Misoprostol .

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Diagram. Pharmacokineticswhat the body does to the drugClinical ImplicationsPharmacodynamicswhat a medication does to the bodyAvailable items. Pharmacokinetics. investigation of the time course of medication and metabolite fixations in distinctive liquids, tissues, and excreta of the body, and of the numerical connections required to create models to decipher such information.
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Misoprostol Pharmacokinetics and Pharmacodynamics Brian Cleary HRB PhD Scholar Health Services Research TCD/CWIUH/RCSI 25 th February 2010

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Overview Pharmacokinetics what the body does to the medication Clinical Implications Pharmacodynamics what a medication does to the body Available items

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Pharmacokinetics investigation of the time course of medication and metabolite focuses in various liquids, tissues, and excreta of the body, and of the numerical connections required to create models to decipher such information

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Chemical Structure www.3dchem.com/imagesofmolecules/Misoprostol.jpg

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Chemistry found in 1973 prostaglandin E1 simple slight auxiliary adjustments to: increment hostile to secretory power increment span of activity (half existence of actually happening prostaglandins seconds) enhance oral bioavailability enhance wellbeing profile

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Absorption quickly consumed after oral measurements crest plasma fixations happen after around 15 to 30 minutes sustenance lessens the rate yet not the degree of retention attendant stomach settling agent utilize diminishes add up to accessibility

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Distribution high fluctuation of plasma levels between and inside reviews mean plasma levels after single oral dosages demonstrate a direct association with measurement over the scope of 200-400 mcg no amassing of misoprostol noted in numerous dosage considers serum protein restricting under 90%, focus autonomous in the helpful range

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Metabolism experiences fast de-esterification to its free corrosive which is clinically dynamic (misoprostol corrosive) misoprostol corrosive further metabolized by oxidation, essentially in the liver

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Excretion for the most part urinary discharge oral organization of radiolabeled misoprostol ~ 80% of identified radioactivity shows up in pee plasma end half-life answered to be in the vicinity of 20 and 40 minutes misoprostol corrosive is conveyed into bosom drain PK ponders in patients with changing degrees of renal weakness have appeared: inexact multiplying of T1/2, Cmax, and AUC contrasted with typical controls no unmistakable relationship between\'s the level of impedance and AUC. no normal measurement alteration suggested in patients with renal disability, yet dose may should be lessened if the standard dosage is not endured does not influence the hepatic blended capacity oxidase (cytochrome P-450) protein frameworks in creatures no known medication collaborations

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Vaginal Administration longer time to crest plasma conc. (70-80min.) longer term of activity more noteworthy general bioavailability (AUC) expansive level of variety in bioavailability between ladies component for direct vagina → uterus transport of progesterone exists

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Sublingual Administration tablet breaks up in approx. 20 mins. shorter time to top conc. than oral and vaginal most astounding pinnacle fixation most noteworthy bioavailability no first pass digestion system in the liver

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Pharmacokinetics in Pregnancy

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Buccal Route comparative focus profile to vaginal organization bring down bioavailability (~50%)

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Rectal Route comparable focus profile to vaginal organization bring down bioavailability (~33%) onset of activity fundamentally slower than different courses

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Pharmacokinetics in Pregnancy

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Clinical Implications

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REF: misoprostol.org

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Pharmacodynamics investigation of the physiological impacts of medications on the body and the components of medication activity and the relationship between medication fixation and impact

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Pharmacodynamics prostaglandins (PGs) instigate myometrial withdrawal in the pregnant and non-pregnant uterus \'triggers of work\' affectability of uterine muscle to PGs increments with incubation PGs prompt to cervical aging and unwinding normally happening PGs quickly separated PGs created as required in tissues-not put away endometrium and myometrium have significant PG blending limit

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Pharmacodynamics part in parturition not completely comprehended NSAIDs meddle with cyclo-oxegenase (included in PG generation) and consequently drag out work EP 1 & EP 2 receptors compression advancing, bottomless in the fundus EP 3 & EP 4 receptors unwinding advancing, found in lower uterine portion changing articulation of receptors might be in charge of varying affectability of myometrium all through development and at conveyance

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Pharmacodynamics direction of PG receptor expression not widely considered progesterone and estrogen thought to assume a part in PG receptor expression progesterone enemy mifepristone increments myometrial reaction to exogenous prostaglandins thought to up-control articulation of constriction advancing PG receptors

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Physiological Effects Uterotonic single oral measurement ↑ tonus (for 1-2h) rehashed oral dosages → customary withdrawals single vaginal measurements will deliver consistent constrictions (managed plasma conc.) expanded tonus more fast and more professed with oral/sublingual (8/11 min.) contrasted and vaginal (20 min.) varying lengths of activity

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Physiological Effects Cervical softening misoprostol diminishes the drive required for cervical dilatation seems to have an activity on collagen, empowering breaking down and disintegration

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Adverse Effects the runs & stomach torment cerebral pain sickness tooting chills/shuddering/fever Hyperpyrexia (>40 °)- measurements >600micrograms Delerium-measurements >800micrograms uterine crack uterine hyperstimulation case reports amniotic liquid embolism

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Formulations Cytotec ® 200 microgram (oral) tab Isprelor ® 25 microgram vaginal tab Gymiso ® 200 microgram (oral) tab Prostokos ® 25 microgram vaginal tab Vagiprost ® 25 microgram vaginal tab Extemp. 1 microgram/ml oral sol. Misopess ® Controlled-Release Hydrogel Polymer Vaginal Insert Licensing issues!!

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References 1. Aronsson A, Bygdeman M, Gemzell-Danielsson K. Impacts of misoprostol on uterine contractility taking after various courses of organization. Murmur. Reprod. 2004;19(1):81-84. 2. Baskett TF. The advancement of prostaglandins. Best Practice & Research Clinical Obstetrics & Gynecology 2003;17(5):703-706. 3. Bygdeman M. Pharmacokinetics of prostaglandins. Best Practice & Research Clinical Obstetrics & Gynecology 2003;17(5):707-716. 4. Chong Y-SMM, Su L-LMM, Arulkumaran SFP. Misoprostol: A Quarter Century of Use, Abuse, and Creative Misuse. Obstetrical & Gynecological Survey 2004;59(2):128-140. 5. Cicinelli EM, De Ziegler DM, Bulletti CM, Matteo MGM, Schonauer LMM, Galantino PM. Guide Transport of Progesterone From Vagina to Uterus. Obstetrics & Gynecology 2000;95(3):403-406. 6. Danielsson KG, Marions L, Rodriguez A, Spur BW, Wong PYK, Bygdeman M. Correlation amongst oral and vaginal organization of misoprostol on uterine contractility. Obstetrics & Gynecology 1999;93(2):275. 7. Khan R-UM, El-Refaey HMDM, Sharma SM, Sooranna DP, Stafford MMDM. Oral, Rectal, and Vaginal Pharmacokinetics of Misoprostol. Obstetrics & Gynecology 2004;103(5, Part 1):866-870. 8. Meckstroth KRMDMPH, Whitaker AKMD, Bertisch SMD, Goldberg ABMDMPH, Darney PDMDM. Misoprostol Administered by Epithelial Routes: Drug Absorption and Uterine Response. Obstetrics & Gynecology 2006;108(3, Part 1):582-590. 9. Norman JE, Thong KJ, Baird DT. Uterine Contractility and Induction of Abortion in Early Pregnancy by Misoprostol and Mifepristone. Obstetrical & Gynecological Survey 1992;47(4):282. 10. Olson DM. The part of prostaglandins in the start of parturition. Best Practice & Research Clinical Obstetrics & Gynecology 2003;17(5):717-730. 11. Rayburn WF, Powers BL, Plasse TF, Carr D, Di Spirito M. Pharmacokinetics of a Controlled-Release Misoprostol Vaginal Insert at Term. Diary of the Society for Gynecologic Investigation 2006;13(2):112-117. 12. Spitz IM, Bardin CW. Mifepristone (RU 486) - A Modulator of Progestin and Glucocorticoid Action. N Engl J Med 1993;329(6):404-412. 13. Tang OS, Schweer H, Seyberth HW, Lee SWH, Ho PC. Pharmacokinetics of various courses of organization of misoprostol. Murmur. Reprod. 2002;17(2):332-336. 14. Tang OS, Gemzell-Danielsson K, Ho PC. Misoprostol: pharmacokinetic profiles, consequences for the uterus and symptoms. Int J Gynaecol Obstet 2007;99 Suppl 2:S160-7.

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Thank You!

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