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Pharmacodynamics and kinetics during pregnancy

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This presentation discuss the following objectives:
-Drug therapy during pregnancy, childbirth, and lactation.
-Physiological changes of drugs in pregnant women.
-Drug toxicity
-Cross-placental transfer of drugs
-Exertion of drugs in breast milk
-Drug safety + ABCDX

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Pharmacodynamics and kinetics during pregnancy

  1. 1. + Pharmacokinetics and pharmacodynamics during pregnancy Group: 3 Presented by: Reem Alyahya
  2. 2. + Introduction  Pregnancy, childbirth and lactation pose unique challenges in terms of drug therapy. The pregnant mother and her unborn child are exceptionally vulnerable from a physiological, clinical and ethical point of view. This warrants careful consideration of a number of important aspects, which could influence the decision for drug therapy,
  3. 3. + Objectives  Drug therapy during pregnancy, childbirth, and lactation.  Physiological changes of drugs in pregnant women.  Drug toxicity  Cross-placental transfer of drugs  Exertion of drugs in breast milk  Drug safety + ABCDX
  4. 4. + Why?  Drug therapy may pose a significant risk during each of the following vulnerable periods in the human reproductive cycle:  Fertilization of the ovum, followed by complete implantation.  The fetus.  The mother and infant.
  5. 5. +
  6. 6. + Drug therapy during pregnancy
  7. 7. + Drug therapy during pregnancy Pharmacotherapy during pregnancy, childbirth and lactation may be necessary for a number of reasons:
  8. 8. +  Chronic illness or disability, particularly: HIV infection and AIDS Diabetes mellitus
  9. 9. + Conti… Hypertension Asthma Epilepsy Migraine Mental health disorders long-term anticoagulant therapy use
  10. 10. + Conti…  Acute illness or trauma during pregnancy.  Pregnancy, labor related disorders and emergencies.  In a few instances, the fetus may actually be the target of the drug therapy administered to the mother, as part of a fetal therapy regimen.
  11. 11. + Pharmacotherapeutic decision- making during pregnancy, childbirth and lactation.
  12. 12. +
  13. 13. + The following aspects must be considered:  Physiological changes during pregnancy that may affect drug action and kinetics.  Drug toxicity during pregnancy.  Cross-placental transfer of drug molecules and their metabolites.  Excretion in breast milk.  Drug safety during pregnancy and lactation
  14. 14. + Physiological changes and drug toxicity.
  15. 15. + Physiological changes and drug toxicity.  Certain physiological changes during pregnancy have implications for drug therapy and may affect any of the four basic kinetic processes namely: Absorption Metabolism and elimination Excretion distribution
  16. 16. + Conti…  the following could alter the way in which drug molecules are handled by the body: 1- Increased progesterone levels:  Cause a decrease in gastrointestinal motility (with resultant constipation)  Decrease in oesophageal sphincter pressure (which causes heartburn).  In addition, placenta-derived human chorionic gonadotropin (hCG) causes nausea and vomiting.
  17. 17. +  The altered gastrointestinal functioning caused by these changes could influence the rate and extent of absorption of orally administered drugs.
  18. 18. + Conti… 2- Pregnancy also results in:  Increased lung perfusion and pulmonary alveolar drug transfer due to improved cardiac output.  Meaning that the absorption will be improved for drugs that are administered via the pulmonary route (i.e. nebulizers and inhalers).
  19. 19. + Conti… 3- Drug distribution may be affected due to:  The increased plasma volume that accompanies pregnancy and which may result in an increased volume of distribution (Vd) of certain drugs.  Pregnancy brings about a decreased blood albumin level, which could result in an increased fraction of free drug molecules.
  20. 20. + Conti… 4- Altered liver functioning may affect :  the plasma concentrations of drugs that follow hepatic metabolism. 5-The increased plasma volume, in turn:  Increases cardiac output (CO), renal blood flow and glomerular filtration rate (GFR).  This could increase the renal excretion of drugs that are significantly eliminated via this route.
  21. 21. + Drug toxicity during pregnancy
  22. 22. + Drug toxicity during pregnancy  Drugs may be toxic to the developing embryo and fetus.  The first trimester of pregnancy is of particular importance, since the teratogenic effects of certain drugs will influence normal development of the unborn child on a structural or functional level.
  23. 23. + Conti…  A teratogen is a drug or other chemical substance that may affect normal embryonic development and cause recognizable congenital defects.  Sufficient precautions in the form of patient education and the use of highly effective contraceptive methods must be taken when treating women of childbearing age or potential.
  24. 24. + Cross-placental transfer of drug molecules and their metabolites
  25. 25. + What is the placenta ?  The placenta is a flattened circular organ in the uterus of pregnant females that nourishes and maintains the fetus through the umbilical cord.
  26. 26. + Transport Across the Placenta
  27. 27. + Placenta & Drugs  The placenta provides a link between the circulations of two distinct individuals but also acts as a barrier to protect the fetus from xenobiotics in the maternal blood.  However, the impression that the placenta forms an impenetrable obstacle against most drugs is widely regarded as false.
  28. 28. + Placental exchange Most drugs with MW < 500 Da cross the placenta, And with MW > 1000 Da do not 1-size Non-ionized drugs tend to cross the placenta more easily than ionized drugs 2-Electrical Charge Traditionally it was taught that protein- bound drugs did not cross the placenta, however as these medications exist in equilibrium with non-bound versions, it appears that this is not true 3-Protein Binding While lipophilicity is generally advantageous with regards to placental transfer, extreme lipophilicity (ex. sufentanil) may impede transfer as highly lipophilic substances can accumulate in the placenta 4-Lipophilicity
  29. 29. + Placental Exchange
  30. 30. + Excretion of drugs in breast milk
  31. 31. + Excretion of drugs in breast milk  During lactation, drugs may pass from the bloodstream to the breast milk, especially if they are lipid-soluble or basic drugs  or if they are water-soluble molecules with a relative molecular mass of less than 100 Da.
  32. 32. + Drug safety + ABCDX
  33. 33. + FDA Categories of Drug Safety During Pregnancy  The pregnancy risk classification used by the US Food and Drug Administration (FDA) is often quoted and consists of five different categories, namely A, B, C, D and X.  Category A drugs are considered to be relatively safe during pregnancy  Category X drugs are absolutely contraindicated.
  34. 34. + DescriptionCategory Controlled human studies show no fetal risks; these drugs are the safest. A Animal studies show no risk to the fetus but no controlled human studies have been conducted, or animal studies show a risk to the fetus but well-controlled human studies do not. B No adequate animal or human studies have been conducted, or adverse fetal effects have been shown in animals but no human data are available C Evidence of human fetal risk exists, but benefits may outweigh risks in certain situations (eg, life-threatening disorders, serious disorders for which safer drugs cannot be used or are ineffective). D Proven fetal risks outweigh any possible benefit. X
  35. 35. + Conti…  It is of great importance to consult suitable drug references when dispensing medicines to pregnant or lactating mothers.  Known teratogens should obviously be avoided during pregnancy.
  36. 36. + examples of known teratogenic drugs to avoid during pregnancy EffectTeratogen Valproate is associated with neural tube defects, as is carbamazepine. Phenytoin may cause malformations in the central nervous system and adversely affect foetal growth. Anticonvulsants Warfarin is associated with haemorrhage in the foetus, as well as malformations in the central nervous system and skeletal system. Anticoagulants ACE inhibitors cause renal damage and may restrict normal growth patterns in the unborn child. Antihypertensive agents Premature closure of the ductus arteriosus.Non-steroidal anti-inflammatory Drugs
  37. 37. + Summary  The decision to choose pharmacotherapy during pregnancy will not always be an optional one. Drug treatment may be unavoidable, but will inevitably expose the unborn child to the effects.  Certain aspects and principles must be considered first, to ensure that the intervention is safe, rational and scientifically sound.
  38. 38. + References  the-fetus-structure-and-function.html   Pharmacotherapy during pregnancy, childbirth and lactation: principles to consider  bstetrics/drugs_in_pregnancy/drugs_in_pregnancy.html?qt=dru gs%20during%20pregnancy&alt=sh
  39. 39. + Any questions?
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This presentation discuss the following objectives: -Drug therapy during pregnancy, childbirth, and lactation. -Physiological changes of drugs in pregnant women. -Drug toxicity -Cross-placental transfer of drugs -Exertion of drugs in breast milk -Drug safety + ABCDX


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