Nifedipine
Nifedipine is a common drug used to treat a variety of disorders from hypertension and angina to preventing premature labour in pregnancy (Aedla, N, et al. 2012). It originated in the early 1970’s from the works of Bayer, who developed the short-acting formulation that proved to be successful in controlling high blood pressure, however due to its side effects, was modified to a long-acting formula which produced fewer side effects and is commonly used in modern obstetric practice (Aedla, N, et al. 2012).
The use of Nifedipine is well established for controlling hypertension in those who struggle with hypertensive disorders, including pregnant women and the wider population, (Aedla, N, et al. 2012) although the focus of this assignment will be the use of Nifedipine to prevent premature labour. According to MIMS Online (2016), this is technically an ‘off the label’ use, however it is common practice in Australia and outlined as an appropriate treatment option for premature labour prevention in the evidence based South Australian Perinatal Practice Guidelines (SAPPG) (South Australian Maternal and Neonatal Clinical Network (SAMNCN) 2014). According to MIMS Online (2016) Nifedipine falls into drug category C. …show more content…
Category C drugs are suspected of causing fetal harm during pregnancy that may be reversible, however the use of category C drugs is somewhat contradicted and a risks verse benefits model of care should be consulted before the use of Nifedipine (Australia, M 2016 & Department of Health Therapeutic Goods Administration (TGA) 2011). Due to ethical limitations on drug trials in pregnancy, there is very limited evidence on the safety, efficacy and ideal dosing regime for many drugs in pregnancy. Hence why drug categorisation is a necessity during pregnancy to aid in the limitation of fetal exposure to potentially teratogenic substances (TGA 2011). Mechanism of Drug The pharmacological actions of Nifedipine alter the action of normal calcium ion channels within muscle cells in the human body. Nifedipine binds to and blocks the flow of positive calcium ions into L-type calcium channels within smooth muscle, acting as a calcium ion antagonist. Consequently resulting in a reduction of calcium in smooth muscle, therefore causing smooth muscle relaxation (Australian Medicines Handbook Pty Ltd (AMH) 2016 & Aedla, N, et al. 2012). Calcium is an essential component of muscle contraction (Marieb, EN & Hoehn, KN 2013), therefore when Nifedipine is used; it can prevent premature labour by exerting a tocolytic effect thus preventing uterine activity necessary for labour to progress (Aedla, N, et al. 2012). A Cochrane Review on calcium channel blockers (CCBs), specifically Nifedipine and their success in preventing preterm labour was published in 2014 and discussed the benefits of the use of Nifedipine reducing neonatal morbidity (Flenady, V et al. 2014). However, it was also discussed that further research is necessary in terms of dosing regimes and long-term effects on the infant through to the childhood years, thus Nifedipine is a category C drug. Although, it is still recommended by the SAPPG’s on account of the benefits outweighing the potential risks associated with preterm labour (Flenady, V et al. 2014 & South Australian Maternal and Neonatal Clinical Network (SAMNCN) 2014). Metabolism of Drug Once administered orally, Nifedipine is rapidly absorbed from the gastrointestinal tract (GIT) however it has significant first-pass effect through the liver that subsequently converts 40% of the drug into inactive products that are excreted in the urine (Clark, SM et al. 2015 & Smith, P et al 2000). Additionally, Nifedipine also has moderately low bioavailability at approximately 50% (Clark, SM et al. 2015). Depending on the formulation of Nifedipine, Clark (2015) discusses that the half-life can range from 2.5 hours to 11 hours in non-pregnant, healthy patients, however this is decreased in pregnant women, as is the peak serum concentration. This is likely caused by the physiological increase in blood volume during pregnancy (Clark, SM et al. 2015). Whereas, the increased rate of clearance of Nifedipine can be attributed to the increased hepatic drug-metabolising enzyme, CYP3A4 and the increase in hepatic blood flow (Bryant, B & Knights, K 2015 & Smith, P et al 2000) during pregnancy. It has therefore been suggested that the dose of Nifedipine is increased in pregnant women and the interval times between doses should be shorter to enhance the therapeutic effect (Clark, SM et al. 2015). Indications for Use
Nifedipine is a common drug used to treat a variety of disorders from hypertension and angina to preventing premature labour in pregnancy (Aedla, N, et al. 2012). It originated in the early 1970’s from the works of Bayer, who developed the short-acting formulation that proved to be successful in controlling high blood pressure, however due to its side effects, was modified to a long-acting formula which produced fewer side effects and is commonly used in modern obstetric practice (Aedla, N, et al. 2012).
The use of Nifedipine is well established for controlling hypertension in those who struggle with hypertensive disorders, including pregnant women and the wider population, (Aedla, N, et al. 2012) although the focus of this assignment will be the use of Nifedipine to prevent premature labour. According to MIMS Online (2016), this is technically an ‘off the label’ use, however it is common practice in Australia and outlined as an appropriate treatment option for premature labour prevention in the evidence based South Australian Perinatal Practice Guidelines (SAPPG) (South Australian Maternal and Neonatal Clinical Network (SAMNCN) 2014). According to MIMS Online (2016) Nifedipine falls into drug category C. …show more content…
Category C drugs are suspected of causing fetal harm during pregnancy that may be reversible, however the use of category C drugs is somewhat contradicted and a risks verse benefits model of care should be consulted before the use of Nifedipine (Australia, M 2016 & Department of Health Therapeutic Goods Administration (TGA) 2011). Due to ethical limitations on drug trials in pregnancy, there is very limited evidence on the safety, efficacy and ideal dosing regime for many drugs in pregnancy. Hence why drug categorisation is a necessity during pregnancy to aid in the limitation of fetal exposure to potentially teratogenic substances (TGA 2011). Mechanism of Drug The pharmacological actions of Nifedipine alter the action of normal calcium ion channels within muscle cells in the human body. Nifedipine binds to and blocks the flow of positive calcium ions into L-type calcium channels within smooth muscle, acting as a calcium ion antagonist. Consequently resulting in a reduction of calcium in smooth muscle, therefore causing smooth muscle relaxation (Australian Medicines Handbook Pty Ltd (AMH) 2016 & Aedla, N, et al. 2012). Calcium is an essential component of muscle contraction (Marieb, EN & Hoehn, KN 2013), therefore when Nifedipine is used; it can prevent premature labour by exerting a tocolytic effect thus preventing uterine activity necessary for labour to progress (Aedla, N, et al. 2012). A Cochrane Review on calcium channel blockers (CCBs), specifically Nifedipine and their success in preventing preterm labour was published in 2014 and discussed the benefits of the use of Nifedipine reducing neonatal morbidity (Flenady, V et al. 2014). However, it was also discussed that further research is necessary in terms of dosing regimes and long-term effects on the infant through to the childhood years, thus Nifedipine is a category C drug. Although, it is still recommended by the SAPPG’s on account of the benefits outweighing the potential risks associated with preterm labour (Flenady, V et al. 2014 & South Australian Maternal and Neonatal Clinical Network (SAMNCN) 2014). Metabolism of Drug Once administered orally, Nifedipine is rapidly absorbed from the gastrointestinal tract (GIT) however it has significant first-pass effect through the liver that subsequently converts 40% of the drug into inactive products that are excreted in the urine (Clark, SM et al. 2015 & Smith, P et al 2000). Additionally, Nifedipine also has moderately low bioavailability at approximately 50% (Clark, SM et al. 2015). Depending on the formulation of Nifedipine, Clark (2015) discusses that the half-life can range from 2.5 hours to 11 hours in non-pregnant, healthy patients, however this is decreased in pregnant women, as is the peak serum concentration. This is likely caused by the physiological increase in blood volume during pregnancy (Clark, SM et al. 2015). Whereas, the increased rate of clearance of Nifedipine can be attributed to the increased hepatic drug-metabolising enzyme, CYP3A4 and the increase in hepatic blood flow (Bryant, B & Knights, K 2015 & Smith, P et al 2000) during pregnancy. It has therefore been suggested that the dose of Nifedipine is increased in pregnant women and the interval times between doses should be shorter to enhance the therapeutic effect (Clark, SM et al. 2015). Indications for Use