Drug Excretion - Issar

Question 1

Glomerular filtration

Answer 1

• Processed through Bowman’s capsule
• If a drug is highly bound to the protein, it will not filter through Bowman’s
• Free portion of drug gets filtered out
• 10% of blood entering glomerulus gets filtered
• 90% of filtrate is reabsorbed

Question 2

Inulin

Answer 2

• Gold standard for measuring renal clearance

* Renal clearance of inulin = glomerular filtration rate (GFR)

Question 3

Creatinine clearance

Answer 3

• Utilized clinically because it’s easier to measure
• Most creatinine is filtered, 10-20% is secreted
• Cl creatinine > GFR (110-130 ml/min)
• How to measure – slide 12
• If plasma creatinine is high/going up → Cl creatinine is low/going down

Question 4

Active tubular secretion

Answer 4

• Active secretion of weak electrolytes, especially weak acids
• Requires carrier and energy
• Competitive inhibition
• P-aminohippuric acid (PAH)
o Used clinically to measure renal clearance

Question 5

What is an example of competitive inhibition?

Answer 5

• Penicillin + Probenecid
o Probenecid has ability to get secreted from kidneys
o Penicillin stays around
o Give them together to increase the efficacy of penicillin

Question 6

Tubular reabsorption

Answer 6

• Reabsorption of lipid soluble (unionized) drugs
• Concentration gradient direction of reabsorption
• Manipulation of urine pH
o Dramatic influence on the reabsorption of filtered species

Question 7

Cl drug/Cl inulin < 1

Answer 7

Partially reabsorbed

Question 8

Cl drug/Cl inulin = 1

Answer 8

Filtered

Question 9

Cl drug/Cl inulin > 1

Answer 9

Actively secreted

Question 10

Biliary excretion

Answer 10

• Only small amounts of most drugs reach the bile by diffusion
• Requires strongly polar groups
• Ex: glucuronides
• Things that are really large (m.w. > 500) will enter bile
• Active biliary secretion reported for organic anions, cations and for polar, uncharged molecules

Question 11

Enterohepatic recirculation

Answer 11

• Creates a reservoir for recirculating drug
• Prolongs duration of action of such drugs
• Ex: morphine
o Via β-glucuronidase enzyme à deconjugation

Question 12

Factors affecting biliary secretion

Answer 12

1. Liver disease or injury
2. Age
   • Infants and elderly
3. Chronic administration of drugs
   • Increases bile flow
   • Ex: phenobarbital
4. Competition between drugs

Question 13

Pulmonary excretion

Answer 13

• Rate of drug loss is dependent upon
o Respiration rate
o Pulmonary blood flow
o Drug solubility
• Ex: Nitrous oxide (insoluble in water)
• Diffusion process applies
o To remove poorly soluble drugs must increase cardiac output
o Highly soluble drugs → slow removal
• Ex: ethanol
• Most drugs removed by lungs are not metabolized

Question 14

Sweat and saliva excretion

Answer 14

• Minor role in excretion of drugs
• Excretion is dependent upon diffusion of non-ionzed form of drug
o pKa and pH
• Drug taste even for IV administered drugs
o This means that drug is secreting through saliva
o Ex: Cipro
• Can be measured through saliva

Question 15

Milk excretion

Answer 15

• Many drugs can be detected in milk
• Drug presence is dependent upon
o Maternal blood concentration
o Plasma protein binding
o Lipid solubility
o pKa
• Milk is more acidic than plasma
o Basic drugs accumulate
o Acidic drug concentration lower in milk than plasma
o Lipid soluble drugs accumulate in milk fat

Question 16

P-gp transporters

Answer 16

• P-gp secretes drugs from GI, liver, kidney, Blood Brain Barrier
o Digoxin
• Quinidine and verapamil ↑plasma [especially after taking digoxin]
o By inhibiting P-gp activity
• St John’s wort, rifampin ↓ plasma [especially after taking digoxin]
o By inducing P-gp activity
• P-gp prevents toxic drugs gaining entry in CNS