Mm Chapter 8. Nonvolatile Anesthetic Agents

Front 1

responsible for termination of effect of many anesthetic drugs

Back 1

As plasma concentration falls, some drug leaves the highly perfused organs to maintain equilibrium. This redistribution from the vessel-rich group is responsible for termination of effect of many anesthetic drugs.

Front 2

______________ freely cross from plasma into the glomerular filtrate.

absorbtion happens how?

Back 2

Non–protein-bound drugs

The nonionized fraction of drug is reabsorbed in the renal tubules, whereas the ionized portion is excreted in urine.

Front 3

Elimination half-life of a drug is proportional to...

inversely proportional to

Back 3

Elimination half-life of a drug is proportional to the volume of distribution and inversely proportional to the rate of clearance.

Front 4

Repetitive administration of barbiturates....

duration of action becomes more dependent ....

Back 4

Repetitive administration of barbiturates saturates the peripheral compartments, so that redistribution cannot occur and the duration of action becomes more dependent on elimination.

Front 5

Barbiturates ____________ the cerebral vasculature.

Back 5

Barbiturates constrict the cerebral vasculature.

This effect may protect the brain from transient episodes of focal ischemia (eg, cerebral embolism) but probably not from global ischemia (eg, cardiac arrest).

Front 6

The accumulation of morphine metabolites (morphine 3-glucuronide and morphine 6-glucuronide) in patients with renal failure has been associated with 2X

Back 6

narcosis and ventilatory depression lasting several days.

Front 7

The stress response to surgical stimulation is measured in terms of the secretion of 3 specific hormones

Back 7

including catecholamines, antidiuretic hormone, and cortisol. Opioids block the release of these hormones more completely than volatile anesthetics

Front 8

Opioids and stress response to surgical stimulation

Back 8

The stress response to surgical stimulation is measured in terms of the secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol. Opioids block the release of these hormones more completely than volatile anesthetics.

Front 9

In sharp contrast to other anesthetic agents, ketamine increases 3X

Back 9

arterial blood pressure,
heart rate,
and cardiac output.

Front 10

In sharp contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart rate, and cardiac output. These indirect cardiovascular effects are 2X

Back 10

These indirect cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of norepinephrine.

Front 11

Induction doses of etomidate transiently inhibit 2x

Back 11

enzymes involved in cortisol and aldosterone synthesis. Long-term infusions lead to adrenocortical suppression that may be associated with an increased mortality rate in critically ill patients.

Front 12

droperidol should be avoided in patients with

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Parkinson disease.

Front 13

Elimination implies drug removal by both

Back 13

biotransformation and excretion.

Front 14

Clearance is measurement of

Back 14

measurement of the rate of elimination

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bioavailability

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is the fraction of unchanged drug that reaches the systemic circulation

Front 16

an acidic environment favors the absorption of

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acidic drugs (A–+ H+ AH),

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an alkaline environment favors absorption of

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favors basic drugs (BH+ H+ + B).

Front 18

Because the veins of the mouth drain into 3X

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superior vena cava, sublingual or buccal drug absorption bypasses the liver and first-pass metabolism.

Front 19

venous drainage of the rectum bypasses

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bypasses the liver, first-pass metabolism is less significant than with small intestinal absorption

Front 20

Albumin often binds

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acidic drugs (eg, barbiturates), whereas 1-acid glycoprotein (AAG) binds basic drugs (local anesthetics).

Front 21

responsible for termination of effect of many anesthetic drugs

Back 21

redistribution from the vessel-rich group

Front 22

volume of distribution (Vd) and is determined by

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dividing the dose of drug administered by the resulting plasma concentration:

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Biotransformation is

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alteration of a substance by metabolic processes.

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primary organ of biotransformation

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The liver

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The 2 end products of biotransformation

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inactive and water soluble

Front 26

depend on biliary excretion

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The kidney

Front 27

Elimination half-life of a drug is proportional to the__________ and inversely proportional to the _____________.

Back 27

volume of distribution (Vd)

rate of clearance.

Front 28

first-order kinetics

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a constant fraction or percentage of drug is distributed or metabolized per unit of time, regardless of plasma concentration

Front 29

zero-order kinetics

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a constant amount of drug may be metabolized per unit of time

Front 30

Dose–response curves express the relationship between

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drug dose and pharmacological effect

Front 31

dose of drug required to produce a given effect in 50% of the population

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median effective dose (ED50)

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dose that results in death in 50% of the population exposed to that dose.

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median lethal dose (LD50)

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the ratio of the median lethal dose to the median effective dose (LD50:ED50).

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The therapeutic index is the ratio

Front 34

Drug receptors are macromolecules—usually proteins embedded into

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cell membranes

Front 35

Endogenous substances (eg, hormones) or exogenous substances (eg, drugs) that directly change cell function by binding to receptors

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agonists.

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bind to the receptors but do not cause a direct effect on the cell.

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Antagonists

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bind reversibly to receptors and can be displaced by higher concentrations of agonists.

Back 37

Competitive antagonists

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Noncompetitive (irreversible) antagonists

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bind to the receptor with such affinity that even high concentrations of agonists cannot reverse the receptor blockade. Competition of two drugs for the same receptor is one source of drug interactions.

Front 39

Receptors affect cell function

2 ways

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either directly (eg, by changing transmembrane ion flux) or by controlling the production of another regulatory molecule (eg, the second-messenger cyclic adenosine monophosphate).

Front 40

Barbiturates depress

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reticular activating system—a complex polysynaptic network of neurons and regulatory centers—located in the brain stem that controls several vital functions, including consciousness. In

Front 41

In clinical concentrations, barbiturates preferentially affect the function of

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nerve synapses rather than axons.

Front 42

Barbiturates suppress

enhance

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suppress transmission of excitatory neurotransmitters (eg, acetylcholine) and enhance transmission of inhibitory neurotransmitters (eg, -aminobutyric acid [GABA]).

Front 43

Barbiturates are ________________ derivatives

Back 43

barbituric acid

Front 44

The sodium salts of the barbiturates are water soluble but markedly ____________

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alkaline

Front 45

Biotransformation of barbiturates principally involves __________ to inactive water-soluble metabolites.

Back 45

hepatic oxidation

Front 46

specific benzodiazepine–receptor antagonist that effectively reverses most of the central nervous system effect of benzodiazepines

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Flumazenil

Front 47

Cerebral

Benzodiazepines

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reduce cerebral oxygen consumption, cerebral blood flow, and intracranial pressure

Front 48

Benzodiazepines reduce the minimum alveolar concentration of volatile anesthetics as much as 30%

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as 30%

Front 49

major types of opioid receptor have been identified

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mu ( , with subtypes -1 and -2), kappa ( ), delta ( ), and sigma ( ).

Front 50

opioid agonists and antagonists

dif.

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Although both opioid agonists and antagonists bind to opioid receptors, only agonists are capable of receptor activation.

Front 51

Endorphins, enkephalins, and dynorphins

Back 51

are endogenous peptides that bind to opioid receptors.

These three families of opioid peptides differ in their protein precursors, anatomic distributions, and receptor affinities.

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important

Opiate–receptor activation

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inhibits the presynaptic release and postsynaptic response to excitatory neurotransmitters (eg, acetylcholine, substance P) from nociceptive neurons.

The cellular mechanism for this neuromodulation may involve alterations in potassium and calcium ion conductance

Front 53

with intrathecal or epidural administration of opioids the Transmission of pain impulses can be interrupted at

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the level of the dorsal horn of the spinal cord with intrathecal or epidural administration of opioids.

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opioids exert their greatest effect within the ____________________,

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central nervous system

Front 55

Most opioids depend primarily on __________for biotransformation.

Back 55

the liver

Front 56

Morphine undergoes conjugation with _________ to form ______________.

Back 56

glucuronic acid

morphine 3-glucuronide and morphine 6-glucuronide.

Front 57

Meperidine is N-demethylated to normeperidine, an active metabolite associated with

Back 57

seizure activity

Front 58

The end products of fentanyl, sufentanil, and alfentanil are _________.

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inactive.

Front 59

The unique ester structure of remifentanil, an ultrashort-acting opioid with a terminal elimination half-life of less than _____________

Back 59

10 min

Front 60

Meperidine

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Cardiovascular

Front 61

opioids __________ cardiac contractility.

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do not depress

Nonetheless, arterial blood pressure often falls as a result of bradycardia, venodilation, and decreased sympathetic reflexes, sometimes requiring vasopressor (eg, ephedrine) support.

Front 62

2 opioids that evoke histamine release

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meperidine and morphine evoke histamine release in some individuals that can lead to profound drops in systemic vascular resistance and arterial blood pressure.

Front 63

The effects of histamine release can be minimized in susceptible patients by
3x

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slow opioid infusion,
adequate intravascular volume,
or pretreatment with H1 and H2 histamine antagonists

Front 64

Intraoperative hypertension during opioid anesthesia, particularly morphine and meperidine, is not uncommon. It is often attributable to

fixed by

Back 64

inadequate anesthetic depth and can be controlled with the addition of vasodilators or volatile anesthetic agents

Front 65

apneic threshold—

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the highest PaCO2 at which a patient remains apneic—is elevated, and hypoxic drive is decreased.

Front 66

3 Opioids can induce chest wall rigidity severe enough to prevent adequate ventilation

Back 66

fentanyl,
sufentanil,
and alfentanil

Front 67

________can effectively blunt the bronchoconstrictive response to airway stimulation such as occurs during intubation.

Back 67

Opioids

Front 68

responsible for a high incidence of nausea and vomiting

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medullary chemoreceptor trigger zone

Front 69

most effective opioid for decreasing shivering.

Back 69

Intravenous meperidine (25 mg)

Front 70

Biliary colic may result from opioid-induced

Back 70

contraction of the sphincter of Oddi.

Front 71

The stress response to surgical stimulation is measured in terms of

Back 71

secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol.

Opioids block the release of these hormones more completely than volatile anesthetics.

Front 72

ketamine functionally "dissociates" the

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thalamus (which relays sensory impulses from the reticular activating system to the cerebral cortex) from the limbic cortex (which is involved with the awareness of sensation).

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thalamus fx

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which relays sensory impulses from the reticular activating system to the cerebral cortex)

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limbic cortex fx

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which is involved with the awareness of sensation

Front 75

keatmine dissociative anesthesia

Back 75

this state of dissociative anesthesia causes the patient to appear conscious (eg, eye opening, swallowing, muscle contracture) but unable to process or respond to sensory input. Ketamine has been demonstrated to be an N-methyl-D-aspartate receptor (a subtype of the glutamate receptor) antagonist. The existence of specific ketamine receptors and interactions with opioid receptors has been postulated.

Front 76

Ketamine is biotransformed in the

Back 76

liver

Front 77

ketamine
Cardiovascular
why 2x

Back 77

ketamine increases arterial blood pressure, heart rate, and cardiac output (Table 8–8). These indirect cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of norepinephrine.

Front 78

ketamine should be avoided in patients with 4x

Back 78

coronary artery disease,
uncontrolled hypertension,
congestive heart failure,
and arterial aneurysms

Front 79

Respiratory
Ketamine

Back 79

potent bronchodilator, making it a good induction agent for asthmatic patients

Front 80

ketamine
Cerebral

Back 80

ketamine increases cerebral oxygen consumption, cerebral blood flow, and intracranial pressure.

Front 81

Mechanisms of Action
Etomidate
2x

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Etomidate depresses the reticular activating system and mimics the inhibitory effects of GABA.

Front 82

Etomidate

it may have disinhibitory effects on the parts of the nervous system that control

Back 82

control extrapyramidal motor activity

Front 83

Cardiovascular

Etomidate

Back 83

has minimal effects on the cardiovascular system. A mild reduction in peripheral vascular resistance is responsible for a slight decline in arterial blood pressure. Myocardial contractility and cardiac output are usually unchanged. Etomidate does not release histamine.

Front 84

Induction doses of etomidate transiently inhibit

Back 84

inhibit enzymes involved in cortisol and aldosterone synthesis. Long-term infusions lead to adrenocortical suppression that may be associated with an increased mortality rate in critically ill patients.

Front 85

Propofol

Mechanisms of Action

Back 85

facilitation of inhibitory neurotransmission mediated by GABA.

Front 86

Structure
Propofol

Back 86

phenol ring with two isopropyl groups

Front 87

mixing lidocaine with propofol

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2 mL of 1% lidocaine in 18 mL propofol

Front 88

Cardiovascular
The major cardiovascular effect of propofol

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decrease in arterial blood pressure due to a drop in systemic vascular resistance (inhibition of sympathetic vasoconstrictor activity), cardiac contractility, and preload.

Front 89

Mechanisms of Action

Droperidol

Back 89

antagonizes the activation of dopamine receptors

in the central nervous system, the caudate nucleus and the medullary chemoreceptor trigger zone are affected. Droperidol also interferes with transmission mediated by serotonin, norepinephrine, and GABA. These central actions account for the tranquilizer and antiemetic properties of droperidol. Peripheral actions include -adrenergic blockade.

Front 90

Prior to administering droperidol,

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a 12-lead electrocardiogram should be recorded. If the QT measures greater than 440 ms for men or greater than 450 ms for women, droperidol should not be given