Nagelhout Chpt 7

Front 1

what is pharmacokinetics?

Back 1

term used to describe the study of the changes in concentration of a drug during the processes of absorption, distribution, metalosim, or biotransformation, and elimination from body

Front 2

what system delivers drug to various tissues?

Back 2

vascular system

Front 3

once in the blood the drug can go where?

Back 3

-either remain w/in vascular system and body water
-bound to proteins
-cross membranes to enter tissues

Front 4

where does the unbound drug go?

Back 4

enters organs, muscles, fat, and site of activity (receptors)

Front 5

the transfer of drug to various sites depends on what?

Back 5

-intrinsic properties of the agent
-molecular size
-degree of ionization
-lipid solubility
-protein binding

Front 6

what does uptake of drug depend on?

Back 6

-amt of blood flow to the tissue and the concentration gradient of the drug across membranes

Front 7

the smaller the molecular size of an agent, the ______it crosses lipid barriers?

Back 7

better

Front 8

molecules with molecular weights greater than ___-___do not cross cell membrane?

Back 8

100-200

Front 9

transport across a membrane can occur how?

Back 9

actively or passively

Front 10

______transport does not require energy and involves transfer of a drug from ana area of high concentration to an area of lower concentration?

Back 10

passive

Front 11

______transport mechanisms are generally faster and require energy?

Back 11

active transport

Front 12

T or F most drugs are salts of either weak acids or weak bases.

Back 12

true

Front 13

the noncharged ionized/nonionized form is lipophilic?

Back 13

nonionized

Front 14

the charged ionized/nonionized form is water soluble?

Back 14

ionized

Front 15

because the nonionzied molecules are lipid solube they can diffuse across cell membranes such as ?

Back 15

-blood-brain
-gastric
-placental

Front 16

ionized molecules are are usually unable to penetrate lipid cell membranes because why?

Back 16

of their low lipid solubility

Front 17

the higher the degree of ionization the more/less access the drug has across tissues such as the GI tract, blood-brain, and placental barriers and liver hepatocytes?

Back 17

less

Front 18

how are ionized drugs excreted?

Back 18

via the renal system

Front 19

whether acidic or basic the degree of ionization of an agent at particular site is determined by what two factors?

Back 19

1-dissociation constant (pKa)
2-ph gradient across teh membrane

Front 20

what is pKa?

Back 20

the negative log of the equilibrium constant for the dissociation of the acid or base

Front 21

acids are proton____-?

Back 21

donors

Front 22

bases are proton ______--?

Back 22

acceptors

Front 23

weak base
pH>pKa=?

Back 23

un-ionized form predominates

Front 24

weak base
ph=pKa?

Back 24

un-ionized equal to ionized

Front 25

weak base
pH < pKa=?

Back 25

ionized form predominates

Front 26

weak acid
pH>pKa?

Back 26

ionized form predominates

Front 27

weak acid pH=pKa=?

Back 27

Unionized equal to ionized

Front 28

weak acid
pH<pKa?

Back 28

unionized form predominates

Front 29

Ion trapping has several anesthesia related applications what are they?

Back 29

-influences on oral absorption of drugs
-maternal-fetal transfer
-central nervous system toxicity of LA

Front 30

the pH of the fetus is more acidic or basic than that of the mother?

Back 30

acidic

Front 31

T or F lidocaine crosses the placenta easily

Back 31

true

Front 32

changes in what have been theorized to influence a drug's clincial effect?

Back 32

protein binding

Front 33

what is teh most abundant plasma protein?

Back 33

albumin

Front 34

what usually binds to albumin?

Back 34

acidic compounds

Front 35

what proteins favor binding to basic drugs?

Back 35

AAG and B-globulin

Front 36

what bind cyclosporine?

Back 36

lipoproteins

Front 37

what binds corticosteroids?

Back 37

transcortin

Front 38

high protein binding prevetns the drug from leaving where, to enter into tissue, which results in high ______concentrations?

Back 38

blood, plasma

Front 39

the degree of protein binding for a drug is proportional to what?

Back 39

it's lipid solubility

Front 40

the bond btwn drug and protein is strong/weak?

Back 40

weak

Front 41

b/c the bond btwn drug and protein is weak they can dissociate when?

Back 41

1-when the plasma conc. of teh drug declines
2-or a second drugs that binds the same protein is introduced

Front 42

displaced free drug becomes available for what?

Back 42

biotransformation and elimination

Front 43

protein binding is expressed in what terms?

Back 43

in percentage of total drug bound

Front 44

warfarin is approx ____% bound to plasma proteins

Back 44

98

Front 45

when hypoalbuminemia exists decreased albumin result in what?

Back 45

the availability of a greater amount of free drug

Front 46

a 5% increase in teh amt of unbound drug in the body produces at most a ___% increase in pharmacologically active unbound drug at the site of action

Back 46

5%

Front 47

when the amt of unbound drug in plasma increase what happens to the rate of elimination?

Back 47

rate of elimination increases

Front 48

after ___half lives teh unbound concentration returns to its previous steady state value?

Back 48

four

Front 49

when plasma proteins are lower than normal total drug concentrations are ________, but unbound concentrations are _______?

Back 49

lowered, not effected

Front 50

what determines how much of the drug is delivered to the systemic circulation?

Back 50

the route of administration

Front 51

when the entire amt amt of drug given is delivered the drug is said to what?

Back 51

have 100% bioavailability

Front 52

what are the routes of drug administration?

Back 52

-enteral (involves GI tract)
-parenteral (subq, IM, IV, intrathecally, epidremally)
-pulmonary
-topical

Front 53

what is the most common and convenient method for administration of a drug?

Back 53

oral route

Front 54

what are disadvantages of oral route?

Back 54

-emotions, physical activity and food intake change GI environ.

Front 55

drugs administered orally have lower or higher bioavailability?

Back 55

lower

Front 56

what is a significant factor in absorption of drug taken orally?

Back 56

the length of time drug remains in stomach

Front 57

what is pH of stomach?

Back 57

1.5-2.5

Front 58

drugs that are highly acidic like __________tend to remain nonionized and are highly absorbed?

Back 58

barbiturates

Front 59

what type of drugs that remain intact in the stomach and pass through are highly absorbed in small intesting?

Back 59

basic drugs

Front 60

what is alkaline environment of small intestine?

Back 60

7-8

Front 61

what is presystemic elimination?

Back 61

the elimination of a drug by the GI system before the drug reaches teh systemic circulation

Front 62

what are the 3 mechasims that cause presystemic elimination?

Back 62

1-stomach acid hydrolyzes the drug
2-enzymes in GI wall deactivate the drug
3-liver biotransforms ingested drug before it reaches the effect site

Front 63

the liver activity that biotransforms the drug before it reaches the effect site is called what effect?

Back 63

first-pass hepatic effect

Front 64

drugs absorbed from GI tract after original ingestion enter what?

Back 64

the portal venous blood and pass through the liver first

Front 65

in the liver what can occur to the drug before it has a chance to enter systemic circulation?

Back 65

extensive hepatic extraction and metabolism

Front 66

what is bioavailability of IV route of drug administration?

Back 66

100%

Front 67

what is bioavailability of IM route of administration?

Back 67

75-100%

Front 68

what is bioavailability of subq route?

Back 68

75-100

Front 69

what is bioavailability of oral route?

Back 69

5-100

Front 70

what is bioavailability of rectal route?

Back 70

30-100%

Front 71

what is bioavailability of inhalation route?

Back 71

5-100%

Front 72

what is bioavailabilty of sublingual route?

Back 72

60-100%

Front 73

what is bioavailability of intrathecal route?

Back 73

low (intentionally)

Front 74

what is bioavailablity of topical route?

Back 74

80-100%

Front 75

what route is the most rapid and allows for titration of doses?

Back 75

IV

Front 76

what route allows for less first pass effect than oral?

Back 76

rectal

Front 77

what route has a lack of first-pass effect and is absorbed directly into systemic cirucation?

Back 77

sublingual

Front 78

what are some examples of drugs that undergo substantial first-pass elimination?

Back 78

-ASA
-glyceryl trinitrate
-isosorbide dinitrate
-levodopa
-lidocaine
-metoprolol
-morphine
-propranolol
-verapamil
-salbutamol

Front 79

P-glycoprotein transporter is part of a larger family of effluc transporters found where?

Back 79

intestine
liver
renal proximal tubular cells
capillary endothelial cells
comprising the BBB

Front 80

what two routes of administration of drugs bypass the presystemic, portal system first-pass effect and are delivered rapidly to the superior vena cava for transport ?

Back 80

sublingual and buccal

Front 81

what route of administration is teh ideal route for prevention from emesis caused by irritation of GI mucosa by the drug?

Back 81

rectal route

Front 82

drugs placed in the _________rectum are abosorbed into the portal system via what vein?

Back 82

proximal, suprior hemorrhoidal vein

Front 83

agents placed in the distal rectum do or do not undergo presystemic elimination?

Back 83

do NOT and therefore have more predictable circulatory levels

Front 84

parentareral administration refers to administration by what?

Back 84

injection

Front 85

with both IM and subq inj. systemic absorption of drug is dependent on what?

Back 85

capillar blood flow to the area
lipid solubility of agent

Front 86

T or F the lungs provide a lg. surface area for drugs administered by inhalatio.

Back 86

true

Front 87

what route is used for administratoin of sustained release agent

Back 87

transdermal

Front 88

what characteristcs must a drug have to be administered via transdermal route?

Back 88

-water and lipid soluble
-have MW < 1000
-dose requirements < 10mg in 24 hr
-pH of 5-9
-area it's applied must be relatively thin epidermis w/ sufficien blood supply

Front 89

what is bioavailability?

Back 89

the extent to which a drug reaches its effect site after its introduction into the circulatory system

Front 90

what factors play a role in the bioavailability of agents?

Back 90

-lipid solubility
-solubility in aqueous and organic solvents
-MW
-pH
-pKa
-blood flow

Front 91

the environment into which a drug is introduced also has impact so what are factors of pt's environment that may affect bioavailability?

Back 91

-age
-sex
-pathology
-pH
-blood flow
-temperature

Front 92

what are compartment models used for?

Back 92

prediction of serum concentrations and changes in drug concentrations in other tissues

Front 93

a single compartment moel represents what through which homogenous distribution occurs?

Back 93

entire body

Front 94

a two-compartment model is used to simplify and explain what that can be extrapolated to more complex models?

Back 94

pharmacokinetic

Front 95

in the two-compartment model what are the names of the two compartments?

Back 95

central compartment (vessel-rich grp)
peripheral compartment (vessel-poor group)

Front 96

what composes teh vessel poor group?

Back 96

muslce
fat
bone
(represents 90% of body mass)

Front 97

the second compartment of two compartment model the peirpheral compartment receives how much of teh cardiac output?

Back 97

25%

Front 98

the central compartment receives what percent of the CO?

Back 98

75%

Front 99

drugs leave central compartment by what two phases?

Back 99

-distribution into tissues
-metabolism and excretion

Front 100

the drug enters what compartment for clearance from teh body?

Back 100

central compartment

Front 101

drugs cross lipid membranes by what?

Back 101

-passive diffuional transfer
-carrier mediated transfer

Front 102

absorption from the gut depends on what?

Back 102

-GI motility
-GI pH
-particle size
-physiochemical interaction w/ gut contents

Front 103

PH partition refers to the fact that weak acids tend to accumulate in compartments w/ relatively high or low pH?

Back 103

high

Front 104

the volume of distribution is a proportional expression that relates to what?

Back 104

the amt of drug in the body to the serum concentration
(the apparent volume in which the drug is distributed after it has been intoduced into the system)

Front 105

what is formula for volume of distribution?

Back 105

Vd= dose of drug/plasma conc. of drug

Front 106

a drug with large Vd has high or low conc. in the plasma?

Back 106

low--very little drug would be available to the organs for elimination

Front 107

what is Vd of drug affected by?

Back 107

-physiochemical properties of drug
-lipid solubility
-plasma protein binding
-molecular size

Front 108

the affinity of a drug for a specific macromolecular component of the cell and its intrisic activity are related to it's what?

Back 108

chemical structure

Front 109

relatively minor modification in the drug structure may result in major changes in what?

Back 109

pharmacologic properties

Front 110

what are stereoisomers?

Back 110

molecules with the same chemical bonds but differnt configurations in their fixed spatial arrangements

Front 111

what are enatiomers?

Back 111

stereoisomers are non-superimposable mirror images of each other

Front 112

what are 3 drug examples of select isomers w/ improved clinical properties?

Back 112

1-cisatrcurium
2-levo-bupivacaine
3-ropivacaine

Front 113

what does the y-axis on the plasma conc. curve represent?

Back 113

plasma concentration

Front 114

what does the x-axis on the plasma conc curve represent?

Back 114

the time after the dose is injected

Front 115

what is the first alpha phase of the plasma conc. curve?

Back 115

distribution phase-represents initial dispersal of drug into the tissue compartments from the central compartment

Front 116

what is the second phase of the plasma conc. curve?

Back 116

a logarithmic plot of the slower eliminaton or beta phase of the curve

Front 117

the plasma concn. curve is an example of what kind of curve?

Back 117

biexponential decay curve

Front 118

a steady state occurs when?

Back 118

a stable plasma concentration of a drug is achieved

Front 119

when is steady state typically reached?

Back 119

with chronic administration ofa drug or
by continuous IV infusion

Front 120

drug metabolism is synomous w/ what term?

Back 120

drug biotransformation

Front 121

what is metabolism?

Back 121

enzyme-catalyzed change in chemical structure of agents and usually involves more than one pathway

Front 122

what is the main organ for drug metabolism?

Back 122

liver

Front 123

the main organ for metabolism is liver but metabolism can also occur where?

Back 123

-plasma
-lungs
-GI tract
-Kidneys
-heart
-brain
-skin

Front 124

what is the goal of metabolism/

Back 124

to change lipid-soluble agents into more water soluble forms so kidneys can eliminate them from the body

Front 125

metabolism usually leads to transformation of active drugs to what?

Back 125

inactive metabolites

Front 126

water-solube drugs are mainly confined to what and do not enter the brain after acute dosing?

Back 126

plasma

Front 127

plasma half-life is directly proportional to what and inverserly proportional to what?

Back 127

proportional to volume of distribution
inversely proportional to overall rate of clearance

Front 128

what are some drugs that are cholineseterase catalyzed?

Back 128

-succs
-cocaine
-procaine
-chloroprocaine
-tetracaine
-neostigmine
-pyridostigmine
-edrophonium

Front 129

what are some nonesterase dependent drugs that undergo phase I hydrolysis?

Back 129

remifenatnil
atracurium
cisatracurium
esmolol
aspirin

Front 130

what does zero order kinetics mean?

Back 130

even at therapeutic levels they exceed teh body's ability to excrete or metabolize them

Front 131

what are phase I reactions that occur during drug metabolism?

Back 131

oxidation
reduction
hydrolysis

Front 132

what are phase II reactions?

Back 132

involve conjugate reactions in which drug metabolite is conjugated w/ endogenous substance such as glucuronic, sulfonic or acetic acid

Front 133

what are oxidative reactions?

Back 133

oxygen is introduced into the molecule or the oxidative state of a molecule is changed so that its relative oxygen content is increased

Front 134

oxidative metabolim reactions are catalyzed by enzymes of what system?

Back 134

cytochrome P-450 system

Front 135

reduction involves gain or loss of electrons?

Back 135

gain of electrons

Front 136

what is hydrolysis?

Back 136

addition of water to an ester or amide to break the bond and form two smaller molecules

Front 137

what is the end result of phase I reactions?

Back 137

a more polar compound that is easily excreted by the kidney

Front 138

why are phase II reactions also referred to as synthetic reactions?

Back 138

the body synthesizes a new compound by donating a functional grp usually derived from an endogenous acid

Front 139

what are some of the intracellular sites that exist for drug metabolizing enzymes?

Back 139

-endoplasmic reticulum
-mitochondria
-cytosol
-lysosomes
-plasma membrane

Front 140

the cytochrome P-450 is also called what system because it includes both oxidation and reduction steps and has low substrate specificity?

Back 140

mixed-function oxidase

Front 141

where are some extrahepatic sites of P-450 system?

Back 141

-kidneys
-lungs
-skin
-intestial mucosa

Front 142

what is elimination half time?

Back 142

the time necessary for the plasma content of the drug to drop to half of its prevailing concentration after a rapid bolus injectin

Front 143

a drug is regarded as being fully emliminated when approx ___% has been eliminated from teh body?

Back 143

95%

Front 144

___half lives is considered sufficient time for the drug's action to be terminated and the agent eliminated from the body?

Back 144

4 half lives

Front 145

what is context sensitive half time?

Back 145

the time to halving of the blood conc. after termination of drug administration by an infusion designed to maintain a constant conc.

Front 146

how is clearance defined?

Back 146

the volume of plasma completely cleared of drug by metabolism and excretion per unit of time

Front 147

clearance is directly proportional to ?

Back 147

dose

Front 148

clearance is inversely related to ?

Back 148

the agent's half life as well as its concentration in the central compartment

Front 149

what are two main organs for clearance?

Back 149

kidney and liver

Front 150

formula for clearance is clearance=?

Back 150

Q (blood flow) x E (extration ratio)

Front 151

what are high clearance drugs?

Back 151

drugs that have high conc ratio of 0.7 or greater rely heavily on perfusion to liver to be cleared

Front 152

what are 3 examples of high clearance drugs?

Back 152

verapamil
morphine
lidocaine

Front 153

what are three drugs that have low hepatic extraction?

Back 153

thiopental
diazepam
theophylline

Front 154

the kidneys excrete water soluble or lipid solule molecules with great ease?

Back 154

water-soluble

Front 155

the excretion of drugs from kidneys involves what 3 processess?

Back 155

1-passive glomerular filtration
2-active tubular secretion
3-some reabsorption

Front 156

the amt of drug made available to renal tubule for elimination depends on what?

Back 156

the amt of free, unbound drug and the glomerular filtration rate

Front 157

lipid soluble agents depend on what to excrete them?

Back 157

liver-(kidney does not excrete lipid soluble agents as efficiently as water soluble compounds)

Front 158

what is an example of a lipid soluble drug that is almost completely reabsorbed?

Back 158

thiopental

Front 159

the pH of _____ can affect the elminiation of drugs via the kidney?

Back 159

urine

Front 160

_________(type of lab) is an indicator of renal function?

Back 160

creatnine clearance

Front 161

why is elimination of drugs via the kidney's altered in neonates?

Back 161

because of poor renal function the first year of life

Front 162

T or F gender differences account for some variability in the pharmaokinetics of many agents.

Back 162

true

Front 163

female pt's have __-___% greater sensitivity to muscle relaxat effects of vec, pan, and roc?

Back 163

20-30%

Front 164

who is more sensitive to propofol male or females?

Back 164

males

Front 165

who is more likely to experience recall under GA, males or females?

Back 165

females

Front 166

males require ____-___% more narcotics for pain mngt vs. females?

Back 166

30-40%

Front 167

temperature affects tissue metabolism and what?

Back 167

blood flow

Front 168

what is the most important pharmacokinetic parameter?

Back 168

clearance

Front 169

what is definition of pharmacogenetics?

Back 169

the study of variations in human genes that are responsible for different responses to drug therapy

Front 170

what is pharmacogenomics?

Back 170

evolution of pharmacogentic reserach involves the identification of drug response markers at the level of disease, drug metabolism, or drug target

Front 171

pharmacotherapy may be affected by 3 types of genetic variation, what are they?

Back 171

1-variations in target proteins
2-enzyme metabolism
3-idiosyncratic effects

Front 172

what are polymorphisms?

Back 172

variations in the DNA sequences that occur in at least 1% of the population

Front 173

most variations in the human genome occur in what type of enzyme genes?

Back 173

drug metabolizing enzyme genes