ADME

Question 1

What is absorption in pharmacokinetics?

Answer 1

It is the movement of a drug from the site of administration to the systemic circulation.

Question 2

What factors influence drug absorption?

Answer 2

Route of administration, membrane polarity, first-pass metabolism, and drug solubility.

Question 3

What are the pros and cons of oral drug administration?

Answer 3

Pros: Easy, cheap, well-accepted. Cons: Variable absorption, GI degradation, first-pass metabolism, low pH instability, mucosal irritation.

Question 4

Why is oral drug absorption sometimes poor in the stomach?

Answer 4

Because of low pH and degradation before reaching systemic circulation.

Question 5

What is first-pass metabolism (FPM)?

Answer 5

Drug metabolism that occurs in the liver before the drug reaches systemic circulation, reducing bioavailability.

Question 6

What are the advantages of sublingual and buccal administration?

Answer 6

Rapid absorption, bypasses FPM, useful in dysphagia, removable if needed.

Question 7

What limits sublingual/buccal absorption?

Answer 7

Salivation rate variability and the requirement not to chew/swallow the dose.

Question 8

What are the pros and cons of IV administration?

Answer 8

Pros: 100% bioavailability, rapid onset, bypasses FPM and GI tract. Cons: Risk of infection, expensive, quick adverse reaction onset.

Question 9

Why might IV administration be used in critical cases?

Answer 9

It allows immediate drug action and is ideal when the GI tract cannot be used.

Question 10

What are the benefits and drawbacks of intramuscular (IM) injection?

Answer 10

Pros: Consistent absorption, depot options, bypasses FPM. Cons: Injection pain, muscle mass variability, peptide degradation, risk of hematoma or abscess.

Question 11

When is subcutaneous (SC) injection preferred?

Answer 11

For large molecule drugs or when oral absorption is poor.

Question 12

CONS OF SC

Answer 12

Pain, irritation, and site rotation needs; variable absorption rates.

Question 13

How does nasal administration work for drugs?

Answer 13

High vascularity enables rapid absorption and bypasses FPM, but dose is limited.

Question 14

What are pros and cons of respiratory drug administration?

Answer 14

Large surface area enables smaller doses, but lung clearance may reduce delivery to alveoli.

Question 15

When is rectal administration beneficial?

Answer 15

In emergencies (e.g., seizures), for infants or elderly, or when oral route is not viable. Avoids some FPM.

Question 16

What determines drug distribution?

Answer 16

Membrane partitioning, drug polarity, and volume of distribution (Vd).

Question 17

How is volume of distribution (Vd) calculated?

Answer 17

Vd = Dose (mg) / Plasma concentration (mg/L)

Question 18

What do different Vd values indicate?

Answer 18

5L = plasma only, 15L = extracellular fluid + plasma, >40L = tissue penetration (especially for lipophilic drugs).

Question 19

What types of plasma proteins bind drugs?

Answer 19

Albumin (acidic drugs), lipoproteins and alpha-1 acid glycoproteins (basic drugs).

Question 20

Which drug fraction is active in plasma?

Answer 20

Only the unbound (free) drug fraction is pharmacologically active.

Question 21

Why do lipophilic drugs have higher Vd?

Answer 21

They accumulate in fat and permeate tissues more extensively.

Question 22

How does gender affect drug distribution?

Answer 22

Females have higher body fat, which increases Vd for lipophilic drugs.

Question 23

What is the primary site of drug metabolism?

Answer 23

The liver.

Question 24

What are the phases of drug metabolism?

Answer 24

Phase I: Functionalization (oxidation, reduction, hydrolysis); Phase II: Conjugation (e.g., glucuronidation, sulfation).

Question 25

What are pro-drugs?

Answer 25

Drugs that are inactive until metabolized into active forms.

Question 26

What role do hepatic drug transporters play?

Answer 26

They influence uptake and efflux of drugs in liver cells (e.g., P-gp, OATP).

Question 27

How does age affect metabolism?

Answer 27

Phase I enzyme activity decreases with age; frailty affects Phase II; albumin synthesis declines.

Question 28

How does gender affect metabolism?

Answer 28

P-gp expression is higher in males; enzyme activities in Phases I & II vary by sex (Phase II generally higher in males).

Question 29

What is enzyme induction?

Answer 29

Chronic drug use increases enzyme expression, decreasing drug effects over time.

Question 30

What is enzyme inhibition?

Answer 30

Blocking enzymes (e.g., CYP3A4 by grapefruit juice), which slows metabolism and may increase drug levels.

Question 31

What are the primary drug excretion routes?

Answer 31

Renal (urine), biliary (feces); minor: lungs, skin.

Question 32

What is the role of P-glycoprotein (P-gp) in excretion?

Answer 32

It helps efflux drugs like digoxin and steroids from cells to bile/urine.

Question 33

What do Organic Anion Transporters (OAT) do?

Answer 33

Transport drugs like ACE inhibitors and antivirals into renal tubules for excretion.

Question 34

How does aging affect renal excretion?

Answer 34

Renal mass and GFR decline with age, reducing drug clearance.

Question 35

Why do females have slower renal clearance than males?

Answer 35

Due to lower baseline glomerular filtration rate (GFR).

Question 36

What is the impact of polypharmacy on excretion?

Answer 36

Multiple drugs may compete for transporters, altering elimination rates.

Question 37

How does aging affect drug absorption?

Answer 37

Reduced gastric acid, slower motility, reduced surface area and blood flow to the GI tract.

Question 38

How does weight affect drug distribution?

Answer 38

Increased fat prolongs lipophilic drug action; decreased lean mass and water raise plasma concentrations.

Question 39

What is different about pediatric drug absorption?

Answer 39

GI pH, faster motility, underdeveloped enzymes, and swallowing issues affect oral drug effectiveness.

Question 40

Why do children have altered drug distribution?

Answer 40

They have larger Vd, higher fat %, and lower protein binding, increasing free drug levels.

Question 41

How does pediatric metabolism differ?

Answer 41

Infants/toddlers often have higher hepatic clearance, but enzyme activity depends on age (ontogeny).

Question 42

How does excretion differ in children?

Answer 42

Newborns have immature kidneys (slow clearance); preschoolers clear unchanged drugs quickly due to higher kidney-to-body ratio.

Question 43

What is Lipinski’s Rule of Five used for?

Answer 43

To predict oral drug absorption based on physiochemical properties.

Question 44

What are the four criteria in Lipinski’s Rule of Five?

Answer 44

1) Molecular weight < 500 Da, 2) Log P < 5, 3) ≤ 5 hydrogen bond donors, 4) ≤ 10 hydrogen bond acceptors.

Question 45

What does Log P represent in Lipinski's rule?

Answer 45

Log P reflects lipophilicity (octanol-water partition coefficient); too high = poor solubility and absorption.

Question 46

What does it suggest if a compound violates more than one of Lipinski’s rules?

Answer 46

It likely has poor oral bioavailability and absorption.