Page 464 - Basic _ Clinical Pharmacology ( PDFDrive )

450 SECTION V Drugs That Act in the Central Nervous System

H O CH 3 N
N C H
2 5
S N
CH CH CH CH
N 2 2 3
H O CH 3 Cl N
Thiopental
F

N
O
C H OC N CH(CH ) Midazolam
3 2
2 5
OH
CHCH 3 Cl
)
CH(CH 3 2
Propofol
HN
O
Etomidate CH 3
Ketamine

FIGURE 25–6 Chemical structures of some intravenous anesthetics.

structures of common clinically used intravenous anesthetics. for continuous infusions, propofol is a good alternative to inhaled
Table 25–2 lists pharmacokinetic properties of these and other anesthetics for maintenance of anesthesia and is a common choice
intravenous agents. for sedation in the setting of monitored anesthesia care. When used
during maintenance of anesthesia, propofol infusion can be supple-
mented with intravenous opioids and neuromuscular blockers as
PROPOFOL needed to completely avoid the use of inhaled anesthetics (total intra-
venous anesthesia, TIVA). Alternatively, a propofol infusion might
In most countries, propofol is the most frequently administered be used to reduce the required concentration of inhaled anesthetics
drug for induction of anesthesia, and it has largely replaced barbi- so that undesired effects can be minimized. Increasingly, propofol is
turates in this setting. Because its pharmacokinetic profile allows also used for sedation in the ICU as well as conscious sedation and

TABLE 25–2 Pharmacokinetic properties of intravenous anesthetics.

Induction Dose Duration of t ½ Distribution Protein CL (mL/kg/ t ½ Elimination
Drug (mg/kg IV) Action (min) V dss (L/kg) (min) Binding (%) min) (h)
Dexmedetomidine NA NA 2–3 6 94 10–30 2–3
Diazepam 0.3–0.6 15–30 0.7–1.7 … 98 0.2–0.5 20–50
Etomidate 0.2–0.3 3–8 2.5–4.5 2–4 77 18–25 2.9–5.3
Ketamine 1–2 5–10 3.1 11–16 12 12–17 2–4
Lorazepam 0.03–0.1 60–120 0.8–1.3 3–10 98 0.8–1.8 11–22
Methohexital 1–1.5 4–7 2.2 5–6 73 11 4
Midazolam 0.1–0.3 15–20 1.1–1.7 7–15 94 6.4–11 1.7–2.6
Propofol 1–2.5 3–8 2–10 2–4 97 20–30 4–23
Thiopental 3–5 5–10 2.5 2–4 83 3.4 11

Note: The duration of action reflects the duration after a typical single IV dose given for induction of anesthesia. Data are for average adult patients.
CL, clearance; NA, not applicable; V dss , volume of distribution at steady state.