Page 351 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 18 The Eicosanoids: Prostaglandins, Thromboxanes, Leukotrienes, & Related Compounds 337

The major eicosanoids produced by leukocytes are leukotrienes, PREP AR A TIONS
which facilitate T-cell proliferation and act as chemoattractants. A V AIL ABLE
Human macrophages synthesize the COX products PGE and
2
TXA and large amounts of leukotrienes.
2
GENERIC NAME AVAILABLE AS
Glaucoma NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS ARE LISTED IN CHAPTER 36.
Latanoprost, a stable long-acting PGF derivative, was the first Alprostadil
2α
prostanoid used for glaucoma. The success of latanoprost has Penile injection, mini-suppository Caverject, Edex, Muse
stimulated development of similar prostanoids with ocular hypo- Parenteral Generic, Prostin VR Pediatric
tensive effects, and bimatoprost, and travoprost are now avail- Bimatoprost Lumigan, Latisse
able. These drugs act at the FP receptor and are administered as Carboprost tromethamine Hemabate
drops into the conjunctival sac once or twice daily. Adverse effects Dinoprostone [prostaglandin E 2 ] Prostin E2, Prepidil, Cervidil
include irreversible brown pigmentation of the iris and eyelashes, Epoprostenol [prostacyclin] Generic, Flolan, Veletri
drying of the eyes, and conjunctivitis. Iloprost Ventavis
Latanoprost Generic, Xalatan
Hypotrichosis Misoprostol Generic, Cytotec
Montelukast Generic, Singulair
Bimatoprost is FDA approved for treatment of eyelash hypotri- Selexipag Uptravi
chosis and has shown efficacy in enhancing eyelash growth after Travoprost Generic, Travatan, Travatan-Z
chemotherapy. The drug is applied in a 0.03% solution to the skin Treprostinil Remodulin, Tyvaso,
at the base of the upper lashes. A common but minor adverse effect Orenitram
is darkening of eyelid skin due to increased melanin production Zafirlukast Generic, Accolate
that is reversible with discontinuation. Recent trials have also dem- Zileuton Zyflo, Zyflo CR
onstrated efficacy in eyebrow hypotrichosis, and emerging studies
have suggested that this drug may have utility for treating alopecia.

REFERENCES
DIETARY MANIPULATION OF Bäck M et al: International Union of Basic and Clinical Pharmacology Review.
ARACHIDONIC ACID METABOLISM Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR
Review 7. Br J Pharmacol 2014;171:3551.
Bhala N et al: Vascular and upper gastrointestinal effects of non-steroidal anti-
The effects of dietary manipulation on arachidonic acid metabo- inflammatory drugs: Meta-analyses of individual participant data from
lism have been extensively studied. Dietary intake of linoleic and randomised trials. Lancet 2013;382:769.
α-linolenic acids, which are, respectively, omega-6 and omega-3 Che XH et al: Dual inhibition of COX-2/5 blocks colon cancer proliferation,
migration, and invasion in vitro. Oncol Rep 2016;35:1680.
essential fatty acids, can modify arachidonic acid metabolism and Choi YM, Diehl J, Levins PC: Promising alternative clinical uses of prostaglandin
the nature of the eicosanoids produced. Two approaches have been F2α analogs: beyond the eyelashes. J Am Acad Dermatol 2015;72:712.
used. The first adds corn, safflower, and sunflower oils, which Christin-Maitre S, Bouchard P, Spitz IM: Medical termination of pregnancy.
contain linoleic acid (C18:2), to the diet, allowing for generation N Engl J Med 2000;342:946.
of 1-series prostaglandins via dihomo-γ-linoleic acid. The second Grosser T, Yu Y, Fitzgerald GA: Emotion recollected in tranquility: Lessons learned
from the COX-2 saga. Annu Rev Med 2010;61:17.
approach adds oils from cold-water fish that contain the omega-3 Hao CM, Breyer MD: Physiological regulation of prostaglandins in the kidney.
fatty acids eicosapentaenoic (C20:5) and docosahexaenoic acids Annu Rev Physiol 2008;70:357.
(C22:6). Diets high in fish oils have been shown to impact Norel X et al: Prostanoid receptors. IUPHAR/BPS Guide to Pharmacology.
indices of platelet and leukocyte function, blood pressure, and http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?famil
yId=58. Accessed on June 7, 2016.
triglycerides with different dose-response relationships. There is an Perrin S et al: New pharmacotherapy options for pulmonary arterial hypertension.
abundance of epidemiologic data relating diets high in fatty fish Exp Opin Pharmacother 2015;16:2113.
to a reduction in the incidence of myocardial infarction and sud- Rao CV et al: Simultaneous targeting of 5-LOX-COX and EGFR blocks progres-
den cardiac death, although there is more ambiguity about stroke. sion of pancreatic ductal adenocarcinoma. Oncotarget 2015;6:33290.
However, such epidemiologic data may be confounded by concur- Smith WL, Urade Y, Jakobsson PJ: Enzymes of the cyclooxygenase pathways of
prostanoid biosynthesis. Chem Rev 2011;111:5821.
rent reduction in saturated fats and inclusion of other elements Smyth EM et al: Prostanoids in health and disease. J Lipid Res 2009;50:S423.
of a “healthy” lifestyle, raising questions about the cardiovascular Stitham J, Hwa J: Prostacyclin, atherothrombosis and diabetes mellitus: Physi-
benefit of dietary omega-3 fatty acids. Nevertheless, data from ologic and clinical considerations. Curr Mol Med 2016:16:328.
prospective randomized trials suggest that such dietary interven- Varnavas DM, Dennis EA: Membrane and inhibitor interactions of intracellular
tions may reduce the incidence of sudden death while experi- phospholipase A2. Adv Biol Regul 2016;61:17.
ments in vitro suggest that fish oils protect against experimentally Wang D, Dubois RN: Eicosanoids and cancer. Nat Rev Cancer 2010;10:181.
induced arrhythmogenesis, platelet aggregation, vasomotor spasm, Woodward DF, Jones RL Narumiya S: International Union of Basic and Clinical
Pharmacology. LXXXIII: Classification of prostanoid receptors, updating
and dyslipidemias. 15 years of progress. Pharmacol Rev 2011;63:471.