prenatal pharmacology (2)
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Dr. Sowmya B.
P. G. Student
Dept. of Pharmacology
KVGMC, Sullia
SPECIAL CONCERNS OF PRENATAL
PHARMACOLOGY
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INTRODUCTION
Pregnancy is a special physiological condition where drug
treatment presents a special concern because
1. The physiological changes of pregnancy affects the
pharmacokinetics of medications used2. Drugs are given to treat the mother but the fetus is always a
recipient
Avoiding medications when pregnant may be desirable, it is
often not possible and may be dangerous
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PHARMACOKINETIC VARIATIONS
Understanding the pharmacokinetic changes that
take place during pregnancy provides practitioners
insight into the treatment of these women.
Absorption
Distribution
Metabolism
Excretion
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Absorption:
Progesterone - Gastric emptying time - especially in 3
rd
trimester.Eg. Digitoxin, salicylates, and phenytoin
C.O and tidal volume - absorption of drugs administered byinhalation route. Eg. Volatile anesthetic (halothane) dose requirement
Concurrent use of vitamins, calcium , iron- binds/inactivates drugs
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Distribution:
in the plasma volume by 30-50%
Plasma albumin level and binding capacity of plasma protein
free, unbound drug
available for metabolism & excretion
Clinical importance: While monitoring plasma concentrations of phenytoin
Body fat-se in volume of distribution fat soluble drugs
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Clearance of drugs like rifampicin is decreased due to the cholestatic
property of oestrogen.
Metabolism
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Elimination
C.O -renal blood flow and GFR- elimination
of drugs- Subtherapeutic drug levels
Example, penicillin and digoxin
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Modify the dose while treating the pregnant women
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PLACENTAL TRANSFER OF DRUGS
o Placenta as a barrier
o The rate of transfer depends on the chemical properties of the
drug,
o Protein binding
o Lipid solubility
o Molecular weight of the drug. Eg. Heparin
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PLACENTAL TRANSPORTERS
o Placental transporterssyncytiotrophoblast
o It may be preferable to treat pregnant women with anti cancerdrugs that are substrates for P- glycoprotein such as Paclitaxel,doxorubicin
o Viral protease inhibitors- substrate for P- glycoprotein- lowconcentration in the fetal blood- increases risk of verticaltransmission
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Fetal albumin
Fetal fat tissue 15% of the body weight at term - limits thedistribution of fat soluble drugs like - barbiturates, GA
FETAL DISTRIBUTION
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FETAL METABOLISM OF XENOBIOTICS/DRUGS
CYP3A7 is mostly expressed in the fetal liver and is
replaced at birth by CYP3A4.
CYP2C are absent in the fetal liver. Hydroxylation of
tolbutamide and demethylation of diazepam
CYP1A2 and CYP2D6 are not expressed in the fetus.
The N-demethylation of caffeine and theophylline is
deficient
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FETAL EXCRETION
The placenta is a major excretory organ. A trapping effect of drugs in the amniotic fluid - equilibrium
between fetal or maternal compartments occurs slowly.
Fetal swallowing may allow certain drugs to be recirculated
Eg. Accumulation of Ampicillin, penicillin, kanamycin,
gentamycin, sulfonamides and some of the cephalosporins.
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PHARMACODYNAMIC ASPECTS OF DRUG
ACTION ON THE FETUS
Maternal drug action
Therapeutic action on the fetus
Toxic action on the fetus Teratogenic action
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MATERNAL DRUG ACTION
Mother may need to take drugs for conditions that arise
during pregnancy. These drugs may affect the fetus or
fetal drug metabolism
Example- Pregnancy induced heart failure (digitalis anddiuretics) pregnancy induced diabetes (insulin)
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THERAPEUTIC ACTION ON THE FETUS
Fetus as a target of drug action
Eg. Corticosteroids-used to stimulate fetal lung
maturation in expected premature birth
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TERATOGENIC ACTION
Teratogenic mechanisms produced by different drugs
are poorly understood and are probably multifactorial.
Defining a teratogen: Teratogens result in characteristic
malformation indicating selectivity of action of the drug
Act predominantly at a defined stage of fetal
development
Dose dependant
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ACTUAL PERIOD OF DEVELOPMENT OF
TERATOGENICITY
Critical period of organogenesis- 2nd& 3rdmonth of gestational
period
Critical period of some Congenital anomalies exceeds the end
of 3
rd
month, eg. Posterior cleft palate & hypospadias coversthe 12th- 14 thweeks of gestation & undescended testis in 7-9 &
PDA in 9-10 months
Critical period of each congenital Anomaly is separate
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SUMMARY
Avoid Unnecessary medication (OTC) during pregnancy
Proportion of free drug to protein-bound drug is altered; this has
important implications for therapeutic drug monitoring
Knowledge of pharmacokinetic changes is important for drugs with anarrow therapeutic window
The periconceptional folic acid can prevent the major proportion of
neural-tube defects.
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