
A
GABA_A receptor.
22
Q
How does propofol enhance the effects of GABA?
A
By acting as a GABA_A receptor agonist.
23
Q
What are the clinical effects of propofol’s action on GABA_A receptors?
A
Sedation and hypnosis.
24
Q
How does propofol promote neuronal inhibition?
A
By promoting chloride ion influx, leading to neuronal hyperpolarization and CNS depression.
25
Why does propofol require an oil-in-water emulsion for IV administration?
Because it is insoluble in water.
26
What is the function of 10% soybean oil in propofol's formulation?
It serves as a medium for solubilization.
27
What component in propofol's formulation acts as an emulsifier?
Lecithin (from egg yolk).
28
Why is 2.25% glycerol included in the propofol formulation?
To maintain isotonicity.
29
What role does 1.2% purified egg phosphatide play in propofol’s formulation?
It aids emulsification.
30
Why does propofol require an emulsification medium?
Without it, propofol would remain inactive due to its insolubility.
31
What is a major drawback of the lipid vehicle used in propofol formulation?
It supports bacterial growth and may increase plasma triglycerides with prolonged infusions.
32
Why must propofol be used within six hours after being drawn into a syringe?
To prevent contamination.
33
What is an important consideration regarding hospital policies for propofol use?
Policies may vary, but generally, it must be used within six hours after being drawn.
34
What preservative is used in Diprivan (brand-name propofol)?
Disodium edetate.
35
What is the pH range of Diprivan, and how does it affect injection pain?
pH ~7–8.5; causes less pain on injection.
36
What preservative is used in generic propofol?
Sodium metabisulfite.
37
What is the pH range of generic propofol, and how does it affect injection pain?
pH ~4.5–6.4; more painful injection compared to Diprivan.
38
What common sensation do many patients report during propofol injection?
A burning sensation.
39
What structural characteristic of propofol contributes to injection pain?
Its non-chiral structure.
40
Why do some clinicians mix lidocaine with propofol?
To reduce injection pain.
41
Why is mixing lidocaine with propofol not recommended?
It can lead to micro-droplet formation after 60–90 minutes.
42
What is the typical onset time of propofol?
15–30 seconds.
43
Why does propofol act rapidly?
Its high lipophilicity allows quick penetration of the blood-brain barrier (BBB).
44
How does cardiac output influence propofol’s onset time?
Higher cardiac output can shorten the onset time to ~15 seconds.
45
What is the distribution half-life of propofol?
2–4 minutes.
46
Where does propofol initially distribute after administration?
Vessel-rich organs.
47
After initial uptake, where does propofol redistribute?
Muscles and fat tissue.
48
What is the duration of action (DOA) range for propofol?
1–15 minutes.
49
How long does it typically take for a patient to awaken after a single IV bolus of propofol?
~4–5 minutes.
50
What is the primary clearance mechanism of propofol?
Hepatic metabolism.
51
How is propofol eliminated from the body?
Rapid breakdown in the liver with subsequent renal excretion.
52
Why is propofol efficiently eliminated from the body?
Its high clearance rate exceeds hepatic blood flow.
53
What percentage of propofol is protein-bound?
98%.
54
Which proteins primarily bind propofol in the plasma?
Albumin and α1-acid glycoprotein (AAG).
55
What percentage of propofol remains unbound and available for action?
2%.
56
What is the clinical effect of the free fraction of propofol?
It is responsible for sedation and hypnosis.
57
How does higher cardiac output affect propofol onset?
It leads to a faster onset.
58
How does lower cardiac output, such as in elderly patients, influence propofol onset?
It results in a slower onset.
59
Why do elderly patients experience a slower onset of propofol?
Due to altered pharmacokinetics, potentially reduced cardiac output, and changes in drug distribution.
60
How does reduced cardiac output in elderly patients affect propofol’s onset?
It slows the onset time.
61
What pharmacokinetic changes in elderly patients contribute to a delayed propofol effect?
Altered drug metabolism and distribution.
62
How does hypovolemia affect the onset of propofol?
It causes a slower onset.
63
How do conditions affecting protein binding influence propofol’s effect?
They increase the amount of free drug, leading to a stronger and potentially faster effect.
64
Name some conditions that can alter propofol’s protein binding.
Liver disease, cirrhosis, malnutrition, alcoholism, end-stage renal disease, late pregnancy.
65
How do CNS depressants like benzodiazepines and alcohol affect propofol's onset and effects?
They potentiate propofol’s effects, leading to a slower onset.
66
How do stimulants like methamphetamine and cocaine influence propofol's onset?
They may reduce onset time by increasing circulation and metabolism.
67
How does injection into a large central vein affect propofol onset?
It leads to a faster onset.
68
How does administration through a peripheral IV affect propofol delivery?
It results in slower delivery to the brain.
69
How does rapid IV push administration influence propofol onset?
It leads to a faster onset.
70
What effect does a slower infusion over 15–30 seconds have on propofol onset?
It causes a delayed onset.
71
How do higher doses or concentrations of propofol affect its onset and sedation depth?
They lead to a more rapid onset and deeper sedation.
72
What is the primary receptor target of propofol?
GABA_A receptors.
73
Besides GABA_A receptors, which other receptor does propofol act on?
Glycine receptors.
74
What type of agonist is propofol for GABA_A receptors?
A selective agonist.
75
Does propofol cause immobility through spinal cord depression?
No, it does not.
76
What is the typical IV dosage range of propofol for induction?
1.5–2.5 mg/kg IV.
77
Why is propofol used in over 90% of anesthesia inductions?
Due to its rapid onset and predictable effects.
78
What is the recommended propofol dose for pediatrics, teenagers, and young adults?
Up to 3–6 mg/kg.
79
How should propofol dosing be adjusted for patients with low systolic function or cardiovascular compromise?
They should receive the lowest effective dose, closer to 1.5 mg/kg.
80
What is a preferred method of administration in certain cases for safety and hemodynamic stability?
Gradual administration (e.g., 100 mg initially, followed by 20 mg increments).
81
What is the typical IV infusion dosage range for the maintenance of anesthesia with propofol?
50–300 mcg/kg/min.
82
Why is propofol often combined with other agents like benzodiazepines, ketamine, or opioids?
To optimize effects while minimizing the propofol dose.
83
When might higher infusion doses of propofol (>100, >150, or >200 mcg/kg/min) be required?
Depending on patient response and procedural requirements.
84
What is the typical IV infusion dosage range for ICU sedation with propofol?
25–100 mcg/kg/min.
85
In what patient population is propofol commonly used for sedation in the ICU?
Critically ill patients requiring mechanical ventilation.
86
Why is propofol not ideal for patients in septic shock?
It may cause hemodynamic instability.
87
In which ICU patients is propofol most beneficial?
Stable ICU patients needing sedation.
88
What is the typical dosage range for procedural sedation with propofol?
25 mcg/kg/min – PRN.
89
Why is propofol ideal for short procedures?
Due to its rapid onset and quick recovery.
90
In what settings is propofol commonly used for procedural sedation?
Out-of-OR procedures, office-based sedation, and minor interventions.
91
How is propofol dosed for procedural sedation?
It is titrated to effect, using just enough to keep the patient comfortable.
92
What is the role of propofol in postoperative nausea and vomiting (PONV) prevention and treatment?
It is effective at subhypnotic doses.
93
What is the intermittent bolus dose of propofol for PONV management?
10–20 mg throughout the procedure.
94
What is the recommended propofol bolus dose at the end of a procedure for PONV prevention?
0.5–1 mg/kg.
95
What continuous infusion rate of propofol is effective for PONV management?
Greater than 16.7 mcg/kg/min.
96
When should propofol be considered for PONV treatment?
Only after conventional treatments (e.g., antihistamines) fail.
97
Why should high doses (0.5–1 mg/kg) of propofol be avoided in PACU for simple pruritus cases?
To prevent unnecessary sedation and side effects.
98
How does propofol affect seizure duration during electroconvulsive therapy (ECT)?
It reduces seizure duration.
99
In what type of surgical procedures is propofol used as an adjunct for seizure control?
Neurosurgical procedures where seizure control is critical.
100
When can propofol be used as an alternative treatment for status epilepticus or local anesthetic systemic toxicity (LAST)?
When benzodiazepines are unavailable.
101
How does propofol attenuate bronchoconstriction?
By inhibiting airway smooth muscle contraction and suppressing airway reflexes.
102
In which patient population is propofol used during anesthesia induction to reduce bronchospasm risk?
Patients with reactive airway disease or asthma.
103
How can propofol assist in treating intraoperative bronchospasm?
By deepening anesthesia when necessary.
104
Is propofol a first-line treatment for bronchoconstriction?
No, it is not a first-line treatment.
105
How does propofol affect cerebral metabolic rate and intracranial pressure (ICP)?
It reduces cerebral metabolic rate and decreases ICP.
106
How does propofol’s effect on ICP compare to that of inhaled anesthetics?
Propofol decreases ICP, while inhaled anesthetics tend to increase it.
107
In what neurosurgical cases is propofol beneficial?
Cases requiring cerebral protection, especially in patients at risk for cerebral ischemia.
108
How is propofol used in traumatic brain injury (TBI) or stroke patients?
To reduce ICP and cerebral metabolic demand.
109
What type of itching can propofol help alleviate?
Opioid- and cholestasis-induced itching.
110
In what medical procedures is propofol used for seizure suppression?
Electroconvulsive therapy (ECT) and neurosurgery.
111
What happens to cerebral perfusion pressure (CPP) with propofol administration?
It decreases.
112
Despite reducing CBF and CPP, how does propofol maintain cerebral stability?
It preserves autoregulation, allowing the brain to adjust blood flow as needed.
113
Why is propofol ideal for neurosurgical anesthesia?
It decreases ICP and metabolic demand.
114
Why is propofol beneficial in procedures requiring ocular pressure control?
Because it reduces intraocular pressure (IOP).
115
What effect does propofol have on EEG at high doses?
It can cause EEG burst suppression, indicating a deeply suppressed brain state.
116
Does propofol significantly affect Somatic Sensory Evoked Potentials (SSEPs)?
No, it does not interfere with SSEPs.
117
Why is it important that propofol does not affect SSEPs?
It allows intraoperative sensory pathway monitoring during spinal and brain surgeries.
118
What type of movement can propofol induce transiently?
Myoclonic movements.
119
How long do propofol-induced myoclonic movements typically last?
Only a few seconds.
120
How does propofol reduce blood pressure (BP)?
By relaxing vascular smooth muscle and inhibiting sympathetic vasoconstrictor activity.
121
What cardiovascular parameters does propofol decrease?
Systemic vascular resistance (SVR) and cardiac output (CO).
122
What causes propofol’s negative inotropic effects?
Decreased intracellular calcium availability in cardiac and smooth muscle cells.
123
How does propofol generally affect heart rate (HR)?
It generally maintains heart rate but can rarely cause severe bradycardia or asystole.
124
Why can propofol cause bradycardia or asystole in rare cases?
Because it suppresses the sympathetic nervous system more than the parasympathetic system.
125
Why is propofol-induced bradycardia not responsive to anticholinergics like atropine or glycopyrrolate?
Because propofol primarily suppresses sympathetic activity rather than increasing parasympathetic tone.
126
What type of medication is required to treat propofol-induced bradycardia?
A beta-adrenergic agonist, such as isoproterenol or epinephrine.
127
What is the incidence of apnea following induction doses of propofol?
Apnea occurs in approximately 35% of patients.
128
At what induction dose range does propofol commonly cause apnea?
1.5–2.5 mg/kg, or up to 3 mg/kg.
129
How does propofol affect the respiratory drive?
It blunts the respiratory drive.
130
How does propofol impact the body's response to arterial oxygen deprivation?
It makes the respiratory drive less responsive to arterial oxygen deprivation.
131
How does propofol affect the ventilatory response to hypoxia?
It blunts the ventilatory response to hypoxia.
132
Does propofol impair hypoxic pulmonary vasoconstriction (HPV)?
No, it does not impair hypoxic pulmonary vasoconstriction.
133
How is propofol primarily metabolized?
Through extensive hepatic metabolism, primarily via phase 2 conjugation (glucuronidation and sulfation).
134
What happens to propofol after metabolism?
It is converted into inactive, water-soluble metabolites that are easily excreted.
135
Does propofol typically impair liver function?
No, it generally does not impair hepatic function.
136
How do liver enzyme levels respond to propofol under normal usage?
They remain stable, indicating a low risk of hepatotoxicity.
137
What is a rare exception where propofol may cause liver damage?
Prolonged high-dose infusions may lead to hepatocellular injury, typically as part of Propofol Infusion Syndrome (PRIS).
138
How are propofol metabolites primarily eliminated?
Via the kidneys.
139
How does propofol affect creatinine levels?
Creatinine levels remain stable, indicating minimal impact on renal function.
140
Is propofol safe for patients with renal dysfunction?
Yes, because its clearance remains unaffected even in patients with pre-existing renal impairment.
141
How is propofol metabolized in the liver?
Via glucuronidation and sulfation.
142
What is a key metabolic disturbance seen in Propofol Infusion Syndrome (PRIS)?
Severe metabolic acidosis.
143
How can PRIS affect muscle tissue and kidney function?
It can cause rhabdomyolysis, which may lead to acute kidney injury (AKI) or acute renal failure (ARF).
144
What cardiac complications are associated with PRIS?
Cardiac dysrhythmias, including potentially fatal arrhythmias.
145
How does PRIS affect the liver?
It can cause hepatomegaly.
146
What lipid abnormality is seen in PRIS?
Hyperlipidemia.
147
What is the primary underlying mechanism of Propofol Infusion Syndrome (PRIS)?
Mitochondrial dysfunction and impaired fatty acid metabolism, leading to cellular energy failure and multi-organ dysfunction.
148
What are some key risk factors for developing PRIS?
Critical illness, mechanical ventilation, high-dose long-term propofol use (>4–5 mg/kg/hr), underlying metabolic disorders, severe infections, and malnutrition.
149
At what propofol infusion rate does the risk of PRIS significantly increase?
Greater than 4–5 mg/kg/hr.
150
How does etomidate's solubility change with pH?
It is water-soluble at acidic pH but becomes lipid-soluble at physiological pH.
151
Why is etomidate’s lipid solubility at physiological pH important?
It allows etomidate to cross the blood-brain barrier and induce anesthesia.
152
What component in IV etomidate formulation contributes to pain on injection and venous irritation?
35% propylene glycol.
153
How can injection pain from IV etomidate be reduced?
Pretreatment with lidocaine.
154
What is a benefit of the lipid emulsion form of etomidate?
It reduces pain and phlebitis.
155
Why is the lipid emulsion form of etomidate not commonly used in the U.S.?
It is not available in the United States.
156
How does the oral transmucosal form of etomidate avoid hepatic first-pass metabolism?
It undergoes systemic absorption directly.
157
What is the typical induction dose of etomidate?
0.2–0.4 mg/kg IV.
158
How long does it take for etomidate to take effect?
30 seconds to 1 minute.
159
Why is etomidate's onset slower than propofol?
Due to its lower lipid solubility.
160
What is the duration of action (DOA) of etomidate?
3–10 minutes.
161
What is the elimination half-life of etomidate?
3–5 hours.
162
How does etomidate distribute in the body?
It has a large volume of distribution (Vd), allowing widespread distribution.
163
How does etomidate’s lipid solubility compare to propofol?
It has moderate lipid solubility compared to propofol.
164
What percentage of etomidate is protein-bound?
76%.
165
How can conditions causing low albumin or α1-acid glycoprotein (AG) levels affect etomidate?
They may alter drug onset and effect.
166
How is etomidate metabolized?
Via hydrolysis by liver CYP450 enzymes and plasma esterases.
167
What role do plasma esterases play in etomidate metabolism?
They contribute to its rapid metabolism.
168
Does etomidate have active metabolites?
No, it has no active metabolites, minimizing prolonged effects.
169
How is etomidate primarily excreted?
85% via the kidneys.
170
What percentage of etomidate is excreted via bile?
12%.
171
How does etomidate affect mean arterial pressure (MAP)?
It helps preserve MAP.
172
Why is etomidate beneficial for maintaining cerebral perfusion pressure (CPP)?
Because it lowers ICP while preserving MAP.
173
How does the incidence of myoclonus with etomidate compare to propofol?
Etomidate has a higher incidence of myoclonus (50–80%) compared to propofol.
174
What EEG effect can etomidate cause at high doses?
EEG burst suppression, indicating deep sedation.
175
How does etomidate affect heart rate (HR), blood pressure (BP), and cardiac output (CO)?
It causes minimal changes in HR, BP, and CO.
176
Does etomidate affect sympathetic nervous system (SNS) tone or baroreceptor function?
No, it does not affect SNS tone or baroreceptor function.
177
Why is etomidate considered highly cardio-stable?
Because it maintains hemodynamic stability, making it a preferred induction agent for hemodynamically compromised patients.
178
Why might premedication with an opioid be required before etomidate induction?
To blunt the sympathetic response during direct laryngoscopy.
179
How does etomidate’s effect on ventilation compare to barbiturates and propofol?
It causes less ventilatory depression.
180
Why is etomidate preferred in patients with compromised respiratory function?
Because it preserves ventilation better than barbiturates and propofol.
181
When is respiratory depression more likely to occur with etomidate?
When combined with opioids or benzodiazepines.
182
How does etomidate affect tidal volume and respiratory rate?
It decreases tidal volume and increases respiratory rate.
183
What respiratory pattern may occur before transient apnea with etomidate?
Brief hyperventilation.
184
Why is etomidate suitable for cases requiring spontaneous ventilation maintenance?
Because it preserves airway reflexes.
185
How does etomidate suppress cortisol production?
By inhibiting 11β-hydroxylase.
186
How long does etomidate-induced cortisol suppression last?
Up to 24 hours.
187
Why might hydrocortisone pre-treatment be considered in some patients receiving etomidate?
To counteract adrenal suppression, particularly in critically ill patients.
188
Why should etomidate be used with caution in septic patients?
Due to its potential to cause adrenal suppression.
189
How does etomidate affect the risk of postoperative nausea and vomiting (PONV)?
It increases the risk of PONV.
190
What is recommended to mitigate etomidate-induced PONV?
Prophylactic antiemetic administration.
191
What enzyme does etomidate induce in the heme synthesis pathway?
δ-Aminolevulinic Acid (ALA) synthase.
192
Why is etomidate contraindicated in patients with acute porphyria?
It induces ALA synthase, which can exacerbate the disorder by worsening heme synthesis defects.
193
What symptoms can acute porphyria cause?
Abdominal pain, neurological symptoms, and metabolic disturbances.
194
What structural feature differentiates oxybarbiturates?
They contain an oxygen atom and have a variable duration of action (DOA).
195
How do thiobarbiturates differ from oxybarbiturates in potency and solubility?
Thiobarbiturates are more potent and lipid-soluble due to the presence of a sulfur atom.
196
What is the effect of N-methyl substitution in barbiturates?
It enhances hypnotic effects but increases seizure risk.
197
How do barbiturates affect GABA_A receptors at low doses?
They potentiate GABA effects, increasing neuronal hyperpolarization.
198
What happens when barbiturates are administered at high doses?
They directly activate GABA_A receptors, leading to profound CNS depression.
199
Why do barbiturates have a rapid onset?
They are highly lipid-soluble, allowing for rapid onset and redistribution.
200
How are barbiturates metabolized and eliminated?
They are metabolized in the liver and eliminated by the kidneys.
201
What factor influences the half-life of barbiturates?
Their classification as ultra-short, short, or long-acting.
202
What type of barbiturate is thiopental (Pentothal)?
An ultra-short-acting barbiturate.
203
What was thiopental previously used for?
Anesthesia induction and intubation.
204
What is the primary mechanism of action (MOA) of thiopental?
It acts as a GABA_A receptor agonist, affecting the Reticular Activating System (RAS).
205
Besides GABA_A receptors, which other receptors does thiopental interact with?
Glutamate, adenosine, and CNS nicotinic acetylcholine (ACh) receptors.
206
How is thiopental metabolized and eliminated?
It undergoes hepatic metabolism and renal elimination.
207
What is the elimination half-life of thiopental?
3–26 hours.
208
Why does thiopental have prolonged effects with repeated dosing?
Due to its long context-sensitive half-time, leading to fat tissue accumulation.
209
How does thiopental affect cerebral metabolic oxygen consumption (CMRO₂), cerebral blood flow (CBF), and intracranial pressure (ICP)?
It reduces CMRO₂, CBF, and ICP.
210
What EEG effect can thiopental cause at high doses?
EEG burst suppression.
211
What are the cardiovascular effects of thiopental?
It causes myocardial depression and hypotension, with reflex tachycardia as compensation.
212
How does thiopental affect the respiratory system?
It causes significant respiratory depression.
213
Why do children recover faster from thiopental?
They have faster hepatic clearance.
214
What adverse reaction is associated with thiopental due to histamine release?
Increased risk of allergic reactions and severe anaphylaxis.
215
What is the risk of thiopental extravasation, and how can it be treated?
Extravasation can cause tissue damage; treatment includes hyaluronidase or phentolamine.
216
How does phentolamine help in treating thiopental extravasation?
It is a non-selective alpha-adrenergic antagonist that vasodilates the affected area.
217
Why is thiopental contraindicated in porphyria?
It can exacerbate the condition.
218
How lipid-soluble is methohexital, and what percentage is protein-bound?
It is highly lipid-soluble with 83% protein binding.
219
What is the distribution half-life of methohexital?
2–4 minutes.
220
What is the elimination half-life of methohexital?
~11 hours.
221
How is methohexital metabolized and excreted?
It is metabolized by the liver and excreted via the kidneys.
222
What is the induction dose of methohexital?
1–3 mg/kg IV.
223
How quickly does methohexital take effect?
Onset is ~30 seconds.
224
What is the duration of action (DOA) of methohexital?
5–10 minutes, making it ideal for electroconvulsive therapy (ECT).
225
Why is methohexital considered suitable for concurrent use with succinylcholine?
It has a rapid onset and offset, similar to succinylcholine.
226
How does methohexital affect cerebral metabolic oxygen consumption (CMRO₂), cerebral blood flow (CBF), and intracranial pressure (ICP)?
It decreases CMRO₂, CBF, and ICP.
227
What cardiovascular effects does methohexital have?
It is a negative inotrope, causing hypotension with compensatory tachycardia.
228
What respiratory effect does methohexital have?
It causes respiratory depression but preserves upper airway reflexes.
229
What neuromuscular effects can methohexital cause?
It may induce myoclonus or seizure-like activity if not followed by succinylcholine.
230
What type of anesthesia does ketamine produce?
Dissociative anesthesia.
231
How does ketamine create dissociative anesthesia?
By causing EEG dissociation between the thalamocortical system (sensory perception) and the limbic system (awareness and emotional response).
232
What is a key advantage of ketamine regarding pain management?
It provides profound analgesia even at sub-dissociative doses.
233
How does ketamine affect cardiovascular stability?
It maintains cardiovascular stability.
234
Why does ketamine not require a lipid emulsion for administration?
Because it is water-soluble and does not require an oil-based formulation like propofol.
235
What are the primary symptoms of ketamine-induced emergence delirium?
Distressing dysphoria, vivid dreams, hallucinations, and confusion.
236
What is a major concern regarding ketamine’s non-medical use?
It has a high potential for abuse.
237
How quickly does ketamine reach peak plasma concentration after IV administration?
Approximately 1 minute.
238
How long does it take for ketamine to reach peak plasma concentration after IM administration?
About 5 minutes.
239
What percentage of ketamine is protein-bound?
10–30%.
240
How does ketamine’s low protein binding affect its activity?
A large portion of free drug is available for action, contributing to its rapid effects.
241
What is the volume of distribution (Vd) of ketamine?
Approximately 3 L/kg.
242
What does a large volume of distribution indicate about ketamine's pharmacokinetics?
It distributes widely throughout the body, including highly perfused tissues like the brain.
243
How is ketamine metabolized?
It is extensively metabolized in the liver via CYP450 enzymes.
244
What is the primary metabolic pathway of ketamine?
Demethylation, producing the active metabolite norketamine.
245
How potent is norketamine compared to ketamine?
It has 20–30% of ketamine’s potency.
246
What happens to norketamine during further metabolism?
It is converted to hydroxynorketamine, which is inactive.
247
How is ketamine eliminated from the body?
Through urine and feces via high hepatic clearance.
248
What physiological factor influences ketamine clearance?
Hepatic blood flow.
249
What is the elimination half-life of ketamine?
2–3 hours.
250
What critical functions does the NMDA receptor play in the body?
Pain perception, memory formation, and synaptic plasticity.
251
What two neurotransmitters are required to activate the NMDA receptor?
Glutamate and glycine (as a co-agonist).
252
How does ketamine exert its analgesic and anesthetic effects?
By blocking the NMDA receptor, reducing excitatory activity.
253
How does ketamine influence AMPA receptors?
Indirectly, by regulating synaptic plasticity and excitotoxicity.
254
How does NMDA receptor inhibition affect AMPA receptor activity?
It alters glutamate release, modifying AMPA receptor-mediated responses.
255
How does ketamine provide an antinociceptive effect?
By inhibiting MAO receptor pathways, altering how painful stimuli are detected and processed.
256
What are the effects of blocking muscarinic receptors with ketamine?
Emergence delirium, bronchodilation, and sympathomimetic effects (increased heart rate and blood pressure).
257
How does ketamine reduce neuronal excitability?
By inhibiting voltage-gated sodium channels, producing local anesthetic-like properties.
258
What anti-inflammatory effects does ketamine have?
It suppresses inflammatory mediator production by inhibiting neutrophil activity and reducing cytokine release in the bloodstream.
259
How does ketamine help in managing neuropathic pain?
By activating innate repair receptors, reducing tissue damage and inflammation.
