prenatal pharmacology (2)

8/12/2019 Prenatal Pharmacology (2)

1/23

Dr. Sowmya B.

P. G. Student

Dept. of Pharmacology

KVGMC, Sullia

SPECIAL CONCERNS OF PRENATAL

PHARMACOLOGY


2/23

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


3/23

PHARMACOKINETIC VARIATIONS

Understanding the pharmacokinetic changes that

take place during pregnancy provides practitioners

insight into the treatment of these women.

Absorption

Distribution

Metabolism

Excretion


4/23

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


5/23

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


6/23

Clearance of drugs like rifampicin is decreased due to the cholestatic

property of oestrogen.

Metabolism


7/23

Elimination

C.O -renal blood flow and GFR- elimination

of drugs- Subtherapeutic drug levels

Example, penicillin and digoxin


8/23

Modify the dose while treating the pregnant women


9/23

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


10/23

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


11/23

Fetal albumin

Fetal fat tissue 15% of the body weight at term - limits thedistribution of fat soluble drugs like - barbiturates, GA

FETAL DISTRIBUTION


12/23

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


13/23

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.


14/23

PHARMACODYNAMIC ASPECTS OF DRUG

ACTION ON THE FETUS

Maternal drug action

Therapeutic action on the fetus

Toxic action on the fetus Teratogenic action


15/23

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)


16/23

THERAPEUTIC ACTION ON THE FETUS

Fetus as a target of drug action

Eg. Corticosteroids-used to stimulate fetal lung

maturation in expected premature birth


17/23


18/23

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


19/23

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


20/23


21/23


22/23

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.


23/23

prenatal pharmacology (2)

Documents