Antihypertensive and Anticonvulsant drugs in OBG

About Drugs in OBG

1. PRESENTED BY MS.SANTOSH KUMARI M.SC.NURSING 1 ST YEAR DRUG PRESENTATION ON ANTIHYPERTENSIVE DRUGS AND ANTICONVULSANT DRUGS

2. ANTIHYPERTENSIVE DRUGS DURING PREGNANCY

3. OVERVIEW OF DRUG CATEGORY AND absorption IN PLACENTA

4. CATEGORIZATION OF DRUGS IN PREGNANCY ( ACCORDING TO FDA)

5. How Drugs Cross the Placenta Fetus's blood vessels are contained in tiny hair like projections ( villi ) of the placenta that extend into the wall of the uterus. The mother's blood passes through the space surrounding the villi ( intervillous space). Only a thin membrane (placental membrane) separates the mother's blood in the intervillous space from the fetus's blood in the villi .

6. Drugs in the mother's blood can cross this membrane into blood vessels in the villi and pass through the umbilical cord to the fetus

7. HYPERTENSION Hypertension is defined as having a blood pressure greater than 140/90 mm Hg Normal blood pressure is 120/80 mm/hg .

8. GESTATIONAL HYPERTENSION is the development of new hypertension in a pregnant woman after 20 weeks. Rise of blood pressure to 140/90mm/hg.

9. CATEGORY OF ANTIHYPERTENSIVE DRUGS ACCORDING TO FDA Category B. Category C. Category D.

10. INTRODUCTION ANTIHYPERTENSIVE- Work against the hypertension. Antihypertensive drugs are essential when the BP is 160/110 mm of Hg to protect mother from Eclampsia. Cerebral hemorrhage. Cardiac failure. Placental abruption.

11. Risk of large organ damage ( kidney) antihypertensives are given to maintain BP <- 140 mm of Hg. First line therapy is either methyldopa or labetalol . Second line drug is nifedipine . ACH inhibitors/ ARB are avoided in pregnancy.

12. These drugs are used in two clinical conditions. Pre- eclampsia and eclampsia. Chronic hypertension.

13. PRE-ECLAMPSIA AND ECLAMPSIA Rise of blood pressure specially where the diastolic pressure is above 110mm Hg. The use is more urgent with proteinuria . Severe pre- eclampsia to bring down the blood pressure during continued pregnancy and during the period of induction of labour.

14. DRUGS MODE OF ACTION DOSE METHYLDOPA Central and peripheral anti adrenergic action. 250-500 mg TID or QID. LABETATOL Adrenoceptor antagonist (alpha or beta blocker). 100 mg TID or QID NIFEDIPINE Calcium channel blocker. 10-20 mg BID HYDRALIZINE Vascular smooth muscle relaxant. 10-20 mg BID.

15. CHRONIC HYPERTENSION Routine use of antihypertensive drugs is not favoured. Antihypertensive drugs should be used only when the pressure is raised beyond 160/100 mm Hg. To prevent target organ damage.

16. HYPERTENSIVE CRISIS Drugs can be used when the BP is _>160/110 mm Hg or the mean arterial pressure (MAP) is _> 125 mm Hg. MAP is the average arterial pressure during a single cardiac cycle. Avoid labetalol I woman having asthma or cardiac failure.

17. DRUG ONSET OF ACTION DOSE SCHEDULE MAXIMUM DOSE MAINTENANCE DOSE LABETALOL 5 MIN 12-20 mg IV every 10 min. 300 mg IV 40 mg/hr HYDRALAZINE 10 MIN 5 mg IV every 30 min 30 mg IV 10mg/hr NIFEDIPINE 10 MIN 10-20 mg ORAL, can repeat 30 min 240 mg/24hr 4-6 hour interval NITROGLYCERI-NE. 0.5- 5 MIN 5ug /min IV Other drugs have failed. Other drugs failed SODIUM NITROPRUSSID-E. 0.5- 5 MIN 0.25-5 ug /kg/min IV Other drugs have failed. Other drugs failed.

18. COMMONLY USED DRUGS CATEGORY C Sympatholytics Methyl- dopa Reserpine Calcium channel blocker Nifedipine Nicardipine

19. CATEGORY B Andrenergic receptor blocking agents Labetalol Propranolol Vasodilators Hydralazine Nitroglycerin Sodium nitroprusside

20. CATEGORY D 5. ACE inhibitors/ ARB. Captopril Trlmisartan Avoided during pregnancy because it can cause various kind of deformities in fetus.

21. PHARMACOKINETICS These drugs transported actively by intestinal amino acid carrier, less than 1/3 of an oral dose absorbed. It is partly excreted unchanged in urine. Antihypertensive effect develop over 4-6 hours and lasts for 12-24 hours.

22. METHYLDOPA Mechanism of action/ Pharmacodynamics : Central or peripheral antiadrenergic action as false transmitter, resulting in reduction of arterial pressure. Effective and safe for mother and the fetus. Indication: Hypertension. Dose: Orally- 250mg TID - may be increased to 1 g QID depending upon the response. IV infusion – 250- 500mg. Contraindications and precautions : Hepatic disorders, psychic patients, congestive cardiac failure, Postpartum ( risk of depression.

23. SIDE EFFECTS Maternal- Postural hypotension, haemolytic anaemia , sodium retension . Nausea, vomiting, diarrhea, constipation. Bradycardia, angina, weight gain. Drowsiness, dizziness, headache, depression, excessive sedation. Fetal – Intestinal ileus .

24. Nursing consideration Assess Blood values: Neutrophils , platelets. Renal studies: Protein, creatinine. Blood pressure before beginning treatment and periodically thereafter. Perform/ Provide Storage of tablets in tight containers. Evaluate Decrease in blood pressure . Allergic reaction: Rash, fever.

25. Teach client/ Family To avoid hazardous activities. Administer one hour before meals. To rise slowly to sitting or standing position to minimize orthostatic hypotension. Not to skip or stop drug unless directed by physician. Notify physician of untoward signs and symptoms.

26. HYDRALAZINE Mechanism of action : Acts by peripheral vasodilators as it relaxes the arterial smooth muscle. Orally it is weak and should be combined with methyldopa or beta- blockers. It increases the cardiac output and renal blood flow. Preparations: Aspresoline , Hydralyn , Rolazine . Dose : Orally: 100mg/day in four hours divided doses IV: 5-10 mg every 20 minute maximum 20 mg.

27. Indication: Essential hypertension. C ontraindications and precautions Coronary artery diseases, mitral valvular rheumatic heart disease. Because of variable sodium retention, diuretics should be used. To control arrhythmias, propranolol may be administered intravenously.

28. Side effects Maternal - hypotension, tachycardia, arrhythmia, palpation, lupus like syndrome, fluid retention, muscle cramps, headache, dizziness, depression, anorexia, diarrhea. Fetal : reasonably safe. Neonatal : thrombocytopenia.

29. Nursing Consideration Assess BP every 15 minutes initially for 2 hours then every hour for 2 hours, and then q4h, pulse q4h. Blood studies: Electrolytes, CBC and serum glucose. Intake: Output and weight daily. Administer To patient in recumbent position, keep in that position for one hour after administration.

30. Evaluate Edema in feet and legs daily. Skin and mucosa membrane for hydration. Dyspnea , orthopnea . Joint pain, tachycardia, palpitation, headache and nausea. Teach Client/ Family To take with food to increase bio- avail-ability. To notify physician if chest pain, severe fatigue, muscle or joint pain occurs.  

31. LABETALOL Mechanism of action : Combined with alfa and beta adrenergic blocking agent. Preparations : Trandate , Normodyne . Dose : Orally – 100mg TID may be increased up to 2400 mg daily. IV- infusion ( Hypertensive crisis) 20-40 mg every 10-15 min until desired effect, maximum up to 220 mg. Indication : Hypertension

32. Contraindications and precautions - Hepatic disorders, Asthma, congestive cardiac failure. Side effects - Tremors, headache, asthma, congestive cardiac failure. Efficacy and safety with short term use appear equal to methyldopa.

33. Nursing Considerations : Assess Intake output and weight daily. Blood pressure and pulse check q4h. Apical or radial pulse before administration. Administer PO, before food and h.s . IV, keep client recumbent for 3 hours.  

34. Perform/ provide Storage in dry area at room temperature. Evaluate Therapeutic response: Decreased BP after 1 to 2 weeks. Edema in feet, legs daily. Skin turgor and dryness of mucus membranes for hydration status.

35. Teach Client/ Family Not to discontinue drug abruptly, taper over 2 weeks. To report bradycardia, dizziness, confusion or depression. To avoid alcohol, smoking and excess sodium intake. Take medication at bedtime to prevent the effect of orthostatic hypotension.

36. NIFEDIPINE Preparations - Adalat , Procardia . Mechanism of action : Direct arteriolar vasodilation by inhibition of slow inward calcium channels in vascular smooth muscle. Dose : Orally- 5-10 mg tid maximum dose 60-120 mg/ day. Indication – Hypertension, angina pectoris. Contraindications and precautions : Simultaneously use of magnesium sulfate could be hazardous due to synergistic effect. Side effects - Flushing, hypotension, headache, tachycardia, inhibition of labour, fatigue, drowsiness, nausea, vomiting.

37. Nursing Considerations Assess Blood levels of the drug, therapeutic levels 0.025 to 0.1ug/ml. Administer Before meals and night.   Evaluate Therapeutic response, cardiac status, BP, pulse, respiration and ECG. Teach Client/ Family To limit caffeine consumption. Stress patient compliance to all aspects of drug use.

38. SODIUM NITROPRUSSIDE Preparations – Nipride , Nitropress . Mechanism of action: Direct vasodilator ( arterial and venous), directly relaxes arteriolar, venous smooth muscle, resulting in reduction of cardiac preload and afterload . Indications Hypertension crisis. To decrease bleeding by creating hypotension during pregnancy

39. Contraindication and precaution : Drug of last resort for acute hypertension. Should be used in critical care unit for very short time ( 10 minutes) Dose : IV infusion 0.25-8 ug /kg/min. Side effects : Maternal- Nausea, vomiting, severe hypotension, restlessness, decreased reflexes, loss of consciousness. Fetal toxicity due to metabolites- cyanide and thiocyanate

40. Nursing Considerations Assess Serum electrolyte, BUN and creatinine. Hepatic function. BP and ECG. Weight and intake output. Administer Using and infusion pump only. Wrap bottle with aluminum foil to protect from light.

41. Evaluate Therapeutic response: Decreased BP, absence of bleeding. Edema – feet and legs. Hydration status.

42. NITROGLYCERINE Mechanism of action: Relaxes mainly the venous but also arterial smooth muscle. Dose - Given as IV infusion 5 ug / min to be increased at every 3-5 min up to 100ug /min. Side effect : Tachycardia, headache, methaemoglobinaemia . Contraindication and precautions : Used in hypertensive crisis for short time only. Contraindicated in hypertensive encephalopathy as it increases blood flow and intracranial pressure

43. Nursing Consideration Assessment Monitor patient closely for change in levels of consciousness and for dysrhythmias . Assess for headaches. Approximately 50% of all patients experience mild to severe headaches following nitroglycerin. Take base line BP and heart rate. Assess for and report blurred vision and dry mouth. Patient and Family Education Take care of the adverse effect of headache. Report blurred vision if present. Change position slowly and avoid prolonged standing.

44. PROPRANOLOL Action Beta adrenergic blocker: Decreases preload, afterload , which is responsible for decreasing left ventricular end diastolic pressure and systemic vascular resistance. Indication – Hypertension, prophylaxis of angina pain. Contraindication – Bronchial asthma, renal insufficiency, diabetes mellitus, cardiac failure.

45. Side effect/ Adverse Reactions Maternal Sever hypotension, sodium retention, bradycardia, bronchospasm , cardiac failure. Fetal Bradycardia and impaired fetal responses to hypoxia, IUGR with prolonged therapy. Doses and routes of administration Orally 80 to 240 mg divided doases .

46. Nursing Consideration Assess BP, pulse and respirations during therapy. Weight daily and report excess weight gain. Intake output ratio. Administer Administer with 240 ml of water on empty stomach. Evaluate Tolerance if taken for long period. Headache, light- headedness, decreased BP. Teach Client/ Family There may be stinging sensation when the drug comes in contact with mucus membranes. To make position changes slowly to prevent fainting.

47. DIAZOXIDE Preparation – Hyperstat . Action – Vasodilator. Indication – Hypertensive crisis when urgent decrease of diastolic pressure is required. Contraindications – Diabetes, heart disease, diuretics should be used simultaneously.

48. Side effect Maternal Fluid and sodium retention. Inhibition of uterine contraction. Hyperglycemia. Severe hypotension. Palpitations. Fetal Hypoxia. Dosage and routes of administration IV- 30 to 50 mg, may be repeated every 10 to 15 minutes or continuous infusion.

49. Nursing Consideration Assess BP q5min for 2 hours, then q1hr for 2 hours and then q4h. Pulse, jugular venous distention q4h. Serum electrolytes, CBC, serum glucose. Weight daily and intake output. Administer To patient in recumbent position, keep in that position for one hour after administration. Perform/ provide Protection from light.

50. Evaluate Therapeutic responses: Primarily decreased diastolic pressure. Edema in feet and legs. Hydration status. Dyspnea and orthopnea . Postural hypotension: Take BP sitting and standing. Teach Patient/ Family To limit caffeine consumption. To report side effects if present. To comply with the regimen.

51. ACE inhibitors/ Angiotensin-II receptor blocker (ARB Mechanism of action - ACE inhibitors, inhibits formation of angiotensin- II from angiotensin- I. ARB blocks angiotensin- II receptors. Dose- Captopril orally 6.25 mg bid Telmisartan orally 20-40 mg a day.

52. Side effect - Maternal- Hypotension, headache, asthma, arrhymias . Fetal- Oligohydraminios , IUGR, fetal tubular dysgenesis , neonatal renal failure, pulmonary hypoplasia . Contraindication and precaution : Should for chronic hypertension in non- pregnant state or postpartum.

53. TITLE- The effect of calcium channel blockers on prevention of preeclampsia in pregnant women with chronic hypertension. AUTHOR – Jiang N , Liu Q , Liu L , Yang WW , Zeng Y .

54. BACKGROUND: This study aims to investigate whether calcium channel blockers plus low dosage aspirin therapy can reduce the incidence of complications during pregnancy with chronic hypertension and improve the prognosis of neonates.

55. MATERIALS AND METHODS: From March 2011 to June 2013, 33 patients were selected to join this trial according to the chronic hypertension criteria set by the Preface Bulletin of American College of Obstetricians and Gynecologists. Patients were administrated calcium channel blockers plus low-dosage aspirin and vitamin C. The statistic data of baseline and prognosis from the patients were retrospectively reviewed and compared.

56. RESULTS: Blood pressure of patients was controlled by these medicines. 39.4% patients complicated mild preeclampsia; however, none of them developed severe preeclampsia or eclampsia, or complicate placental abruption. 30.3% patients delivered at preterm labour; 84.8% patients underwent cesarean section.

57. The neonatal average weight was 3,008 ± 629.6 g, in which seven neonatal weights were less than 2,500 g. All of the neonatal Apgar scores were 9 to 10 at one to five minutes. Small for gestational age (SGA) occurred in five (15%).

58. CONCLUSIONS: Calcium channel blockers can improve the outcome of pregnancy women with chronic hypertension to avoid the occurrence of severe pregnancy complication or neonatal morbidity.

59. ANTICONVULSANTS DRUGS DURING PREGNANCY

60. INTRODUCTION Due to eclampsia. Other causes are – epilepsy, meningitis, cerebral malaria and cerebral tumours . Proved by history, examination and investigations.

61. Commonly used anticonvulsant is magnesium sulfate. Diazepam, Phenytoin and Phenobarbitone are also used.

62. IN 2013 ACCORDING TO FDA FROM CATEGORY A TO CATOGORY D BECAUSE OF THE RISK OF FETAL DEMINERALIZATION.

63. PHARMACOKINETICS Absorption by oral route is slow, mainly because of its poor aqueous solubility. Widely distributed in the body and is 80-90% bound to plasma proteins. Metabolized in liver. Excreted by the kidney.

64. MAGNESIUM SULFATE Action – Decrease acetylcholine in motor nerve terminals, which is responsible for anticonvulsant properties, thereby reduces neuromuscular irritability.

65. It also decreases intracranial edema and helps in diuresis . Its peripheral vasodilatation effect improves the uterine blood supply.

66. Use – It is a valuable drug lowering seizure threshold in women with pregnancy – induced hypertension. The drug is used in preterm labor to decrease uterine activity.

67. Dosage and Route For control of seizures, 20 ml of 20% solution IV slowly in 3 to 4 minutes and 10ml of 50 percent solution IM, and continued 4 hourly for 24 hours postpartum.

68. Repeat injections are given only if the knee jerks are present, urine output exceeds 100ml in previous 4 hours and the respirations are more than 10/minute.

69. The therapeutic levels of serum magnesium is 4 to 7 mEq /L. 4 gm IV slowly over 10 min, followed by 2 gm/ hr and then 1 gm/hr in drip of 5 percent dextrose for tocolytic effect.

70. Side effects Maternal – Severe CNS depression ( respiratory depression and circulatory collapse), evidence of muscular paresis ( diminished knee jerks). Fetal – Tachycardia, hypoglycemia. Antidote – Injection calcium gluconate 10% 10 ml IV.

71. Nursing Considerations Assess Vital signs 15 min after IV dose. Monitor magnesium levels. If using during labour, time contractions, determine intensity. Urine output should remain 30 ml/hr or more, if less notify physician.

72. Administer Only after calcium gluconate is available for treating magnesium toxicity. Using infusion pump or monitor carefully IV at less then 150 mg/min, circulatory collapse may occur. Only dilution.

73. Perform/Provide Seizer precautions, place client in single room with decreased stimuli, padded side rails. Positioning of the client in left lateral recumbent position to decrease hypotension and increase renal blood flow.

74. Evaluate Mental status, sensorium , memory. Discontinue infusion if respirations are below 12/min or fetal distress.

75. Teach Client/ Family On all aspects of the drug: action, side effects and symptoms of hypermagnesemia . To remain in bed during infusion.

76. DIAZEPAM ( VALIUM) Action - Depresses subcortical levels of CNS, anticonvulsant, and antianxiety . Dosage and Route of Administration PO, 2 to 10 mg tid – qid .

77. IV, 5 to 20 mg ( bolus), 2mg/min, may repeat q5 – 10 min, not to exceed 60 mg, may repeat in 30 min if seizures reappear.

78. Side effect Mother – Hypotension, dizziness, drowsiness, headache. Fetus - Respiratory depressant effect, which may last for even three weeks after birth .

79. Nursing Consideration Assess BP in lying and standing positions, if systolic pressure falls 20 mmHg, hold drug and inform physician . Blood studies: CBC. Hepatic studies.

80. Administer IV into large vein to decrease chance of extravasation . PO with milk or food to avoid GI symptoms.

81. Provide Assistance with ambulation during beginning therapy since drowsiness and dizziness may occur. Safety measures include side rails.

82. Evaluate Therapeutic response Mental status, sleeping pattern. Physical dependence, headache, nausea, vomiting.

83. Teach Patient/ Family D rug may be taken with food. To avoid alcohol ingestion. Not to discontinue medication abruptly. To rise slowly as fainting may occur.  

84. PHENYTOIN ( DILANTIN) Action – Inhibits spread of seizure activity in motor cortex. Dosage and route of administration Eclampsia: 10 mg/kg IV at the rate not more than 50mg/minute, followed 2 hours later by 5 mg/kg.

85. Side effects Maternal Hypotension, cardiac arrhythmias and phlebitis at injection site.

86. Fetal Prolonged use by epileptic patients may cause craniofocal abnormalities, mental retardation, microcephaly and growth deficiency.

87. Nursing Consideration Blood studies: CBC, Platelets every 2 weeks until stabilized. Discontinue drug if neutrophils < 1600/mm2 Administer After diluting with normal saline, never water.

88. Evaluate Mental status, memory. Respiratory depression. Sore throat, brushing. Teach Patient/ Family All aspect of drug administration, when to notify physician.

89. PHENOBARBITONE ( LUMINAL) Action - Decreases impulse transmission and increases seizure thresholds at cerebral cortex level. Dose and Route of Administration – 120 to 240mg/day in divided doses.

90. Side effects Maternal – Sedation, drowsiness, hangover headache, hallucination. Fetal – Withdrawal syndrome.  

91. Nursing consideration Assess Blood studies, liver function tests during long term treatment. Therapeutic level 15 to 40 mg/ml.

92. Evaluate Mental status, mood affect and memory. Respiratory depression. Fever, sore throat bruising, rash. Teach Patient/ Family All aspects of drug administration and when to notify physician.  

93. Effect of magnesium sulphate on fetal heart rate parameters : a systematic review. AUTHOR – Nensi A , De Silva DA , von Dadelszen P , Sawchuck D , Synnes AR , Crane J , Magee LA

94. ABSTRACT To examine the potential effects of intravenous magnesium sulphate (MgSO4) administration on antepartum and intrapartum fetal heart rate (FHR) parameters measured by cardiotocography (CTG) or electronic fetal monitoring (EFM).

95. They took a systematic review of randomized controlled trials, observational studies, and case series, by qualitatively analyzed. Result of 18 included studies, all changes were small and not associated with adverse clinical outcomes

96. Maternal administration of MgSO4 for eclampsia have a small negative effect on FHR, variability, and accelerative pattern, but is not sufficient clinically to warrant medical intervention.