prostaglandin E2 (PGE2, dinoprostone, Prepidil, Cervidil)
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Pharmacology
dinoprostone Tradenames: Prepidil, Cervidil
Indications
- cervical gel:
- to facilitate maturation of cervix in pregnant women at or near term (cervical ripening)
- induction of labor[4]
- suppositories:
- to terminate pregnancy from 12th through 28th week of gestation
- to evacuate uterus in cases of missed abortion or intra- uterine fetal death
- management of benign hydatidiform mole
Adverse effects
- common (> 10%)
- less common (1-10%)
- fever, back pain, bradycardia, uterine hyperstimulation
- uncommon (< 1%)
- hypotension, cardiac arrhythmias, bronchospasm, vasomotor & vasovagal reactions, dizziness, syncope, flushing, hot flashes, wheezing, dyspnea, pain & tightness of chest, cough, chills, shivering
Mechanism of action
- fever:
- PGE2 may be most important hypothalamic prostaglandin involved in eliciting fever
- naproxen may be most effective NSAID at reducing hypothalamic PGE2 formation
- mast cell activation:
- PGE2 may protect against mast cell release
- long-term potentiation (LTP)
- mediates COX-2 regulation of synaptic plasticity in hippocampal perforant path-dentate gyrus synapses[3]
Comparative biology
- in brain macrophages, PGE2 levels rise with aging in mice[5]*
- increase in PGE2 promotes sequestration of glucose into glycogen, reducing glucose flux & mitochondrial respiration.
- leads to neuroinflammation & cognitive decline
- inhibiting effect of PGE2 by either genetic or pharmacologic reverses brain dysfunction:
- synaptic proteins rise, mitochondrial function improves, neuroinflammation is reduced, & spatial memory deficits are reversed[5]
- PGE2 stimulates muscle stem cells & helps repair muscle damage[6]*
- during aging, activity of 15-PGDH that degrades PGE2 progressively increases in muscle macrophages
- inhibiting macrophage 15-PGDH activity in older mice, by either genetic or pharmacologic interventions, raises levels of PGE2 & restores aged muscle, functionally & anatomically similar to muscle of young mice[6]
* contrast effects of macrophage PGE2 in aging brain vs aging muscle
More general terms
Additional terms
- arachidonate cyclooxygenase cascade
- fever
- naproxen (Naprosyn, Aleve Anaprox)
- prostaglandin E2 receptor EP2 subtype; prostanoid EP2 receptor; PGE receptor, EP2 subtype (PTGER2)
- prostaglandin E2 receptor EP3 subtype; PGE receptor, EP3 subtype; PGE2-R; prostanoid EP3 receptor (PTGER3)
References
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ 3.0 3.1 Chen C et al, J Neurophysiol 87:2851, 2002
- ↑ 4.0 4.1 Deprecated Reference
- ↑ 5.0 5.1 5.2 Minhas PS, Latif-Hernandez A, McReynolds MR et al. Restoring metabolism of myeloid cells reverses cognitive decline in ageing. Nature 2021 Feb; 590:122 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33473210 https://www.nature.com/articles/s41586-020-03160-0
- ↑ 6.0 6.1 6.2 Palla AR, Ravichandran M, Wang YX et al. Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength. Science 2021 Jan 29; 371:eabc8059 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33303683 https://science.sciencemag.org/content/371/6528/eabc8059