Pharmacokinetics and Pharmacodynamics of Anesthetics

Fig. 1.1
The relationship among the pharmacokinetic processes of absorption, distribution, metabolism, and excretion with the central, peripheral, and site of action compartments

Upon closer examination, PK includes even the kinetics of drug released from the dosage form prior to absorption—such as drug being transferred from syringe to systemic circulation (i.e., i.v. bolus) or the complex disintegration, solvation, and dissolution of drug released by an advanced drug delivery system (ADDS) into the gastrointestinal (GI) tract milieu for permeation (passive diffusion and active or facilitated transport) across the GI endothelial barrier to the systemic circulation. Additional terms associated with the PK of a drug include absorption, distribution, excretion, and metabolism (see Fig. 1.1). A general term describing the sum of drug excretion and metabolism is elimination. An even more general PK term, disposition, describes the kinetic time course of drug distribution, excretion, and metabolism. The input function of drug (e.g., i.v. bolus, p.o.) combined with the disposition is the drug PK. Most importantly, clinicians can generally only control the input function of drugs, while thebodyor physiology controls the disposition.

An essential hypothesis of PK is that there is a quantitative relationship between drug concentration and pharmacological effect [1]. Clinical PK incorporates the fundamentals of PK to dose calculations, infusion rates, predictions of drug concentrations, dosing intervals, and time to eliminate the drug from the body. The primary objective of clinical PK is to maximize efficacy while minimizing toxicities, through a process called therapeutic drug monitoring (TDM). A complete TDM protocol entails monitoring-defined therapeutic endpoints (which include plasma drug concentration if appropriate) and adverse reactions. Adjustments of doses can be guided by TDM to provide individualized regimens. Clinical PK can be affected by numerous covariates, such as age, genetics, gender, race, comorbid disease states, and concomitant medications, resulting in drug interactions. These factors should be considered into the dosing regimen for each patient.


The absorption of a drug is largely dependent on the route of delivery. Drugs can be administered by depot type of routes: oral, inhaled, subcutaneous, intramuscular, sublingual, rectal, intraocular, intranasal, vaginal, and transdermal. Although intravenous and intra-arterial technically do have an aspect of absorption (i.e., release of drug from a syringe or i.v./i.a. bag), these routes deliver drug directly into the systemic circulation and are a special subset of PK input (i.e., instantaneous absorption processes having a bioavailability of 1.0). The physicochemical properties (i.e., solubility, pKa, ionization, polarity, molecular weight, partition coefficient) play a critical role in the absorption of drugs. The route of delivery impacts the rate of absorption as well as the extent of absorption. Bioavailability is defined as the rate and extent of drug absorption or the percentage or fraction of the parent compound that reaches systemic (plasma) circulation. The bioavailability of the same drug in the same patient may be different depending on the route of administration. Drug references frequently provide the bioavailabilities of drugs and are typically denoted as F. The extent of absorption, but not the rate, can be described by the parameter area under the curve (AUC). In an acute setting, the rate of absorption, generally k a , tends to be more important, whereas the extent of absorption tends to be more important in chronic use medications. The salt factor (S) is the fraction of a dose that is the active base form of the drug and pragmatically can be viewed as an attenuation of F (e.g., “effective dose” = F*S*dose). Probably, the most frequently used routes of administration of drugs in anesthesiology are oral, intravenous/intra-arterial, inhaled, and local (epidural, interscalene, etc.).

The absolute bioavailability, F, is determined by comparing the availability for any given extravascular (e.v.) route of administration measured against an i.v. point of reference of availability of the drug administered intravenously (Eq. 1.1):

$$ F=\frac{AU{C}_{e.v.}/ Dos{e}_{e.v.}}{AU{C}_{i.v}/ Dos{e}_{i.v.}} $$


Since anesthetics and pain management medications can be delivered via numerous routes of administration, the value of F is important in determining the “effective dose” for these e.v. drugs. The physicochemical properties, previously mentioned, of the drug affect the drug’s ability to partition from lipid to aqueous phases, and therefore, F. Food, drug interactions, and gastrointestinal (GI) motility can all affect drug solubility and absorption. First-pass metabolism, which is pre-systemic metabolism of the drug, can occur in the GI tract and the liver prior to reaching systemic circulation. All of these factors can affect F and the route will sometimes dictate the countersalt needed, thus affecting S, as well.

For inhaled anesthetics, three major factors influencing absorption are solubility in the blood, alveolar blood flow, and the partial pressure gradient between alveolar gas and venous blood. The solubility of inhaled anesthetics in blood is described by blood/gas partition coefficients (Table 1.1). The inhaled anesthetics are absorbed almost completely and rapidly through the lungs. A lower blood/gas partition coefficient indicates a more rapid onset and dissipation of anesthetic action.

Table 1.1
Partition coefficients of commonly used inhaled anesthetics




Nitrous oxide

Blood/gas partition coefficient





Brain/blood partition coefficient





Muscle/blood partition coefficient





Fat/blood partition coefficient





Volume of Distribution

The volume of distribution V d is a PK parameter characterizing the extent of drug distribution into the tissue from the blood. The physicochemical properties of a drug, plasma protein binding, and tissue binding influence V d. It has also been termed apparent volume of distribution because it does not correlate with an actual physiological volume compartment in the human body, but rather, it is the inferred volume in which the drug appears to be dissolved. It is inferred because as Eq. 1.2 shows, the clinician knows the dose given and Cp (drug plasma concentration) is measured; the V d is inferred or calculated from the two values of dose and Cp. The lower limit for nearly all drugs is 3 L or the actual average volume of human plasma. As the apparent or inferred volume of distribution increases in size, the interpretation begins to focus on the distribution of drug into extravascular tissues. The apparent or inferred V d can be calculated using Eq. 1.2:

$$ {V}_{\mathrm{d}}=\frac{{\mathrm{Dose}}_{\mathrm{i}.\mathrm{v}.}}{\mathrm{Cp}} $$


If the plasma concentration Cp of a drug is small immediately following a single-bolus dose, this generally indicates substantial drug permeation into the tissue(s), and the resultant V d is >40–80 L, indicating extensive distribution into the tissue. In contrast, if V d is small (close to 3 L), a large fraction of the drug is assumed to reside in the blood plasma, thus suggesting a little amount of drug has permeated into the extravascular tissue(s). While V d provides insight as to whether the drug is residing in the blood or tissue, its value does not determine which specific tissue compartment the drug permeates into.

V d is useful in determining the loading dose necessary to achieve a targeted Cp. The usual loading dose equation is Loading Dose = V d × Cptarget. For drugs that have a large V d, a greater loading dose is necessary to achieve the targeted Cp. Drugs with a small V d require a reduced loading dose to obtain the targeted Cp.

As shown in Table 1.1, the inhaled anesthetics have high brain/blood, muscle/blood, and fat/blood partition coefficients. In particular, most inhaled anesthetics distribute extensively into the fat tissues.


Clearance is an independent PK parameter quantifying the rate the body is able to eliminate a drug. More specifically, clearance is the volume of blood that is completely cleared of the drug per unit time. The units are in volume/time, usually liters per hour (L/h) or milliliters per minute (mL/min). While the liver is primarily responsible for drug metabolism and the kidneys are primarily responsible for parent drug and metabolite excretion (filtration and secretion), other routes of elimination include the chemical decomposition, feces, skin, and lungs. Hepatic metabolism and elimination are components of drug clearance. Total clearance is characterized by Eq. 1.3:

$$ {\mathrm{Cl}}_{\mathrm{Total}}={\mathrm{Cl}}_{\mathrm{Hepatic}}+{\mathrm{Cl}}_{\mathrm{Renal}}+{\mathrm{Cl}}_{\mathrm{Other}} $$


Total clearance ClTotal is used in most dose calculations without taking into account the specific route of elimination. Clearance is an important parameter because it controls the steady-state concentration Cpss as shown in Eq. 1.4:

$$ {\mathrm{Cp}}_{\mathrm{ss}}=\frac{(S)(F)\left(\mathrm{Dose}/\tau \right)}{\mathrm{Cl}} $$


S is the salt factor, F is the bioavailability, and tau (τ) is the dosing interval.


Drug metabolism occurs primarily in the liver, though metabolism can also occur at other sites such as the gastrointestinal wall, kidneys, and blood-brain barrier. Metabolism can be characterized as phase I or phase II reactions. Phase I reactions include oxidation, epoxidation, dealkylation, and hydroxylation reactions catalyzed by the cytochrome P450 enzyme system. A majority of the cytochrome P450 enzymes reside in the microsomes of hepatocytes where it metabolizes the highest number of substrates (chemical, drugs, and pollutants) in the body. Phase II reactions are glucuronidation and sulfation processes.

Many drug interactions involve the cytochrome P450 enzyme system. Certain drugs, termed inducers, may increase the activity of specific cytochrome P450 isozymes, leading to increased metabolism of drugs which are substrates of that particular isozyme. The reduction in plasma concentration of the drug substrates may lead to decreased therapeutic effects. Other drugs are inhibitors of cytochrome P450 enzymes, decreasing the metabolism of drugs that are substrates. The increase in substrate plasma concentration may result in not only enhanced pharmacological effects but also enhanced toxicological effects. Clinicians are encouraged to consider dosing adjustments based on known drug interactions to achieve therapeutic effects while minimizing adverse reactions.


Excretion frequently refers to the irreversible clearance of a drug typically through the kidneys. The three major physiological processes occurring in the kidneys governing renal excretion are glomerular filtration, active secretion, and reabsorption. The glomerular filtration of an adult patient may be estimated by the Cockcroft-Gault equation [3] (Eq. 1.5):

$$ {\mathrm{Cl}}_{\mathrm{Cr}}\left(\mathrm{mL}/ \min \right)=\frac{\left(140-\mathrm{age}\right)\times \mathrm{IBW}}{72\times \mathrm{SCr}}\left(\mathrm{Multiplied}\;\mathrm{by}\;0.85\;\mathrm{if}\;\mathrm{female}\right) $$


ClCr is the creatinine clearance in mL/min, the age of the patient is in years, SCr is the serum creatinine, and IBW is the ideal body weight of the patient in kilograms (kg). For female patients, the resultant ClCr is multiplied by 85 % to account for lower muscle mass typically exhibited by females. The Cockcroft-Gault equation utilizes serum creatinine, which is a by-product of muscle metabolism and is freely filtered by the glomerulus. Creatinine is not actively secreted nor is it reabsorbed. For drugs that are primarily eliminated via the renal route, dose adjustments may be made on the basis of creatinine clearance (ClCr) and are provided by drug package inserts or drug information references.

Elimination Rate Constant and Half-Life

The dependent parameter K is a first-order rate constant. It is a function of V d and Cl. K can be described as the percentage or fraction of the amount of drug that is cleared from the body per unit time. The units are typically expressed as 1/h (hr−1) or 1/min (min−1). As shown in Eq. 1.6, K can be viewed as a proportionality constant between V d and Cl:

$$ K=\frac{\mathrm{Cl}}{V_{\mathrm{d}}} $$


A large K value indicates rapid elimination of the drug. If two drug concentrations are drawn within the same dosing interval, K can be determined using Eq. 1.7 [4]:

$$ K=\frac{Ln\left(\raisebox{1ex}{$C{p}_1$}\!\left/ \!\raisebox{-1ex}{$C{p}_2$}\right.\right)}{\varDelta t} $$


Ln is natural log and Δt is the time elapsed between Cp1 and Cp2. The determination of K is integral to calculating half-life, t 1/2, as shown in Eq. 1.8:

$$ {t}_{1/2}=\frac{Ln(2)}{K}=\frac{\left({V}_d\right)\ast Ln(2)}{Cl} $$


Equation 1.8 also shows the relationship among t 1/2 and V d and Cl. The t 1/2 is the amount of time it takes for the drug currently in the body to reduce by 50 %. The t 1/2 can also predict the amount of time it takes for a patient to achieve steady-state drug concentrations (assuming no loading dose and the same dose was administered at the same interval). For example, after one t 1/2, Cp is 50 % of the final steady-state Cpss. Under these conditions, a patient is considered to be clinically at steady state if the drug concentration is >90 % of the true steady-state level. As shown in Table 1.2, it would take approximately 3.3 half-lives for a patient to achieve 90 % of the true steady state. Conversely, it would take 3.3 half-lives for a patient to eliminate 90 % of the drug once the administration of the drug has ceased. To note, t 1/2 determines the dosing interval, but V d and Cl determine the size of the dose.

Table 1.2
The number of half-lives and the expected percent of true steady-state concentration Cpss or percent of drug eliminated

Number of t1/2

Percent of Cpss or percent eliminated
















The time-course conversion of drug concentration (Ce) into a pharmacological effect (response) is pharmacodynamics. The biosensor process is the detection of the drug’s presence, Ce. Frequently, the biosensor process is the receptor system on the cell’s surface. The white and black biosensor process rectangles indicate that the drug (Ce) either stimulates (white) or inhibits (black) the zero-order and first-order constants k in or k out, respectively. The biosignal is similar to the second messenger, in that it directs the end response. While the pathway in between the biosignal and the response can contain nonlinear and time-varying processes (circadian, drug-induced—such as drug tolerance), it still is the biosignal that is responsible for the end response. Alterations of k in or k out are frequently the sites for the nonlinearities or time-varying processes. This model is known as an “indirect” model and is relatively general; the most important aspect of this model is that a change in Cp is not instantaneously realized as a change in response (Fig. 1.2). Somewhere along the pathway of D, drug, diffusing out of Cp in to Ce or in the translation of D binding to the receptors to produce the response, there is a rate-limiting step that causes the response to lag behind changes in Cp.


Fig. 1.2
The indirect model (bottom) is laid over a generic diagram of how cells (top) generally convert drug (D) into a pharmacological or physiological response (response). In this example, phosphorylated protein A acts as the biosignal responsible for the end response

A subset model of the indirect model is the direct model. In the direct model, the pharmacodynamic system very rapidly converts the Ce concentration of drug to response relative to the rate at which the Ce or Cp steady state is achieved. Or in other words, there is no time lag, as in the indirect model, between changes in Cp or Ce and response. Typical direct models have the form of 
$$ E={E}_0\pm \frac{E_{\max }{\mathrm{Cp}}^{\gamma }}{{\mathrm{EC}}_{50}^{\gamma }+{\mathrm{Cp}}^{\gamma }} $$
, where E 0 is the endogenous baseline (i.e., value of E in the absence of drug), E max is the maximal effect achievable, EC50 is the concentration of drug that produces ½ of the E max response, and γ is the Hill coefficient. When γ > 1, the PD is said to have positive cooperativity; when γ < 1, the PD has negative cooperativity; and when γ = 1, the PD has no cooperativity (see Fig. 1.3 for a comparison of γ).


Fig. 1.3
Comparison of three different values of γ for the same E max model with baseline. E 0, E max, and EC50 are kept constant for all three plots to show the behavior of γ

In the more commonly used model, notice that as “dose” or the x-axis changes, the effect or response instantaneously changes. Another way to view this relationship between “dose” and “response” is to assume that the “dose” or “log (Cp)” has reached steady state or equilibrium before the effect has been measured. The direct model can still be used to simulate drug tolerance by either attenuating E max or increasing EC50 as a function of Cp or Ce. The utility of this model cannot be overstated as it has provided many researchers and clinicians with useful pharmacodynamic insights.

Therapeutic Range and Therapeutic Monitoring

Most drugs have established therapeutic ranges. Therapeutic ranges are typically expressed as a range of drug plasma concentrations that achieve an optimal effect while minimizing adverse reactions. However, drugs that require constant monitoring of drug concentrations are ones that have narrow therapeutic ranges, a low threshold for serious adverse reactions, or must reach a minimum plasma concentration to achieve an effect.

In anesthesiology, the minimum alveolar concentration (MAC; Table 1.3) of inhaled anesthetics is used as the target to achieve the necessary therapeutic effect. MAC is the amount of inhaled anesthetic required to inhibit physical movement in response to a noxious stimuli in 50 % of patients [5]. MAC values can also be used to compare the relative potencies between two inhaled anesthetic agents.

Table 1.3
Minimal alveolar concentration of commonly used inhaled anesthetics




Nitrous oxide

MAC in O2 in adults





The continuous monitoring of plasma concentrations of intravenous anesthetics is not performed due to practicality. The half-lives and durations of action of most intravenous anesthetics are relatively short. It may take several hours for the laboratory to determine anesthetic concentrations. Therefore, anesthetic concentrations do not provide rapid feedback for clinicians to make necessary adjustments to doses during the course of surgery or medical intervention. Thus, monitoring of intravenous anesthetics is reliant on the signs and symptoms of anesthesia for the attainment of therapeutic efficacy and respiratory depression and blood pressure for toxicology.

Table 1.4 summarizes the pharmacokinetic (distribution, metabolism, and renal excretion) and pharmacodynamic properties (onset of action and duration of action) of various anesthetic agents.

Drug Tables (Tables 1.5 and 1.6)

The mechanism of action, indications, contraindications, cautions, pregnancy category, clinical pearls, dosing options, drug interactions, and side effects of commonly-used anesthetic agents are presented in Table 1.5 Lidocaine, with its numerous routes of delivery and dosing options, are presented in Table 1.6.

Table 1.4
Pharmacokinetic and pharmacodynamic properties of anesthetic agents



Renal excretion

Onset of action

Duration of action


Distributes quickly and extensively to the brain, heart, liver, kidneys, and lungs [6]

0.17 % of isoflurane is metabolized by the liver

Rapidly eliminated by lungs

7–10 min [7]

Does not distribute well into adipose tissue


Distributes well to the brain [8]

3–5 % hepatic via CYP2E1

Rapidly eliminated by lungs

1.2 min [9]

4–14 min

Does not distribute well into adipose tissue

Exhaled gases, up to 3.5 %, excreted renally as inorganic fluoride


Not available

0.02 % [10]

Rapidly eliminated by lungs

Single agent, 5–16 min [11]

<0.02 % as metabolite through urine

With oxygen, 2–3 min [11]

With NO2, 1.5–2 min [11]

Nitrous oxide

0.5 blood/gas partition coefficient [12]

<0.004 %

Rapidly eliminated by lungs

2–5 min

Minimum [115]


Distributes well into adipose tissue; 6–12 times blood

Primarily to inactive metabolites, but pentobarbital (active) is also formed
30–60 s

10–30 min [65]


Distributes quickly into brain, within 30 s; redistribution occurs within 30 min into less vascular areas

Extensive [13]

Less than 1 % excreted unchanged in urine

2–45 s [14]

4–8 min after doses of 45–125 mg [15]

Does not distribute well into adipose tissue

15–30 min after higher doses of 240–310 mg [15]


Rapid distribution: 1–8 min [16]

Rapid and extensive by cytochrome P4502B6 [17]

<0.3 % excreted unchanged; 88 % excreted as metabolite

30 s (10–50 s); onset is infusion rate related [18]

3–10 min


Rapid distribution [116]
2 % excreted unchanged in urine

30–60 s

3–5 min


Rapid distribution into highly perfused tissues [19]

Extensive by cytochrome P450

4 % excreted unchanged in urine

IV: 30 s

IV: 5–10 min

IM: 3–4 min

IM: 12–25 min


Rapid distribution into highly perfused tissues

Plasma cholinesterases

Undergoes renal excretion

6–12 min

1 h


Not available

Rapid by cholinesterase

2 % excreted unchanged in urine
1 h


1.5 L/kg

90 % by cytochrome P450 1A2 [20]; two active metabolites: monoethylglycinexylidide (MEGX) and glycinexylidide (GX)

10 % excreted unchanged in urine

Dental: <2 min

2 h

Local: 2–4 min


0.7–4.4 L/kg

Undergoes hepatic metabolism [21]

Undergoes renal excretion [21]

2–3 min

1 h


2.5 L/kg

Extensive hepatic metabolism

6 % excreted unchanged in urine [22]

5–10 min [23]

1.5–8 h


36–60 L

Extensive hepatic metabolism by cytochrome P450 1A2

1 % excreted unchanged in urine

Brachial: 15–30 min

1.5–8 h

Cesarean: 2.5–25 min

Epidural: 6–8 min [24]


Extensively distributes into liver, lung, heart, and brain

Extensive hepatic metabolism by hydroxylation and N-demethylation

5–10 % excreted unchanged in urine

Epidural: 5–15 min

2 h

Nerve block: 10–20 min


1–2 L/kg

Primarily hepatic by carboxylesterase

2–5 % excreted unchanged in urine [25]

1–6 min

1 h


Not available

Extensive by plasma esterases
Topical: 30 s

Topical: 2.5 h

Topical, liposomal: 30 min

Topical, liposomal: 2.5 h

Spinal: 3–5 min

Spinal: 2–3 h


54–66.9 L [26]

Extensive by hepatic metabolism

Undetectable unchanged drug in urine

Epidural: 8–20 min

Epidural: 7.5–10.5 h


134 L [27]

Extensive by hepatic metabolism

<10 % excreted unchanged in urine

Infiltration, nerve block, retrobulbar: 2–5 min [28]

Infiltration, nerve block: 4–10 h

Epidural: 15–30 min [29]

Epidural: 6–10 h

Table 1.5
Drug information of anesthetic agents

Drug name, mechanism of action, indication

Contraindication, caution, pregnancy category, breast feeding

Clinical pearls

Dosing options

Drug interactions and side effects

Isoflurane (Florane™, Terrell™) [7, 30]

Contraindications: (1) known sensitivity to isoflurane, (2) patients at risk for malignant hyperthermia

Low blood/gas partition coefficient, producing rapid induction and recovery from anesthesia

Induction: 1.5–3 % with O2 or O2/nitrous oxide mix; anesthesia obtained within 7–10 min

Drug interactions [31]:

 MOA: modulation of GABAA receptors, potentiating inhibitory synaptic transmission [32]

Caution: (1) hyperkalemia, (2) malignant hyperthermia

Pungent odor may limit rate of induction

Maintenance: 1–2.5 % with NO; additional 0.5–1 % with O2 only

clarithromycin, class I and III antiarrhythmics, dolasetron, droperidol, fluconazole, fluoxetine, haloperidol, hydromorphone, ondansetron, oxycodone, quetiapine, risperidone, St. John’s wort, telithromycin, tricyclic antidepressants, ziprasidone

 Indications: induction and maintenance of anesthesia

Pregnancy category: C

Good cardiovascular stability; not proarrhythmic

MAC [7, 33]:


Concurrent use with neuromuscular-blocking agents (atracurium, cisatracurium, pancuronium) may result in prolongation of neuromuscular-blocking effects
Breast feeding: infant risk has not been ruled out

Lower incidence of hepatotoxicity [34]
Side effects:
Common: nausea, vomiting, hypotension, cough, excessive salivation, headache
Serious: bradycardia, cardiac arrest, myocardial infarction, hyperkalemia, malignant hyperthermia, decreased liver function, hepatic necrosis, liver failure, seizure, myoglobinuria, renal failure, respiratory depression [7]

Sevoflurane (Ultane™, Sojourn™) [35, 36]

Contraindication: patients at risk for malignant hyperthermia

Low blood/gas partition coefficient, producing rapid induction and recovery from anesthesia

0.5–3 % concentration with or without concomitant use of nitrous oxide [37]


Drug interactions [38]: hydromorphone, oxycodone, St. John’s wort

 MOA: modulation of GABAA receptors, potentiating inhibitory synaptic transmission [39]

Caution: (1) hyperkalemia, (2) malignant hyperthermia

FDA limits its use to 2 MAC hours (1 MAC for 2 h or 2 MACs for 1 h) due to its by-product, compound A, that has caused renal injury in rat models [40]
Side effects:

 Indication: general anesthesia

Pregnancy category : B

Not as pungent as isoflurane or desflurane
Common: bradycardia, hypotension, nausea, vomiting, somnolence, agitation, cough, interrupted breathing, shivering
Good cardiovascular stability
Serious: AV block, hemorrhage, QT prolongation, torsades de pointes, hyperkalemia, malignant hyperthermia, hepatic necrosis, liver failure, hypersensitivity, seizure, laryngeal spasm, respiratory depression
Breast feeding: infant risk has not been ruled out

Desflurane (Suprane™) [41, 42]

Contraindication: patients at risk for malignant hyperthermia

Low potency

Induction: initiate with 3 % in O2 or nitrous oxide/O2 and increase by 0.5–1 % every 2–3 breaths or as tolerated (up to 11 %) until loss of consciousness [41]

 MOA: modulation of GABAA receptors, potentiating inhibitory synaptic transmission [43]

Pregnancy category: B

High cost

Concentrations exceeding 12 % have been reported to be safe [44]

Drug interactions [45]: cisatracurium, hydromorphone, oxycodone, St. John’s wort

 Indication: general anesthesia

Breast feeding: infant risk has not been ruled out

Low blood/tissue solubility

Maintenance: 2.5–8.5 % with or without concomitant NO2

Side effects:
MAC [46, 47] :


Common: hypotension, salivation, nausea, vomiting, cough [48]
Serious: bradycardia, cardiac arrest, heart failure, hypertension, malignant hypertension, shock, sinus arrhythmia, torsades de pointes, hyperkalemia, pancreatitis, hepatic necrosis, liver failure, rhabdomyolysis, nephrotoxicity, interrupted breath, laryngeal spasm

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Sep 18, 2016 | Posted by in ANESTHESIA | Comments Off on Pharmacokinetics and Pharmacodynamics of Anesthetics
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