Chapter 29 Exercises — The Peptide Drugs Already in Your Pharmacy

Thirty-four items. Work them in order if you can. Items marked † are the harder ones: they require you to combine material from more than one section, or to argue a position rather than recall a fact. No answers are given here. If you want to check yourself on the factual items, the quiz for this chapter has an answer key.

A reminder that applies to every item below: nothing in this chapter or these exercises is medical guidance. Where an item asks you to reason about a drug, it is asking you to reason about evidence and category, never about what anyone should take.

Part 1 — The inventory

A. Without looking back at the chapter, write down as many approved peptide drugs as you can name in ninety seconds. Then check your list against §29.1 and §29.10. How many did you get, and how many of the ones you missed had you actually heard of before?

B. For each of the following, state in one line what it is used for: teriparatide, desmopressin, cosyntropin, icatibant, linaclotide, terlipressin, glucagon, secretin.

C. Name three peptide drugs that a hospital pharmacy stocks and that essentially nobody in that hospital would describe as peptides. For each, say what functional category clinicians file it under instead.

D. Explain why the number of approved peptide drugs is usually given as a range rather than an exact figure. Name at least three specific inclusion decisions that move the total.

E. † Sources sometimes state an exact count of approved peptide drugs. Draft two different, defensible inclusion rules — one that would yield a low count and one that would yield a high count — and state approximately how each would change the total and why.

F. Go back to Chapter 1 §1.8 and re-read the stem table. Which of the drugs in this chapter have names that would have told you they were peptides? Which would not have, and why not?

Part 2 — Teriparatide and the pulsatility paradox

G. State the paradox in two sentences: what does continuously elevated parathyroid hormone do to bone, and what does intermittent exposure do?

H. Teriparatide is PTH(1–34) rather than full-length PTH(1–84). Give two distinct reasons a manufacturer might prefer the fragment.

I. Distinguish anabolic from antiresorptive bone agents. Which class does teriparatide belong to, and which class dominates osteoporosis prescribing?

J. † Chapter 3 §3.5 argued that pulsatility carries information. Write a paragraph explaining how teriparatide converts that observation from a caution into a design parameter. Then name one other peptide system in this book where the same conversion has not been achieved, and say what would have to be true for it to be.

K. Abaloparatide is described as a PTHrP analog rather than a PTH analog. What does that distinction mean, and why does the same receptor accept both?

L. † Trace the teriparatide osteosarcoma labeling history in five steps, from the rodent finding to the label revision. At which step did the decisive evidence arrive, and what kind of evidence was it? Then compare the situation with the GLP-1 receptor agonist thyroid C-cell question from Chapter 8: name two structural similarities and one important difference. Do not conclude that either finding is meaningless.

M. Write the four-line 📊 Evidence Rating block you would issue for the claim "teriparatide increases bone mineral density in men with osteoporosis." Do not guess at evidence you do not have — if you would need to look something up before rating, say what.

Part 3 — Desmopressin and receptor subtype selectivity

N. Name the two vasopressin receptor subtypes discussed in §29.3, the tissue each sits in, and the physiological effect each produces.

O. Desmopressin was modified at two positions relative to vasopressin. State what each modification was intended to achieve. One of them does two jobs at once — which, and what are they?

P. Desmopressin has three quite different approved indications. Draw the causal chain from V2 receptor activation to each of the three, in one line apiece.

Q. † The chapter issues two separate ✅ ratings for desmopressin, and states that the second is "deliberately narrow." Rewrite the enuresis claim so that it would not deserve a ✅, changing nothing except the wording of the claim. Then explain what you changed and why it matters.

R. State the principal safety risk associated with desmopressin and explain, mechanistically, why that risk follows directly from what the drug is designed to do.

Part 4 — Calcitonin and honest contraction

S. List the three separate developments that together caused calcitonin's clinical role to contract. Which of the three, on its own, would have been sufficient?

T. Explain why salmon calcitonin rather than human calcitonin is the therapeutic agent.

U. In the PROOF trial, one dose arm separated from placebo and a higher one did not. Give three distinct explanations for that pattern and say what additional information would let you distinguish among them.

V. † The chapter rates "calcitonin for osteoporotic fracture reduction" as ⚠️ → ❌ while stating that this rating does not travel to calcitonin's other uses. Write out the rating you would issue for "calcitonin for short-term management of hypercalcemia," and explain in one sentence why issuing a different rating for the same molecule is required rather than optional.

W. † Write a short paragraph, in your own words, explaining to a skeptical friend why calcitonin's contraction is evidence for the reliability of the regulatory process rather than against it. Anticipate and answer the obvious objection.

X. Name one thing calcitonin is still used for, and say what distinguishes that use from the one that contracted.

Part 5 — The peptides nobody calls peptides

Y. Cyclosporine is orally bioavailable, which most peptides are not. Name the three structural features responsible and say what each one defeats.

Z. N-methylation is described as doing two things at once. Name both, and say which of the two has more to do with crossing membranes than with resisting enzymes.

AA. Vancomycin, bacitracin, polymyxin B, and daptomycin share a structural theme. Name it and explain what evolutionary problem it solves for the organism that makes such a molecule.

AB. † Cyclosporine acts on an intracellular target, which Chapter 1 §1.6 lists as essentially off-limits to peptides. Explain how the exception is possible, and then state precisely what the existence of one exception does and does not license you to conclude about oral peptide claims in general.

AC. Oral vancomycin and intravenous vancomycin are the same molecule used for different infections. Explain the logic, and name the section of this chapter where the same principle appears under a different drug.

Part 6 — Modern approvals, diagnostics, and the argument

AD. Explain why linaclotide's minimal systemic absorption is a specification rather than a shortcoming. Contrast it explicitly with oral semaglutide's roughly 1% bioavailability. Then explain the logic of a stimulation test, and say why cosyntropin can be a 24-residue fragment rather than full-length ACTH.

AE. Icatibant is an antagonist rather than an agonist. Say what that means mechanically, and why peptide antagonists are harder to design than peptide agonists.

AF. † Sort the following into the six functional boxes of §29.10: oxytocin, leuprolide, bacitracin, secretin, insulin, terlipressin, plecanatide, octreotide, icatibant. Any that do not fit cleanly — say why, and pick the best available box with a justification.

AG. † State the §29.10 objection ("box six is empty for regulatory reasons, not biological ones") in its strongest form, then give the three independent responses the chapter offers. Which of the three do you find weakest, and what would strengthen it?

AH. † Apply the §29.10 prior to a specific compound you have heard claims about. Write out: the claim as stated by whoever makes it, which of the six boxes it falls in, and what would have to be true for it to move into a different box. Do not conclude the compound does not work — conclude only what the prior licenses.