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

6. 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

8. Factors affecting absorption

10. 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

11. 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.

12. 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)

13. 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)

15. 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.

16. 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……
* *

17. 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

20. 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:
1. Lower fetal liver enzyme activity
2. Drugs eliminated through the fetal kidney, into the
amniotic fluid, are then swallowed by the fetus

21.  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

22. 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.

25. Coffee…..?

26. Pharmacodynamics

27. 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

28. Agonists Antagonists

29. • 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

30. Why are NSAIDs unsafe in pregnancy?
Ibuprofen

31. 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?

32. 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)