Drug Pharmacokinetics in relation to Renal System

Question 1

What do absorption, distribution, metabolism, excretion, and action of a drug all involve?

Answer 1

Its passage across cell membranes

Question 2

What is the common barrier to drug distribution?

Answer 2

Plasma membrane

Question 3

What does the plasma membrane consist of?

Answer 3

A bilayer of amphipathic lipids with their hydrocarbon chains oriented inward to the center of the bilayer to form a continuous hydrophobic phase and their hydrophilic heads oriented outward

Question 4

What is transmembrane movement of drug generally limited to?

Answer 4

Unbound drug

Question 5

What do drug-protein complexes constitute?

Answer 5

An inactive reservoir of drug that can influence both therapeutic as well as unwanted drug effects

Question 6

What type of membrane passage is an important factor in filtration across the glomerulus in the kidney?

Answer 6

Paracellular passage through intercellular gaps (passive transport)

Question 7

What is facilitated diffusion?

Answer 7

Carrier-mediated transport process in which there is no input of energy

Question 8

Excretory organs, the lung excluded, eliminate ____ compounds more efficiently than substances __________

Answer 8

polar; with high lipid solubility.

Question 9

What is the most important organ for excreting drugs and their metabolites?

Answer 9

The kidney

Question 10

Excretion of drugs and metabolites in the urine involves 3 distinct processes. What are they?

Answer 10

1. Glomerular filtration
2. Active tubular secretion
3. Passive tubular reabsorption

Question 11

Even in healthy persons, renal function is not _______ .

Answer 11

constant

Question 12

During adulthood, there is a slow decline in renal function. Approximately what % is lose each year?

Answer 12

1%

Question 13

So you would expect that w/ the elder their renal function will have….

Answer 13

substantial degree of functional impairment

Question 14

The amount of drug entering the tubular lumen by filtration depends on _____________. (2)

Answer 14

the glomerular filtration rate (GFR) and the extent of plasma binding of the drug

Question 15

Only ________ drug is filtered

Answer 15

unbound

Question 16

What type of tubular secretion occurs in the proximal renal tubule and add drug to the tubular fluid?

Answer 16

active, carrier-mediated tubular secretion

Question 17

Which transporters are responsible for secretion of amphipathic anions and conjugated metabolites (such as glucuronides, sulfates, and glutathione adducts)?

Answer 17

P-gp and the multidrug-resistance–associated protein type 2 (MRP2), localized in the apical brush-border membrane

Question 18

Where are membrane transporters mainly located?

Answer 18

In the distal renal tubule

Question 19

What are membrane transporters responsible for?

Answer 19

Any active reabsorption of drug from the tubular lumen back into the systemic circulation (though most of this reabsorption is by non-ionic diffusion)

Question 20

What characteristic of drugs promote their passage through membranes (and thus to sites of action) but hinder their excretion from the body?

Answer 20

Lipophilic

Question 21

What is a major route of elimination for 25-30% of drugs?

Answer 21

Renal excretion

Question 22

Majority of therapeutic agents are?

Answer 22

Lipophilic compounds

Question 23

Where are drugs filtered through?

Answer 23

the glomerulus

Question 24

Where are drugs reabsorbed into systemic circulation ?

Answer 24

During passage through renal tubules

Question 25

Where are the enzyme systems involved in the biotransformation of drugs localized?

Answer 25

Primarily in the liver, but also important are GI tract, kidneys and lungs

Question 26

What are the 4 most important parameters governing drug disposition?

Answer 26

1. Bioavailability (fraction of drug absorbed into systemic circulation)
2. Volume of distribution (apparent space in body available to contain drug vs. available in systemic circulation)
3. Clearance (efficiency in eliminating drug from systemic circulation)
4. Elimination t1/2 (rate of removal of drug from systemic circulation)

Question 27

Principles of drug clearance are similar to those of _______

Answer 27

renal physiology

Question 28

Example of renal physiology that is like drug clearance is:

Answer 28

Creatinine clearance is defined as the rate of elimination of creatinine in the urine relative to its concentration in plasma

Question 29

Renal clearance of a drug results in ________

Answer 29

its appearance in the urine.

Question 30

The rate of filtration of a drug depends _________ (2)

Answer 30

on (1) the volume of fluid that is filtered in the glomerulus and (2) the unbound concentration of drug in plasma because drug bound to protein is not filtered.

Question 31

The rate of secretion of drug by the kidney will depend on (4)….

Answer 31

(1) the drug’s intrinsic clearance by the transporters involved in active secretion as affected by (2) the drug’s binding to plasma proteins, (3) the degree of saturation of these transporters, and (4) the rate of delivery of the drug to the secretory site.

Question 32

(non-ionized/ionized) compounds may be reabsorbed far more rapidly than ______________

Answer 32

Non-ionized; ionized polar molecules

Question 33

What type of drugs are susceptible to “ion-trapping” in the urine?

Answer 33

Weakly acidic drugs

Question 34

What is an example of a common drug that’s a weak acid?

Answer 34

Aspirin (pKa = 3.0)

Question 35

What happens to the excretion of aspirin as the pH of urine increases (alkalinizes)?

Answer 35

More salicylate is in its ionized form at equilibrium, and more salicylic acid is diffused into the tubular lumen of the kidney

Question 36

Urinary alkalinization is also believed to speed clearance of (4)

Answer 36

phenobarbital, chlorpropamide, methotrexate, and chlorphenoxy herbicides

Question 37

What is the first line tx only for moderately severe salicylate poisoning that does not meet criteria for hemodialysis?

Answer 37

Urine alkalinization

Question 38

How do you alkalinize urine? Urine alkalinization is contraindicated in the presence of renal failure, or when the fluid administration may worsen pulmonary edema or congestive heart failure. Acetazolamide is not used to alkalinize urine as it promotes acidemia.

Answer 38

100-150 mEq of sodium bicarbonate in 1L of D5W is infused IV at twice the maintenance fluid requirements and then titrated to effect.

Question 39

What has to be treated b/c it will hamper efforts to alkalinize the urine? Why?

Answer 39

Hypokalemia due to H+-K+ exchange in the kidney