Saturday, 23 March 2019

Chosing antihypertensives preconceptionally or at early pregnancy?? Safety of antihypertensives in pregnancy


Q.1. Why antihypertensives in pregnancy period? Antihypertensive therapy is used to protect the mother from ill effects   of severe hypertension  such as A) cerebrovascular   hemorrhage  B) cardiac failure  C) abruption and D) eclampsia. But one should make it clear that the value of antihypertensives in mild   moderate  disease in unclear because ,maternal  death and stroke is rare and eclampsia is unusual in these  women with essential hypertension. By that I don’t mean that you should not prescribe antihypertensives in esn HTN in preg women ,.But we have to be judicious as I am quoting below.
. Q.2. Should we use antihypertensive drugs   at all in mild hypertension ? Unfortunately  drug  treatment  for mild preeclampsia has been disappointing as shown by the Cochrane review  which  concluded  that treatment   induced decrease  in blood pressure  may  adversely affect  fetal  growth.
Q.3. At what BP we should initiate antihypertensives if not startd  already?? The risk benefit profile  in mild to moderate  disease needs to be re examined  and my dear members may I draw your kind attention that  ACOG recommends anti hypertensives  only when diastolic blood pressure is 105-110  mm Hg or higher although many clinicians start anti hypertensives at diastolic  blood pressure of 100 or higher.
Q.4: What is the aim then ? What is the message to practicing Obstetricians then?  There is consensus that antihypertensives  should be  prescribed when systolic blood pressure  is > 160 mm Hg or diastolic blood pressure is > 110 mm Hg
Q.12:-When Methyldopa becomes as  first line ?? Where an adrenoceptor antagonist is contraindicated methyldopa is used as first line therapy.
Q.12: Which agent shpoluld never be used?  ACE   inhibitors must not be used antetatally   especially  during second  and third trimester. Reported complications with ACE inhibitors  include contractures persistent PDA pulmonary hypoplasia respiratory  distress syndrome prolonged neonatal  hypertension and neonatal death.


Methyldopa (a2 Adrenergic agonists   central inhibition of sympathetic drive ) –Dosage – 250 -500 mg  po q6-12 h – Max dose 4 g/ 24h  -- benefits – Proven to be  safe , and efficacious decreased second  trimester fetal losses – Adverse effects – Maternal fatigue depression orthostatic hypotension xerostomia elevated liver  enzymes

Nifedipine ( calcium channel  blocker inhibits  extracellular calcium influex into  cells through  slow calcium channels )—Dosage 10-20 mg oral  q4-6 hour –Max Dose  240 mg /24h –Benefits –Effective for refractory HTN Potent  tocolysis in preterm labor lowers  BP  without  effects on blood flow in the umbilical artery –Adverse effects – Maternal effects flushing headache  palpitations interaction with magnesium sulfate  profound hypotension no increase risk of congenital  malformations
Labetalol (a and B) blocker reduction in cardiac output )  Dosage 100 mg po bid  Max dose  2400 mg/ 24 hour  - Benfits  - Effective BP control lowers BP without altering cerebral autoregulation lower risk of arrhythmia than  with vasodilatory agents , Adverse  effects – Fetal bradycardia  nenonatal  hypoglycemia impaired  fetal response  to hypoxia decreased uteroplacental   flow avoid in patients  with asthma  and CHF.
Oral  or intravenous therapy can be decided on the basis of the  presentation . hypertensive crisis can be classified as:
Hypertensive urgency  which is defined as severely elevated blood pressure  is responsible for signs symptoms or laboratory evidence of end organ damage. Rapid but controlled reduction in BP  intravenous   medication  is required. One should target to reduce MABP by 25% within hour  of  presentation   . If  initial  reduction  is well  tolerated  reduction to normal levels can be achieved over ensuing  24 hours.
The objective of treating acute severe hypertension is to prevent potential cerebrovascular  and cardiovascular complications such as encephalopathy hemorrhage  by some for sustained systolic BP  values of at least 180mmHg and for sustained  diastolic values of at least 110 mm Hg The  definition of   sustained hypertension is not clear ranging from 30 mm  to 2 hours . Others  use mean arterial pressure to guide  management. Antihypertensive  therapy  should be initiated urgently if mean arterial pressure  is more than 140 mm Hg  as above this cerebral  auto regulation of pressure  is not reliable. Agents used for treatment   of acute severe hypertension  should be initiated at low doses given that women with preeclampsia  are intravascular  volume depleted and are at increased risk for hypotension.  A latest review has generated uncertainty about the agent of first choice among them bur labetalol and nifedipine are usually preferred as compared to hydralazine  which is associated with more adverse outcomes.
What are the therapeutic options  in the treatment  of acute severe hypertension
Labetalol Onset of action – 5 min , Dosage- 20 mg iv bolus then 40 mg after 10 min then 80 mg every  10 min upto a maximum total  dose of 220 mg a continuous  infusion of 1-2 mg/ min may also be used  ,

Nifedipine –onset  of action – 10 min ,Dosage- 10mg po can be repeated in 30 min then 10-20 mg q4 -6h with a maximum dose of 240 mg/24 hours


Nitroglycerine –onset  of action, dosage – Initial infusion rate of 10 mg/ min  and titrated to the desired pressure by doubling  the dose very five minutes ,  Adverse effects – Methemoglobinemia may result  from high dose iv infusion

Hydralazine –onset  of action – 10-20 min , Dosage-  5-10 mg iv every  15-20  min until a desired  response  is obtained , Adverse effects – Profound maternal hypotension and Oliguria fetal  distress . Maternal  pyridoxine responsive polyneuropathy and drug  induced  lupus neonatal thrombocytopenia and lupus


Sodium nitroprusside – onset of action 0.5 to5  min  , dosage – 0.2 -5 ug /kg/ min infusion for use in refractory hypertension , adverse effects – Fetal  cyanide and thiocyanate  toxicity

The blood pressure and pulse rate should be monitored every 5 min and the goal  of therapy is to decrease the diastolic BP  to 90-100 mm Hg.



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