Page 188 - pharma 1 theoretical updated MNU_Neat

Clinical pharmacy 2024/2025 Level 3 Pharm D Pharmacology 1 (PO 502)
Substance P

● Substance P belongs to the tachykinin family of peptides.

● Substance P is widely distributed in the central and peripheral nervous
Site
systems and in the cardiovascular system. It is also present in the
gastrointestinal tract.

● It exerts a variety of central actions that implicate the peptide in behavior,
anxiety, depression, nausea, and emesis.
● It is present in peripheral afferent pain fibers and participates in nociception.

● It is a potent arteriolar vasodilator, producing marked hypotension in humans
Function mediated by release of nitric oxide from the endothelium.
● Substance P causes contraction of venous, intestinal, and bronchial smooth

muscle.
● It stimulates secretion by the salivary glands and causes diuresis and
natriuresis by the kidneys.

● The actions of substance P is mediated by three Gq protein-coupled
Receptors
tachykinin receptors designated NK 1, NK 2, and NK 3.
NK1 receptor antagonists (Aprepitant and fosaprepitant)

● Several nonpeptide NK1 receptor antagonists have been developed. These compounds

are highly selective and orally active and enter the brain.
● These antagonists may be useful in treating depression and in preventing chemotherapy-

induced emesis.
● The first of these to be approved for the prevention of chemotherapy-induced and
postoperative nausea and vomiting is aprepitant.
● Fosaprepitant is a prodrug that is converted to aprepitant after intravenous administration

and may be a useful parenteral alternative to oral aprepitant.
● Substance P and NK1 receptors are present in a variety of tumor cells, and NK1 receptor

antagonists exert an antitumor action. Thus, drugs such as aprepitant may have potential
as anticancer agents.
Kinins as bradykinin

• Kinins are most potent vasodilator on arteries (10 times > histamine) but of it is of short
duration.

• Kinins formed from precursor kininogen by the actions of the enzymes called kallikreins.
• kallikreins are resent in the plasma, kidneys, pancreas, intestines and salivary glands.

• Production of kallikreins & kinins increase inflammatory lesions and produce all
symptoms of inflammation.
➢ Kinins are rapidly degraded by kininase II which is same as ACE and has a very short

t1/2 (<15 seconds)

| P a g e 172