Medicinsk abort Kristina Gemzell Danielsson, MD, PhD, FFSRH (RCOG) Karolinska University Hospital, Karolinska Institutet and Hong Kong University Development of safe and effective abortion care §  70ies, Prostaglandin analogues discovered by Sune Bergström and his team at KI, Awarded the Nobel Price in 1982 §  Induced uterine contractions and cervical ripening; §  Shown to act in synergy with progesterone receptor modulator àDeveloped to Medical abortion Bygdeman M, Gemzell Danielsson K, Marions L: JAMWA 55: 3: 195-6, 2000. Bygdeman & Swahn 1985 Mode of action of mifepristone Leads to the regression of the corpus luteum Decreases ß-HCG Blocks the receptors of Gestational progesterone sac   The endometrium and the gestational sac separates from the uterine wall   The uterine muscle becomes more sensitive to prostaglandin and contracts   The cervix opens Medicinsk abort §  Optimal mifepristone dos §  Optimal prostaglandin- typ, dos, administrationsväg §  Graviditetslängd versus effektivitet §  Acceptans Medical abortion Mifepristone §  Mifepristone - alone is not effective (60-80%) §  Mifepristone primes the cervix, increases contractility and increases the sensitivity of the myometrium to PG §  Non-linear pharmacokinetics. Low side effects §  Provided the dose is enough for priming of the cervix and the myometrium –increasing the dose doesn't increase efficacy and cannot compensate for an insufficient prostaglandin analogue/ dose/ route Medicinsk abort 600 mg mifepristoneà 200 mg 1988 Frankrike 49d., 0.4 mg misoprostol 1991 UK 63d.,1mg gemeprost (1992 Kina 49d., 0.6mg miso) (25mg tabl) 1992 Sverige 63d.,1mg gemeprost, 1994 II trimester 2000 USA 49d., 0.4 mg misoprostol 2009 EMA 63d. 200mg mifepristone, 1mg gemeprost 2012 EMA 63d. 200mg mifepristone, 0.8 mg misoprostol pv. (Medabon) 2016, USA 70d, 200mg mifepristone, 0.8 mg misoprostol bc What is Misoprostol? §  An orally active prostaglandin analogue §  Several advantages over other prostaglandin analogues (safe, less side effects, stable at room temperature, flexible administration, cheaper) §  Marketed in 1985 §  Potential to reduce maternal mortality §  Correct dosage and administration is vital for success and to prevent complications. §  WHO essential medicine list; 5 indications Medical abortion Misoprostol §  Misoprostol– alone highly effective §  Side effects mild and dose dependent §  Priming with mifepristone increases efficacy, allows lower dose and less side effects §  Route of administration more important than the dose §  Oral misoprostol not effective beyond 49-56 days. Cannot be compensated for by: à increased dose of mifepristone à increased dose of oral misoprostol à repeat doses of oral misoprostol Why is the route of administration important? Misoprostol, farmakokinetik Zieman et al. 1997