Nurse Anesthesia Summer Objectives

Front 1

Describe the characteristics of an ideal anesthetic agent.

Back 1

Absence of airway irritant effects.
Absence of cerebral vasodilation
Absence of excessive myocardial depression
Absence of flammability.
Absence of hepatic or renal toxicity
Bronchodilation
Compatibility with epinephrine
Easily vaporized at ambient temperature
Low blood solubility to ensure rapid induction and recovery from anesthesia
Minimal metabolism
Potency
Skeletal muscle relaxation
Suppression of excessive sympathetic nervous system activity

Front 2

Define: Pharmacokinetics, pharmacodynamics, receptors.

Back 2

Pharmacokinetics- quantitative study of the absorption, distrubution, metabolism, and excretion of injected and inhaled drugs and their metabolites.
Pharmacodynamics- study of intrinsic sensitivity or responsiveness of receptors to a drug and the mechanisms by which these occur. Basically what the drug does to the body.
Receptors-Site of drug action

Front 3

Differentiate between an agonist, antagonist, competitive and non-competitive antagonism

Back 3

Agonist- Drug that activates a receptor by binding to the receptor
Antagonist-Drug that binds to the receptor without activating it and at the same time prevents an agonist from stimulating the receptor.
Competitive antagonism-is present when increasing concentrations of the antagonist progressively inhibit the response to an unchanging concentration of agonist.
Non-competitive antagonism-present when, after administration of an antagonist, even high concentrations of agonist cannot completely overcome the antagonism.

Front 4

. Define the following terms: hyperreactive, hyporeactive, hypersensitivity, tolerance, tachyphylaxis, idiosyncrasy, additive, synergistic.

Back 4

Hyperreactive-term used for people in whom an unusual low dose of drug produces its expected pharmacologic effects
Hyporeactive- Describes persons who require exceptionally large doses of drug to evoke expected pharmacologic effects
Hypersensitivity-Term usually reserved for individuals who are allerigic (sensitized) to a drug.
Tolerance-Hyporeactivity aquired from chronic exposure to a drug
Tachyphylaxis- Tolerance that develops acutely within only a few doses of a drug.
Idiosyncrasy- is present when an unusual effect of a drug occurs in small percentage of individuals regardless of the dose of drug administered.

Additive- a secound drug acting with the first drug will produce an equal effect to an algebraic summation.
Synergistic- Two drugs interact to produce an effect greater than an algebraic summation.

Front 5

Describe how the 2 compartments models may affect drug accumulation.

Back 5

In the 2 compartment model, the drug is introduced by IV injection directly into the central compartment. The drug subsequently distributes to the peripheral compartment only to return eventually to the central compartment, where clearance from the body occurs. The central compartment includes intravascular fluid and highly perfused tissues (lungs, heart, brain, kidneys, liver). In adults, these highly perfused tissues receive almost 75% of the cardiac output but represent about 10% of the body mass.

Front 6

. Differentiate between the alpha and beta phases of plasma decline of a drug.

Back 6

Alpha phase-distribution. The distribution phase of the plasma concentration curve begins immediately after IV injection of a drug and reflects that drug’s distribution from the circulation (central compartment) to peripheral tissues (peripheral compartments).
Beta phase-elimination. The elimination phase of the plasma concentration curve follows the initial distribution phase and is characterized by a more gradual decline in the drug’s plasma concentration. This gradual decline reflects the drug’s elimination from the circulation(central compartment) by renal and hepatic clearance mechanisms.

Front 7

Define elimination half-time

Back 7

Elimination half time is the time necessary for the plasma concentration of a drug to decrease to 50% during the elimination phase. Elimination half time of a drug is directly proportional to its Vd and inversely proportional to its clearance

Front 8

Define elimination half-life.

Back 8

In contrast to elimination half time, defines the time necessary to eliminate 50% of the drug from the body after its rapid IV injection. The amount of drug remaining in the body is related to the number of elimination half-times that have elapsed. About five half times are required for nearly total elimination of drug from the body (remember steady state).

Front 9

Define the relationship of T1/2 to VD and CL.

Back 9

Elimination half time of a drug is directly proportional to its Vd and inversely proportional to its clearance.

Front 10

Discuss factors important to drugs given orally.

Back 10

It has disadvantages such as (a) emesis caused by irritation of the gastronintestinal mucosa by the drug (b) destruction of the drug by digestive enzymes or acidic gastric fluid and (c) irregularities in absorption in the presence of food or other drugs. When a drug is given orally the onset of drug effect is largely determined by the rate and extent of absorption from the GI tract.

Front 11

Define: 1st pass effect, when it occurs and when it does not.

Back 11

Drugs absorbed from the GI tract enter the portal venous blood and thus pass through the liver before entering the systemic circulation for delivery to tissue receptors.

Front 12

Differentiate body mass and blood flow between the body tissue compartments

Back 12

After systemic absorption of a drug, the highly perfused tissues (heart, brain, kidneys, liver) receive a disproportionately large amount of the total drug. As the plasma concentration of drug decreases below that in highly perfused tissues, drug leaves these tissues to be redistributed to less well-perfused sites, such as skeletal muscles and fat. The vessel rich group (%body mass 10, %blood flow 70), muscle group (%body mass 50, %blood flow 19), fat group (%body mass 20, %blood flow 6), vessel poor group (%body mass 20, %blood flow <1).

Front 13

Explain the impact that tissue blood flow would have in distribution and duration of
drugs.

Back 13

Uptake of a drug by tissues is principally determined by tissue blood flow if the drug in question can penetrate membranes rapidly. With continuing elimination of drug, the plasma concentration declines below that in tissues and drug leaves tissues to reenter the circulation. A tissue that accumulates drug preferentially may act as a reservoir to maintain the plasma concentration and thus prolong its duration of action.

Front 14

Discuss the factors that determine tissue uptake and storage of drugs.

Back 14

Uptake of a drug by tissues is principally determined by tissue blood flow if the drug in question can penetrate membranes rapidly. With continuing elimination of drug, the plasma concentration declines below that in tissues and drug leaves tissues to reenter the circulation. A tissue that accumulates drug preferentially may act as a reservoir to maintain the plasma concentration and thus prolong its duration of action.

Front 15

Define what characteristics will make a drug diffusible.

Back 15

The lipid solubility and ionization.

Front 16

Discuss drug distrubution in the CNS.

Back 16

Distribution of ionized water soluble drugs to the CNS from the circulation is restricted because of the limited permeability characteristics of the BBB

Front 17

Define VD and give examples of drugs that have large VD’s and small VD’s.

Back 17

Vd value depicts the distribution characteristics of a drug in the body. Vd is calculated as the dose of drug administered IV divided by the resulting plasma concentration of drug before elimination begins. Non-depolarizing neuromuscular blocking drugs (poor lipid solubility) have low Vd. Thiopental and diazepam (highly lipid soluble) have high Vd.

Front 18

Define ionization and relate this to diffusibilty

Back 18

The degree of drug ionization is a function of its dissociation constant (pK) and the pH of the surrounding fluid. When the pK and the pH are identical, 50% of the drug exists in both the ionized and nonionized form. Solubility characteristics of the ionized and nonionized molecules determine the ease with which drugs may diffuse through lipid components of cell membranes.

Front 19

. Discuss how protein binding affects distrubution, VD, and CL

Back 19

Protein binding has an important effect on distribution of drugs because only the free or unbound fraction is readily available to cross cell membranes. Vd of a drug is inversely related to protein binding. For example, high protein binding limits passage of drug into tissues, thus resulting in high drug plasma concentrations and a small calculated Vd. Clearance of a drug is also influenced by protein binding because it is the unbound fraction in the plasma that has ready access to hepatic drug metabolizing enzymes, and it is also this unbound fraction of drug that undergoes glomerular filtration

Front 20

Discuss what factors influence the amount of protein binding.

Back 20

The extent of protein binding parallels lipid solubility of the drug. The fraction of total drug in plasma that is protein bound is determined by the drug’s plasma concentration and the number of available binding sites. Low plasma concentrations of drugs are likely to be more highly protein bond than are higher concentrations of the same drug. Binding of drugs to plasma albumin is often nonselective. Renal failure may decrease the fraction of a drug bound to protein even in the absence of chainges in plasma concentrations of albumin or other proteins.

Front 21

Discuss how a steady state of plasma concentration can be achieved.

Back 21

The time necessary for a drug to achieve a steady state plasma concentration with intermittent dosing is about five elimination half times

Front 22

Explain the concept of hepatic clearance, biliary clearance, and renal clearance.

Back 22

Hepatic clearance of a drug is the product of hepatic blood flow and the hepatic extraction ratio. If the hepatic extraction ratio is high (>0.7), the clearance of drug will depend on hepatic blood flow, whereas changes in enzyme activity will have minimal influence. Thus, a high hepatic extraction ration results in perfusion-dependent elimination. (p13 fig 1-8). If the ER is <0.3, only a small fraction of the drug delivered to the liver is removed per unit of time.
Biliary Excretion- Most of the metabolites of drugs produced in the liver are excreted in bile into the GI tract. Often, these metabolites are reabsorbed form the GI into the circulation for ultimate elimination in the urine.
Renal clearance- Water soluable compounds are excreted more efficiently by the kidneys than are compounds are compounds with high lipid solubility. Drug elimination by the kidneys is correlated with endogenous creatinine clearance or serum creatinine concentration.

Front 23

Define the role of metabolism

Back 23

The role of metabolism (biotransformation) is to convert pharmacologically active, lipid-soluable drugs into water soluble and often pharmacologically inactive metabolites. Increased water solubility decreases the Vd for a drug and enhances its renal excretion and occasionally GI elimination.

Front 24

. Differentiate between first order and zero order kinetics

Back 24

First order kinetics depends on the plasma concentration of drug in the sense that the absolute amount of the drug eliminated per unit of time is greatest when its plasma concentration is greatest. Zero order kinetics occurs when the plasma concentration exceeds the capacity of metabolizing enzymes. As a result, the absolute amount of drug eliminated per unit of time during zero order kinetics is the same regardless of the drug’s plasma concentration.

Front 25

List and discuss the four basic pathways of drug metabolism.

Back 25

The 4 basic pathways of metabolism are (a) oxidation, (b) reduction, (c) hydrolysis, and (d) conjugation. Phase I reactions include oxidation, reduction an hydrolysis which increase the drugs polarity and prepare it for phase II reactions. Phase II reactions are conjugation reactions that covalently link the drug or metabolites with a high polar molecule (carbohydrate or an amino acid) that renders the conjugate more water soluble for subsequent excretion.

Front 26

Discuss the influence of the P450 system on drug metabolism.

Back 26

The cytochrome P-450 enzyme (CYP) system is a super family of membrane bound heme proteins that catalyze the metabolism of endogenous compounds. The system is composed of mostly hepatic microsomal enzymes but there are also mitochondrial P-450 enzymes. Microsomal enzymes catalyze most of the oxidation, reduction, and conjugation reactions that lead to metabolism of drugs. A loss of electron results in oxidation. Gain of an electron results in reduction.

Front 27

Define non-microsomal induction.

Back 27

Nonmicrosomal enzymes catalyze reactions responsible for metabolism of drugs by conjugation, hydrolysis, and to a less extent, by oxidation and reduction. The enzymes are principally in the liver but are also found in plasma and the GI tract.

Front 28

Define the following terms in relation to the dose response curve: potency, efficacy, therapeutic index, effective doses, slope.

Back 28

Potency- the potency of a drug is depicted by it location along the dose axis of the dose-response curve. Increased affinity of a drug for its receptor moves the dose-response curve to the left.
Efficacy- the maximal effect of a drug reflects its intrinsic activity or efficacy. This efficacy is depicted by the plateau in dose-response curves. It must be recognized that undesirable effects (side effects) of a drug may limit dosage to below the concetration associated with its maximal desirable effect.
Therapeutic index (margin of safety)- is a ratio between ld50 and ed50. The higher the value of the therpeutic index the safer the drug.
Effective doses-the dose required to produce a specified effect to produce that effect in a given percentage of patients (ED50, ED90).
Slope- The slope of the dose-response curve is influenced by the number of receptors that must be occupied before a drug effect occurs. A steep dose-response curve is characteristic of neuromuscular blocking drugs and inhaled anesthetics (minimal alveolar concentration [MAC]); it means that small increases in dosage evoke intense increases in drug effect.

Front 29

Discuss how bioavailability, renal function, liver and cardiac disease and age can influence a pt’s response to a drug.

Back 29

Different patients response differently to amount of drug given (bioavailability) depending on the individual’s metabolism. Renal function impacts the rate of elimination of a drug. Liver disease can result in high plasma concentrations of active drug because metabolism is impaired. Decreased cardiac output decreases hepatic blood flow and thus delivery of the drug to the liver for metabolism. Older individuals have larger body fat composition which can increase Vd and lead to accumulation of lipid-soluble drugs such as diazepam and thiopental. The elderly have decreased protein bind and decreased renal function.

Front 30

List receptor subtypes.

Back 30

Examples of clinically important protein-coupled receptor systems include adrenergic, opioid, muscarinic cholinergic, dopamine, and histamine receptors. Multiple subtypes of receptors (alpha1 and alpha2, beta1 and beta 2, mu1 and mu2, H1 and H2).

Front 31

Discuss the concept of “second messenger

Back 31

Agonists activates membrane bound receptor. G protein is activated and produces effector. Effector stimulates second messenger synthesis. Second messenger activates intercellular process. (p.22)

Front 32

Differentiate between up and down regulation and how one influences the amount of the other.

Back 32

The concentration of receptors in the lipid portion of cell membranes is dynamic, either increasing (up-regulation) or decreasing (down-regulation) in response to specific stimuli. For example, prolonged treatment of asthma with a beta agonist may result in tachyphylaxis associated with a decrease in the concentration of receptors. Conversely, chronic interference with the activity of receptors as produced by a beta antagonist may result increase numbers or receptors in cell membranes such that an exaggerated response occurs if the blockade is abruptly reversed (D/C of propanolol).

Front 33

Discuss how an agonist would influence the dose response curve.

Back 33

An agonist would cause the dose response curve to go uphill from left to right.

Front 34

Discuss the receptor occupancy and receptor activation theory.

Back 34

Receptor occupancy theory-It is assumed that the intensity of effect produced by binding of drugs to receptors is proportional to the fraction of receptors occupied by the drug.
Receptor activation theory- when an agonist binds to receptors, it converts the receptors from a nonactivated to an activated state. Full agonist are able to convert most of the receptors they occupy to the activated state; partial agonist convert only a fraction of the receptors they ocuppy to the actiated state; and antagonist do not activate any of the receptors they occupy to the activated state.

Front 35

Identify bonding forces that occur between drugs and receptors.

Back 35

Covalent bond is formed by sharing a pair of electrons between atoms, thus forming a strong bond that plays little role in reversible binding of drugs to receptors. Ionic bonds arise from electrostatic forces existing between groups of opposite charge. Hydrogen bonds occur between hydroxyl or amino groups and and electronegative carboxyl oxygen group. Van der Waals forces are weak bonds between atoms or groups of atoms of different molecules.

Front 36

Give an example of non-receptor drug action.

Back 36

Antacids in neutralizing stomach acid.

Front 37

Discuss the determinants of alveolar partial pressure.

Back 37

The PA and ultimately the Pbr of inhaled anesthetics are determined by input (delivery) into alveoli minus uptake (loss) of the drug from the alveoli into arterial blood

Front 38

Identify the factors that determine alveolar partial pressure.

Back 38

Anesthetic input (Transfer of inhaled anesthetic form anesthetic machine to aveoli)
Inspired partial pressure
Aveolar ventilation
Characteristics of anesthetic breathing system
Functional residual capacity
Anesthetic Loss (Transfer of inhaled anesthetic form alveoli to arterial blood)
Blood-gas coefficent
Cardiac Output
Aveolar-to-venous partial pressure difference
Anesthetic Loss (Transfer of inhaled anesthetic from arterial blood to brain
Brain-blood partition coefficient
Cerebral blood flow
Arterial to venous partial pressure difference

Front 39

Define concentration and second gas effect.

Back 39

Concentration effect- The concentration effect states that the higher the PI, the more rapidly the PA approaches the PI.
Second gas effect-Reflects the ability of high-volume uptake of one gas (first gas) to accelerate the rate of increase of the PA of a concurrently administered “companion” gas (second gas).

Front 40

Discuss how alveolar ventilation influences rate and depth of anesthesia.

Back 40

Increased alveolar ventilation, like PI, promotes input of anesthetics to offset uptake. The net effect is a more rapid rate of increase in the PA toward the PI and thus induction of anesthesia.

Front 41

Define partition coeffecient.

Back 41

The solubility of the inhaled anesthetics in blood and tissues is denoted by the partition coefficent. A partition coefficent is a distrubution ratio describing how the inhaled anesthetic distributes itself between two phase at equilibrium. For example, a blood:gas partition coefficient of 0.5 means that the concentration of inhaled ansthetic in the blood is half that present in the alveolar gases when the partial pressures of the anesthetic in these two phase are identical.

Front 42

Discuss the differences between B-G, tissue-blood and oil-gas partition coefficients
and their impact upon induction and emergence from anesthesia.

Back 42

B-G coefficient- Blood can be considered a pharmacologically inactive reservoir, the size of which is determined by the solubility of the anesthetic in the blood. When the blood:gas coefficient is high, a large amount of anesthetic must be dissolve in the blood before the Pa equilibrates with the PA. When blood solubility is low, minimal amounts of inhaled anesthetic must be dissolved before equilibration is achieved; therefore the rate of increase of PA and Pa and thus onset of drugs effects such as the induction of anesthesia are rapid.
Tissue:Blood coefficient- Determines uptake of anesthetics into tissues and the time necessary for equilibration of tissues with the Pa.
Oil:Gas coefficient- parallel anesthetic requirements.

Front 43

Explain the complications that may occur with using N20 in a patient with a pneumothorax.

Back 43

Passage of NO into an air-filled cavity surrounded by a compliant wall causes the gas space to expand. Conversely, passage of NO into an air-filled cavity surrounded by a noncompliant wall causes an increase in intracavity pressure.

Front 44

. Explain what is meant by the following statement: “A change in cardiac output is analogous to the effect of a change in solubility of an inhalation agent.” (p.30)

Back 44

For example, doubling cardiac output increases the capacity of blood to hold anesthetic, just as solubility increases the capacity of the same volume of blood. An increased cardiac output results in more rapid uptake, so the rate of increase in PA and thus induction of anesthesia in slowed. A decrease cardiac output speeds the rate of increase of the PA, because there is less uptake opposed to input.

Front 45

Explain how a right to left shunt will impact induction.

Back 45

When a right to left shunt is present, the diluting effect of the shunted blood on the partial pressure of anesthetic in blood coming from ventilated alveoli results in a decrease in the Pa and a slowing in the induction of anesthesia.

Front 46

Explain why the uptake of a volatile agent is greatly decreased after about 15 minutes.

Back 46

Highly perfused tissues in the adult account for <10% body mass but receive 75% of cardiac output. As a result of the small mass and high blood flow, these tissues, known as vessel-rich group tissues, equilibrate rapidly with the Pa. Indeed, after bout 3 time constants, approximately 75% of the returning venous blood is at the same partial pressure as the PA. For this reason, uptake of a volatile anesthetic is decreased greatly after 3 time constants (5-15 minutes depending on the blood solubility of the inhaled anesthetic).

Front 47

Discuss how the solubility of an inhaled anesthetic and the duration of anesthesia influences recovery. List other factors that can retard recovery.

Back 47

Recovery from anesthesia is depicted by the rate of decrease in the Pbr as reflected by the PA. In contrast to induction of anesthesia, which may be accelerated by the concentration effect, it is not possible to speed the decrease in PA by this mechanism.

Front 48

Define the following: diffusion hypoxia, MAC.

Back 48

Diffusion hypoxia occurs when inhalation of nitrous oxide is discontinued abruptly, leading to a reversal of partial pressure gradients such that NO leaves the blood to enter alveoli. This initial high-volume outpouring of NO from the blood into the alveoli can so dilute the PAO2 by NO, there is also dilution of the PACO2, which decreases the stimulus to breathe. Thus, it is common practice to fill the lungs with O2 at the end of anesthesia to ensure that arterial hypoxemia will not occur as a result of dilution of the PAO2 by NO.
Minimal Alveolar Concentration of an inhaled anesthetic is defined as that concentration at 1 atm that prevents skeletal muscle movement in response to supramaximal painful stimulus (surgical incision) in 50% of patients. MAC is an anesthetic 50% effective dose (ED50).

Front 49

Discuss: mechanisms of anesthesia theories.

Back 49

Mechanism of immobility- MAC is based on the characteristic ability of inhaled drugs to produce immobility by virtue of actions of these drugs principally on the spinal cord rather than on higher centers.

Front 50

Differentiate between the anatomic locations of the sympathetic and parasympathetic nervous systems.

Back 50

The preganglionic fibers of the SNS arise from the cells in the thoracolumbar portions of the spinal cord, whereas the cell bodies of the preganglionic fibers of the PNS originate in the craniosacral region. The effector organs of the SNS have adrenergic receptors (beta, alpha, and dopamine). The preganglionic fibers of the SNS and PNS release acetylcholine as the neurotransmitter at the preganglionic neuronal site; the postganglionic fibers release NE or Dopamine as the neurotransmitter.

Front 51

Describe the sympathetic receptors

Back 51

Alpha1-Blood vessels, pancreas (inhibition), intestine and bladder
Alpha 2-Postganglionic(inhibition of NE release), PLT (aggregation),
Beta 1-Heart, Fat Cells
Beta 2-Blood vessels, bronchioles, uterus, kidneys (rennin secretion), liver (glycogenolysis, gluconeogenesis), pancreas (insulin secretion)
Dopmine- blood vessels (dilation)

Front 52

Describe the parasympathetic receptors.

Back 52

Muscarinic- heart, bronchioles(constrict), salivary glands, intestine, bladder
Nicotinic- neuromuscular junction (muscle contraction), autonomic ganglia (SNS stimulation)

Front 53

Discuss the effects of the three naturally occurring catecholamines and what receptors they stimulate.

Back 53

NE- Alpha1 and Beta1
Dopamine- D1
Epi- Alpha1, Beta1, Beta2

Front 54

Discuss the uses of beta agonists and beta antagonists.

Back 54

Beta Agonists stimulate B1, B2, A1, and A2 receptors. Highly selective B2 agonists produce relaxation of bronchial, uterine, and vascular smooth muscle.
Beta Antagonists (Beta-Blockers) are useful in the treatment of systemic hypertension, ischemic heart disease, CHF, and certain types of cardiac dysrhytmias.

Front 55

Discuss the uses of anticholinergics and anticholinesterases.

Back 55

Anticholinergics prevent muscarinic effects of ACh by competing for the same receptors as are normally occupied by the neurotransmitter. Atropine and scopolamine cross the BBB while glycopyrrolate doesn’t.

Anticholinesterases inhibit the enzyme ACh-esterase, which is normally responsible for the rapid hydrolysis of Ach after its release from cholinergic nerve endings. In the presence of anticholinesterase, Ach accumulates at nicotinic and muscarinic receptor sites.