LEC 22 Drug Absorption, Distribution, and Elimination

Question 1

What are the major mechanisms of drug diffusion?

Answer 1

• Lipid diffusion (passive)
• Active transport

Less significant: Aqueous diffusion, endo/pinocytosis, facilitated diff.

Question 2

What is Fick’s Law?

the actual equation and what everything means

Answer 2

1. Concentration gradient (Co – Ci)
2. Permeability coefficient, governed by lipid solubility, ionization
3. Thickness of the biological membrane
4. Area of the absorbing surface

Question 3

What determines the aqueous solubility of a drug?

Answer 3

Electrostatic charge of the molecule

Degree of Ionization, Polarity

Question 4

Which drugs cross membranes by lipid diffusion?

in relation to charge

Answer 4

Non-ionized

Non charged

Question 5

Why are weak acids and weak bases able to cross biological membranes?

Answer 5

Both are uncharged and therefore more lipid soluble

Question 6

Weak acids are (ionized or non-ionized) when protonated?

Answer 6

Non-ionized

Protonated form can cross membrane

Question 7

Weak bases are (ionized or non-ionized) when protonated?

Answer 7

Ionized

Protonated form CANNOT cross membrane

Question 8

What is the Henderson-Hasselbach equation?

Answer 8

Question 9

The pH at which 50% of the weak acid or base is ionized is the what?

Answer 9

pKa

Question 10

For acids, is a lower or higher pKa a stronger acid?

Answer 10

Lower

Question 11

For bases, is a lower or higher pKa a stronger base?

Answer 11

Higher

Question 12

At pH’s below the pKa, weak acids are mostly what?

Ionized or nonionized?

Answer 12

Nonionized

can cross the membrane

Question 13

At pH’s above the pKa, weak bases are mostly what?

Answer 13

Nonionized

can cross the membrane

Question 13

At pH’s above the pKa, weak bases are mostly what?

Answer 13

Nonionized

can cross the membrane

Question 14

Lipid diffusion across membranes is directly proportional to what?

aside from ionization

Answer 14

Surface Area

Question 15

What affects absorption of orally administered drugs?

Answer 15

• Physical form of drug (liquid vs solid) - solid takes longer
• Differences in pH of GI tract
• Differences in surface area
• Gastric emptying time
• Bacterial breakdown/Intestinal metabolism of drugs
• “First Pass Effect”
• Enterohepatic Circulation

Question 16

Explain the “First Pass Effect”

Answer 16

• All drugs reach the liver before they get to the systemic circulation
• Drugs are absorbed in the small instestine and travel to liver via portal vein
• Low levels of drug in systemic circulation

Question 17

Explain enterohepatic circulation.

Answer 17

• Drugs that are secreted into the bile are shuttled between the bile, intestine and liver.
• Very low levels reach systemic circulation

Question 18

What advantage does sublingual administration have over oral administration of a drug?

Answer 18

The drug avoids the portal system

Question 19

What are the advantages or rectal administration of a drug?

Answer 19

• Nausea & vomiting - pt can’t keep the drug down orally
• Some of the drug is absorbed systemically and some through portal vein - bc of rectal veins

Question 20

What are the advantages of inhalation of a drug?

Answer 20

• Large tissue area for absorption
• Highly vascularized
• Bypasses first pass effect
• Good for local delivery to lung and airways

Question 21

What are the advantages of injections?

Answer 21

• Reliability, precision, and compliance
• bypass problems of oral admin

Question 22

What are the advantages of subcutaneous and intraperitoneal admin of drugs?

Answer 22

• slow and even distribution
• depot
• avoids first pass effect

Question 23

What is the main advantage of intramuscular injections?

Answer 23

Speed

Question 24

What are the advantages of intravenous admin of drugs?

Answer 24

• Fastest and most reliable method for achieving a desired blood concentration
• bypasses liver and gut

Question 25

What is the bioavailability of a drug?

Answer 25

the fraction of the dose that is absorbed by a given route

Question 26

What factors influence distribution of a drug?

Answer 26

• Regional differences in blood flow and tissue mass
• Solubility
• Barriers, especially blood brain barrier
• Binding - protein bound and ionized do not cross membranes, ionized can be ion trapped
• Transport mechanisms

Question 27

The brain, spinal cord, kidney, liver, and heart together recieve about how much of total cardiac output?

Answer 27

70%

Question 28

The brain alone recieves about how much of the total cardiac output?

Answer 28

20-25%

Question 28

What are the important membrane barriers in the body with regards to drug distribution?

Answer 28

• Blood brain barrier
• Placental barrier
• Testicular barrier

Question 29

Explain the concept of ion trapping.

Answer 29

• Weak bases are typically more nonionized in the blood (pH=7.4)
• Nonionized can diffuse across the nephron’s membrane into the urine
• The urine is more acidic (pH=6) and converts the base back to the ionized form d/t protonation
• Now that the base is charged, it cannot diffuse back across the membrane and is essentially trapped in the urine.
• More drug will be concentrated in the urine

Question 30

Where are most drugs eliminated?

Answer 30

Kidney

Question 31

What are the 3 most important processes involved in drug elimination in the kidney?

Answer 31

• Glomerular Filtration - only unbound drug in filtered here
• Active tubular secretion - membrane transporters in renal tubules
• Passive back diffusion (reabsorption) - nonionized weak acids and bases reabsorbed along with H2O

Question 32

Why does tight drug binding to proteins reduce the drug’s glomerular filtration?

Answer 32

Proteins are not filtered