Pharmacokinetics/dynamics

Question 1

Describe total body water and breakdown in 70kg patient

Answer 1

TBW: 42 L ECF + ICF
Intracellular 28L
Extracellular: 14L
* Plasma volume: 4L
* Interstitial fluid: 10L

Question 2

What volume of distribution makes something lipophilic vs hydrophilic?

Answer 2

lipophilic Vd > 0.6L/kg or 42L
hydrophilic Vd < 0.6L/Kg or 42L

Question 3

If a drug has a long half life, what can you do to reach steady state faster? Why?

Answer 3

Give a loading dose, it takes 5 half lives to reach steady state

Question 4

What is alpha curve in 2 compartment model?

What afeccts how steep it is?

Answer 4

distribution from central compartment

volume of distrubtion. the greater the Vd the steeper the curve

Question 5

what is beta curve in 2 compartment model?

Answer 5

elimination from central compartment

Question 6

What is K12?

Answer 6

central compartment to pheripheral compartment

Question 7

waht is K21?

Answer 7

pheripheral compartment back to central compartment

Question 8

Elimation half life?

Answer 8

time for 50% of drug to be removed from BODY

Question 9

what is elimination half time?

Answer 9

time for 50% to be removed from PLASMA

Question 10

At what point has the drug been cleared?

Answer 10

when 96.9% eliminated from the plasma

Question 11

Does half life tell us the off set of anesthetic drugs?

Answer 11

no, way more complicated than that,

Question 12

What is an acid?

Answer 12

donates a proton (hydrogen ion)

Question 13

what is a base?

Answer 13

accepts a proton (hydrogen ion)

Question 14

what do strong acids and bases do in water?

Answer 14

dissociate totally
or ionize completely

Question 15

what do weak acids and bases do in water?

Answer 15

a fraction is ionized and a fraction is non-ionized

Question 16

what is Pka?

Answer 16

pH where half the drug is ionized and half is non-ionized

Question 17

ionized is water soluble or lipid soluble? Active or inactive?

Answer 17

water soluble, inactive

Question 18

Acid in Acid will be ionized or non-ionized?

Answer 18

non-ionized

Question 19

acid in base will be ionized or non-ionized?

Answer 19

ionized

Question 20

Weak acids are usually paired with waht?

Answer 20

+ ion like:
sodium
calcium
magnesium

Question 21

weak bases are usually paired with what?

Answer 21

(-)ion:

chloride or sulfate

Question 22

What kind of drugs does albumin bind?

Answer 22

mostly acidic drugs
also some basic and neutral drugs too

Question 23

what does alpha 1 glycoprotein bind?

Answer 23

basic drugs

Question 24

what does beta-globulin bind?

Answer 24

basic drugs

Question 25

are changes in plasma protein binding clinically relevant?

Answer 25

rarely

Question 26

when are changes in plasma protein binding actually clinically relevant?

Answer 26

CPB: hemodilution and heparinization ECMO: ceftriaxone, fentanyl, and midazolam

Question 27

describe zero order kinetics

Answer 27

drug elimination at a constant rate this occurs when drug>enyzme levels

Question 28

waht drugs follow zero order kinetics?

Answer 28

aspirin alcohol warfarin heparin theophyline phenytoin

Question 29

describe first order kinetics

Answer 29

drug is eliminated at a constant fraction this occurs when drug is less than enzymes

Question 30

what drugs follow first order kinetics?

Answer 30

basically everything

Question 31

what would happen to first order kinetics if an enzyme pathway became saturated?

Answer 31

it would change to zero order kinetics

Question 32

3 parts of hepatic metabolism?

Answer 32

modification conjugation elimination

Question 33

What are the three types of hepatic modification? And what happens during modification?

Answer 33

oxidation reduction hydrolysis (adds water to split compund? ^ polarity

Question 34

What happens during conjugation?

Answer 34

adds highly polar water soluble substance to the drug/molecule

Question 35

how is hepatic elimination carried out?

Answer 35

relies on ATP dependent carrier proteins

Question 36

what drugs undergo enterohepatic circulation and what is the implication?

Answer 36

diazepam and warfarin this is why they have a long DOA

Question 37

What are the two ways things are eliminated renally?

Answer 37

1. Glomerular filtration 2. Organic anion & cation transporters

Question 38

what do organic anion transporters (OAT eliminate?

Answer 38

lasix, thiazide diuretics, and penicillin

Question 39

what do organic cation transporters (OCT) eliminate?

Answer 39

morphine, meperidine, dopamine

Question 40

what drugs are reabsorbed in acid vs basic urine?

Answer 40

acidic urine reabsorbs acidic drugs basic urine reabsorbs basic urine

Question 41

What are two things that will acidify the urine?

Answer 41

cranberry juice or ammmmonium chloride

Question 42

what two things will alkalize the urine?

Answer 42

sodium bicarb acetazolamide

Question 43

name the 4 types of plasma metabolism. Which are enzyme dependent and which are not?

Answer 43

pseudocholinesterase (enzyme) non-specific esterases (enzyme) alkaline phosphatase (enzyme) hoffman elimination (ph and temp dependent)

Question 44

What drugs undergo metabolism by psuedocholinesterase?

Answer 44

succinylcholine mivacurium ester LAs tetracaine procaine chloroprocaine cocaine

Question 45

what drugs undergo non specific esterase metabolims?

Answer 45

remifentanil remimazolam esmolol (RBC esterases) etomidate (+hepatic) atracurium (+hoffman) clevidipine

Question 46

what drugs undergo metabolism via alkaline phosphatase?

Answer 46

fospropofol

Question 47

what drugs undergo hoffman elimination?

Answer 47

cisatracurium atracurium (+non-specific esterases)

Question 48

What 2 things determine hepatic clearance?

Answer 48

1.liver blood flow 2. hepatic extraction ratio (ER)

Question 49

when is hepatic clearance perfusion dependent vs capacity dependent?

Answer 49

if ER >0.7 perfusion dependent (liver blood flow) if ER < 0.3 capacity dependent (livers ability to extract the drug)

Question 50

enzyme induction/inhibition only affects what kind of heaptic clearnace?

Answer 50

capacity dependent

Question 51

Drugs with low hepatic ER?

Answer 51

Roc diazepam lorazepam methadone thiopental theophylline phenytoin

Question 52

drugs with intermediate hepatic ER

Answer 52

midazolam vecuronium alfentanil methohexital

Question 53

Which cyp-45 enzyme metabolises 50% of all drugs?

Answer 53

CYP3A4

Question 54

CYP 2D6 metabolises what drugs?

Answer 54

codeine oxycodone hydrocodone

Question 55

CYP 3A4 Enzyme inducers?

Answer 55

ethanol rifampin barbiturates tamoxifen carbmazepine St. Johns wort

Question 56

CPY 3A4 inhibitors

Answer 56

grapefruit juice cimetidine erythromycin azole antifungals SSRIs

Question 57

CYP 2D6 inducers

Answer 57

disulfram

Question 58

CYP 2D6 Inhibitors

Answer 58

Isoniazid SSRIs quinidine

Question 59

other generic enzyme inhibitors

Answer 59

omeprazole

Question 60

Other generic enzyme inducers

Answer 60

tabaco smoke phenytoin

Question 61

what can happen with continuous admin of an agonist?

Answer 61

down regulation of the receptor

Question 62

what canhappen with continuous admin of an antagonist?

Answer 62

up regulation of the receptor

Question 63

name an inverse agonsit

Answer 63

propranolol it decreases cAMP

Question 64

how many enantiomers does one chiral carbon have?

Answer 64

2

Question 65

what does dextrorotaty mean?

Answer 65

rotates light clockwise

Question 66

what does levorotatory mean?

Answer 66

rotates light counterclockwise

Question 67

what does racemic mean?

Answer 67

two enantiomers in equal ammounts

Question 68

name two specific enantiomers and their significance

Answer 68

s-bupivicaine (levobupivicaine) less cardo toxic than r-bupivicaine s-ketamine: more potent and less likely to cause emergence delirium than r-ketamine

Question 69

Name a major flaw with the concept of context sensitive half time?

Answer 69

only shows time for central compartment concentration to reach 50%, context sensitive half-time does not show wake up time.

Question 70

which drug admin route has lowest bioavailability?

Answer 70

intrathecal. 0% bioavailability because drug is delivered directly to affect site.

Question 71

What is Glucuronidation?

Answer 71

When glucuronic acid is added to a moledulce during phase 2 reaction. I.E. morphine > morphine 3 glucuronide.

Question 72

Name two drugs that are enantimoers but are not prepared in racemic mixtures?

Answer 72

ropivicane levobupivicaine

Question 73

name some medications which are racemic mixtures

Answer 73

ephedrine ketamine desflurane

Question 74

name some medications that are weak bases

Answer 74

ephedrine (sulfate) morphine (sulfate)

Question 75

name some medications that are weak acids

Answer 75

(sodium) thiopental (sodium) methoexidal