maternal pharmacokinetic and dynamic review lecture 1.pptx

medicine for midwife

1. Review of Maternal Pharmacokinetics and pharmacodynamics ABDI NUH ANDI HASSAN

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. 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. 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. Drug therapy during pregnancy

6. Drug therapy during pregnancy Pharmacotherapy during pregnancy, childbirth and lactation may be necessary for a number of reasons: ?

7. Chronic illness or disability , particularly:

8. Conti…

9. 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.

10. Pharmacotherapeutic decision-making during pregnancy, childbirth and lactation.

11. 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

12. Physiological changes and drug toxicity.

13. 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

14. 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.

15. 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).

16. 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.

17. 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.

18. Drug toxicity during pregnancy

19. 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.

20. 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.

21. Cross-placental transfer of drug molecules and their metabolites

22. 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 .

23. Functions of placenta Attach the fetus to the uterine wall Provide nutrients to the fetus Allow the fetus to transfer waste products to the mother's blood

24. Transport Across the Placenta

25. Exchange of materials across the placenta Mother to Foetus Foetus to Mother Oxygen Glucose Amino acids Lipids, fatty acids & glycerol Vitamins Ions; Na, Cl , Ca , Fe Alcohol, nicotine + other drugs Viruses Antibodies Carbon dioxide Urea Other waste products

26. 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.

27. 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

28. Excretion of drugs in breast milk

29. 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.

30. Drug safety + ABCDX

31. 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.

32. Description Category 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

33. 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.

34. 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.

35. Any questions?