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3 - Pharmacology relevant to pregnancy
- from Section 1 - Basic science, epidemiology and service organization
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- By Christopher Kelly, University Hospital of South Manchester, Malachy Columb, University Hospital of South Manchester
- Edited by Kirsty MacLennan, Kate O'Brien, W. Ross Macnab
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- Book:
- Core Topics in Obstetric Anaesthesia
- Published online:
- 05 December 2015
- Print publication:
- 26 October 2015, pp 13-23
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Summary
There are specific issues with regard to therapeutics and pharmacology in the expectant mother and during the postpartum period. There are general changes in the pharmacokinetics and pharmacodynamics, considerations relating to the placenta, potential effects on the fetus and impacts on breastfeeding.
Pharmacokinetics
Bioavailability
The absorption of a drug is the method by which it moves into the body and into the circulating blood, and is characterized as the bioavailability. This can be via a wide range of routes, those used most commonly by the anaesthetist are intravenous (IV), inhalational, epidural, intrathecal, oral, intramuscular (IM), sublingual, intranasal, rectal and transdermal. Despite the enhanced cardiac output in pregnancy, the absorption of drugs is minimally affected, but pregnancy-induced emesis may reduce the bioavailability of orally administered drugs. The increased minute ventilation associated with pregnancy can speed the onset and offset of inhalational agents.
Volume of distribution (VD)
The distribution of a drug throughout the body is dependent on various factors: physicochemical characteristics of the drug (molecular size, lipid solubility, ionization and protein binding), regional blood flow and any cellular transport mechanisms. The volume of distribution (VD) can be greatly affected by pregnancy. Increases in circulating blood volume and total body water provide a larger VD for most drugs. Pregnancy alters the plasma protein profile, potentially changing binding characteristics and the fraction of free drug available for action. Increased cardiac output will speed the distribution of drugs.
Placental transfer
The fetus is also, in effect, an additional compartment into which drugs may distribute. The factors affecting the extent to which drugs cross the placenta into fetal circulation are similar to those for any phospholipid membrane bilayer. Placental transfer will be facilitated for more lipid-soluble drugs, compared to hydrophilic polar or ionized molecules. Likewise, the greater the proportion that is free drug or in the unbound state, the faster it will equilibrate. The extents to which the drug is ionized and protein bound may be different in mother and fetus because of the reduced pH in the fetus, and this may impact on the effective concentration gradients. This situation may change or be exacerbated by labour, during which maternal and fetal acidoses may develop.
Metabolism
Metabolism of drugs is largely unaffected by normal pregnancy. It is possible that the pathological state of HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome may impair liver function and thus the metabolism of drugs.
Chapter 18 - Mechanical ventilation
- from Section 3 - Special critical care tools and techniques
- Edited by Marc van de Velde, Helen Scholefield, Lauren A. Plante
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- Book:
- Maternal Critical Care
- Published online:
- 05 July 2013
- Print publication:
- 04 July 2013, pp 187-199
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Summary
This chapter reviews the major physiological adaptations during pregnancy and also highlights changes in the reference ranges of common laboratory values encountered in pregnancy. Pregnancy induces a myriad of changes involving the cardiovascular system, respiratory system, gastrointestinal and hepatobiliary systems and genitourinary system. Pregnancy is associated with an overall increase in the serum concentrations of total cortisol, free cortisol, aldosterone, deoxycorticosterone, corticosteroid binding globulin, and adrenocorticotropic hormone. Pituitary enlargement occurs in pregnancy by estrogen mediated proliferation of prolactin-producing cells. During the first trimester of pregnancy, total thyroxine and total tri iodothyronine concentrations begin to increase and peak at mid-gestation, primarily as a result of increased production of thyroid-binding globulin. The immunological adaptations of pregnancy, particularly at the maternal-fetal interface, comprise complex mechanisms that enable the fetus to grow while preventing the mother from rejecting the fetus.
Contributors
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- By Victoria M. Allen, Frederic Amant, Sarah Armstrong, Thomas F. Baskett, Michael A. Belfort, Meredith Birsner, Renee D. Boss, Leanne Bricker, Josaphat K. Byamugisha, Giorgio Capogna, Michael P. Casaer, Frank A. Chervenak, Vicki Clark, Filip Claus, Malachy O. Columb, Charles Cox, Jean T. Cox, Vegard Dahl, John Davison, Jan Deprest, Clifford S. Deutschman, Roland Devlieger, Karim Djekidel, Steven Dymarkowski, Roshan Fernando, Clare Fitzpatrick, Sreedhar Gaddipati, Thierry Girard, Emily Gordon, Ian A. Greer, David Grooms, Sina Haeri, Katy Harrison, Edward J. Hayes, Michelle Hladunewich, Andra H. James, Tracey Johnston, Bellal Joseph, Erin Keely, Ruth Landau, Stephen E. Lapinsky, Susanna I. Lee, Larry Leeman, Hennie Lombaard, Stephen Lu, Alison MacArthur, Laura A. Magee, Paul E. Marik, Laurence B. McCullough, Alexandre Mignon, Carlo Missant, Jack Moodley, Lisa E. Moore, Kate Morse, Warwick D. Ngan Kee, Catherine Nelson-Piercy, Clemens M. Ortner, Geraldine O’Sullivan, Luis D. Pacheco, Fathima Paruk, Melina Pectasides, Nigel Pereira, Patricia Peticca, Sharon T. Phelan, Felicity Plaat, Lauren A. Plante, Michael P. Plevyak, Dianne Plews, Wendy Pollock, Laura C. Price, Peter Rhee, Leiv Arne Rosseland, Kathryn M. Rowan, Helen Ryan, Helen Scholefield, Neil S. Seligman, Nadir Sharawi, Alex Sia, Bob Silver, Mieke Soens, Ulrich J. Spreng, Silvia Stirparo, Nova Szoka, Andrew Tang, Kha M. Tran, Els Troost, Lawrence C. Tsen, Derek Tuffnell, Kristel Van Calsteren, Marc Van de Velde, Marcel Vercauteren, Chris Verslype, Peter von Dadelszen, Carl Waldman, Michelle Walters, Linda Watkins, Paul Westhead, Cynthia A. Wong, Gerda G. Zeeman, Joost J. Zwart
- Edited by Marc van de Velde, Helen Scholefield, Lauren A. Plante
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- Book:
- Maternal Critical Care
- Published online:
- 05 July 2013
- Print publication:
- 04 July 2013, pp ix-xiv
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