W8: Pharma Applications

Question 1

Define biologics and list three types

Answer 1

therapeutic substances produced through a biological process, e.g., recombinant DNA technology)

• Substances identical to body’s key signaling proteins
• Monoclonal antibodies (mAbs)
• Receptor constructs (fusion proteins)

Question 2

Types of mAbs: describe how they are derived and their components

Chimeric
Humanized

Answer 2

Chimeric: IgG with human constant regions and rodent variable regions

Humanized: all human except rodent CDR residues

(CDR - complementarity determining region: peptides that are prominent determinants of antigen binding affinity and specificity)

Question 3

Nomenclature: Ultimate syllable:

“-mab” =
“-cept” =
“-nib” =

Answer 3

"-mab" = monoclonal antibody
"-cept" = receptor fusion protein
"-nib"   = kinase inhibitor

Question 4

Nomenclature for mAb: Penultimate syllable before “-mab”:

“-xi-“ =
“-zu-“ =
“-u-“ =
“-mo-“ =

Answer 4

“-xi-“ = chimeric (mouse variable regions; human constant regions)

“-zu-“ = humanized (chimeric monoclonal antibody genetically engineered; all human except CDR portion of variable region)

“-u-“ = fully human

“-mo-“ = murine (mouse)

Question 5

Nomenclature: Antepenultimate syllable:

“-li-“ or “-lim-“ =

Answer 5

“-li-“ or “-lim-“ = immune system (not consistently used)

Question 6

Types of mAb?

abciximab
alemtuzumab
adalimumab
ibritumomab

Answer 6

abciximab - chimeric human/mouse antibodies (ximabs)

alemtuzumab - humanized antibodies (zumabs)

adalimumab - fully human antibodies (umabs)

ibritumomab - murine antibodies (momabs)

Question 7

All approved mAbs are of the IgG/M/A/E class

Answer 7

IgG

Question 8

What is most common method of mAb administration?

Answer 8

Parenteral:

1. IV (intravenous)
2. SC (subcutaneous)
3. intramuscular injection

Question 9

mAb are primarily catabolized and eliminated via

Answer 9

Primarily intracellular catabolism, following endocytosis

renal elimination relatively unimportant due to large MW

Question 10

Which mAb has the highest and lowest half-life?

Human
Humanized
Mouse
Chimeric

Answer 10

Highest: Human
Lowest: Mouse

low to high: Mouse - Chimeric - Humanized - Human

Question 11

Long half-life of humanized mAb IgG is due to recycling by __ in the __ cell and circulating __

Answer 11

FcRn (neonatal Fc receptor for IgG)

endothelial cell, monocytes

Question 12

IgG is protected from degradation via __. IgG elimination occurs via __ __.

Answer 12

FcRn

intracellular catabolism

Question 13

Define enteric-coated (EC) pills

Answer 13

Tablets coated with material which does not disintegrate in the acidic conditions of the stomach but only in the alkaline conditions of the intestine

Question 14

Define excipients

Answer 14

Natural or synthetic substances that are included in a pharmaceutical dosage form (inert ingredients)

no direct therapeutic action, but to aid the manufacturing process, to protect, support or enhance stability, and solubility and for facilitating bioavailability or patient acceptability

Question 15

IR (immediate release) vs. ER (extended release)

Answer 15

IR - immediate release of drug

ER - dissolve a drug over time in order to be released slower and steadier into the bloodstream

Question 16

Define authorized generic drugs and ‘standard’ generic drugs. How are they different?

Answer 16

Authorized generic drug - describes an approved brand name drug that is marketed without the brand name on its label (may have a different color or marking)

Standard generic drug - drug with same active ingredients made by different company

Question 17

Define biosimilar/biobetter drugs? Caveates

Answer 17

drugs highly similar to an FDA-approved biological product

caveat: structurally and functionally different from the reference product they are designed to resemble (unlike generic drugs)

Question 18

4 phases of clinical drug study

Answer 18

Phase 1: safety (20-80 pp)

Phase 2: efficacy (optimal dose estimate) (20-300)

Phase 3: clinical trial, double blinded (placebo vs. drug) (300-3000)
FDA approved for efficacy but not monitored for safety yet

Phase 4: monitor over years for safety (adverse effects usu. found)

Question 19

Approved use vs. off-label use

Answer 19

both use of FDA approved drug

approved use - use outlined in FDA guideline

off-label use - use of FDA drug for reasons not outlined in FDA (different condition, different dose, or in a different population)

Question 20

Define the terms: Iatrogenic, Nosocomial

Answer 20

Both referring to unfavorable outcome in medical context

Iatrogenic - adverse effects or complications caused by or resulting from medical treatment or advice (e.g., medical error, negligence, adverse effects of prescription drugs)

Nosocomial - originating or taking place in a hospital, acquired in a hospital, especially in reference to an infection

Question 21

Define pharmacovigilence

Answer 21

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems, usually AFTER the FDA approval process has been completed.

Question 22

Define black box warning

Answer 22

warnings emphasizing significant and serious safety data regarding prescription drugs (strongest warning that the FDA requires)

Question 23

Define contraindication

Answer 23

a condition which makes a particular treatment or procedure inadvisable

Question 24

X-rays in pregnancy are __ contraindicated (because of concern for the developing fetus) unless the X-rays are absolutely necessary.

Answer 24

relatively

relative contraindication: a condition which makes a particular treatment or procedure somewhat inadvisable but does not rule it out

(absolute contraindication: absolutely inadvisable)

Question 25

Adverse drug reaction is __, whereas Serious drug reaction is __.

Answer 25

noxious, life-threatening