important drugs in obstetrics and gynaecology

Very good slide

1. DRUGS IN OBSTETRICS AND GYNECOLOGY Presenter : Dr.Gunja Thakur Moderator : Dr Vandana Saini Mam Dr Nivedita (SR) Dr Akshara ( SR)

2. LABELLING REQUIREMENTS: In 1979 the FDA deleloped a letter classification system ( A,B,C,D,X) for prescribing medications in pregnancy. New FDA (2014) labeling requirements were created and went into effect in 2015

3. Labeling subsection and categories as per FDA 2015 PREGNANCY LACTATION MALES AND FEMALES OF REPRODUCTIVE POTENTIAL . PREGNANCY REGISTRY . RISK SUMMARY PREGNANCY TESTING RISK SUMMARY CLINICAL CONSIDERATIONS CONTRACEPTION CLINICAL CONSIDERATIONS DATA INFERTILITY DATA

4. FDA PREGNANCY DRUG CATEGORIES A-Controlled studies in humans show no risk to the fetus B-No controlled studies in humans; animal studies show no risk to the fetus. C-No controlled studies in animals or humans D-risk to the fetus exists; however, benefits outweigh risks in certain situations E-Controlled studies in both animals and humans demonstrate fetal abnormalities; the risk in pregnant women outweighs any possible benefit

5. VITAMINS : FOLIC ACID 4 mg / day • Govt supply has Ministry of HEALTH and family welfare supply dosage 4 weeks prior to conception up to 12 weeks Twins-1000 micrograms a day recommended by Goodnight et al Folic acid deficiency lead to megaloblastic anemia. Benefits-prevent neural tube defects( spina bifida,spinal cord defect) Cleft lip and palate. Premature birth Low birth weight

6. IRON SUPPLEMENT Dose- Treatment 100mg elemental iron and 500mcg of folic acid per day ( Anaemia muktbharat ) Prophylaxis-1 tablet daily for 100 days, starting after the first trimester To be repeated for 100 days post-partum

7. Oral iron preparations Ferrous sulphate- (65 mg/tablet elemental iron ) best efficacy, has highest Gastrointestinal side effects. Ferrous Fumarate – ( 50mg/ tablet or 100mg / capsule) best efficacy, has high GI side effects. Ferrous Ascorbate- ( 100mg/tablet) better absorption and less GI side effects. Ascorbic covert ferric to ferrous. Iron polymaltose complex- ( 100mg/tablet) less GI side effects, absorption not affected by milk or food. Ferrous Bisglycinate - ( 60mg/ tablet) lesser dose , less GI side effects.

8. ORAL IRON Advantages 1. Cheap 2. Easy to administer 3. No anaphylaxis Disadvantage 1. Poor absorption 2. GI side effects are ( i ) Constipation (ii) Vomiting (iii) Epigastric pain (v) Metallic taste (vi) Staining of teeth (vii) Heartburn (viii) dark colour stool 3. Poor compliance

9. Parenteral iron therapY 1. certainty of its administration. 2. more rapid iron supply that oral iron therapy without the gastrointestinal side effects of oral substitution . 3. avoids blood transfusion associated risks

10. Indications of Parenteral Iron Therapy Poor tolerance to oral therapy Poor absorption of iron in chronic diarrhea, ulcerative colitis, celiac disease or inflammatory bowel disease. Non-compliance with oral iron therapy Women in third trimester or near term with moderate to severe anemia. Presence of concurrent disease like chronic renal failure when patient is on haemodialysis .

11. Calculation of dose of parentral iron (mg) can be done using different formulae. • Ganzoni’s formula- • hemoglobin deficit x weight(kg) × 2.4 + 1000 (for stores) • 250 mg x Deficit of Hb % • 0.23 x body weight (kg) x (150-patient Hb in g/L)+500 • 0.3 x body weight in pounds x hemogobin deficit + 500 mg

12. • Intravenous Iron: Two preparations are now used. • Oral Iron is stopped 48 hour before parenteral therapy • Injection Iron sucrose: It can be administered as IV infusion by diluting 300 mg in 300 ml normal saline over 30 minutes. Total iron requirement is calculated 300 mg is given bi-weekly ( maximum 600mg per week)

13. Ferric Carboxy Maltose (FCM) Macromolecular iron complex of polynuclear (III) hydroxide in carbohydrate shell. Dose: 15 mg/kg/day, Maximum – 1000 mg/setting. Repeat dose on day 7 and 14. Not to exceed > 2500 mg. category C drug, it has now been recommended and allowed by Drug Controller of India for use in pregnancy if required. Test dose not required. It was previously given in puerperium. It is in 250 ml normal saline and is given in I.V. Infusion over 30 minutes. It is also being used for women who are unable to tolerate oral iron.

14. Calcium supplements and vitamin D Calcium Supplements : Carbonate Citrate Lactate Gluconate All this forms have good bioavailability. CALCIUM CARBONATE : The most common, has the highest content of elemental iron and best efficacy.

15. CALCIUM DAILY RECOMMENDED DIETARY ALLOWANCES ( RDA) for calcium in pregnancy and lactation is 1000 mg / day.( GOI December 2014) vitamin D3 is 15 micrograms/day ( 600IU/day). [Williams 26edition page 187] DOSE – 1g calcium/day Regime – 1 tablet twice a day starting from 14 wks pregnancy upto 6 month post partum. 1 calcium tablet = 500mg elemental calcium + 250 IU vitamin D3.

16. It is not advisable to take both calcium tablets together as > 800 mg calcium interferes with iron absorption. Calcium tablets should not be taken empty stomach since it causes gastritis. Calcium and Iron Folic Acid (IFA) tablets should not be taken together since calcium inhibits iron absorption. IFA tablets should be taken preferably two hours after a meal

17. VITAMIN B12 RDA in pregnancy -2.6 micrograms Lactation - 2.8 micrograms Vitamin B12 deficiency in pregnancy due to – 1. Vegetarian diet 2. Excessive ingestion of vitamin C 3. Reduced carrier proteins – transcobalamine . Preparations – Methylcobalamin injection 2500mcg. B12 tablets. Vitamin B12 deficiency in mother lead to : Megaloblastic anemia Muscle weakness Numb or tingling sensation In hand and feet Anorexia Fatigue

18. OXYTOCICS IN OBSTETRICS DEFINITION: Oxytocics are the drugs of varying chemical nature that have the power to excite contractions of the uterine muscle. Oxytocin Ergot derivatives Prostaglandins

19. OXYTOCIN HALF-LIFE 3-4 MINUTES. DURATION OF ACTION 20 MINUTES. IT IS RAPIDLY METABOLIZED AND DEGRADED BY OXYTOCINASE. MODE OF ACTION Oxytocin acts through receptor and voltage-mediated calcium channels to initiate myometrial contractions. Myometrial oxytocin receptor concentration increases maximum during labor Oxytocin acting on decidual tissue promote prostaglandin release. Bound intracellular calcium is eventually mobilized from the sarcoplasmic reticulum to activate the contractile protein. uterine contractionsproduced are similar to physiological, i.e. Causing fundal contraction with relaxation of the cervix

20. PREPARATIONS ( i ) Synthetic oxytocin is widely used. It has only got oxytocic effect without any vasopressor action. The Oxytocin is available in ampoules of 5 IU/mL (ii) Syntometrine -A combination of Oxytocin 5 units and ergometrine 0.5 mg. (iii) Desamino -oxytocin-It is not inactivated by oxytocinase and is 50-100 times more effective than oxytocin. It is used as buccal tablets containing 50 IU. (iv) Oxytocin nasal solution contains 40 units/ mL.

21. EFFECTIVENESS In the first trimester, the uterus is almost refractory to oxytocin. In the second trimester, relative refractoriness persists, and, as such, oxytocin can only supplement other abortifacient agents in induction of abortion. In later months of pregnancy and during labor , it is highly sensitive to oxytocin even in small doses. Oxytocin loses its effectiveness unless preserved at the correct temperature (between 2°C and 8°C)

22. INDICATIONS Uses in pregnancy, labour or puerperium. (A) Therapeutic : pregnancy, labour, puerperium. (B) diagnostic : contraction stress test ( CST), oxytocin sensitivity test ( OST)

23. Oxytocin in EARLY PREGNANCY To accelerate abortion-inevitable or missed and to expedite expulsion of hydatidiform mole To stop bleeding following evacuation of the uterus Used as an adjunct to induction of abortion along with other abortifacient agents (PGE1 or PGE2)

24. Oxytocin in Late pregnancy : 1. To induce labour 2. Augmentation of labor Labor : 1. Active management of third stage of labor AMTSL ( 10IU/IM within 1 minute of delivery of fetus and before delivery of placenta.) Rule out twins pregnancy first. 2. Treatment of PPH- 40IU in 500ml of NS/RL at the rate 40- 60 drops/ min. 3. Breast engorgement:2 IU I/M

25. DANGERS OF OXYTOCIN:MATERNAL AND FETAL 1 . Uterine hyperstimulation (overactivity) There may be excessive duration of uterine contraction (hypertonia) or increased frequency (>6 in 10 min time) of contractions ( polysystole ) It is often associated with abnormal FHR pattern. 2 . Uterine rupture-may be seen with violent uterine contractions common. High-risk cases are: grand multipara, malpresentation, contracted pelvis, prior uterine scar (hysterotomy) and excessive oxytocin use.

26. 3 . Water intoxication is due to its antidiuretic function when used in high dose (30-40 mIU /min). Water intoxication is manifested by hyponatremia, confusion, coma, convulsions, congestive cardiac failure and death. It is prevented by fluid intake and output record, use of solutions like NaCL /RL not in D5/DNS and by avoiding highdose oxytocin a time. 4 . Hypotension: Bolus IV injections of oxytocin cause hypotension, especially when patient is hypovolemic or with a heart disease. Occasionally, oxytocin may produce anginal pain.

27. 5. Antidiuresis: Antidiuretic effect is observed when oxytocin infusion rate is high (40-50 mIU /min) and continued for a long time. 6 . Fetal : Fetal distress, fetal hypoxia or even fetal death may occur due to uterine hyperstimulation. Uterine hypertonia or polysystole causesreduced placental blood flow

28. METHODS OF ADMINISTRATION OF OXYTOCIN A) Controlled intravenous infusion B) Intramuscular CONTROLLED INTRAVENOUS INFUSION: Oxytocin infusion should be ideally by infusion pump. Fluid load should be minimum. It is started at low dose rates (1-2) mIU /min) and increased gradually. For induction of labor For augmentation of labor

29. FOR INDUCTION OF LABOUR Principles: Because of safety, the oxytocin should be started with a low dose and is increase at an interval of 20- 30 minutes where there is no response. When the optimal response is achieved (uterine contraction sustained for about 45 seconds and numbering 3 contractions in 10 minutes), the administration of the particular concentration in mIU /minute is to be continued. This is called oxytocin titration technique. The objective of oxytocin administration is not only to initiate effective uterine contractions but also to maintain the normal pattern of uterine activity till and at least 30-60 minutes beyond that

30. Regulation of the drip: The drip is regulated by- (1) Manually, counting the drops per minute commonly practiced (2) Oxytocin infusion pump which automatically controls the amount of fluid to be infused Convenient regime: start with a low dose (1-2 mIU /min) and to escalate by 1-2 mIU /min at every 20 min intervals up to 8 mIU /min. The patient should preferably lie on one side or in semiFowler’s position to minimize venacaval compression. High-dose oxytocin begins with 4 mIU /min and increased 4 mIU /min at every 20-30 min interval. It is mainly used for augmentation of labor and in active management of labor. Risks of tachysystole and Fetal heart irregularities more with high dose. For augmentation of labor • Oxytocin infusion is used during labor or for augmentation of labor or in the active management of labor . • The procedure consists of low rupture of the membranes followed by oxytocin infusion when the liquor is clear. • Fetopelvic disproportion must be ruled out beforehand

31. OBSERVATION DURING OXYTOCIN INFUSION 1. Rate of flow of infusion by counting the drops per minute or monitoring the pump. 2. Uterine contractions-number of contractions per 10 min duration of contraction and period of relaxation are noted. ‘Fingertip’ palpation for the tone of the uterus.mild ( tip of nose),moderate(chin),strong (forehead). Montevideo units- define uterine activity. Uterine performance is the product of contraction intensity in mm Hg multiplied by the number of contractions in a 10-minute span. For example, three contractions in 10 minutes, each with 50-mm Hg intensity, would equal 150 Montevideo units. FHR monitoring is done by auscultation at every 15 min interval or by continuous EFM Assessment of progress of labor (descent of the head. And rate of cervical dilatation

32. INDICATIONS OF STOPPING THE INFUSION Tachysystole - Abnormal uterine contractions occurring frequently (more than 5 contraction in 10 min) or lasting more than 60 sec . Normal uterine contraction: Mild- 2-3 contractions each lasting for 20 sec. Moderate-3-4 contraction each for 20-30 sec) , Good – 4-5 contraction each for 40 sec. Evidences of fetal distress . Appearance of untoward maternal symptoms .

33. CABETOCIN

34. Carbetocin is a long-acting synthetic oxytocin analogue, 1- deamino-1-monocarbo-(2-O-Methyltyrosine)-oxytocin, firstly described in 1987. It has a half-life of 40 minutes(around 4–10 times longer than oxytocin) . uterine contractions occur in less than two minutes after intravenous administration of optimal dosage of 100 mcg . A single dose of carbetocin has been hypothysed to act as a 16 hours intravenous oxytocin infusion regarding the increase in uterine tone and the reduction of the risk of PPH in elective caesarean section. Carbetocin , given 100 μg as an IV bolus over 1 minute, instead of continuous oxytocin infusion, can be administered in elective caesarean section for the prevention of PPH

35. Oxytocin Synthetic cyclic peptide form. Intavenous (IV): immediate action and peak after 30min. Intramuscular ( IM): 3-7 min produces longer lasting up to 60 min. Half life- 1-6 minute. Requires protection from light. Storage at 2-8 °C continuously. Heat stable Carbetocin Long acting synthetic analogue. Intavenous (IV)- systain uterine contractions within 2 minutes. Followed by rhythmic contractions for 60 minutes. IM- sustained uterine contractions within 11 min and lasting for 120 minutes. Half life – 40 minutes 5. Storage up to 30 °C

36. Clinical indications   Oxytocin Heat –stable Carbetocin Induction of labour Yes No Augmentation of labour Yes No Prevention of PPH Yes Yes Treatment of PPH Yes No

37. ERGOT DERIVATIVES: EROMETRINE, METHERGINE CHEMISTRY: Ergometrine is an alkaloid isolated by Dudley and Moir in 1935 from Ergot, a fungus Claviceps purpurea that develops commonly in cereals like rye, wheat, etc. The alkaloids are detoxified in the liver and eliminated in the urine. Methergine is a semisynthetic product derived from lysergic acid. MODE OF ACTION: Ergometrine acts directly on the myometrium. It excites uterine contractions which come so frequently one after the other with increasing intensity that the uterus passes into a state of spasm without any relaxation in between. It should not be used in the induction of abortion or labor. it is highly effective in hemostasis to stop bleeding from the uterine sinuses, either following delivery or abortion. Methergine is slower in producing Uterine response taking 96 seconds in contrast to 55 seconds by ergometrine when administered intravenously

38. COMPOSITION OF DIFFERENT ERGOTS PREPARATION Preparations Ampoules Tablet Ergonetrine 0.25 – 0.5 mg 0.5 – 1 mg Methergine 0.125 – 0.250 mg 0.125 – 0.5 mg Syntometrine 0.5 mg ergonetrine + 5 units oxytocin  

39. MODE OF ADMINISTRATION Ergometrine and methergine can be used parenterally or orally. It produces tetanic uterine contractions, The preparation should be used either in the late second stage of labor (after the delivery of the anterior shoulder) or following delivery of the baby. Syntometrine should always be administered intramuscularly

40. HAZARDS 1.Common side effects are nausea and vomiting. 2. Because of its vasoconstrictive action, it may precipitate rise of blood pressure, myocardial infarction. Stroke and bronchospasm. 3. Prolonged use may lead to gangrene of the toes due to its vasoconstrictive effect. 4. Prolonged use in puerperium may interfere with lactation by lowering prolactin level

41. USES OF ERGONETRINE AND METHERGINE Ergometrine should not be used during pregnancy, first stage of labor, second stage prior to crowning of the head and in breech delivery prior to crowning. COMMENTS: As a hemostatic in uterine hemorrhage. following expulsion of the fetus irrespective of duration of pregnancy, ergometrine or methergine is the drug of choice. On the contrary, oxytocin is predominantly to initiate uterine contractions (induction) and to accelerate uterine contractions in labor

42. INDICATIONS OF ERGOMETRINE/ METHERGINE IN OBS Prophylactic- • Active management of third stage of labor as prophylaxis to excess bleeding following delivery Therapeutic- • To stop the atonic uterine bleeding, following delivery, abortion or expulsion of hydatidiformmole

43. CONTRAINDICATIONS of Ergots 1) Suspected pleural pregnancy: If given accidentally with the delivery of the first baby, the second baby is compromised by the tetanic contractions of the uterus 2) Organic cardiac diseases: Results in sudden squeezing of blood from the uterine circulation into the systemic circulation causing overloading of the right heart and failure. 3) Severe pre-eclampsia and eclampsia: Sudden rise of blood pressure or development of fits (eclampsia). 4) Rh-negative mother: More risk of fetomaternal microtransfusion . 5)Heart disease or severe hypertensive disordersbecause of its vasoconstrictive effect, it may cause transient hypertension or cardiac failure, especially when given intravenously. Oxytocin is a better substitute in such cases

44. PROSTAGLANDINS ( PGS) Derivatives of prostanoic acid . “local hormones” paracrine/autocrine hormones as they act on locally at their site of production. first described and named by Von Euler in 1935. Are 20-carbon carboxylic acids with a cyclopentane ring formed from polyunsaturated fatty acid, arachidonic acid. PGE1,PGE2 and PGF2a are exclusively used in clinical practice. Inactivation is done in lungs and liver.

45. • Prostaglandins in obstetrics: Increased biosynthesis of PGs of E and F in the uterus is a prerequisite for labor in both term and preterm. Half-life is about 1-2 minutes. Decidua is the main source of PGF Fetal membranes (amnion) produce PGE Myometrium mainly produce PGI, PGF promotes myometrial contractility. PGE, induces labor with cervical effacement and dilatation. It shortens induction to delivery interval. Promote myometrial contraction irrespective of the duration of gestation, whereas oxytocin acts predominantly on the uterus at term or in labor. This helps the use of PGs to effect first trimester medical termination of pregnancy and also for induction of labor at term.

46. Side effects : are less when used vaginally. USE IN OBSTETRICS ■ Induction of abortion (MTP and missed abortion). ■Termination of molar pregnancy. ■ Induction of labor. ■ Cervical ripening prior to induction of abortion or labor ■ Management of atonic postpartum hemorrhage .

47. Advantages- Powerful oxytocic effect, irrespective of duration of gestation Induction of labor (PGE2, PGE1): In cases with (a) low preinduction score; (b) IUFD Used in induction of abortion (PGE1,) with success . It has got no antidiuretic effect ( cf oxytocin) PGE1 (misoprostol) can be used for augmentation of labor

48. Disadvantages and Side Effects Compared to oxytocin Nausea, vomiting, diarrhea, pyrexia, bronchospasm, tachycardia and chills Cervical laceration may occur (PGF2a) when used as an abortifacient Tachysystole (hyperstimulation) of the uterus, may occur during induction and may continue for a variable period Risk of uterine rupture in cases with previous scar

49. CONTRAINDICATIONS Hypersensitivity to the compound Uterine scar Active cardiac, pulmonary, renal or hepatic disease; hypotension (PGE2) Bronchial asthma (PGF2 alpha)

50. PGS USED IN OBS Misoprostol ( PGE1) DINOPROSTONE ( PGE2) CABROPROST ( PGF2 alpha)

51. METHYL ESTER OF PGE1( MISOPROSTOL) Rapidly absorbed and is more effective than oxytocin or dinoprostone for induction of labor. Misoprostol (PGE1,) has been used for cervical ripening Approved as a 100- 200 ug Tablet for peptic ulcer prevention. Misoprostol has been found to be as effective as PGE2, for cervical ripening and induction of labor. To date, no evidence of teratogenic or carcinogenic effects has been observed PGE1

52. Misoprostol recommended regimens ( FIGO 2017) < 13 weeks gestation 1. pregnancy termination – 800ug sl every 3 hours or PV / buccal every 3-4 hour ( 2-3 doses) 2. Missed abortions – 800 ug every 3 hour( × 2 ) 0r 600 ug sl every 3 hour( ×2 ) 3. Incomplete abortion- 600ug po( ×1) or 400ug sl ( ×1) or 400-800 ug pv ( × 1) 13-16 weeks gestation pregnancy termination- 13-24 weeks – 400 ug pv / sl / bucc every 3 hour. 25-26 weeks- 200ug pv / sl / bucc every 4 hours. Fetal death- 200ug pv / sl / bucc every 4-6 hours. Inevitable abortion- 200ug pv / sl / buccevery 6 hours.

53. > 26 weeks gestation 27-28 week : 200ug pv / sl / bucc every 4 hour > 28 week: 100 ug pv / sl / bucc every 6 hour. Fetal death – 27-28 weeks 100ug pv / sl / bucc every 4 hour > 28 weeks- 25 ug pv every 6 hour or 25ug po every 2 hours. Induction of labour- 25 ug pv every 6 hours or 25 ug po every 2 hour. Postpartum usePPH prophylaxis- Effective in the management of AMTSL ( 600mcg orally). PPH treatment atonic PPH ( 800mcg S/L )

54. Advantages of over PGE : Misoprostol is cheap, stable at room temperature, long shelf-life, easily administered (oral, vaginal or rectal) and has less side effects. Induction delivery interval is short. Need of oxytocin augmentation is less. Failure of induction is less. Risks: Incidence of tachysystole (hyperstimulation); Fetal heart rate changes and meconium passage are high. Rupture of uterus, though rare, has also been observed. It should not be used for cases with previous cesarean birth because the risk of rupture is high.

55. Prostaglandin E2 (DINOPROSTONE) Vaginal pessary (vaginal insert) releasing dinoprostone approximately 10 mg over 24 hours. It is removed when cervical ripening is adequate. Placed in posterior fornix. PGE2 gel-0. 5 mg ( Dinoprostone ) into the cervical canal,below the level of internal os . Repeat 6 in hour permit 3 doses total . Use induction of labor causing cervical effacement and dilatation. It reduces the need of oxytocin . PGE2 preparations are relatively expensive and require refrigeration otherwise it becomes unstable at room temperature

56. 15 METHYL PGF2 ALPHA ( CARBOPROST TROMETHAMINE) 250 micrograms IM Every 15-90 min ( 8 doses maximum) Use- Postpartum haemorrhaga Side effects- Nausea, vomiting, diarrhea Contraindication- bronchial asthma, active cardiac renal or hepatic disease.

57. ANTIHYPERTENSIVE DRUGS First line therapy- methyldopa Or labetalol Second line drug is nifedipine. ACE inhibitors are avoided in pregnancy. Sympatholytics - methyl dopa Adrenergic receptor blocking agent- lobetalol Vasodilators – Hydralazine, Nitroglycerin , sodium nitroprusside. Calcium channel blockers- Nifedipine, nicardipine.

58. Methyldopa Category B 250 mg BD – increased to 1 gm qid Side effect- maternal – postural hypotension, hemolytic anemia, sodium retention, excessive sedation. Fetal-intestinal ileus Hydralazine Category c Orally-100mg/ day in 4 divided doses. 5 mg lv or im f/b 10mg doses at 15-20 min upto 3 doses Tachycardia, headache, hypotension Labetalol Category C Orally-100 mg tds up to 2400 mg daily Iv- 10mg F/b 20 mg in 20 min, then 40 mg then 80 mg Or constant infusion 1-2 mg/ min Asthma precipitation, bradycardia, hypotension, tremors.

59. Nifedipine Category C 5-10 tds maximum dose 60-120mg/day Flushing, hypotension, tachycardia, Headache Sodium nitroprusside   I/v infusion-0.25- 8 ug/kg/min Maternal-severe hypotension, nausea, vomiting. Fetal toxicity due to metabolites-cyanide and thiocynate Nitroglycerin   I/v infusion 5 ug/ min increased every 3-5 mina upto 100ug/min Tachycardia, headache, methemoglobinea .

60. TOCOLYTIC AGENTS Calcium channel blockers Nifedipine Dose- 10-20 mg every 3-6 hr Side effects – maternal hypotension, headache, flushing Magnesium sulfate Loading dose 4-6 g i/v ( 10-20% solution) over 20-30 min followed by 1-2 g/hr for 12hour after contractions have stopped. MgSO4 relatively safe. Maternal S/E- Headache, flushing, perspiration, headache. Neonatal S/E- cardiac arrest, hypotonia, respiratory distress. Oxytocin antagonists Atosiban I/v infusion-300 micrograms/ min Initial bolismay be needed Nausea, vomiting, chest pain( rarely)

61. Betamimetics 1 Terbutaline Oral- 2.5 mg – 5 mg every 4-6 hrs for 48- 72 hours. SC- 250ug every 20-30 min 4-6 dosages for 48-72 hour Hyperglycemia, hyperinsulinemia, tremors, pulmonary edema, sudden maternal death 2 Ritodrine Oral/intravenous – 50 ug/ min and increase every 20 min to maximum 350 ug/min for 48-72 hours Tachycardia, palpitations, headache, hyperglycemia, maternal hallucinations, pulmonary edema 3 Isoxsuprine Oral- 10-20 mg every 6 hours for 48 hour I/v – 200-500 mcg/ min till control is achieved then 10 mg IM every 8 hourly for one week Same as other betamimetics Nitric oxide ( glyceryl trinitrate GTN) Patches Headache Hypotension May cause cervical ripening

62. Diuretics Frusemide (Loop diuretic)- Dose - 20-80 mg divided in 6- 12 hourly ( PO/IM/ IV) Use – cardiomyopathies, cerebral edema , renal insufficiency, CHF, pulmonary edema . Side effects- hypokalemia , metabolic alkalosis, hypomagnesemia, hyperuricemia, dehydration, hypotension. Spironolactone- potassium sparing diuretics, not produce hypokalemia . Aldosterone receptor antagonist acts at distal segment of distal tubule. Dose- 25- 400mg/ day in 1-2 divided dose. Side effects- metabolic acidosis, gynecomastia, peptic ulcer, gastritis.

63. ANTICONVULSANTS Magnesium sulfate Mode of Actions : It decreases the acetylcholine release from the nerve endings and reduces the motor end plate sensitivity to acetylcholine. It also blocks the calcium channels. It causes vasodilatation, increases cerebral, uterine and renal blood flow. It decreases intracranial edema ( so use in neuroprotection)

64. REGIMENS OF MGSO4 Intramuscular ( pritchard ) Loading dose – 4 g (20% solution) IV over 3-5 minute followed by 5 g (50%) IM deep IM (5 g in each buttock) Total 14gm Maintenance dose – 5 g (50%) IM 4 hourly in alternate buttock Intravenous ( zuspan ) – Loading dose - • 4 g (20%) IV slow over 5-10 minute. Maintenance dose- • 1-2 g/h IV infusion

65. Sibai – Loading dose 4-6 g over 15-20 min 9 100ml NaCL ) Maintence dose – 2g/hr IV infusion. Low dose ( dhaka ) regime ( suitable for lean Asian women)- Loading dose- 4g IV slowly over 15 min. 3g IM in each buttock. Total 10g. Mainatenance - 2.5g IM in alternate buttock every 4 hr until 24 hrs after first dose

66. Repeat injections are given only if The knee jerks are present, urine output exceeds 30 mL/h and the respiration rate is more than 12/minute. The therapeutic level of serum magnesium is 4-7 mEq /L. Serum magnesium levels may be monitored in selected cases (renal insufficiency, absent deep tendon reflexes). To control fits, optimum serum magnesium level is 4.8-8.4 mg/dL (4-7 mEq /L) to be maintained

67. Magnesium toxicity and serum Mg level is seen as : (a) Loss of deep tendon reflexes >7 mEq /L (b) respiratory depression more than 10 mEq /L (c) cardiac arrest more than 25 mEq /L. Magnesium sulfate is continued for 24 hours after the last seizure or delivery whichever is later. For recurrence of fits, further 2 g IV bolus is given over 5 minute in the above regimens

68. Detection of Magnesium Toxicity Loss of deep tendon reflexes Decreased respiratory rate (<12 per minute) Urine output (<30 mL/h) Chest pain, heart block, pulmonary edema O2 saturation monitoring (PaO2 <95%)

69. • Management for Magnesium Toxicity To stop magnesium therapy Estimation of serum magnesium and creatinine levels Injection calcium gluconate 10 mL (10% solution), IV slowly Fluid loading and forced diuresis Contraindicated in patients with myasthenia gravis

70. PHENYTOIN Centrally acting anticonvulsant (for other anticonvulsant drugs. • Doses- Eclampsia: 10 mg/kg IV – at the rate not more than 50 mg/min followed 2 hrs later by 5 mg/kg Epilepsy: 300-400 mg daily orally in divided doses Status epilepticus: 18 mg/kg slow IV (50 mg/ min); Maintenance dose of about 100 mg is given at an interval of 6-8 hrs. BP and ECG monitoring should be done

71. • Side effects- • Maternal- Hypotension, • cardiac arrhythmias, • phlebitis at the injection site. Fetal hydantoin syndrome ( low nasal bridge,hypertelorism midfacial hypoplasia, hypoplasia of distal phalanges and nails, growth impairment and intellectual disability.)

72. ANTIEPILEPTICS IN PREGNANCY Drug Abnormalities Affected EmbryofetalRisks Valproate Neural tube defects, clefts, cardiac anomaly, development delay, attention deficit hyperactivity 7-10%   Phenytoin Fetal hydantoinsyndrome 5-10 % Yes Carbamazepin Fetal hydantoin syndrome, spina bifida 2-5% Yes Phenobarbital Clefts, cardiac anomalies, urinary tract malformation. 6-20% Suggested Lamotrigine Increased risk for clefts( registry data) Up to 2% Suggested Topiramate Clefts 2-3 % Suggested Levetiracetam Theoretical,Skeleton abnormalities, impaired growth in animals 1-3 % Suggested

73. ANTICOAGULANTS

74. Heparin Unfractionated heparin Low-molecular- weight heparin (LMWH) Mode of action- Inhibits action of thrombin, enhances the activity of antithrombin III, increases factor Xa inhibitor. Antidote : Protamine sulfate Dose- 5,000-10,000 IU to be administered parenterally. DVT and pulmonary embolism :loading dose 5,000 units IV followed by continuous infusion of 18 units/kg/hr Pregnancy : 5,000-10,000 SC every 12 hrs (with monitoring) LMWH : Enoxaparin 1 mg/kg twice daily safe a SC, less antithrombotic effect.

75. Side effects of heparin - Maternal : Hemorrhage , urticaria with long- term use thrombocytopenia and osteopenia, hyperkalemia Protamine sulfate reverses the action of UFH. Fetal : not cross the placenta and not secreted in the breast milk and not teratogenic. Low-molecular-weight heparins-as effective and safe as unfractionated heparin. Longer half-life and once daily dose is convenient. Standard dose does not require monitoring

76. Warfarin Interferes with synthesis of vitamin K dependent factors (II, VII, IX, X) Dose- 5-10 mg orally daily for initial 2 days then 3-9 mg daily (taken at the same time each day) depending upon the prothrombin time (INR) (INR 2.5-3.5) Maternal :Hemorrhage Fetal : Warfarin embryopathy (5%), nasal hypoplasia, bone stipplings , optic atrophy, mental retardation, microcephaly, chondrodysplasia punctata. Women with mechanical heart valves, warfarin is preferred. To avoid first trimester

77. CORTICOSTEROIDS IN OBS

78. Benefits- lower rates of perinatal death. Neonatal death Intraventricular hemarrhage Necrotizing enterocolitis Mechanical ventilation Betamethasone injection . Used for pulmonary maturity in threatened preterm labour (12 mg IM every 24 hours for 2 doses) Dexamethasone injections can also be used (6 mg I/M 6 hourly for 4 doses). Both betamethasone and dexamethasone equivalent in stimulating fetal lung maturation (murphy 2007) williams802

79. OTHERS DRUGS- DROTAVERINE Used as analgesic for pain relief in labour. Also used for pain relief in post operative period and for colicky abdominal pain like renal and ureteric colic.

80. Drotaverine Hydrochloride Highly potent antispasmodic agent that can be used to relieve smooth muscle spasm. Not cross the placental barrier. no anticholinergic action Routes of administration : Oral: 1 tablet (40-80 mg): Subcutaneous/IM/IV Uses Active management of labor : given only after labor is established (e. Cervix >4-5 cm dilated) One ampoule (40 mg) is given IM or slow IV (2 ml i.e. 40 mg of drug diluted in 10 ml of saline) repeated every 2-3 hours for maximum 3 doses. Dysmenorrhea : one to two tablets (40-80 mg) three times a day for 3-5 days. Uterine cramps due to IUCD in-situ: one to two tablets (40-80 mg) three times a day. Side effects : No adverse reactions have been reported. Incidence of allergy is negligible. With high doses, hypotension may occur if the drug is administered in a non-recumbent position.

81. Epidosin Used in active management of labor to facilitate dilatation and effacement of cervix. Mechanism of action: Chemically it is valethamate bromide. It has anticholinergic. Spasmolytic action on smooth muscles. Indications : acceleration of labor (after latent phase is over], delayed dilatation of cervix in labor , and spasmodic dysmenorrhea Routes : subcutaneous, IM, IV, and oral routes. Dose : In active management of labor it is given only after labor is established (i.e. Cervix >4-5 cm dilated). One amber colored photodegradation) ampoule (8 mg) is given by (prevents IM or IV route; the dose is repeated every 20- min to 1 hour for 3 doses. Success Rate: 84% in primigravida and 94% in multipara

82. Antihelminths Common cause of iron deficiency anemia is worm infestation. Prophylatically de worming drugs used Albendazole and mebendazole Albendazole- 400 mg single dose HS, category C drug but avoid in first trimester. Mebendazole - 100mg BD × 3 days Or 500mg single dose.

83. Tranexamic Acid Antifibrinolytic agent. Use- PPH, non hormonal therapy for menorragia . Preparations- 500mg and 1 g tablet., 500mg injection per 5 ml vial. Safe in pregnancy ( category B).

84. TERATOGENIC AND FETOTOXIC AGENTS Alcohol Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Carbamazepine Cyclophosphamide Nitrofurantoin NSAIDS Phenobarbital Phenytoin Vaproic acid , Warfarin Radioactive Iodine Fluconazole Isotretinoin Lead,Lithium Mercury, Marijuana • Methimazole Methamphetamine Ribavirin Sulfonamides Tamoxifen Tetracyclines Tobacco , toluene ,Topiramate

85. THANK YOU