Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medical methods of terminating early pregnancy, i.e., prostaglandins, progesterone synthesis inhibitors and progesterone receptor antagonists are reviewed and compared to vacuum aspiration from the research literature. All of these methods have decreasing effectiveness up to the 9th week, when rates of incomplete abortions increase to about 40%. 1 PGF analogue and 3 PGE analogues are available and feasible for clinical use as early abortifacients. Gastrointestinal side effects are universal with the PGF, but only 20-40% with the PGE analogues. Epostane is a progesterone synthesis inhibitor, blocking 3beta-OH-steroid dehydrogenase. RU-486 and ZK 98734 are progesterone receptor antagonists. These drugs cause progesterone withdrawal over a few days, causing detachment of the trophoblast, impaired beta-hCG production, increased sensitivity of the myometrium to PGs and possibly ripening of the cervix. A single 800 mg dose of RU-486 induced complete abortion in 85% of women up to 10 days after the missed period. For routine clinical use RU-486 is taken for 3 days and sulprostone or gemeprost (PG analogs) are given intramuscularly or vaginally, with results comparable to vacuum aspiration. Bleeding lasts longer with the combined medical treatment, averages 62-81 ml, but may be severe enough to require transfusion in 0.15%. About 40% of women had nausea and vomiting. Progesterone and hCG levels declined rapidly after 3 days, and prolactin levels rose. With PGs, cortisol levels rise and the pregnancy hormones fall more rapidly. The antiprogestins decrease glucocorticoid activity but not enough to affect the feedback system. While no psychological studies have been reported comparing the combined medical abortion treatment with vacuum aspiration, prostaglandin treatment was preferred over aspiration. Home treatment with PGs, however, reduced proportion of women needing morphine analgesia from 40 to 5% compared to hospitalization.
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PMID:Medical methods to terminate early pregnancy. 222 1

The spinal cord is one of the sites where non-steroidal anti-inflammatory drugs (NSAIDs) act to produce analgesia and antinociception. Expression of cyclooxygenase(COX)-1 and COX-2 in the spinal cord and primary afferents suggests that NSAIDs act here by inhibiting the synthesis of prostaglandins (PGs). Basal release of PGD(2), PGE(2), PGF(2alpha) and PGI(2) occurs in the spinal cord and dorsal root ganglia. Prostaglandins then bind to G-protein-coupled receptors located in intrinsic spinal neurons (receptor types DP and EP2) and primary afferent neurons (EP1, EP3, EP4 and IP). Acute and chronic peripheral inflammation, interleukins and spinal cord injury increase the expression of COX-2 and release of PGE(2) and PGI(2). By activating the cAMP and protein kinase A pathway, PGs enhance tetrodotoxin-resistant sodium currents, inhibit voltage-dependent potassium currents and increase voltage-dependent calcium inflow in nociceptive afferents. This decreases firing threshold, increases firing rate and induces release of excitatory amino acids, substance P, calcitonin gene-related peptide (CGRP) and nitric oxide. Conversely, glutamate, substance P and CGRP increase PG release. Prostaglandins also facilitate membrane currents and release of substance P and CGRP induced by low pH, bradykinin and capsaicin. All this should enhance elicitation and synaptic transfer of pain signals in the spinal cord. Direct administration of PGs to the spinal cord causes hyperalgesia and allodynia, and some studies have shown an association between induction of COX-2, increased PG release and enhanced nociception. NSAIDs diminish both basal and enhanced PG release in the spinal cord. Correspondingly, spinal application of NSAIDs generally diminishes neuronal and behavioral responses to acute nociceptive stimulation, and always attenuates behavioral responses to persistent nociception. Spinal application of specific COX-2 inhibitors sometimes diminishes behavioral responses to persistent nociception.
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PMID:Prostaglandins and cyclooxygenases [correction of cycloxygenases] in the spinal cord. 1127 57