Stoelting Study 1

Front 1

1. What is pharmacokinetics?

Back 1

1. Pharmacokinetics is the study of the absorption, distribution, metabolism, and elimination of inhaled or injected drugs and their metabolites. It is also the study of the time it takes for these processes to occur. It can be thought of as what the body does to the drug. (18; IS)

Front 2

2. What is pharmacodynamics?

Back 2

2. Pharmacodynamics is the study of the responsiveness of receptors to drugs, · the pharmacologic effects of the drugs, and the mechanism by which these effects occur. More simply put, it is the study of the relationship between a specific dose of drug and its effect on the body. It can be thought of as what : the drug does to the body. (18; 34)

Front 3

3. What is the role of receptors in drug pharmacology?

Back 3

3. Receptors are components of a cell, often lying within the cell membrane. Attachment of a drug to a receptor leads to a chain of events whose end result is the pharmacologic effects of the drug. Understanding receptors furthers the understanding of a drug's activity and effect, the selectivity of the receptor for a given drug, and the pharmacologic activity of receptor · agonists and antagonists. (18; 34)

Front 4

4. What are three methods by which the effect of a drug is terminated?

Back 4

4. The three methods by which a drug's effects are terminated are through its redistribution to inactive tissue sites, metabolism, and/or excretion. (18; 34)

Front 5

5. What is a racemic mixture? Give an example of a drug used in clinical anesthesia · that is a racemic mixture.

Back 5

5. A racemic mixture refers to a drug or compound that is made up of a 50:50 mixture of two enantiomers of a compound. Racemic mixtures of drugs actually represent two distinct drugs or compounds whose stereochemistries differ. Examples of drugs used in clinical anesthesia that are racemic mixtures include bupivacaine, ketamine, and volatile anesthetics. (18; 24-2S)

Front 6

6. What is the significance of the administration of racemic mixtures in clinical anesthesia?

Back 6

6. Because racemic mixtures of drugs actually represent two distinct drugs whose stereochemistry is different, the molecular interactions of each of these drugs with receptors results in different effects for each enantiomer. Each enantiomer may have different pharmacokinetic and pharmacodynamic properties, as well as different physiologic effects. For example, only one enantiorner may be responsible for the drug's desired result, whereas the other may be responsible for the drug's side effects

Front 7

7. What are agonist drugs?

Back 7

7. Agonist drugs are drugs that bind to and activate receptors. (18; 35) 8

Front 8

8. What are antagonist drugs?

Back 8

Antagonist drugs are drugs that bind to but do not activate receptors. Antagonists do not allow agonists to bind to the receptors while bound themselves, and therefore block the clinical response that would nonnally result from the binding of an agonist drug to the receptor. (18; 36)

Front 9

9. Define competitive and noncompetitive antagonism. Which of these is overcome by higher concentrations of the drug?

Back 9

AntagoIDst drugs bind to but do not activate receptors. Once occupied by a receptor, an antagonist whose effect can be overcome by increasing the concentration of an agonist at the receptor is considered a competitive antagonist. ;ompetitive antagonism, increasing concentrations of the agonist nist. With competitive antagonism, increasing concentrations of the agonist vely overcome, and thus "compete" with, the antagonist. An npetitive antagonist is a nondepolarizing neuromuscular . Nondepolarizing neuromuscular blocking drugs bind to and acetycholinecholine receptors in the neuromuscular blocking the effect of acetylcholine at that receptor. The effects of nondepolarizing neuromuscular blocking drugs can be overcome by increasing the concentration of acety1choine molecules at the receptor.This is the basis for the reversal of the effect of nondepolarizing neuromuscular blocking drugs by acetylcholine esterase inhibitors, such as neostigmine. Noncompetitive antagonism exists when increasing or even high concentrations of an agonist cannot overcome, or cannot "compete," with the antagonist. In these situations the receptor remains blocked despite the high concentration of agonist available at the receptor. (18; 36)

Front 10

10. What does an additive drug effect mean? Give an example.

Back 10

10. An additive drug effect occurs when a second drug is administered with a first drug and then the first and second drug together produce an effect that is equal to the sum of their individual effects. An example of this is when the first and second drugs are inhaled anesthetics and their combined effect is equal to the sum of their respective minimum alveolar concentration values.

Front 11

11. What does a synergistic drug effect mean? Give an example.

Back 11

11. A synergistic drug effect occurs when a second drug is administered with a first drug and the first and second drug together produce an effect that is greater than that expected from the sum of their individual effects (additive effect). An example of a synergistic drug effect is when the first and second drugs are aminoglycoside antibiotics and nondepolarizing neuromuscular blocking drugs. The resulting neuromuscular blockade produced is greater than the addtd effect of each individual drug. A synergistic drug effect occurs when nondepolarizing neuromuscular blocking drugs are administered in I combination with aminoglycosije antibiotics despite the inability of aminoglycoside antibiotics to produce clinically significant neuromuscular blockade when administered alone. (18; 44, 463)

Front 12

12. When an individual is described as hyporeactive to a drug, what does it, refer to?

Back 12

12. An individual described as being hyporeactive to a drug has a decreased clinical effect from that expected from the administration of a particular dose of a drug. A hyperreactive individual responds in the opposite way, when a particular dose of a drug produces an increased clinical effect from that pected. (18; 44)

Front 13

13. What is drug tolerance?

Back 13

13. When an individual is administered a drug on a chronic basis the receptors to which the drug binds can develop a decreased responsiveness to the drug. The patient thus develops an acquired hyporeactivily to the drug. This results m a decreased clinical response elicited b~ a particular dose of drug, such that the dose of drug that results in a particular effect must be increased from the dose that previously resulted in the effect. The patient under these · circumstances is said to hav.e developed a tolerance to the drug. (18; 45-46)

Front 14

14. What is drug cross-tolerance?

Back 14

14. When an individual is administered a drug on a chronic basis the patient may develop a tolerance to the drug. The administration of another drug that produces similar effects to the first drug may also result in a decreased clinical response. The patient thus also develops an acquired hyporeactivity to the second drug that is similar to the first drug. The patient under these circumstances is said to have developed a cross-tolerance to the second drug.

Front 15

15. What does tachyphylaxis to a drug refer to?

Back 15

15. Tachyphylaxis is a term used to describe tolerance to a drug that develops acutely after just a few doses of the drug have been administered. (18; 45-46)

Front 16

16. What does an idiosyncratic reaction to a drug refer to?

Back 16

16. When an individual experiences an unusual effect of the drug it is termed an idiosyncratic reaction. Patients who are susceptible to an idiOlyncratic reaction after the administration of a drug will demonstrate a reaction regardless of the dose of drug that is administered. It is believed that patients become susceptible to an idiosyncratic reaction of a drug secondary to hypersensitivity or genetic differences. (18; 4~)

Front 17

17. What does a dose-response curve illustrate? Draw and label one.

Back 17

A dose-response Curve is a graph depicting the relationship between a dose of drug administered on the x-axis and the pharmacologic effect that results from its administration on the y-axis.

Front 18

18. How is the potency of a drug depicted on a dose-response curve?

Back 18

18. The potency of a drug is depicted by its location on the x-axis of the doseresponse curve. Another method by which the potency of a drug can be quantified is by the dose of drug that is required to produce the maximal effect of the drug.

Front 19

19. What does the effective dose 50 (EDso) refer to?

Back 19

· The effective dose 50 (EDso) of a drug is the dose of the drug required to produce a given effect in 50% of the people to whom that dose of drug is administered. The EDso of a drug only corresponds to one specific effect of that drug. (19; 4S)

Front 20

20. How would an increased affinity of a drug for its receptor influence its doseresponse curve?

Back 20

20. An increased affinity of a drug for its receptor would move its dose-response curve to the left. This corresponds to an increased potency of the drug. A decreased affinity of a drug for its receptor would move its dose-response curve to the right, reflecting a decrease in drug potency. (19; 44)

Front 21

21. What is reflected by the slope of a dose-response curve? What clinical problem may be associated with a steep dose-response curve?

Back 21

21. The slope of a dose-response curve reflects how much clinical effect results from the addition of drug. The number of receptors that must be occupied by a drug before a drug effect occurs will influence the slope of a dose-response curve. In the case in which a majority of the receptors must be occupied before seeing an effect of the drug, the slope of the dose-response curve would be steep. When a dose-response curve is steep, it indicates that small Increases in the administered drug may result in large increases in the effect of the drug. linically, a small difference between a therapeutic and toxic concentration of drug may be associated with drugs whose dose-response curve is steep. (19; 44)

Front 22

22. What is a drug's efficacy? How is it depicted on the dose-response curve? What may limit a drug's efficacy clinically?

Back 22

22. The efficacy of a drug is the maximal clinical effect of the drug. An effect greater than the maximal one cannot be achieved even with the administration of more drug. The efficacy of a drug is depicted as the plateau on its doseresponse curve. The maximal effect of a drug may not be possible to achieve clinically secondary to undesirable side effects cf the drug that occur when maximal drug effects are apploached. This may limit the efficacy of a drug clinically. (19, Fig. 2-1; 4S)

Front 23

23. Can individual variability alter the dose-response curve?

Back 23

23. Individuals may vary with respect to the pharmacokinetics and/or the pharmacodynamics of a drug. Pharmacokinetic. are affected by indi'ridual differences in renal function, liver function, cardiac function, and patient age. Phannacoynanucs are affected by inlividual differences in enzyme activity and genetic differences. This may be reflected as alterations in the position 01 the dosesponse curvefor!he drug. (19; 46)

Front 24

24. What is the role of the volume of distribution and clearance of a drug in the evaluation of the pharmacokinetic properties of the drug?

Back 24

24. The pharmacokinetics of administered drugs is the study of a drug's absorption, distribution, metabolism, and elimination. The volume of distribution of a drug reflects the apparent volume in which the drug will di;tribute itself. The clearance of the drug involves either its elimination via the kidneys or its metabolism by the liver. (19; IS-17)

Front 25

25. Describe the two-compartment model used to describe the pharntacokinetic properties of a drug that has been administered as a bolus.

Back 25

25. The two-compartment phannacokinetic model is a conceptual model used to describe the biphasic manner in which the body appears to handle drugs administered as a bolus. The model describes two compartments in which the bolused drug will distribute itseli Initially, the drug will enter the central compartment. The central compartment, which is of a smaller volume, consists of the blood, plasma, and highly perfused organs such as the heart, I lungs, kidneys, and liver. With time the drug will then transfer into the peripheral compartment. The peripheral compartnent, which contains a large volume, consists of all other tissues or sites in which a drug may distribute itself. The transfer of drugs between these two compartments is depicted as rate constants. (l9, Fig. 2-2; 26-29, figs. 2-14, 2-15, 2-16)

Front 26

26. What is the volume of distribution of a drug'?

Back 26

26. The volune of distribution of a drug is calculated as the dose of drug administered intravenously divided by the plasma concentration. Although the volume of distribution is a calculated number, it does not refer to absolute anatomic volumes but to a conceptual volume. The volume of distribution is used to conceptualiz~ how much of the drug stays in the central compartment (plasma) after its intravenous injection. A volume of distribution for a given drug may be as small as the plasma volume of the patient, implying that nearly all the administered drug remains in the central compartment. Conversely, the volume of distribution of a drug mayre large, implying the drug transfers quickly into the peripheral tissues, the volume of distribution is therefore a calculated number Uied 10 descrire a specific drug's potential to transfer from the plasma to the tissues after its intravenous administration.

Front 27

27. What are three properties of a drug that will determine how much of the drug will pass from the plasma into the tissues after its intravenous administration?

Back 27

27. Three properties of a drug that will determine how much of the drug will pass from the plasma into the tissues after its intravenous administration include its capacity to bind to plasma proteins, its degree of ionization, and its lipid solubility. Because these three factors will determine how much of the drug will stay in the central compartment after its intravenous administration, they also influence the drug's apparent volume of distribution. For example, drugs that are highly bound to protein, with I high degree of ioniz~tion, and a low lipid solubility will tend to remain in the plasma and have a high plasma concentration. These drugs will have a small calculated volume of distribution. (20; 17, 22)

Front 28

28. How are drugs cleared from the body? How might the clearance rate of drugs be defined pharmacokinetically?

Back 28

28. Drugs are cleared from the body through its elimination or metabolism. The clearance rae Df a drug is defined as the volume of plasma that is cleated ,)f drug per unit time. By knowing the clearance rate of a drug, the anesthesiologist is better able to administer a given drug at a rate in which inadequate levels of the drug in the plasma or the accumulation of drug levels in the plasma are minimized. (

Front 29

29. What is the role of the kidneys in the clearance of drugs from the plasma? How might the function of the kidneys in this regard be evaluated clinically?

Back 29

29. The kidneys are primarily responsible for clearing drugs from the plasma through the excretion of drugs in the urine. Drugs that are water soluble and not bound to proteins are most efficiently excreted by the kidney. Clinical indicators of the capacity of the kidneys to eliminate drugs incbde the creatinine clearance or serum creatininf v~ues, An abnormal laboratory value indicates thm Iilre ~I(t!~i!mmlill:y function, implying

Front 30

30. What is the role of the liver in the clearance of drugs from the plasma? How is this accomplished by the liver?

Back 30

30. Although the kidneys, lungs, and gastrointestinal tract have limited potential for the metabolism of drugs, the liver is the organ primarily responsible for the metabolism of drugs, which facilitates their clearance from the plasma. Metabolism is the conversion of lipid-soluble drugs to water-soluble drugs, which allows for their ~xcretion by the kidneys. Lipid-soluble drugs are poorly excreted by the kidneys because trey are so easily reabsorbed by the renal tubules. Often the metabolism of drugs to a more water-soluble form :onverts the drug from a pharmacologically active to an inactive metabolite. The enzymes responsible for the metabolism of many drugs are located in the liver, specifically in the hepatic smooth endoplasmic reticulum, and are referred to as microsomal enzymes. The microsomal enzymes include the protein enzymes of the cytochrome P-4S0 system, which are believed to be responsible for the metabolism of many drugs. The principal determinant of lll1crosomal enzyme activity is most likely genetic, accounting for the large ltion among individuals with respect to the rate of drug metabolism. Microsomal enzymes may also be induced, increasing their activity and subsequently accelerating the rate of metabolism and clearance of some administered drugs. A drug that classically causes induction of the hepatic somal enzymes is phenobarbital.

Front 31

32. What is the elimination half-time of a drug? What is the clinical relevance of a irug's elimination half-time?

Back 31

2. The elimination half-time of a drug is the time necessary for the plasma concentration of a drug to decrease by 50% during the elimination phase. The drug is almost completely eliminated after five elimination half-times have passed. By knowing the elimination half-time of a drug, the anesthesiologist is theoretically better able to administer a given drug at a rate in which ogist is theoretically better able to administer a given drug at a rate in which doses of a drug more frequently than five elimination talI-times would result in the drug being administered at a late greater than its clearance. The result would be an acclIllulation of the drug in the plasma. Drug accumulation does not occur when the rate of elimination of the drug is equal to the rate of drug administration. (21;

Front 32

33. What is the time necessary to achieve a steady-state plasma concentration of drug · when it is administered as intermittent boluses? After a therapeutic concentration of drug is achieved in the plasma, how can a continued, unchanging plasma concentration be maintained?

Back 32

· The time necessary to achieve a steady-state [iasma concentration of drug when it is administered as interrni:tent boluses is about five elimination halftimes of the drug. In clinical practice this is often circumvented through the intravenous administration of a large initial dose of drug, or loading dose, · to quickly achieve a therapeutic drug concentration. After a therapeutic concentration of tre drug is achieved in the plasma, the clinician can give continuous or intennittent intravenous injections of the drug at a rate approximately equal to the rate of drug elimination to maintain an unchanging plasma concentration.

Front 33

34. Why might measured pharmacokinetic properties of drugs differ from what is observed clinically?

Back 33

34. Pharmacokinetic properties of drugs are measured !n healthy, ambulatory adults. Observed pharmacokinetics of drugs may be very different in patients with chronic diseases, at the extremes )f age, with abnormal hydration or nutritive status, or with decreased skeletal muscle mass. Patients with renal · insufficiency or hepatic dysfunction are especialy likely to have prolongation of the eliminatioll half-time of an administered drug. In the presence of hepatic or renal dysfunction, the maintenance dose of a drug should be adjusted downward to prevent drug accumulation. (21; 17-22, 46-47)

Front 34

35. What is the context-sensitive half-time? What is its clinical usefulness1

Back 34

35. The context-sensitive half-time refers to the time required for the concentration of a particular drug to reach a specific percent after the discontinuation of its administration as a continuous intravenous infusion for a Specific duration. The conten-sensitive half-time of a drug depends mostl~ on the drug's lipid solubility and clearance mechanisms and is not directly related to its elimination half-time. Computer-simulated models of the (Context-sensitive half-time of a drug may be useful clinically in anesthi!sia to predict the duration of a particular drug's effects after its discontinuation. (21, Fig. 2-4;

Front 35

36. What is the time to recovery from anesthesia dependent on? Why might a bispectral index monitor be useful in decreasing the time to recovery from anesthesia?

Back 35

36. The time to recovery from anesthesia is dependent on multiple factors. In general, however, if the plasma concentration of a drug administered is just above that required for awakening, the time to recovery would be less than it otherwise would have been. For this reason, the use of a bispectral index monitor may be useful in allowing the anesthesiologist to better estimate the depth of anesthesia obtained with a given plasma concentration of drug for a given patient. That patient may then be maintained at a plasma concentration just greater than that required for awakening, thus decreasing the amount of plasma concentration of the drug that would be required before awakening. 'flus, m turn, leads to a decrease in the time to recovery from anesthesia. (22,

Front 36

37. What does the effect-site equilibration time refer to? What is its clinical usefulness?

Back 36

37. The effect-sitt equilibJation time refers to the interval of time required between the time that a specific drug concentration is achieved in the plasma and a specific effect of the drug can be measured. The effect-site equilibration time reflects the time necessary for the circulation to deliver the drug to its site of action, such as the brain. Knowledge of the effect-site equilibration time reflects the time necessary for the circulation to deliver the drug to its site of action, such as the brain. Knowledge of the effect-site equilibration e for a particular drug may be clinically useful in determining dosing ! intervals or in the titration of particular drugs. (22;

Front 37

38. What is the pharmacokinetic relevance of the degree of ionization of a drug? What factors determine the degree of ionization of a drug?

Back 37

38. The degree of ionization of a drug is a key factor in the pharmacokinetics of a drug with respect to its pharmacologic activity, solubility in lipids, transfer out of the central compartment, and clearance from the central compartment. Most drugs are weak acids or weak bases and, under physiologic conditions, exist in both ionized and nonionized fOnDs. The pK of a drug is a constant that determines the degree of ionization of the drug at physiologic pH, or in solutions in which the pH deviates from physiologic pH. The pKa of a drug is defined as the pH of the drug at which the drug vill be 50% ionized. Therefore, when the pKa of a drug and the pH of the surrounding fhud are identical, 50% percent of the drug exists in the ionized form. When the pK of a drug is close to the pH of the surrounding fluid, small changes in the pH of the surrounding fluid can result in large changes in the degree of ionization of the drug. Drugs that are weak acids tend to be highly ionized in a basic solution and nonionized in an acidic pH. The opposite is true for drugs that are weak bases, such that these drugs tend to be highly nonionized in a b.sic solution and ionized in an acidic pH. (22, Table 2-1; 17)

Front 38

39. What is the principal advantage of the intravenous administration of drugs?

Back 38

39. The principal advantage of the intravenous administration of drugs lS that the plasma concentration of drug that is achieved is more predictable than when drugs are administered orally or intramuscularly. After the intravenous j administration of a drug, the higWy perfused tissues will receive a proportionally larger amount of the total dose of drug than other tissues. The highly perfused tissues include the brain, heart, liver, and kidneys. Intravenously administered anesthetic drugs that are lipid soluble therefore read the brain rapidly and cross the blood-brain barrier to exert their effects. (22; 30)

Front 39

40. What is the first-pass hepatic effect of drugs? When does it apply? What is its clinical effect?

Back 39

:\.O. The first-pass effect refers to the extensive metabolism of a drug before reaching the systemic circulation and exerting its pharmacologic effect. A drug administered orally becomes absorbed from the gastrointestinal tract, enters the portal venous blood, and then passes through the liver before entering the systemic circulation. This only applies to drugs administered orally and is referred to as the first-pass hepatic effect. The clinical effect is most significant when drugs are extensively metabolized by the liver. These drugs have large differences between the oral and intravenous doses that need to be administered for a similar pharmacologic effect. Examples of drugs that f undergo extensive metabolism by the liver include lidocaine and propranolol.

Front 40

41. What is the first-pass pulmonary effect of drugs? When does it apply? What is its clinical effect?

Back 40

41. The first-pass pulmonary effect of drugs refers to the uptake of basic lipophilic amines by the lung. Examples of these drugs include lidocaine, propranolol, and fentanyl. Clinically, the first-pass pulmonary effect may influence the peak arterial concentration of these drugs. The lungs may also serve as a reservoir from which drug is released back inn the systemic circulation.

Front 41

42. Describe the redistribution of a drug after its intravenous administration. What is the clinical relevance of redistribution?

Back 41

42. After the intravenous administration of a drug, highly perused tissues rapidly take up drug from the plasma. Eventually the plasma concentration of drug will drop below the concentration of drug in the highly perfused tissues. The drug will then leave the highly perfused tissues, move into the plasma, and be delivered to less well-perfused tissue sites. This transfer of drug to inactive tissue sItes, such as skeletal muscle and fat, is known as redistribution. A clinical example of redistribution can be seen after the administration of an intravenous bolus dose of thiopental for the induction of anesthesia. The transfer of drug to inactive tissue sites, or redistribution, is responsible for waning of the pharmacologic effect of the drug. Clinically, the redistribution Jf thiopental after the administration of an induction dose is reflected by patient awakening after the administration of the drug. Repeated doses or a continuous infusion of a drug such as thiopental can saturate the inactive tissue sites. As these sites become saturated, redistribution becomes a prolonged effect. The body tissues then depend on metabolism as the principal method of elimination of the drug. The result is a prolonged pharmacologic effect of the drug. In the case in which the drug is thiopental, the clinical effect may be delayed awakening.

Front 42

43. What are receptors? How are receptors identified and classified?

Back 42

43. Receptors are components of a cell that selectively interact with compounds that are external to the cell. The interaction of the receptor with the compound results in the translation of the stimulus into a specific effect. Receptors are typically protein macromolecules present in the cell membrane, whereas the compounds with whicr: they interact are frequently drugs in the plasma. Receptors are identified and classified on the basis of their effects after being stimulated by agonists or blocked by antagonists. Examples of classes of receptors include the alpha, beta, dopamine, histamine, and fiU receptor types. These classifications are useful to summarize the pharmacologic effects of agon:.st and antagonist drugs.

Front 43

45. Name an example of a receptor type that acts as a protein (ion) channel.

Back 43

45. Receptors for the neurotransmitter gamma-aminobutyric acid (GABA) are an example of protein (ion) channels. This type of receptor results in ion flow into or out of the cell when activated. In this example, after activation of the receptor by GABA, the ion channel changes configuration such that there is flow of chloride ions into the cell. (2

Front 44

46. Name an example of a receptor type that opens an ion channel via membraneound G proteins when stimulated.

Back 44

46. An example of a receptor that opens an ion channel via membrane-bound G proteins when stimulated is the muscarinic receptor. The muscarinic receptor couples to the membrane bound guaIine nucleotide binding protein (G protein) after its activation by an agonist. The result of this coupling is opening of the pot,ssium ion channel and tow of potassium ions through the channel.

Front 45

47. Name an example of a receptor type that acts via membrane-bound G proteins and an intracellular second messenger to exert its intracellular effects.

Back 45

47. Like the muscarinic receptor, other receptors act via binding of the receptor to a G protein. Unlike the muscarinic receptor, however, the coupling of the receptor with a G protein may result in activation of an intracellular second messenger to exert its intracellular effects. An example of a second messenger is cyclic adenosine monophosphate (cAMP), whose activity is regulated by adenylate cyclase. Adenylate cyclase cm be stimulated through a stimulatory G protein, positively affecting its activity and resulting in an increase in the intracellular leve of cAMP.

Front 46

48. Name an example of a receptor type that acts through the activation of phospholipase C.

Back 46

Alpha-l receptors act by interacting with the membrane-bound enzyme phospholipase C once activated. Activation of phospholipase C catalyzes reactions, leading to second messengers that stimulate the release of calcium from intracellular stores. I

Front 47

49. Why is the sterompecificity of drugs important with respect to their interaction with the receptor?

Back 47

49. The stereospecificity of a drug is often important in how it configures with the receptor to exert its pharmacologic response. Most drugs are synthesized as racemic mixtures containing about 50% each of the dextro (d) and levo (l) isomers. These stereoisomers of the same drug may have distinctly different biologic properties. The inactive isomer may be an impurity that does not contribute to its pharmacologic effect. The inactive isomer may, however, contribute to undesired drug effects.

Front 48

50. Are the number of receptors in lipid cell membranes static or dynamic? Give an example of down-regulation and up-regulation of a receptor.

Back 48

50. The numbel of receptors in lipid cell membranes is dynamic. Receptors mcrease in number (up-regulation) or decrease in number (down-regulation) in response to specific stimuli. Beta-adrenergic receptors are an example of a receptor that can behave this way. When beta-adrenergic receptors are chronically stimulated, down-regulation of the receptor can result. This can be seen to occur after chronic asthma treatment with beta agmists. The decrease in :he number of beta receptors under these conditions explains the resulting tachyphylaxi$. When beta receptors are chronically blocked, up-regulation of the receptor can result. The increased number of receptors can result in an exaggerated response if the blockade is discontinued. This explains the exaggerated hypertension that can result from discontinuation of a patient's beta-blockade therapy.

Front 49

51. How does aging change the responsiveness of receptors?

Back 49

51. The mechanism by which the responsiveness of receptors changes is not well understood. The change in receptor responsiveness that occurs with age appears to occur independent from a change in the number of receptors.

Front 50

52. During steady-state conditions, what is the relationship between the concentration of drug at the receptors and the flasma concentration of drug?

Back 50

During steady-state conditions the concentration of a drug at the receptor is believed to be directly proportional to the plasma concentration of the drug. This allows for pharmacodynamic studies to be performed that evaluate the dose of drug required for specific response