Pharmacokinetics Continued

Question 1

Factors affecting distribution

Answer 1

• Amount of free drug
• Specialized barriers
• Blood flow (higher = better distribution)

Question 2

Volume of Distribution (Apparent volume)

Answer 2

• A proportionality factor that relates the amount of drug in the body to the concentration of drug measured in a biological fluid; does not indicate which tissues/fluids drug distributes to
• Small Vd = limited distribution
• Large Vd = extensive distribution into tissues
• Vd (liters) = A (dose - amt of drug in body)/ C (plasma concentration)

Question 3

Redistribution

Answer 3

• A concentration equilibria is achieved with drugs redistributed to less well perfused organs; plays part in termination of a drug’s pharmacological effect
• Brain, heart, liver, kidneys –> sk mm, skin –> adipose, bone, CT

Question 4

Metabolism is sometimes referred to as ________

Answer 4

Biotransformation

Question 5

Most metabolically active tissue per unit weight is ________

Answer 5

The liver

Question 6

Phase I of Metabolism

Answer 6

• Making molecules lipophillic
• Oxidation –> (electrophiles)
• hydrolysis and/or reduction –> nucleophiles

Question 7

Phase II of Metabolism

Answer 7

• Making molecules hydrophilic to be excreted into urine
• Glutathione conjugation, sulfation, acetylation, and glucuronidation

Question 8

Cytochrome P450

Answer 8

Monooxygenase enzyme found in the ER and liver that functions to oxidize drugs in Phase I to make them readily available for Phase II

Question 9

Felines lack what key element needed for Phase II?

Answer 9

critical enzymes necessary to perform glucuronidation; can compensate with acetylation and sulfonation

Question 10

Causes of enzyme induction

Answer 10

increased enzyme transcription/translation or decreased enzyme degradation

Question 11

Causes of enzyme inhibition

Answer 11

increased enzyme degradation, inhibition of enzyme synthesis, or enzyme inactivation by proteins/metals

Question 12

Factors affecting metabolism

Answer 12

• enzyme inhibition/induction
• age (decreased in young and elderly)
• reduced hepatic blood flow (heart failure)
• gender (hormone influences)
• mutations: Beagles & Irish wolfhounds w/ inability to metabolize caffeine

Question 13

Prodrug activation

Answer 13

conversion of an inactive parent drug into an active metabolite

Question 14

Excretion

Answer 14

the elimination of unchanged drug and metabolized drug products from the body

Question 15

The main route of drug excretion is ________-

Answer 15

the kidney

Question 16

What happens to drugs in the liver?

Answer 16

they are metabolized to become more water soluble to be excreted in the urine

Question 17

Functions of the kidney in drug elimination

Answer 17

removing hydrophilic drugs that haven’t been metabolized and by-products of cellular metabolism (creatinine)

Question 18

Mechanisms of Renal Excretion

Answer 18

1. Glomerular filtratrion - non-protein bound drugs (passive), dependent on CO
2. Active tubular secretion - movement of unwanted materials from capillaries (needs energy)
3. Tubular reabsorption - into blood, depends on lipid solubility of drug and urine pH

Net Renal Excretion = GF + AS - TR

Question 19

Weakly acidic drugs would be better eliminated by a carnivore or an herbivore?

Answer 19

Herbivore, because have basic urine so drugs would be in ionized form and thus excreted in urine

Question 20

What happens to metabolites in bile?

Answer 20

they are dumped into the intestine, then excreted into feces or reabsorbed into circulation to be filtered by the kidney

NOT the major route of elimination for most drugs

Question 21

Clearance

Answer 21

volume of fluid cleared of drug from the body per unti of time (mL/min or L/hr); describes ability of the body to eliminate a drug

Cl_B = Cl_(renal) + Cl_(hepatic) + Cl_(other)