Pharm I Drug Dispostion Part Ii

Front 1

Which drugs are more likely to be bound by plasma proteins (acidic, basic or neutral)?

Back 1

Primarily acid and netural, HOWEVER: some basic drugs can bind to 1) ∂1-acid glycoprotein, which is an acute phase reactant protein AND 2) lipoproteins

Front 2

T/F binding to plasma proteins is usually specific.

Back 2

False, while it can be it's usually not.

Front 3

T/F the t-1/2 of plasma protein binding is long.

Back 3

false, binding and release is very short

Front 4

Is binding to plasma proteins is rarely reversible?

Back 4

No, it is ALWAYS reversible… lasting miliseconds

Front 5

How do plasma proteins influence the rate of movement of drug across the membrane? (2) what effect does protein binding have on drug (distribution, clearance and half-life)?

Back 5

(1) concentration gradients are based on only the free drug not bound. (2) distribution=slower… clearance=slower… half-life=longer

Front 6

What is the exit of drug from the plasma dependent upon? Active transport or concentration gradient.

Back 6

concentration gradient

Front 7

At SATURATION, do changes in plasma binding proteins levels alter the amount of FREE drug in the plasma?

Back 7

no (NOTE free drug is what has the biological effect)

Front 8

At SATURATION, do changes in plasma binding protein levels alter the amount of TOTAL drug in the plasma?

Back 8

yes (NOTE changes in the plasma protein level can make you think you need to adjust the dose, but you don't if the concentration of FREE drug is unchanged)

Front 9

What can cause changes in plasma ∂-glycoprotein levels (which sequester basic drugs)?

Back 9

age, pregnancy and some disease states.

Hint 9

None

Front 10

What is the half-life of a drug related to?

Back 10

the amount of plasma protein binding

Front 12

Stop Here

Front 13

Do you have to adjust the dose of a drug if there is more plasma protein binding?

Back 13

No, you only change dosage if free drug levels change

Front 14

What can cause the plasma albumin levels to change?

Back 14

age, pregnancy and disease, among other things.

Hint 14

None

Front 15

Besides absorption, what other two things do plasma proteins influence?

Back 15

1. Hepatic or other organ extraction of drugs… 2. Solubilizes some drugs for that are often poorly soluble in water

Front 16

Is active transport effected by the concentration of plasma proteins?

Back 16

no, since it's not concentration related

Front 17

a) What offsets the displacement of drugs plasma proteins in terms of drug effect duration? b) What is the danger in displacement of drug from plasma protens

Back 17

a) displacement increase the amount of free drug, but it also increase the amount of drug available for metabolism and excretion. b) increasing dosage based on lower plasma concentrations… since once the plasma proteins are saturated, the amount of unbound drug will increase disproportionally to the increase in dose.

Front 18

a) What can decrease albumin? b) What can decrease the amount of ∂1-acid glycoprotein (basic drug binding protein)?

Back 18

a) many things… b) aging, oral contraceptives, and pregnancy

Front 19

Which type of drug binding (basic or acid) is decreased by uremia?

Back 19

acidic drugs, because they are the ones bound to plasma protein and are the ones displaced by the urea

Front 20

What is the average volume in liters of the following? A) total body water. B) extracellular water. C) whole blood? D) plasma. E. intracellular water.

Back 20

A) total body water = 42 L (60%)… B) Extracellular water = 14 L (20%)… C) Whole Blood = 6 L … D) Plasma = 3 L… Intracellular water = 28 L

Hint 20

None

Front 21

a) Give the equation for determining the volume of distribution (Vd)… b) when is Vd measured?

Back 21

a) Vd = Dose ÷ [plasma] (@equilibrium)… b) after a single dose @ equlibrium

Front 22

What is indicated by Vd = plasma volume?

Back 22

most of the drug is bound to plasma proteins

Front 23

What is the clinical importance of knowing the Vd?

Back 23

its value lies in calculating dose

Hint 23

None

Front 24

How do you calculate dose for a IV (100% bioavailability)?

Back 24

Rearrange Vd equation: dose = Vd X [desired plasma]

Front 25

How do you calculate dose for drugs with less than 100% bioavailability? (give equation)

Back 25

Dose = (Vd X [desired plasma]) ÷ F… where F= fraction absorbed into systemic circulation: BA

Front 26

What can alter Vd?

Back 26

age, sex, disease, changes in skeltal muscle, fat mass, plasma protein synthesis, fat/muscle ratio, and hydration. etc…

Front 27

a) What is Total Body Clearance? b) Show equation for determining total Clearance.

Back 27

a) Total Cl: fluid volume (Vd) cleared per unit time… b) Total Cl = K(elim) X Vd, where K(elim) is the elimination constant

Front 28

(1) What is the equation for determining half-life?… (2) What is the relationship between t-1/2 and total body clearance (ClT)?… (3) While the Total body clearance Clt can be used to determine how rapidly a drug is eliminated from the whole body, what does it assume?

Back 28

(1) T1/2= (0.693 X Vd) ÷ Total body Cl… (2) it is inversely proportional… (3) Total body clearance (Clt) assumes the body were one compartment

Front 29

The change in which organ functions can alter clearance and therby the half-life of a drug? What else can alter the clearance and half-life of a drug?

Back 29

Kidney, liver, lungs… aging too… can change the clearance and half-life of a drug

Hint 29

None

Front 30

What effect does increased clearance have on length of half-life?

Back 30

increased clearance --> decreased half-life

Front 31

Which organ is the major factor in non-metabolized drug clearance?… (2) Which organ reflects metabolism?

Back 31

(1) Non metabolized: kidney… (renal clearance CL-R)… (2) metabolism: Liver (which is due to liver enzymes, as well as, billiary excretion)

Front 32

How do you calculate hapatic clearance?

Back 32

hepatic Cl = (drug in bile + metabolite in hepatic venous blood) ÷ [plasma]

Front 33

How do you determine hepatic clearance in humans?

Back 33

Cl-hepatic = (drug in bile + metabolite in hepatic venus blood) ÷ plasma concentration… however it can also be calculated like this: Hepatic Cl = Total Cl - renal clearance (Cl-R)

Front 34

When would a log scale plot of half-life be a straight line?

Back 34

it would be a straight line when elimination follows first order kinetics and the drug occupies only one compartment

Front 35

What is the difference between ∂ and ß half-life and which is presumed when discussing half-life?

Back 35

a) ∂-half-lfe = distribution… ß-half-life is elimination… b) elimination

Front 36

When would a drug's half-life in the plasma not correlate with the drugs action? (4 reasons)

Back 36

1. Metabolite is an active form of the drug… 2. Drug activates a nuclear steroid receptor… 3. Drug binds irreversibly to receptor… 4. Drug is an ultra-short acting barbituate

Front 37

Is elimination half-life route of administration and dose dependent? Why?

Back 37

not usually, elimination half-life is dervied from a first order rxn, where the plasma concentration does not saturate the rate-limiting step… thus it's calculated after during elimination (ß-t-1/2)and not during distribution

Front 38

Give the equation for calculating the elimination rate constant k(elim)

Back 38

K(elim) = 0.693÷ t1/2

Front 39

Give the equation for t-1/2

Back 39

t-1/2 =0.693÷K(elim) = 0.693 x Vd ÷ Cl

Front 40

In which order rxn is the t-1/2 constant? Zero order or first order?

Back 40

first order, where elimination is not constant

Front 41

What order rxn is seen when the rate limiting step is saturated? b) Give 3 examples of the above-order metabolized drugs

Back 41

a) zero order… b) aspirin (when given @ high dose for RA exhibits zero), ethanol (almost always zero order) and phenytoin (plasma disappearance of therapeutic level is zero order… thus it has a narrow therapeutic index and shows difficulty calculating dose.)

Front 42

What is the time needed to reach the steady state of a drug dependent upon?

Back 42

half-life (NOT dose, nor dosing rate)

Front 43

What is the final average steady state dependent upon? Is the plateau effect also dependent on the factors steady state is?

Back 43

Final average steady state is dependent upon dose and frequency of administration… (2) no, the plateau effect is independent of dose and frequency

Hint 43

None

Front 44

What two factors are steady state levels dependent upon?

Back 44

1. amount of drug absorbed/time and 2. Clearance

Front 45

What two factors result in smaller fluctuation in plasma concentration?

Back 45

1. Frequent doses… 2. Slower absorption

Front 46

What percent of steady state is reached given these numbers of half-lives: 1, 2,3, and 4… what is this called?

Back 46

1 t1/2= 50%… 2 t1/2= 75%… 3 t1/2= 87.5% … 4 t1/2= 93.75%… this is called the plateau effect

Front 47

What is the difference between average steady state and plateau steady state?

Back 47

a) The average steady state takes into account all plasma concentration including fluctuation from initial dose to plateau… b) Plateau is the steady state after multiple doses

Front 48

As stated earlier, average steady state is dependent upon frequency of dose and absorption, what is plateau steady state dependent upon?

Back 48

Half-life: For final average steady state: Total input and output... such that input = output at steady state, where the quantity cleared is equal to one dose

Hint 48

None

Front 49

After drug withdraw, what is percentage of plasma level are reduced by the following half-lives? 1, 2, 3, and 4

Back 49

same as above, except reduced: 1 t1/2= 50%… 2 t1/2= 75%… 3 t1/2= 87.5% … 4 t1/2= 93.75%

Front 50

Give the equation for calculating a single does

Back 50

Single dose = (Vd x desired plasma concentration) ÷ Bioavailability

Front 51

Which is the following an example of, dose of dosage (dosing rate)? 3 mg tid

Back 51

Dosage, where in this example dosage = 25 mg… tid is the dosing interval… (Note: Dose is an absolute quantity, in contrast to dosage, which is a quantity per unit time)

Front 52

How do you calculate the dose, given the dosing rate?

Back 52

dose = dosage (or dosing rate) X dosing interval

Front 53

At steady state plateau, what is dosage equal to?

Back 53

Dosage is the replacement of cleared drug… in = out

Front 54

Show the equation for calculating maintenance dosage.

Back 54

Dosage = (Clearance X plasma concentration) ÷ Bioavailability (fraction absorbed)

Front 55

Show the equation used for calculating loading dose.

Back 55

Loding dose = (Vd x desired plasma concentration) ÷ Bioavailability (fraction aborbed)

Front 56

When would you want to use a modified loading dose?

Back 56

When the time it take for steady state plateau is long, e.g., 14 hours and wating for 4 half lives to occur would take too long

Front 57

which type of kinetics for a drug make dosing difficult? (zero or first order)… Why?

Back 57

zero order are difficult to dose, because in zero order kinetics small changes in dose can cause a large change in plasma levels, whereas in first order kinetics when you double the dose you double the plasma levels

Front 58

Why is it important to adjust dose for an obese person?

Back 58

you have to consider whether or not the drug is lipophilic, for example, the drug does not enter fat then a large dose based on weight will lead to an overdose… thus for a drug with a low therapeutic index a small error could be serious.

Front 59

When should one use a different Vd to calculate dose for an obese person? In these cases, what should one use to recalculate Vd?

Back 59

when drugs do not enter body fat… (2) Ideal body weight (IBW)

Front 60

When is body surface area an important consideration?

Back 60

When the total body surface are is elevated relative to IBW, such as in the obese patient. In these cases you need to increase the dose.

Front 61

When calculating dose for an obese person, what weight do you use? How do you find this weight for men and women?

Back 61

Ideal body weight: IBW for men = 52 kg +1.9 x inches in height above 5')… IBW for women = 49 kg + 1.7 kg x (inches above 5')

Front 62

Do you have to adjust loading dose of a drug for a person with impaired renal function?

Back 62

No, Loading dose = (Vd x desired plasma conc.) ÷ F (Bioavailability)

Front 63

Do you have to adjust maintenance dose in a person with impaired renal function?

Back 63

Yes! Maintenance dose = (clearance X desired plasma conc.) ÷ bioavailability (F)

Front 64

How do you calculate renal function? What is the equation?

Back 64

Calculate renal function with creatinine clearance… Creatinine clearance = [(140-age) X (weight in Kg)] ÷ [72 X (Serum creatinine in mg/dL)]