newer abortifacients

1,785 views
1,482 views

Published on

Pharmacotherapy of Abortifacients

Published in: Education, Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,785
On SlideShare
0
From Embeds
0
Number of Embeds
4
Actions
Shares
0
Downloads
47
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • PGs activate membrane receptors locally near their sites of formationfour distinctPGI2 (IP), PGE2 receptors (EPs 1–4) PGF2 (FP)
  • progresses but remains smaller than the response to oxytocin.Uterine responsiveness to PGs increases as pregnancy progresses
  • rapid metabolismresulting in a lack of oral activity and a short duration ofaction when given parenterally, (2) numerous side effects, and(3) chemical instability leading to a short shelf life. Misoprostoldiffers structurally from prostaglandin E by the presence of amethyl ester at C-1, a methyl group at C-16 and a hydroxylgroup at C-16 rather than at C-15. The methyl ester at C-1increases the anti-secretory potency and duration of action ofmisoprostol, whilst the movement of the hydroxyl group fromC-15 to C-16 and the addition of a methyl group at C-16improves oral activity, increases the duration of action, andimproves the safety profile of the drug.
  • mutagenicity studies of misoprostol have been negative anmisoprostol has not been shown to be embryotoxic, fetotoxic or teratogenic
  • These molecular diagrams show the structural similarities among progesterone, norethindrone, and mifepristone. You can also see how mifepristone has been modified at the 11- and 17-carbon positions to create a steroid molecule with new properties
  • Decreased endogenous progesterone coupled with blockade of progesterone receptors in the uterus increases uterine prostaglandin levels and sensitizes the myometrium to their contractile actions. Mifepristone also causes cervical softening, which facilitates expulsion of the detached blastocystAn endometrial biopsy was performed3 days after mifepristone intake. Mifepristone induced inhibitionof glandular secretory activity, degenerativechanges in glandular cells, vascular changes (reduction ofstromaledema and stromalextravasation) and an increase inglandular mitotic activity. These endometrial responseswere significantly related to the dose of mifepristone administered[14].5.1.1. Effects
  • The antiglucocorticoid effects of mifepristone are dosedependentand are apparent at single doses of mifepristonein the order of 4–6 mg/kg. The antiglucocorticoid effectlasts for at least 24 h after a single dose of mifepristonegiven at midnight [21]. Mifepristone at a dose of 400 mg (6mg/kg) antagonized the suppressive effect of 1 mg of dexamethasoneon the hypothalamo–pituitary–adrenal axis(HPA) [23]. Administration of dexamethasone at doses 1mg counteracts the antiglucocorticoid effects of a 6 mg/kgdose of mifepristone [23].In conclusion, mifepristone displays antiglucocortiincrease in ACTH and lipotropin hormone)and on the peripheral effects (suppression of cutaneousvasoconstriction, or decrease in circulating eosinophils inducedby glucocorticoids) [19–24]. Mifepristone binds tothe glucocorticoid receptor in human mononuclear
  • it is bound by 1-acid glycoprotein, which contributes to the drug's long t1/2 RU 42 848, which results from the loss of two methyl groups from the 4-dimethylaminophenyl in position 11 RU 42 698, which results from terminal hydroxylation of the 17-propynyl chain
  • When mifepristone is used to produce a medical abortion, a prostaglandin is given 48 hours after the anti-progestin. Intramuscular sulprostone, intravaginalgemeprost, and oral misoprostol have been used. It has been well proven that pretreatment with the antiprogesteronemifepristone 36–48 h before PG administration canincrease the success rate, shorten the induction-to-abortion intervaland reduce the amount of PGs required in second-trimesterabortion
  • Agents used for feticide arehypertonic saline, 1% lidocaine and potassium chloride (Elimianet al., 1999; Bhide et al., 2002; Senat et al., 2003). Feticidewith potassium chloride reduced the PG requirement for midtrimestermedical abortion, compared with similar proceduresconducted without feticide (Elimianet al., 1999). Up to 20weeks of pregnancy, the contractions induced by PG make feticide
  • Since the introduction of the method, extensive research is ongoingfocusing on improving efficacy, defining the optimal dose/type and route of the administration of PG analogueToday, mifepristone is available in 29 countries worldwide (http://www.gynuity.org/documents/mife_approval_2005_map.pdf).
  • Ulipristal's anti-ovulatory actions likely occur due to progesterone regulation at many levels, including inhibition of LH release through the hypothalamus and pituitary, and inhibition of LH-induced follicular rupture within the ovaryA 30-mg dose of ulipristral can inhibit ovulation when taken up to five days after intercourse
  • Ulipristal acetate [ella, ellaOne] has recently been licensed in the E.U. and the U.S. as an emergency contraceptive. Studies comparing ulipristal to levonorgestrel (progesterone-only emergency contraception, or POEC) demonstrate that ulipristal is at least as effective when taken up to 72 hours after unprotected sexual intercourse. In addition, ulipristal remains effective up to 120 hours (5 days) after intercourse, making ulipristal a more versatile emergency contraceptive than levonorgestrel, which does not work well beyond 72 hours after unprotected intercourse. The most severe side effect in clinical trials using ulipristal has been a self-limited headache and some abdominal pain.
  • You can see that the nitrogen group has a CH3 on it and there is an OH group in the double ring instead of an NH2 group. Enough to make a difference in a biosynthesis scheme!At two stages in the biosynthesis of purines (adenine and guanine) and at one stage in the synthesis of pyrimidines (thymine, cytosine, and uracil), one-carbon transfer reactions occur which require specific coenzymes.These coenzymes are synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it thinking that it is folic acid. In fact, methotrexate looks so good to the enzyme that it binds to it quite strongly. All the folic acid reductase enzymes in the cell bind merrily to the methotrexate and ignore any folic acid they might see. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Again, without DNA, no cell division.
  • The absence of reduced folates shuts down the one-carbon transfer reactions crucial for the de novo synthesis of purine nucleotides and thymidylate and interrupts the synthesis of DNA and RNA. The toxic effects of methotrexate may be terminated by administering leucovorin, a fully reduced folate coenzyme, which repletes the intracellular pool of FH4 cofactors
  • Pharmacokinetics.Limited pharmacokinetic information is available for methotrexate in pregnant women. Because of its potential for teratogenesis if used in early pregnancy, pharmacokinetic studies have typically involved men and nonpregnant women. Such studies have suggested that, at 24 hours after high-dose therapy, a methotrexate concentration of 5.0 μmol/L is indicative of an increased risk of toxicity.50A single study has investigated methotrexate pharmacokinetics in early intrauterine pregnancy.42 In 10 women up to 49 days’ gestation who received 50 mg/m2 of methotrexate intramuscularly, serum levels peak within 1 to 2 hours, which is similar to that reported for nonpregnant subjects.51 The mean peak serum concentration was 4.4 ± 0.9 μmol/L and did not exceed 5.0 μmol/L at 24 hours in any patients. Serum levels were nondetectable within 48 hours. The mean area under the curve and renal clearance of methotrexate were 11.5 ± 2.2 μmol/hr per liter and 7.89 ± 1.98 L/hr, respectively. The renal clearance rate was the same as that for men and nonpregnant women receiving methotrexate in lower doses for rheumatoid arthritis or asthma
  • The FDA-approved regimen for medical abortion up to 49 days’ gestation is mifepristone 600 mg followed in 2 days by misoprostol 400 µg orally. This regimen has an efficacy rate of 95%.1 The efficacy rates of evidence-based alternative mifepristone/misoprostol regimens have reached 99%.2Acceptable alternatives that have been proven in clinical studies include lowering the dose of mifepristone to 200 mg, administering misoprostol vaginally instead of orally, extending the use of mifepristone/vaginal misoprostol to gestations through 63 days, administering misoprostol at home, allowing for flexibility in the timing of vaginal misoprostol dosing and the follow-up visit, and using the combination of methotrexate/ misoprostol.Medical abortion is safe, effective, and well-accepted by women and providers, as demonstrated by numerous clinical studies. With the introduction of this method into general medical practice in the United States, we have an unprecedented opportunity to improve and extend the services that we provide to women who seek abortion.Ref:
  • To avoid the risks of uncontrolled hemorrhage, methotrexate and other drugtreatments have been used successfully for treatment of cervical pregnancies. In many centers, including ours, chemotherapyis now the first line of therapy in the stable woman. The general guidelines for methotrexate use for ectopic pregnancy are asdescribed earlier (see p. 263). The drug has been injected directly into the gestational sac, with or without potassium chlorideto induce fetal death. It has been given systemically in single high-dose therapy with folinic acid rescue, in lower -doseprolonged courses, and as a single low-dose regimen. It also has been given in various combinations, for example, intraamnionically,after failure of systemic therapy .
  • probably because ofchemical trauma to the fetal membranes and the decidua,
  • Oliguria caused by the antidiuretic effect of high-dose oxytocin. The oxytocin-induced oliguria was reversible several hours after discontinuing the oxytocin
  • This isbecause of rapid intravascular absorption of hypertonic salinefrom the amniotic cavity or inadvertent i.m. or i.p. injection ofsaline resulting in hypernatremia and necrosis of the affectedtissue
  • newer abortifacients

    1. 1. NEWER ABORTIFACIENTS Dr.Rachana Menon Moderator: Dr.Anuradha HV DEPT OF PHARMACOLOGY
    2. 2. OUTLINE  History & problem statement  Physiology of Fertilization and Implantation  Pharmacology of Abortifacients  Newer agents  Non pharmacological treatments  Conclusions
    3. 3. INTRODUCTION • Abortion - termination of pregnancy before 28 weeks of gestation or viability • WHO definition- termination of pregnancy before 22 weeks or when the fetus weigh 500 g or less • Spontaneous or induced • Abortion is important as it contributes to approximately 50% of maternal death worldwide
    4. 4. HISTORY  Shennong - 2700 BCE  Ancient Egypt with its Ebers Papyrus  Classical Greece-Silphium  Hippocratic Oath – Hippocratic Corpus contain descriptions of abortive techniques.  Aristotle, in his treatise (350 BCE)  Islamic tradition and Christianity
    5. 5. The Soviet Union (1919), Iceland (1935) and Sweden (1938).  In 1935 Nazi Germany, a law was passed permitting abortions for those deemed "hereditarily ill," Beginning in the second half of the twentieth century, abortion was legalized in a greater number of countries
    6. 6. HISTORY (Contd.) • 1973- Misoprostol ( Nsaid) • 1988- Mifepristone + sulprostone ( France) • 1994-MTX / Misoprostol • 1997- Misoprostol for abortion • 2000- FDA approved RU 486+ Misoprostol
    7. 7. PROBLEM STATEMENT  53 million abortions performed each year  Abortion is important as it contributes to approximately 50% of maternal death worldwide Unsafe conditions, especially in developing countries.  Approximately 13% of all maternal deaths - poor access to safe practice  Service is not available legally  Morbidity with loss of fertility and the sequelae of chronic pelvic pain
    8. 8. Fertilization
    9. 9. ABORTION • Medical or surgical termination of pregnancy before the time of fetal viability. – FIRST TRIMESTER – First 12 WEEKS – SECOND TRIMESTER – 13-24 WEEKS OF GESTATION
    10. 10. INDICATIONS • Persistent heart disease • Advanced hypertensive vascular disease • Invasive carcinoma of the cervix. • Medical and surgical disorders • Cases of rape or incest • Birth of a fetus with a significant anatomical or mental deformity • Unwanted pregnancy • anatomical or mental deformity.
    11. 11. CLASSIFICATION • CARBOPROST • SULPROSTONE • DINOPROSTONE • GEMEPROST • MISOPROSTOL • MIFEPRISTONE • LILOPRISTONE • ONAPRISTONE • ULIPRISTAL • METHOTREXATE
    12. 12. First Trimester  Mifepristone + PG analog  misoprostol /gemeprost up to 63 days of gestational age  Methotrexate + a PG analog up to 49 days gestation  PG analogue alone..  Vacuum aspiration • Dilation and curettage • Dilatation and evacuation • Induction method Second Trimester
    13. 13. PROSTAGLANDIN ANALOGUES • Carboprost • Sulprostone • Gemeprost • Misoprostol • Dinoprostone
    14. 14. Prostaglandins – Structural Features Prostaglandins are a class of eicosanoids 2- total number of double bonds in the side chain group α- orientation of the OH group at 9 position of cyclopentolate ring is above the plane of that ring
    15. 15. Contd..
    16. 16. PGI2 (IP) PGD2 (DP1 and DP2) PGE2 receptors (EPs 1–4) PGF2 (FP) EP2, EP4, IP, and DP1 activate adenylyl cyclase Gs. cAMP levels, EP1, FP, and activate phosphatidylinositol metabolism EP3, can couple to both elevation of intracellular Ca and a inc/ decrease in cyclic AMP
    17. 17. Pharmacological action on Uterus • Nonpregnant uterus - contracted by PGF2 relaxed by PGEs. • Sensitivity prominent before menstruation .Relaxation is greatest at midcycle.. • Pregnant uterus –PGI2and high conc of PGE2 - relaxation. Low dose PGE2 / PGF2 -Contraction. • PGE2 / PGF2 IV to produces a dose-dependent increase in uterine tone and in the frequency and intensity of rhythmic uterine contractions. • Cervix- soft and makes it more yielding
    18. 18. CARBOPROST  Carboprost tromethamine PGF2α analogue  First analogue to be tested clinically on a large scale for the termination of second trimester pregnancy.  Intra-amniotically (viable second-trimester pregnancy)  Dose: IM 125 µg /ml  Limited value as a primary method for abortion  Post partum haemorrhage – ADR: diarrhoea (most common) – fever chills vomiting – Cardiovascular collapse, P.HTN HEAMORRAGIC CYSTITIS PID
    19. 19. SULPROSTONE • PGE2 methyl sulphonylamide • Used in the 1980s for the termination of second- trimester pregnancy • ADR: severe cardiovascular complications- MI attributed to coronary spasm, broncho constriction • WITHDRAWN FROM THE MARKET • USES: PPH
    20. 20. GEMEPROST  PGE1 analogue USES :dilate the cervix before VA in late-first and early- second-trimester abortion  Second trimester : Gemeprost is more efficacious when compared with intra-amniotic PGF2α or extra-amniotic PGE2 and dinoprostone intracervically  A vaginal pessary- 1mg 3 hrs before the procedure Vaginal bleeding, cramps, nausea, vomiting, diarrhea, headache, muscle weakness , backache ,chest pain
    21. 21. DINOPROSTONE • Synthetic derivative of PGE2 • ROUTE OF ADMINISTRATION : vaginal/ oral • Intravaginal suppository 20mg 3-5 hrs repeated. (17hrs) • Half life 2.5-5 mins. Excreted in urine • Induction abortion in second trimester/ early abortion (US) • Cervical ripening-10mg tab / 0.5 mg gel 6 hrly • Benign hydatiform mole • Menstrual regulation • SIDE EFFECTS PROLONGED VAGINAL BLEEDING SEVERE MENSTRUAL CRAMPS GI TOXICITY Controlled release formulation
    22. 22. MISOPROSTOL Presence of a methyl ester at C-1 increase anti secretory activity A methyl group at C-16 and a hydroxyl group at C-16 rather than at C-15 Incease oral activty and duration of action
    23. 23. PHARMACOLOGICAL ACTION Uterotonic • Single oral dose ↑ tonus (for 1-2h) • Repeated oral doses→regular contractions • Single vaginal dose will produce regular contractions (sustained plasma conc.) • Increased tonus more rapid with oral/sublingual (8/11min.) compared with vaginal (20 min.)
    24. 24. Cervical softening • Reduces the force required for cervical dilatation • Encouraging disintegration of total collagen content • increase in collagen solubility an increase in collagenolytic activity. • an influx of inflammatory cells into the cervical stroma • Increase matrix metalloproteinases • leads to the degradation of collagen and cervical softening
    25. 25. PHARMACOKINETICS  After oral administration, rapidly absorbed from the GI tract. Rapid first-pass metabolism  DE ESTERIFICATION-MISOPROSTOL ACID  t1/2 20-40 mins  DOSE:400 μg oral misoprostol, the plasma misoprostol level increases rapidly and peaks at about 30 minutes declines rapidly by 120 minutes and remains low thereafter.  ROUTES OF ADMINISTRATION : Oral, vaginal, sublingual, buccal or rectal  Mainly urinary excretion
    26. 26. VAGINAL BUCCAL SUBLINGUAL RECTAL Longer time to peak plasma concentration (70-80min.) Similar concentration profile to vaginal administration Tablet dissolves in approx. 20 minutes Similar concentration profile to vaginal administration Greater overall bioavailability (AUC) Lower bioavailability (~50%) Shorter time to peak concentration than oral and vaginal Lower bioavailability (~33%) Longer duration of action(8hrs) Highest peak concentration Onset of action significantly slower than other routes Large degree of variation in bioavailability between women Greatest bioavailability Mechanism for direct vagina → uterus transport of progesterone exists No first pass metabolism in the liver
    27. 27. THERAPEUTIC USES 1. Medical Abortion: 600mg(RU 486) 400 µg (24-38 hrs) FDA (2000) Moistening the tablets appears to slightly increase plasma levels 2.Cervical Ripening Before Surgical Abortion • 400 µg of misoprostol vaginally 3 to 4 hours • 400 µg orally 8 to 12 hours, or 400 mcg sublingually 2 to 4 hours prior to suction curettage. Buccal administration is widely used
    28. 28. SECOND TRIMESTER : D&E • INCOMPLETE ABORTION • single dose of 600µg orally OR 800µg vaginally, or a single dose of 400µg sublingually.. 1.400 µg vaginally for 3-4 hrs 2.400 µg + 600 µg of buccal misoprostol for at least 90 minutes 3.600 µg Buccal Misoprostol 2-4 hrs
    29. 29. Cervical Ripening Before Other Procedures • The optimal dosing regimen for cervical ripening before hysteroscopy is unclear. • 200, 400 or 1000 µg of vaginal misoprostol or 400 µg of oral misoprostol given at least 9 to 12 hours preoperatively • NSAID induced gastric ulcer and chronic heavy smokers • 200 µg for 4 times a day Orally
    30. 30. Adverse drug reaction • Diarrhoea & abdominal pain Headache • Nausea • Flatulence • Chills/shivering/fever • – Hyperpyrexia (>40 )- doses >600 µg • – Delerium- doses >800 µg • Uterine rupture • Uterine hyperstimulation case reports • Amniotic fluid embolism • Misoprostol is considered a teratogen!!!!
    31. 31. Click to add title ANTIPROGESTINS  MIFEPRISTONE  ONAPRISTONE  ULIPRISTAL  LILOPRISTONE
    32. 32. MIFEPRISTONE Known as RU 486- 1981  It is insoluble in water  Rapidly dissolves in the gastric ileum when ingested orally.  Remains stable after 3 years at ambient temperature
    33. 33. CHEMICAL STRUCTURE  19-nortestosterone- derived compound at the 11β position  Is a beta-aryl-substituted C11 -antiestrogens • C11 b side chain- antagonistic properties to glucocorticosteroid and progestational hormones p-dimethylaminophenyl group
    34. 34. Blockage of the progesterone receptor results in vascular damage, decidual necrosis and bleeding
    35. 35. MECHANISM OF ACTION  Progesterone antagonist ( PA) CELL AND PROMOTER SPECIFIC CAPACITY COMPETITIVE ANTAGONISM
    36. 36. H H H dimerize H HP? hsp90 H hsp70 hsp59 Rhsp70 H HRE target gene 5’ flanking region Gene Transcription
    37. 37. CONTD… MIFEPRISTONE NCoR/SMRT SRC-1/NcoA-2 p300,CBD
    38. 38. Pharmacological actions • Decidual breakdown by blockade of uterine PR • Detachment of the blastocyst which decreases hCG production • Decrease in progesterone secretion from the corpus luteum – increase uterine PG levels – sensitizes the myometrium to their contractile actions. • Cervical softening, which facilitates expulsion of the detached blastocyst 2-5mg/kg
    39. 39. Ovulation  A fall in estradiol  Inhibition of folliculogenesis  Delay or prevent ovulation depending on the timing of administration : UNCLEAR MECHANISM  Impair secretory endometrium and produces WITHDRAWAL BLEEDING 3 mg/kg/day
    40. 40. Anti glucocorticoid effect • Exerted both on the central actions of cortisol -inhibition of feedback control of cortisol and peripheral action • Binds to the glucocorticoid receptor in human mononuclear leukocytes 4-6 mg/kg and above
    41. 41. Anti androgenic action • Modest anti androgenic action • 30 mg/kg for anti androgenic activity
    42. 42. Pharmacokinetics  Orally active with good bioavailability  t1/2 of 20-40 hrs  RU 42 633,mono demethylated metabolite most widely found in plasma  Bound by α 1-acid glycoprotein.  Hepatic metabolism and enterohepatic circulation  Metabolic products are found predominantly in the faeces N-demethylation and terminal hydroxylation of the 17-propynyl chain. with CYP450 3A4
    43. 43. Drug interactions • Ketoconazole • Itraconazole • Erythromycin • Grapefruit juice  Rifampicin  Dexamethasone  Phenytoin  phenobarbital  carbamazepine Increase serum levels of mifepristone. lower serum levels of mifepristone.
    44. 44. Therapeutic uses • Emergency postcoital contraception 600 mg of mifepristone within 72 hrs. • Cervical ripening- 36–48 h following treatment • First and Second trimester TOP. • Labour induction 600mg daily for 2-3 dys • Medical management of fetal death • Potential use in IVF,fibroids,Endometriosis • Cushing syndrome UNDER TRIAL • Burns, GR depentant HTN • Arthritis,glaucoma,HIV
    45. 45. Mifepristone-Misoporstol Regimens FDA Protocol Alternate Protocol Gestational age limit 49 days 63 days Mifepristone dose 600 mg. oral 200 mg. oral Misoprostol dose, route, and timing 400 µg oral Office administration 48 hours later 800 µg vaginal or buccal Home self-administration 6 - 72 hours later (vaginal) 24 - 36 hours later (buccal) Office follow-up visit 10-15 days after mifepristone 4 - 10 days after mifepristone Minimum office visits 3 2
    46. 46.  Vaginal bleeding- 8-17 days  Endometrial hyperplasia (5-10mg)  Abdominal pain  Uterine cramps  Nausea  Vomiting  Diarrhea due to the prostaglandin  Fulminant septic shock associated with Clostridium sordellii  BLACK BOX WARNING FDA!!!! SIDE EFFECTS
    47. 47. ULIPRISTAL • Derivative of 19-norprogesterone SPRM • Acting as a partial agonist at progesterone receptors • Dimethyl-aminophenol group at the 11 position, with an additional acetoxy group at the C17
    48. 48. Pharmacological actions • In high doses, - anti-proliferative effects in the uterus • Inhibit ovulation…. can block ovarian rupture at or even just after the time of the LH surge • Ulipristal may also block endometrial implantation of the fertilized egg • Weak glucocorticoid antagonist
    49. 49. • Uses: Emergency contraceptive ( US &EU 2010) • DOSE:30 mg orally once, given as soon as possible, but no later than 120 hours • Remains effective up to 120 hours (5 days) after intercourse • The half-life-32 hours • Metabolism occurs predominantly by (CYP) 3A4 hepatic isoenzyme high plasma protein binding • ADR:Self-limited headache and some abdominal pain
    50. 50. Onapristone • pure PA and has no progesterone agonistic effects • Devoid of any progestogenic or antiproliferative effects on the endometrium of post-menopausal women • Shorter half-life • Effective endocrine agent in experimental breast cancer models • Onapristone developed liver function test abnormalities, the development of this drug and recruitment to the study stopped in 1995.
    51. 51. Anti-metabolite Methotrexate
    52. 52. MTX is an antifolate belonging to the antimetabolite class of antineoplastic agent. • MTX is a cell cycle specific chemotherapeutic agents that acts on S-phase & • thus inhibit DNA synthesis Folic acid Tetrahydrofolic acid Dihydrofolate reductase Co enzy for one carbon transfer reaction
    53. 53. ` An essential component of DNA Key metabolic event
    54. 54. Pharmacokinetics Readily absorbed from the GI tract at doses of <25 mg/m2 • 7-hydroxy-methotrexate NEPHROTOXIC • t ½ 8 hrs IM • 50% of methotrexate binds to plasma proteins • Up to 90% of a given dose is excreted unchanged in the urine within 48 hours • Retained in the form of polyglutamates for long periods • Weeks in the kidneys and for several months in the liver SULFONAMIDE SALICYLATES TETRACYCLINE CHLORAMPHENICOL PHENYTOIN
    55. 55. Methotrexate/Misoprostol Regimens • Methotrexate: 50 mg/m2 IM or 50 mg PO • Misoprostol: 800 µg PV 3–7 days later • Efficacy decreases after 49 days’ gestation • Rh immune globulin to Rh negative patients before misoprostol • Initial follow-up ~1 week after methotrexate • Subsequent care based on results of physical exam, ultrasonography • If Bhcg has fallen by >80% over 7days,procedure was successful
    56. 56. • Prior to MTX administration the following laboratory parameters should be confirmed: Guidelines for parenteral administration of intermediate- or high-dose methotrexate (HDMTX) WBCs > 1500/mm3 Neutrophils > 200/mm3 Platelets > 75,000/mm3 s.bilirubin<1.2mg/dl SGPT (ALT)<450 U Normal s. Cr. Creatinine clearance>60ml/min Previous mucositis should be healed & pleural effusions should be drained prior to MTX administration
    57. 57. Contraindications • Anemia (Hgb < 10 g/dL)/ leucopenia/thrombocytoenia • Known coagulopathy • Active renal or liver disease • Uncontrolled seizure disorder • Acute inflammatory bowel disease • Intrauterine device in situ • High intial hcg concentration >5000mU/ml • Ectopic pregnancy > 4cm in size as in TVS
    58. 58. Regimens for medical abortion and their effectiveness Regimens Effectiveness Use up to Mifepristone + misoprostol or mifepristone + gemeprost >96% 9 weeks from last menstrual period Misoprostol alone >83% 12 weeks from last menstrual period Methotrexate + misoprostol >90% 9 weeks from last menstrual period
    59. 59. SOME OLDER TECHINQUES
    60. 60. Older days…  Hystrecotomy (sectio parva)  Intra-amniotic injection of hypertonic saline/hyperosmolar urea  Intra- or extra-amniotic administration of ethacryidine lactate (Rivanol)  Parenteral/intra-amniotic / extra-amniotic administration of prostaglandin (PG) analogues  I.V / i.m. administration of oxytocin
    61. 61. ETHACRIDINE LACTATE • Ethacridine lactate/Rivanol is a yellow dye with antiseptic properties • MOA: Stimulates endogenous PG and thromboxane production, promoting cervical priming and initiating labour • DOSE:0.1%-solution of ethacridine lactate - extra- amniotic space through a sterile catheter at a dose of 10 mL per gestational week • 20-40 hrs mini labour • Maximum of 150 ml
    62. 62. Hypertonic Saline One of the first described instillation methods • When used alone, intra-amniotic hypertonic saline has a long latent period until the onset of contractions • Time to abortion of 30 hours • Addition of oxytocin to this regimen improves the efficacy and expulsion time
    63. 63. Hypertonic Saline (Contd.) Use of concentrations exceeding 20%. • Maternal hypernatremia • Coagulopathy • Hemorrhage transfusion • Cervical laceration SIDE EFFECTS
    64. 64. IV OXYTOCIN  First described by Winkler and associates  100 units per 500 mL of DNS, is infused over 3 hours  1 hour is allowed for diuresis to preclude water intoxication  The dose is increased 50 units per 500 mL of DNS until delivery is achieved  Maximum of 300 units  Mean time to delivery of 8.2 hours
    65. 65. UREA • Rapidly traverses cell membranes • Osmotic diuretic • Has a long instillation to abortion interval when used alone • Intra-amniotic urea, 80 to 90 g, with intravenous oxytocin • Average time to expulsion of 19 to 29 hours
    66. 66. SIDE EFFECTS  Puncture of the intra-amniotic space  The introduction of a Foley catheter into the extra-amniotic space  Long induction-to-abortion interval  Need for curettage after the expulsion of the fetus  The IV infusion of oxytocin -water intoxication.  Hypertonic saline – DIC
    67. 67. HERBAL MEDICINES
    68. 68. ABORTION AND MYTH!!!! • LAMINARIA • Angelica/Dong Quai • Black Cohosh • Blue Cohosh • Cotton Root Bark • Evening Primrose • Parsley • Pennyroyal. • Pineapple and Papaya • Vitamin C
    69. 69. In India… MTP Act - 1971  Aims to improve the maternal health  Prevent large number of unsafe abortions and consequent high incidence of maternal mortality & morbidity  Legalizes abortion services  Promotes access to safe abortion services to women  De-criminalizes the abortion seeker  Offers protection to medical practitioners who otherwise would be penalized under the Indian Penal Code (sections 315-316)
    70. 70. MTP Act: addressing a public health priority • Up to 20 weeks gestation • With the consent of the women. If the women is below 18 years or is mentally ill, then with consent of a guardian • Opinion of two RMPs required for termination of pregnancy between 12 and 20 weeks WHEN CAN PREGNANCIES BE TERMINATED??
    71. 71. MEDICAL ABORTION • MTP using Mifepristrone (RU 486) & Misoprostol approved for up to 7 weeks termination • Only an RMP (as defined by the MTP Act) can prescribe the drugs • Has to follow MTP Act, Rules & Regulations • Can prescribe in his/her clinic, provided he/she has access to an approved place • Should display a certificate from owner of approved place agreeing to provide access
    72. 72. Thank you

    ×