Drug Elimination and Renal Clearance Part 2

Question 1

What kind of drugs are excreted renally?

Answer 1

1. Nonvolatile
2. Water soluble
3. Low MW
4. Slow biotransfomration by liver

Question 2

What are the mechanisms of excretion?

Answer 2

1. Globular filtration
2. Active tubular secretion
3. Tubular reabsorption

Question 3

What molecules are filtered by the glomerulus?

Answer 3

Small molecules (<500 MW) including nonionized and ionized

Question 4

What doesn’t get filtered by filtration?

Answer 4

Protein bound drugs and large MW

Question 5

What is the major driving force of filtration?

Answer 5

Hydrostatic pressure within the glomerular capillaries

Question 6

How is GFR measured?

Answer 6

Using a drug that is eliminated primarily by filtration

Question 7

What can change the half-life of a drug in filtration?

Answer 7

Changes in binding affinity for plasma proteins

Question 8

What is used to measure GFR?

Answer 8

Inulin and creatinine (secreted)

Question 9

Why is clearance of inulin used?

Answer 9

GFR is equal to inulin (120mL/min)

Question 10

What is the relationship of GFR and free or bound drug?

Answer 10

1. GFR correlates with body SA
2. As the free drug concentration in plasma increase, the glomerular filtration for the drug increases proportionaly, thus increasing renal drug clearance for some drugs

Question 11

Why is tubular secretion an active process?

Answer 11

1. Carrier mediated system requires energy input because drug is transported against its concentration gradient

Question 12

What are the properties of a carrier system?

Answer 12

Capacity is limited and may be sacrutarted
Drugs with similar structures may compete for the same system

Question 13

What does secretion depend on?

Answer 13

RPF

Question 14

How is secretion measured?

Answer 14

PAH and Diodrast (Cl of drugs represent effective RPF)

Question 15

How is a half-life affected during secretion?

Answer 15

Not affects by protein binding

Question 16

What is tubular reabsorption?

Answer 16

After the drug is filtered, it can be an active or passive process involving transporting back into the plasma

Question 17

What happens if a drug is completely reabsorbed?

Answer 17

The value of Cl is 0

Question 18

What happens if a drugs is partially reabsorbed without being secreted?

Answer 18

Cl values are than GFR of 120mL/min

Question 19

What influences reabsorption of acids and bases?

Answer 19

Influenced by pH of the fluid in the renal tubule and the pK of the drug

Both factors determine the percentage of dissociated (ionized) and undissociated (nonionized) drug

Question 20

What type of molecule is most likely to under reabsorption?

Answer 20

Nonionized (undissociated) are more lipophilic and has a greater membrane permeability

Easily reabsorbed from tubule back to body

Question 21

What is the normal pH of urine?

Answer 21

4.5-8

Question 22

When would you have acidic urine?

Answer 22

Morning, ascorbic acid, protein diet

Question 23

When would you have basic urine?

Answer 23

Afternoon, vegetable and fruit diet, sodium bicarbonate

Question 24

What causes intravenous fluids to alter the urine pH?

Answer 24

sodium bicarbonate and ammonium chlorid

Question 25

What is the Henderson Hasselback equation?

Answer 25

Used to predict dissociation and thus the likelihood of a drug being reabsorbed or excreted at a certain urine pH Unionized: likely reabsorbed Ionized: likely excreted

Question 26

Describe weak acid drug's relationship with tubular reabsorption?

Answer 26

pKa 3-8, extent of dissociation will be affected by changes in urine pH

Question 27

Describe weak base drug's relationship with tubular reabsorption?

Answer 27

The greatest effect of urinary pH on reabsorption occurs for weak bases with pKa of 7.5-10.5

Question 28

What are factors that increase RBF and urine flow rate?

Answer 28

1. Diuretics and alcohol 2. Rate of urine flow can influence amount of drug reabsorbed

Question 29

What is the effects of alcohol and diuretics?

Answer 29

1. Increase blood flow 2. Decrease reabsorption 3. Increase rate of excretion

Question 30

What is effect of reabsorbed drug amount influencing urine flow rate?

Answer 30

1. Nonpolar and nonionized drugs are sensitive 2. Alcohol, diuretics and methylxanthines can increase flow

Question 31

What influences filtration?

Answer 31

Protein binding

Question 32

What influences the secretion?

Answer 32

Competitive inhibitors

Question 33

What influences reabsorption?

Answer 33

Urinary pH and flow

Question 34

What undergoes reabsorption?

Answer 34

Nonionized

Question 35

What undergoes secretion?

Answer 35

Weak acids and bases

Question 36

What undergoes filtration?

Answer 36

Ionized or un

Question 37

Type filtration trasport?

Answer 37

Passive

Question 38

Type of secretion transport?

Answer 38

Active

Question 39

Type of reabsorption transport?

Answer 39

Passive/active

Question 40

How do you find amount excreted in urine

Answer 40

1. Calculated by measuring amount of drug in urine 2. Urine needs to be sampled for 3-4 half-lives

Question 41

How do you calculate renal clearance?

Answer 41

Question 42

Describe renal clearance when steady-state occurs?

Answer 42

All of the excreted eliminated unchanged in the urine from one dose occurs over one dosing interval

Question 43

What is this τ ?

Answer 43

Dosing interval

Question 44

How do you find renal clearance at steady state?

Answer 44

Question 45

How do you determine non renal clearance?

Answer 45

1. If you know renal clearnace 2. Determined from renal clearance if F is known 3. Not the same as hepatic

Question 46

How do you calculate NR Cl?

Answer 46

Question 47

What is inulin?

Answer 47

Used to estimate GFR since it is know to only be excreted by GF

Question 48

What is Cl ratio?

Answer 48

The ratio of drug Cl to inulin Cl, an indication for the mechanism of renal excretion of the drug?

Question 49

What is the Cl ratio of partial reabsorption of drug?

Answer 49

Question 50

How can you calculated Renal Cl if it is the summation of all kidney processes?

Answer 50

Question 51

What is the Cl ratio of drug filtration only?

Answer 51

Question 52

What is the Cl ratio of drug that is actively secreted?

Answer 52

Question 53

In what instances is is filtration the sole process of excretion?

Answer 53

1. Drug is not bound to plasma proteins 2. Not reabsorbed 3. The amount of drug filtered at any time will always be Cp * GFR

Question 54

In what instances is filtration and secretation with negligible reabsorption the sole process of excretion?

Answer 54

The overall excretion rate will exceed GFR

Question 55

What is the difference between low and high drug plasma concentrations in regards to filtration and active secretion?

Answer 55

L: active secretion is not saturated, and the drug is excreted by filtration and active secretion H: the percentage of drug excreted by active secretion decreases due to saturation. Renal Clearance decreases because excretion rate (of Active Secretion) decreases

Question 56

What is occurring in this graph?

Answer 56

The decline of renal clearnace As the drug plasma level increases to a concentration that saturates the active tubular secretion, glomerular filtration becomes the major component for renal clearance.

Question 57

What is occurring in this graph?

Answer 57

Renal Cl decreases because the total excretion rate of the drug increases to the point where it is approximately equal to the filtration rate

Question 58

What are the components of Cl?

Answer 58

Renal and nonrenal clearance

Question 59

What is Clr composed of?

Answer 59

Filtration, reabsorption and secretion

Question 60

What is Creatinine Cl?

Answer 60

Mostly filtered but also secreted, indicates the filtration capacity (GFR) of the kidney in a given patient

Question 61

Where does Creatinine come from?

Answer 61

Muscle mass

Question 62

What is the assumptions that is made when the adjusting doses based on renal function?

Answer 62

Decreasing renal function does not change the non renal clearance Reasonable until sever renal impairment is observed at which point changes in protein binding capacity and affinity as well as changes in enzymatic and transporter affinity and activity may be seen

Question 63

How do we determine Cl graphically?

Answer 63

given by the slope of the curve obtained by plotting the rate of drug excretion in urine (dDu/dt) against Cp

Question 64

Compare lines A and B

Answer 64

A: a drug that is excreted rapidly, dDu/dt is large, the slope is steeper, and clearance is greater B: Drug is excreted slower through kidneys and the slope is smaller

Question 65

Identify the variables of this model?

Answer 65

ClR = renal clearance of parent drug, Clf = formation clearance of parent drug to metabolite, Cm = plasma concentration of the metabolite, Cp = plasma concentration of the parent drug Vss = total volume of distribution of parent drug, Vss(m) = apparent volume of distribution of metabolite, (Cl - ClR - Clf) clearance of parent drug minus the renal and formation clearances, F = absolute bioavailability of parent drug.)

Question 66

What are diuretics?

Answer 66

Chemicals that enhance urinary output

Question 67

What are examples of diuretics?

Answer 67

1. Anti-Diuretic Hormone inhibitors 2. Na+ reabsorption inhibitors 3. Loop diuretics 4. Osmotic diuretics

Question 68

What are anti-Diuretic Hormone inhibitors?

Answer 68

Alcohol

Question 69

What are Na+ reabsorption inhibitors?

Answer 69

caffeine, drugs for hypertension or edema Results in H2O reabsorption

Question 70

What are loop diuretics?

Answer 70

Inhibit medullary gradient formation

Question 71

What are osmotic diuretics?

Answer 71

Substance not reabsorbed so water remains in urine, high glucose of diabetic patient