Effects of Eicosanoids | |
Blood vessels | - PGF2a is a vasoconstrictor. - TXA2 is a potent vasoconstrictor, and it also has a smooth muscle mitogenic effects. - PGI2 & PGE2. promote vasodilatation by ↑ cAMP and by intracellular Ca². - PGI2 inhibits proliferation of smooth muscle cells. - PGD, also has a vasodilator effects, is aldominant mediator of flushing induced by niacin (lipid-lowering drug). |
GIT | - Most of the PGs and TXs activate gastrointestinal smooth muscle. - PGE2 & PGF2α à Longitudinal muscle contraction. - PGF2α (Strong) & PGI2 (weak) à Circular muscle contraction. - PGE2 à Circular muscle relaxation. - LTs à also have powerful contraction effects. |
LUNG | - PGI2 & PGE2 Bronchial smooth muscle relaxation. - PGF2α, TXA2 & PGD2 à Bronchial smooth muscle contraction. - Cysteinyl LTs (LTC4, LTD4 and LTE4) à Bronchial smooth muscle contraction. - Being about 1000 times more potent than histamine. - Stimulate bronchial mucus secretion and cause mucosal edema. - Bronchospasm occur bout 10% of people taking NSAIDS, because of a shift in arachidonic acid from COX to 5-LOX. |
Platelet | - Low concentration of PGE2 à enhance platelet aggregation. - High concentration of PGE2à inhibit platelet aggregation. - PGF2α & PGD2 à inhibit platelet aggregation. - TXA2 à Induce platelet aggregation. TXA2 is the major products of COX-1 isoform enzyme. Platelet COX-1-derived TXA2 biosynthesis is increased during platelet activation and aggregation and is irreversibly inhibited by chronic administration of aspirin at low doses. |
| - PGs play important roles in maintaining blood pressure & regulating renal function - COX-1-derived products promote salt excretion in the collecting ducts. |
Uterine | - PGF2α & TXA2 à uterine smooth muscle contraction. - PGF2α together with oxytocin is essential for the onset of parturition. |
Male sex organ | - Smooth muscle-relaxing PGs such as PGE1 à enhance penile erection by relaxing smooth muscle of the corpora cavernosa. |
BRAIN | Fever: - PGE2 à increases body temperature. - Endogenous pyrogens release interleukin-1 (IL-1), which in turn promotes synthesis and release of PGE2. - PGE2 synthesis is blocked by aspirin and other antipyretic compounds. Sleep: - PGD2 induces natural sleep, while PGE2 cause wakefulness. Neurotransmission: - PGE2 may inhibits NE release from postganglionic sympathetic nerve ending. Inflammation: PGE2 & PGI2 are the predominant prostanoids associated with inflammation, markedly enhance edema formation and leukocyte infiltration by promoting blood flow in the inflamed region. |
EYE | PGE and PGF derivatives lower intraocular pressure (IOP), by increase aqueous humour outflow (the mechanism is unclear). |
Other | Bone Metabolism: - PGs increase bone turnover by stimulating bone resorption and formation Cancer: - COX-2 derived PGE2 can promote tumour growth by binding its receptors and activating signalling pathways which control cell proliferation, migration, apoptosis, and/or angiogenesis. However, the prolonged use of high dosages of COX-2 selective inhibitors is associated with unacceptable CV side effects. - Large studies and clinical trials indicate that long term use of NSAIDS, can decrease the incidence of certain malignancies, including colorectal. oesophageal, breast, lung, and bladder cancers. |
Prostaglandin Analogues |
Synthetic prostaglandin analogues are molecules which are manufactured to bind to a PG receptors. |
Prostaglandin E1 Analogues |
- PGE, effects Vasodilation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle. |
Alprostadil (Caverject®) |
- Alprostadil is a PGE1 analogue. - Uses: 1) Maintaining a patent ductus arteriosus in newborns (Firstly; see N.B. below): - In certain types of congenital heart disease, it is important to maintain the potency of the neonate's ductus arteriosus until corrective surgery can be carried out. This can be achieved with Alprostadil. - Route of administration: because of rapid pulmonary clearance, it must be continuous IV infusion into a large vein. - Dose: initial rate: 0.05-0.1 mcg/kg/min, may be increased to 0.4 mcg/kg/min, prolonged infusion has been associated with ductal rupture. 2) Impotence (Erectile Dysfunction; ED): - Dosage form: urethral suppositories and in injectable form. - Penile suppository inserted into the urethra. - Injected by syringe directly into the corpus cavernosum of the penis, avoid injection in midline. - Onset of action: 5 to 10 minutes. - Duration of action: Injectionà 1 to 3 hours, supp.--> 30 to 60 minutes. - Most common side effects: pain at place of injection or pain of urethra (suppository only) and painful erection. - N.B: - The ductus arteriosus, is a normal part of a baby's circulatory system before birth that usually closes shortly after birth. If it remains open, it's called a patent ductus arteriosus. - Patent ductus arteriosus (PDA); is a persistent opening between two major blood vessels leading from the heart. - Large patent ductus arteriosus left untreated can allow poorly oxygenated blood to flow in the wrong direction, weakening the heart muscle and causing heart failure and other complications. - PGE1 & PGE2 are responsible for keeping the ductus patent, NSAIDS such as indomethacin or ibuprofen (as IV) may been used to help close a PDA. - NSAIDS during pregnancy in third trimester, increase the risk of premature closure of the ductus arteriosus. |
Misoprostol (Cytotec) (Misotac) |
- Misoprostol is a PGE1 analogue, with oxytocic properties. - It is approved for use in the prevention of NSAID-induced gastric ulcers; - NSAIDS inhibit prostaglandin synthesis, and a deficiency of prostaglandins within the gastric mucosa may lead to diminishing bicarbonate and mucus secretion and may contribute to the mucosal damage caused by these agents. - It produces uterine contractions and is contraindicated during pregnancy. - Off-label uses of Misoprostol: - Labor induction, abortion, missed miscarriage and postpartum bleeding; - Misoprostol effects are dose dependent and include cervical softening and dilation, uterine contractions. - Routes of administration; include oral, vaginal, sublingual, buccal, or rectal. - In abortions mainly used in combination with Mifepristone (Antiprogestin). - Dear pharmacists this drug is prescribed only by obstetricians and gynaecologists by a trusted prescription; So don't prescribe this drug by any way because may be used by prostitutes for abortion (illegally). |
Prostaglandin E2 Analogues |
Dinoprostone (Cervidil) |
- Dinoprostone is a PGE2 analogue, with oxytocic properties. - It administered vaginally (vaginal insert) for labor induction. - It cause softening the cervix and causing uterine contraction. |
Prostaglandin F2α Analogues | |
Carboprost (Hemabate) | |
- Carboprost is a PGF2 analogue, with oxytocic properties. - It induces contractions and can trigger abortion in early pregnancy. It also reduces postpartum bleeding. - Used in treatment of postpartum hemorrhage in the presence of uterine atony that has not responded to usual therapy (i.e., IV oxytocin, uterine massage, IM ergot alkaloids). | |
Latanoprost (Xalatan) | Bimatoprost (Lumigan) |
Travoprost (Travatan) | Unoprostone (Rescula) |
- Latanoprost , Bimatoprost , Travoprost and Unoprostone are used as ophthalmic solution to control the progression of glaucoma or ocular hypertension by reducing intraocular pressure. - Latanoprost was the first prostanoid used for glaucoma, the success of Latanoprost has stimulated development of similar prostanoids with ocular hypotensive effects. - Used once or twice daily. - Side effects; irreversible brown pigmentation of the iris and eyelashes, drying of the eyes and conjunctivitis.
- Bimatoprost (LATISSE); is used in treatment of hypotrichosis (inadequate or not enough lashes) to grow eyelashes longer, fuller and darker, Only apply once daily at the base of upper lashes. Don't apply to lower lid, significant improvement by 2 months after starting treatment. | |
Prostacyclin Analogues |
Epoprostenol (Flolan) |
- Epoprostenol has 2 major effects: 1) direct vasodilation of pulmonary and systemic arterial vascular beds, 2) inhibition of platelet aggregation. - Used in treatment pulmonary arterial Hypertension (PAH). - Side effects; Flushing, headache, nausea/vomiting, hypotension, bradycardia and anxiety. |
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