Pharmacology OBG.pptx explained the mechanics of medicine explained.

the basics of pharmacology is crucial to manage the obstetrical conditions.

1. Pharmacology

2. By the end of this session, you will be able to….

3. Match the drug class to the definition and the example drug

4. Pharmacokinetics

5. Absorption The movement of a drug into the bloodstream following administration The absorption process affects the bioavailability of a drug – how much of a drug is available to reach and influence the target site The rate and the amount of absorption (how quickly and how much of it is absorbed) influence the choice of drug formulation and the route of administration Hepatic first-pass metabolism is when a fraction of a drug administered via the PO route is metabolised in the liver before its distribution

6. Factors affecting absorption

7. Absorption considerations in obstetrics Reduced gastric motility (due to increased progesterone and decreased motilin) in pregnancy results in….. Reduced PO drug absorption rate but potentially increased absorption amount Pain also reduces gut motility i.e labour

8. Distribution Is the movement of the drug around the body Most drugs need to bind to a plasma protein to be transported around the circulation. Only the free drug can have an effect on the target. As this free drug is used up the plasma proteins release more bound drug to maintain the equilibrium.

9. Distribution considerations in midwifery Up to 50% increase in plasma volume during pregnancy may dilute the concentration of drugs. No corresponding increase in plasma protein….potential for loading doses? The fetus and breast milk are distinct body compartments so drugs will be distributed to them too. Indirect fetal harm i.e reduction in maternal circulation and reduced oxygenation = IUGR Direct fetal harm i.e from substances crossing the placental barrier = Thalidomide (congenital abnormality)

10. Drug exposure and timing in pregnancy Some drugs present different risks according to trimester of exposure Pre-embryonic stage : miscarriage Embryonic stage : greatest risk of congenital abnormality Fetal stage : Neonatal bleeding and CNS damage Drugs are usually split into 3 categories: Consistent evidence of teratogenic effects High index of suspicion of adverse fetal effects but limited data Effects in pregnancy are unknown (majority of drugs on the market)

11. Metabolism Metabolism is the first part of drug elimination from the body where enzymes mainly found in the liver detoxify and then conjugate (make water soluble) the drug ready for elimination. This is done by a group of enzymes called cytochromes or CYP enzymes Most drugs are excreted in urine so the body needs to make them water soluble so the kidneys can filter them into the urine.

12. Metabolic considerations Liver function is affected by: age, liver damage and genetic variation Liver enzymes can be inhibited by some drugs and food i.e cranberry or grapefruit juice, resulting in…. Some drugs also induce liver enzymes resulting in…… * *

13. Metabolic considerations in obstetrics Varies between women… Some drugs render the oral contraceptive pill and emergency hormonal contraception (morning-after pill) ineffective due to enzyme induction. i.e antiepileptic Increased bodily hormones create an increased workload for the liver and for some women there is a resulting increased metabolic activity resulting in faster elimination of drugs, reducing the time the drugs are effective for. Conversely, some enzymes can have reduced metabolic rates in pregnancy

14. Excretion consideration in obstetrics Increased fluid volume & waste products – increased workload for the kidneys GFR increase to twice normal rate in pregnancy – but no need to adjust dosage except for penicillins , to maintain an adequate bactericidal level Drugs which are transferred to the fetus are eliminated very slowly due to: Lower fetal liver enzyme activity Drugs eliminated through the fetal kidney, into the amniotic fluid, are then swallowed by the fetus

15. The removal of drug metabolites from the body by: sweat, tears, saliva, breath, breast-milk, faeces But mostly they are filtered out of the circulation and into urine by the nephrons in the kidneys by the processes of: glomerular filtration – small molecule ‘sieving’ and tubular secretion. Glomerular filtration rate (GFR) is the volume of fluid filtered into all the nephrons each minute and is considered the best measure of renal function (Jordan, 2010). Renal function can be affected by: BP, dehydration, diuretics, UTIs and Acute Kidney Injuries (AKI) Excretion

16. Drug elimination half life Half life is the time taken for the concentration of a drug in the blood to reduce to half its maximum value. Measured in hours. A drug with an 8 hour half life and maximum level of 16mg: 16mg to 8mg = 8 hours 8mg to 4 mg = 8 hours 4mg to 2mg = 8 hours 2mg to 1mg = 8 hours 1mg to 0.5mg = 8 hours So it takes 40 hours to get close to being cleared from the plasma when one dose is taken.

17. Coffee…..?

18. Pharmacodynamics

19. How do Drugs Work? In our bodies, cells signal each other (chemically or electronically) to perform physiological functions. Drugs mimic or block these signals to affect the function of the organs and body systems Cell signals are picked up by receptors on other cells and drugs can also bind to these receptors Drugs can initiate a response and initiate a physiological process - Agonists Or stop a cell signal from reaching its receptor and prevent physiological process- Antagonists

20. Agonists Antagonists

21. Methyldopa works by stimulating alpha receptors in the brain ( specificity -only for this receptor) This causes the brain to send nerve signals to the blood vessels that makes them relax and widen. The result of this is a lowering of blood pressure. Example: Methyldopa

22. Why are NSAIDs unsafe in pregnancy? Ibuprofen

23. Adverse reactions (side effects) Caused by drugs acting at sites other than the target site, surplus free drug circulating as all receptors are saturated drug molecules find other sites on which to exert the same effect. No drug has only one effect. Type A – Known/predictable/common – e.g. constipation ferrous sulphate [effects on other systems] or hypotension caused by labetalol – [exaggeration of intended effect]. Account for 80% of ADRs Increases as dose increases Type B – Idiosyncratic/unpredictable e.g. anaphylactic shock How do you report a suspected drug reaction to the manufacturer?

24. Anaphylaxis A rare but potentially fatal hypersensitivity reaction that can occur following the administration of any drug, as well as food, fluid or topical applications, taking anything from several minutes to several hours to appear Likely to occur when Sudden onset and rapid advancement of symptoms Life-threatening airway and/or breathing and/or circulation problems Mucosal and/or skin changes (although may be absent in up to 20% cases)