antihypertensive and anticonvulsant drugs in obg

PRESENTED BYMS.SANTOSH KUMARIM.SC.NURSING 1ST YEAR

DRUG PRESENTATION ON

ANTIHYPERTENSIVE DRUGS AND ANTICONVULSANT

DRUGS

ANTIHYPERTENSIVE DRUGS DURING PREGNANCY

OVERVIEW OF DRUG CATEGORY AND absorption IN PLACENTA

CATEGORIZATION OF DRUGS IN PREGNANCY ( ACCORDING TO FDA)

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.

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

HYPERTENSION

Hypertension is defined as having a blood pressure greater than 140/90 mm Hg

Normal blood pressure is 120/80 mm/hg.

GESTATIONAL HYPERTENSION

is the development of new hypertension in a pregnant woman after 20 weeks.

Rise of blood pressure to 140/90mm/hg.

CATEGORY OF ANTIHYPERTENSIVE DRUGS ACCORDING TO FDA

Category B. Category C. Category D.

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.

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.

These drugs are used in two clinical conditions.

Pre- eclampsia and eclampsia. Chronic hypertension.

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.

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.

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.

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.

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

SODIUMNITROPRUSSID-E.

0.5- 5 MIN 0.25-5 ug/kg/min IV

Other drugs have failed.

Other drugs failed.

COMMONLY USED DRUGS

CATEGORY C SympatholyticsMethyl-dopaReserpine Calcium channel blockerNifedipineNicardipine

CATEGORY B Andrenergic receptor blocking

agentsLabetalolPropranolol VasodilatorsHydralazineNitroglycerinSodium nitroprusside

CATEGORY D 5. ACE inhibitors/ ARB.CaptoprilTrlmisartanAvoided during pregnancy because it

can cause various kind of deformities in fetus.

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.

METHYLDOPAMechanism 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.

SIDE EFFECTSMaternal- Postural hypotension, haemolytic

anaemia, sodium retension. Nausea, vomiting, diarrhea,

constipation. Bradycardia, angina, weight gain. Drowsiness, dizziness, headache,

depression, excessive sedation.Fetal – Intestinal ileus.

Nursing considerationAssess 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.

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.

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.

Indication: Essential hypertension.Contraindications 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.

Side effects

Maternal - hypotension, tachycardia, arrhythmia, palpation, lupus like syndrome, fluid retention, muscle cramps, headache, dizziness, depression, anorexia, diarrhea.

Fetal: reasonably safe. Neonatal: thrombocytopenia.

Nursing ConsiderationAssess 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.

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. 

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

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.

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. 

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.

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.

NIFEDIPINEPreparations - 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.

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.

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

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

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.

Evaluate Therapeutic response: Decreased BP,

absence of bleeding. Edema – feet and legs. Hydration status.

NITROGLYCERINEMechanism 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

Nursing ConsiderationAssessment 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.

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.

Side effect/ Adverse ReactionsMaternal 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.

Nursing ConsiderationAssess 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.

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.

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.

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.

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.

ACE inhibitors/ Angiotensin-II receptor blocker (ARBMechanism 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.

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.

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.

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.

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.

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.

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%).

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.

ANTICONVULSANTS DRUGS

DURING PREGNANCY

INTRODUCTION Due to eclampsia. Other

causes are – epilepsy, meningitis, cerebral malaria and cerebral tumours.

Proved by history, examination and investigations.

Commonly used anticonvulsant is magnesium sulfate.

Diazepam, Phenytoin and Phenobarbitone are also used.

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

DEMINERALIZATION.

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.

MAGNESIUM SULFATE

Action – Decrease acetylcholine in

motor nerve terminals, which is responsible for anticonvulsant properties, thereby reduces neuromuscular irritability.

It also decreases intracranial edema and helps in diuresis.

Its peripheral vasodilatation effect improves the uterine blood supply.

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.

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.

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.

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.

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.

Nursing ConsiderationsAssess 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.

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.

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.

Evaluate Mental status, sensorium,

memory. Discontinue infusion if

respirations are below 12/min or fetal distress.

Teach Client/ Family On all aspects of the drug:

action, side effects and symptoms of hypermagnesemia.

To remain in bed during infusion.

DIAZEPAM ( VALIUM)Action - Depresses subcortical levels of

CNS,anticonvulsant, and antianxiety.Dosage and Route of

Administration PO, 2 to 10 mg tid – qid.

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.

Side effect Mother – Hypotension,

dizziness, drowsiness, headache.

Fetus - Respiratory depressant effect, which may last for even three weeks after birth.

Nursing ConsiderationAssess BP in lying and standing

positions, if systolic pressure falls 20 mmHg, hold drug and inform physician.

Blood studies: CBC. Hepatic studies.

Administer IV into large vein to decrease

chance of extravasation. PO with milk or food to avoid

GI symptoms.

Provide Assistance with ambulation

during beginning therapy since drowsiness and dizziness may occur.

Safety measures include side rails.

Evaluate Therapeutic response Mental status, sleeping

pattern. Physical dependence,

headache, nausea, vomiting.

Teach Patient/ Family Drug may be taken with food. To avoid alcohol ingestion. Not to discontinue medication

abruptly. To rise slowly as fainting may

occur. 

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.

Side effects Maternal Hypotension, cardiac

arrhythmias and phlebitis at injection site.

Fetal Prolonged use by epileptic

patients may cause craniofocal abnormalities, mental retardation, microcephaly and growth deficiency.

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.

Evaluate Mental status, memory. Respiratory depression. Sore throat, brushing.Teach Patient/ Family All aspect of drug

administration, when to notify physician.

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.

Side effects Maternal – Sedation,

drowsiness, hangover headache, hallucination.

Fetal – Withdrawal syndrome. 

Nursing considerationAssess Blood studies, liver function

tests during long term treatment.

Therapeutic level 15 to 40 mg/ml.

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.

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

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).

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

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.