pharmacokinetics

Question 1

drug has Vd of .35mL/kg. in 70kg patient, what IV loading dose must be administered to achieve a plasma concentration of 8mg/dL

Answer 1

196mg
(.35L/kg x 70 = 24.5L)
(24.5L x 8mg/L) / 1 =
loading dose = (Vd x desired CP) / bioavailability

Question 2

Vd=

Answer 2

amount of drug/desired plasma concentration

Question 3

Vd assumes two things

Answer 3

1. drug distributes instantaneously (full equilibration occurs at time =0)
2. Drug is not subjected to biotransformation or elimination before it fully distributes

Question 4

review distribution of body water in 70kg patient
tbw
extracellular (plasma volume, ISF)
intracellular

Answer 4

Question 5

lipophilic drug characteristics

Answer 5

Vd exceeds TBW (>.6L/kg or >42L)
distributes into TBW and fat
requires higher dose to achieve plasma concentration

Question 6

hydrophilic drug characteristics

Answer 6

Vd less than TBW (<.6L/kg or <42L)
distributes into some or all of body water but not fat
require lower dose to achieve given plasma concentration

Question 7

Vd is affected by which 2 characteristics

Answer 7

drug (molecular size, ionization, protein binding)
patient (pregnancy and burns)

Question 8

loading dose=

Answer 8

Vd x (desired plasma concentration/ bio availability)
IV: bio availability =1

Question 9

clearance is directly proportional to (3)

Answer 9

blood flow to clearing organ
extraction ratio
drug dose

Question 10

clearance is inversely proportional to (2)

Answer 10

half life
drug concentration in central compartment

Question 11

review this graph

Answer 11

alpha: redistribution- steepest part of curve
beta: elimination from central compartment- less steep part of curve
A+B represents plasma concentration over time

Question 12

k12

Answer 12

rate constant for drug transfer from central compartment to peripheral compartment

Question 13

k21

Answer 13

rate constant for drug transfer from peripheral compartment to central compartment

Question 14

ke

Answer 14

rate constant for drug elimination from body

Question 15

describe three compartment model

Answer 15

different rate constants going to and from each compartment.

Question 16

elimination half life versus elimination half time

Answer 16

time it takes for 50% of drug to be removed after rapid IV injection versus

time it takes for 50% of drug to be removed from the plasma during the elimination phase

Question 17

amount of drug eliminated and half times

Answer 17

drug is considered eliminated after 96.9% is gone

Question 18

half time measures what

Answer 18

constant fraction and not constant amount

Question 19

define context sensitive half time

Answer 19

time required for plasma concentration to fall by 50% after the infusion is stopped

Question 20

review the context sensitive half time graph as it relates to phenylpiperdines

Answer 20

Question 21

an acid _______ a proton while a base ________ a proton

Answer 21

acid: donates a proton
base: accepts a proton

Question 22

ionization is dependent on two things

Answer 22

pH of solution and pKa of drug

Question 23

pKa =

Answer 23

pH where 50% of drug is ionized and 50% is non ionized

Question 24

henderson hasslebach equation

Answer 24

pH= pKa + log (base/conjugate acid)

Question 25

weak bases in an acidic versus basic solution

Answer 25

in an acidic solution, more ionized and water soluble in a basic solution, more non ionized and lipid soluble

Question 26

weak acids in acidic versus basic solution

Answer 26

in an acidic solution, weak acids are more non ionized and lipid soluble in a basic solution, weak acids are more ionized and water soluble

Question 27

a drug that is a weak acid is paired with

Answer 27

a positive ion such as sodium, calcium, or magnesium

Question 28

a drug that is a weak base is paired with

Answer 28

a negative ion such as chloride or sulfate

Question 29

what LA is most likely to undergo fetal ion trapping

Answer 29

lidocaine. (maternal alkalosis and fetal acidosis)

Question 30

percent change of drug bound by plasma protein

Answer 30

percent change = ((new value- old value)/old value) x 100 (96-98)/96 x 100 = 100% increase in un bound initial: 98% bound then: 96% bound

Question 31

albumin key facts

Answer 31

most plentiful plasma protein primary determinant of plasma oncotic pressure t1/2 3 weeks carries a negative charge primarily binds with acidic drugs also binds with neutral and basic drugs

Question 32

what decreases Cp (plasma clearance) of drugs that bind to albumin (5)

Answer 32

liver disease renal disease old age malnutrition pregnancy

Question 33

what kind of drugs that a1 acid glycoprotein bind to

Answer 33

acidic

Question 34

plasma clearance of drugs that bind to a1 acid glycoproein are decreased by

Answer 34

neonates and pregnancy

Question 35

plasma clearance of drugs that bind to a1 acid glycoproein are increased by

Answer 35

surgical stress MI chronic pain RA advanced age

Question 36

what kind of drugs do beta globulin proteins bind to

Answer 36

acidic

Question 37

plasma clearance of drugs that bind to beta globulins are increased or decreased by

Answer 37

n/a

Question 38

zero order kinetics versus first order kineticcs

Answer 38

zero: constant amount of drug is metabolized per unit of time first: constant fraction of drug is metabolized per unit of time

Question 39

what kind of metabolism does this represent

Answer 39

zero order kinetics (more drug than enzyme)

Question 40

what kind of metabolism does this represent

Answer 40

first order kinetics (less drug than enzyme)

Question 41

3 phases of drug metabolism

Answer 41

phase 1: modification (oxidation, reduction, hydrolysis) phase 2: conjugation phase 3: excretion

Question 42

phase 1: modification biotransformation is carried out by what happens during 3 reactions

Answer 42

increases polarity biotransformation via p450 system oxidation: removes electrons from compound reduction: adds electrons to a compound hydrolysis: adds water to a compound to split it apart (usually an ester)

Question 43

phase 2: conjugation

Answer 43

adds on endogenous, highly polar, water soluble substrate to the molecule. produces a water soluble biologically inactive molecule ready for excretion some drugs do not need phase 1 and go directly to this

Question 44

substrates used for phase 2 conjugation

Answer 44

glucoronic acid glycine acetic acid sulfuric acid methyl group

Question 45

describe enterohepatic circulation

Answer 45

some conjugates compounds are excreted in the bile, reactivated in the intestine, and then reabsorbed into systemic circulation. usually has long effects ex) diazepam, warfarin

Question 46

phase 3: elimination

Answer 46

involves ATP dependent carrier proteins that transport drugs across cell membranes. present in kidneys, liver, GI tract

Question 47

extraction ratio of 1

Answer 47

100% of the drug delivered to the clearing organ is removed

Question 48

extraction ratio of .5

Answer 48

means 50% of the drug delivered to the clearing organ is removed.

Question 49

a perfusion dependent elimination has an extraction ratio of______ and clearance is dependent on ____________________________

Answer 49

>.7 clearance is dependent on liver blood flow. increased liver BF, increased clearance

Question 50

a capacity dependent elimination has an extraction ratio of ______ and clearance is dependent on ______________________________

Answer 50

<.3 clearance is dependent on changes in hepatic enzyme activity or protein binding enzyme induction increases clearance enzyme inhibition decreases clearance

Question 51

drugs that have low hepatic extraction ratios

Answer 51

rocuronium diazepam lorazepam methadone thiopental theophylline phenytoin

Question 52

drugs that have intermediate hepatic extraction ratios

Answer 52

midazolam vecuronium alfentanil methohexital

Question 53

drugs that have high hepatic extraction ratios

Answer 53

fentanyl sufentanil morphine meperidine naloxone ketamine propofol lidocaine bupivicaine metoprolol propanolol alprenolol nifedipine diazepam verapamil

Question 54

examples of enzyme inducers include

Answer 54

tobacco smoke barrbiturates ethanol phenytoin rifampin carbamazepine

Question 55

examples of enzyme inhibitors include

Answer 55

grapefruit juice cimetidine omeprazole isoniazid SSRI's erythromycin ketoconazole

Question 56

drugs metabolized via CYP3A4

Answer 56

opioids: fentanyl, alfentanil, sufentanil, methadone benzos: midaz, diazepam LA's: bupiv, ropiv

Question 57

drugs metabolized by CYP2D6

Answer 57

codeine -->morphine oxycodone hydrocodone

Question 58

drugs metabolized by CYP1A2

Answer 58

theophylline

Question 59

lipophilic drugs that do not undergo bio transformation have what fate in the renal system

Answer 59

reabsorbed in peritubular fluid via diffusion

Question 60

two processes that deliver drug to the urine

Answer 60

1. GFR: only free fraction unbound drug is filtered at glomerulus 2. organic anion (OAT) and cation (OCT) transporters:

Question 61

drugs that utilize OAT

Answer 61

furosemide, thiazide diuretics, PCN

Question 62

drugs that utilize OCT

Answer 62

morphine, meperidine, dopamine

Question 63

acidic urine and drug excretion

Answer 63

favors reabsorption of acidic drugs excretion of basic drugs AAA- acidic drugs are better absorbed in acidic medium

Question 64

alkalotic urine and drug excretion

Answer 64

favors reabsorption of basic drugs excretion of acidic drugs BBB- basic drugs are better absorbed in a basic medium

Question 65

how to help acidify the urine to help eliminate basic drugs

Answer 65

ammonium chloride or cranberry juice

Question 66

how to help alkalize urine to help eliminate acidic drugs

Answer 66

sodium bicarb or acetazolamide

Question 67

drugs metabolized by nonspecific plasma esterases (6)

Answer 67

esmolol, remifentanil, atracurium, remimazolam, etomidate, clevidipine

Question 68

which drug utilizes alkaline phosphatase for metabolism/elimination

Answer 68

fospropofol

Question 69

drugs metabolized by pseudocholinesterases

Answer 69

succ, cocaine, mivacurium, ester LA's

Question 70

drugs metabolized via hoffman elimination

Answer 70

ciisatracurium atracurium(+ non specific plasma esterases)

Question 71

peusdocholinesterase deficiency extends DOA of

Answer 71

succ mivacurium cocaine ester LA's