lecture 2- pharmacokinetics con't

Question 1

creatinine clearance is based on

Answer 1

muscle mass

Question 2

why is it significant if you have too much creatinine in your blood

Answer 2

mean your kidneys aren’t functioning properly

Question 3

creatinine clearance definition

Answer 3

s the volume of blood plasma that is cleared of creatinine per unit time. from Cockcroft and Gaul

Question 4

females have a correction factor for cc and this does what

Answer 4

makes it lower, 85%

Question 5

in calculating IBW for a female, compare actual body weight to ideal body weight and use which one ?

Answer 5

the lower value

Question 6

MDRD calculation

Answer 6

more accurate calculation for excessive body weight and renal dysfunction , but really not practical/ used

Question 7

what qualifies a patient as being obese

Answer 7

30% over their IBW

Question 8

if a patient is obese, use

Answer 8

adjusted body weight

Question 9

dialysis diffusion vs ultrafiltration

Answer 9

diffusion moves across the barriers. ultrafiltration is taking off a lot of fluid.

Question 10

during dialysis, med will be removed if unbound volume is

Answer 10

<3.5L/kg. so if highly bound to albumin, it wont be removed.

Question 11

during dialysis, med will be removed if clearance is

Answer 11

<10ml/min/kg. if highly renal eliminated, its already a med that is hydrophilic and small so it will move easily through dialysis filters

Question 12

if the med has a dosing interval longer than its half life

Answer 12

you can expect it might be removed during dialysis

Question 13

if a med has a molecular weight less than 1000 daltons

Answer 13

it will be removed during dialysis

Question 14

when you put someone on dialysis, you assume that they have a creat clearance of about

Answer 14

30ml/min

Question 15

single dose concentration graph

Answer 15

med peaks and then eliminates slowly at consistent rate.

Question 16

continuous IV infusion

Answer 16

if you want to maintain something that has a short half life, redistributes quickly

Question 17

intermittent dosing

Answer 17

get to therapeutic, wears off.

Question 18

we cannot tell the effect of a med until

Answer 18

that med is ate steady state

Question 19

steady state

Answer 19

amount of drug administered over time = amount of drug eliminated during the same time period. rate in = rate out. how quickly are you taking it in vs how quickly are you eliminating it.

Question 20

how to do half life percentages

Answer 20

1 half life is 50%, and then each next one is halfway between the previous and 100%…. 50, 75, 87.5, 93.75, 96.875

Question 21

does a loading dose shorten the time to ready steady state

Answer 21

NO. loading doses bring you to therapeutic but elimination hasn’t caught up

Question 22

would you reach steady state faster if the dose was given at one half of the medications life?

Answer 22

no. you cant just change the dosing interval. have to account for elimination. rate in vs rate out.

Question 23

tips for interpreting drug levels

Answer 23

never treat an isolated number and check the dosing history. treat the pt not the #!

Question 24

trough checks

Answer 24

efficacy

Question 25

peaks check

Answer 25

toxicity

Question 26

trough level

Answer 26

is the lowest concentration reached by a drug before the next dose is administered

Question 27

peak level

Answer 27

he highest concentration of a drug in the patient's bloodstream.

Question 28

if an elderly person has reduced first pass metabolism

Answer 28

more drug gets to general circulation, can lead to toxicity

Question 29

elderly fat % and free water

Answer 29

increased rat, reduced free water

Question 30

what is the impact of the elderly having reduced albumin concentration and/or increased alpha1 acid glycoprotein ?

Answer 30

increased toxicity because reduced carrier proteins so more free levels

Question 31

gastric pH and emptying time in neonates and infants

Answer 31

higher, reduced

Question 32

CYP450 in neonates and infants

Answer 32

reduced/immature

Question 33

protein binding in neonates and infants

Answer 33

reduced

Question 34

renal clearance in neonates/infants

Answer 34

reduced

Question 35

pharmacodynamics

Answer 35

the effects of drugs and mechanisms of their actions

Question 36

drugs will either..

Answer 36

find their target cell, or be distributed, metabolized, and excreted.

Question 37

most drugs bind to

Answer 37

cellular receptors

Question 38

what do drugs do on cellular receptors

Answer 38

initiate biochemical reactions that alter the cell's physiology

Question 39

where do drugs exert their primary action

Answer 39

the cellular level

Question 40

drug receptors are generally made up of what

Answer 40

proteins or glycoproteins present on the cell surface, on an organelle within the cell or in the cytoplasm

Question 41

receptor mediated responses plateau once...

Answer 41

....receptor saturation occurs. (you can give a med, not get the effect you want, and doesnt matter how much more you give. you only have so many receptors.

Question 42

although we have a finite number of receptors on a given cell, how does the body compensate?

Answer 42

thru up and down regulation. defense mechanism. body will produce more receptors. so you can't just d/c a drug without considering this. must taper

Question 43

once a drug has bound to a receptor, what are the 3 things that could occur?

Answer 43

1) an ion channel is opened or closed 2) biochemical messengers, often called second messengers are activated 3) a normal cellular function is physically inhibited or initiated

Question 44

biochemical messengers aka second messengers

Answer 44

(cAMP, cGMP, Ca+++, inositol phosphates) these initiate a series of chemical reactions within the cell, and transfuce the signal stimulated by the drug.

Question 45

affinity

Answer 45

strength of binding between a drug | and its receptor. makes the receptor do what it normally does

Question 46

dissociation constant (Kp)

Answer 46

the measure of a drug’s affinity for a given receptor. The concentration of drug required in solution to achieve 50% occupancy of its receptors.

Question 47

agonist

Answer 47

drugs which alter the physiology of a cell by binding to plasma membrane or intracellular receptors. agonist's stop the normal effect

Question 48

strong agonist

Answer 48

an agonist which causes maximal effects even though it may only occupy a small fraction of receptors on a cell.

Question 49

weak agonist

Answer 49

an agonist which must be bound to many more receptors than a strong agonist to produce the same effect.

Question 50

antagonist

Answer 50

inhibit or block actions caused by agonists.

Question 51

competitive antagonist

Answer 51

competes with agonist for receptors. -During the time that a receptor is occupied by an antagonist, agonists cannot bind to the receptor. Because the antagonism can be overcome by high doses of agonists, competitive antagonism is said to be “surmountable.

Question 52

noncompetitive antagonist

Answer 52

binds to a site other than the agonist-binding domain. Induces a conformational change in the receptor such that the agonist no longer “recognizes” the agonist-binding domain. § “Insurmountable” because even high doses of agonist cannot overcome this antagonism.

Question 53

irreversible antagonism

Answer 53

with the receptor. -Rate of antagonism can be slowed by high concentrations of antagonist. -Once an irreversible antagonist binds to a particular receptor that receptor cannot be “reclaimed” by an agonist. with agonists for the agonist-binding receptor. -Irreversible antagonists combine permanently agents compete

Question 54

efficacy

Answer 54

The degree to which a drug is able to cause maximal effects. - If Drug A reduces blood pressure by 20mmHg and Drug B reduces blood pressure by 10mmHg, then Drug A has greater efficacy than Drug B.

Question 55

potency

Answer 55

the amount of drug required to produce 50% of the maximal response that the drug is capable of causing. potency has more to do with dosing

Question 56

potency is used to compare drugs that are..

Answer 56

in the same chemical class. drugs within the same chemical class will usually have similar maximal efficacy if a high enough dose is given.

Question 57

efficacy

Answer 57

used to compare drugs with different mechanisms. like toradol (NSAID) and morphine (narc)

Question 58

dose response curves show

Answer 58

the magnitude of drug action against the concentration/dose of drug required to induce those actions. -the curve represents the effects and dose of a drug within an individual animal or tissue rather than in the population

Question 59

effective concentration50% EC50

Answer 59

The concentration of drug which induces a specified clinical effect in 50% of the subjects to which the drug is administered.

Question 60

Lethal Dose 50% LD50

Answer 60

the conc of drug which induces death in 50% of the subjects to which the drug is administered.

Question 61

therapeutic index

Answer 61

a measure of the safety of a drug. calculated by dividing the LD50 by the ED50

Question 62

margin of safety

Answer 62

the margin between therapeutic and lethal doses of a drug

Question 63

Altered absorption

Answer 63

Drugs may inhibit absorption of other drugs across biologic membranes (antiulcer agents that coat the stomach may decrease GI absorption of other drugs)

Question 64

Altered metabolism:

Answer 64

Clinically important drug interactions can occur when the P450 isoenzymes are inhibited or induced.

Question 65

Plasma protein competition:

Answer 65

Drugs that bind to plasma proteins may compete with other drugs for the protein binding sites. Displacement of drug ‘A’ from plasma proteins by drug ‘B’ may increase the concentration of unbound drug ‘A’ to toxic levels.

Question 66

Altered Excretion:

Answer 66

``` Drugs may act on the kidney to reduce excretion of specific agents (e.g. probenecid competes with sulfonamides for the same carrier, increasing the risk of sulfonamide toxicity). ```

Question 67

addition

Answer 67

the response elicited by combined drugs is EQUAL TO the combined responses of the individual drugs. 1+1=2

Question 68

synergism

Answer 68

the response elicited by combined drugs is GREATER THAN the combined responses of the individual drugs. 1+1=3

Question 69

potentiation

Answer 69

A drug which has no effect enhances | the effect of a second drug. 0+1=2

Question 70

antagonism

Answer 70

Drug inhibits the effect of another drug. Usually, the antagonist has no inherent activity. 1+1=0

Question 71

Midazolam is a significant substrate of CYP3A4. Erythromycin is a CYP3A4 inhibitor. How would you manage this drug interaction?

Answer 71

substrate means metabolized by. so too much free versed... this patient may be hard to wake up use a different drug than erythromycin.

Question 72

propofol is a strong CYP3A4 inhibitor. What types of side effects would you expect from sedatives that are metabolized by this enzyme when given together?

Answer 72

so if you give prop with versed... more sedated, longer emergence inhibition causes buildup

Question 73

Carbamazepine is a very strong inducer of CYP3A4. How might you have to alter the dose of midazolam if given together?

Answer 73

you'll need more versed because its getting metabolized faster

Question 74

tolerance

Answer 74

represents a deresponsed to a drug. Clinically, this is observed when the dose of a drug must be increased to achieve the same effect.

Question 75

tolerance can be ___ or ___ in nature

Answer 75

metabolic(drug metabolized more rapidly after chronic use) or cellular(decreased number of receptors, "downregulation"

Question 76

dependence

Answer 76

patient needs drug to function normally. noted when cessation produces withdrawal symptoms. dependence maybe physical and/or psychological

Question 77

withdrawal

Answer 77

occurs when a drug is not administered to a person who has been dependent it