Foundations 2 Week 2

Question 1

Drugs are eliminated by the kidney in three processes: glomerular filtration, tubular secretion. You would like to prescribe a drug, which tightly binds to albumin, to a patient with severe malnutrition (and thus a low serum albumin level). Would you expect drug elimination to be faster or slower? Due to which of the three processes?

Answer 1

Faster drug elimination. Albumin-bound drugs will not be filtered through the glomerulus, because albumin is a large protein. By decreasing serum albumin, a greater proportion of total body drug will be free to be filtered.

Lecture/LI: Pharmacokinetics: Drug Elimination: 1) Describe the mechanisms involved with drug elimination by the kidneys and to be able to differentiate the difference in the three processes: glomerular filtration, tubular secretion and reabsorption.

Question 2

Phenytoin and ethanol are classic drugs with zero-order clearance. What does this mean about how much phenytoin or ethanol is cleared per unit time? How does this differ from first order clearance?

Answer 2

Zero order: constant amount of drug cleared per unit time. First order: constant percent of drug cleared per unit time.

Lecture/LI: Pharmacokinetics II/Quantitative Approaches.
5) Explain the differences between zero order and first order drug clearance. (MKS1e)

Question 3

If volume of distribution of a hypothetical drug is increased, would you expect the half-life to increase or decrease?

Answer 3

Increase. Half-life is proportionate to 0.693 x volume of distribution and inversely proportionate to clearance.

Lecture/LI: Pharmacokinetics II/Quantitative Approaches
1) Describe the relationship between elimination half-life, clearance and the volume of distribution

Question 4

What is the genetic basis underlying why some patients may experience substantial sedation from a standard dose of codeine?

Answer 4

Codeine is a prodrug converted to morphine (active analgesic) by CYP2D6. Genetic variants of CYP2D6 can confer heightened metabolizing capacity (thus more morphine, and sedation) or diminished metabolizing capacity (thus poor analgesia).

Lecture/LI: Pharmacogenomics
3) Give examples of inter-individual variability in drug biotransformation, elimination and efficacy and explain the underlying genetic or genomic basis for this variability.

Question 5

CYP2D6a*1 – what is the gene superfamily, family, and allele represented here?

Answer 5

CYP superfamily, family 2, subfamily D, isoform 6, allele *1

Lecture/LI: Pharmacogenomics
4) Interpret the nomenclature for human cytochrome P450 alleles.

Question 6

In which plane of motion does abduction/adduction occur? What type of motion at the neck occurs in this plane?

Answer 6

Coronal (around an anterior-posterior axis); this represents movement of the limbs. Neck movement in the coronal plane is lateral bending (e.g. L ear to L shoulder)

Lecture/LI: Intro to Anatomy and Histology; 4. Describe the three anatomical planes and the body movements that occur within them. (MKS-1a)