Download Drugs Safety in Pregnancy

Drug Use in
Pregnancy and lactation
Drug use during pregnancy and lactation •
requires special consideration because both
the mother and the child are affected.
Few drugs are considered safe, and drug •
use is generally contraindicated.
Many pregnant or lactating women take •
drugs for acute or chronic disorders or
habitual use of alcohol and tobacco.
Drugs taken by a pregnant woman
reach the fetus primarily by crossing
the placenta, the same route taken by
oxygen and nutrients, which are
needed for the fetus's growth and
development. Drugs that a pregnant
woman takes during pregnancy can
affect the fetus in several ways
Principles of Therapy: Pregnancy
• Give medications only when clearly
indicated, weighing benefits to the mother
against the risks to the fetus.
• Any drugs used during pregnancy should
be given in the lowest effective doses and
for the shortest effective time.
• The choice of drug should be based on the
stage of pregnancy and drug information.
Principles of Therapy: Pregnancy
(Cont,d)
• During the first trimester, an older safe
drug is preferred over a newer drug of
unknown teratogenicity.
• Counsel pregnant women about the use of
immunizations during pregnancy.
Principles of Therapy: Pregnancy
(Cont,d)
• Live virus vaccines (measles, mumps, polio,
rubella) should be avoided because of
possible harmful effects to the fetus.
• Inactive virus vaccines (influenza, rabies,
hepatitis B) and toxoids (diphtheria,
tetanus) are considered safe for use.
• Hyperimmune globulins can be given to
pregnant women who are exposed to
hepatitis B, rabies, tetanus, or varicella.
Principles of Therapy: Pregnancy
(Cont,d)
• Hyperimmune immunoglobulin are IGIVs
with high titers of antibodies against viruses
or toxins.
• Hyperimmune IGIVs are available for
hepatitis B virus, rabies, tetanus, and
digoxin overdose.
• Intravenous administration of the
hyperimmune globulins reduces risk or
severity of infection.
Principles of Therapy: Lactation
• Most systemic drugs taken by the mother
reach the infant in breast milk.
• For some, the amount of drug is too small
for others effects are unknown or
potentially adverse.
• Give medications only when clearly
indicated.
• For contraindicated drugs, the mother
should stop the drug or stop breast
feeding.
Principles of Therapy: Lactation
(Cont,d)
• Any drugs used during lactation should be given
in the lowest effective dose for the shortest
effective time.
• Stopping breast feeding during maternal drug
therapy is not recommend unless necessary.
• In some instances, mothers may pump and
discard breast milk while receiving therapeutic
drugs, to maintain lactation.
• Women with HIV infection should not breast-feed.
The virus can be transmitted to the nursing
infant.
Physiologic – Pharmacokinetics Changes
• Physiologic Change:
– 50% Increase in plasma volume and body
water.
• Pharmacokinetic Change:
– Water soluble drugs are distributed and
“diluted” more than in the nonpregnant state.
– Drug dosage requirements may increase.
– This effect may be offset by other
pharmacokinetic changes of pregnancy.
Physiologic – Pharmacokinetics Changes
(Cont,d)
• Physiologic Change:
– Increased weight (~14 Kg) and body fat
• Pharmacokinetic Change:
– Fat-soluble drugs are distributed more widely.
– Drugs distributed to fatty tissues tend to
linger in the body because they are slowly
released from storage sites.
Physiologic – Pharmacokinetics Changes
(Cont,d)
• Physiologic Change:
– Decreased serum albumin.
– The rate of albumin production is increased.
However, serum levels fall because of plasma volume
expansion.
– Many plasma protein-binding sites are occupied by
hormones that increase during pregnancy.
• Pharmacokinetic Change:
– More free drug is available for therapeutic or adverse
effects on the mother and for placental transfer to the
fetus.
– A given dose of a drug is likely to produce greater
effects than it would in the nonpregnant state.
Protein binding Pic.
Physiologic – Pharmacokinetics Changes
(Cont,d)
• Physiologic Change:
– Increased renal blood flow and glomerular filtration
rate secondary to increased cardiac output.
• Pharmacokinetic Change:
– Increased excretion of drugs by the kidneys,
especially those excreted primarily unchanged in the
urine (digoxin, lithium).
– In late pregnancy, the increased size of the uterus
decreases renal blood flow in supine position.
– This results in decreased excretion and prolonged
effects of renally excreted drugs.
Drug Effects On The Fetus
• The fetus which is exposed to any drugs
circulating in maternal blood, is very sensitive to
drug effects
• Drugs may cause teratogenicity or other adverse
effects.
• Drug teratogenicity most likely occurs during the
first trimester, when fetal organs are formed.
• During the 2nd and 3rd trimesters, drug adverse
effects are: growth retardation, respiratory
problems, infection, or bleeding.
Drug Effects On The Fetus
(Cont,d)
• Overall, effects are determined mainly by:
– The type and amount of drugs
– The duration of exposure
– The level of fetal growth and development
when exposed to the drugs.
• Both therapeutic and nontherapeutic
drugs may affect the fetus.
Fetal Therapeutics
• A few drugs are given to the mother for
their therapeutic effects on the fetus,
They include:
– Digoxin for fetal tachycardia or heart failure
– Levothyroxine for hypothyroidism
– Penicillin for exposure to maternal syphilis
– Prenatal Betamethasone to promote
surfactant production in preterm infants.
Dietary Supplements
• Pregnancy increases nutritional needs and
vitamin and mineral supplements are commonly
used.
• Folic acid supplementation is especially
important, to prevent neural tube birth defects
(spina bifida). Such defects occur early in
pregnancy, often before the woman realizes
she is pregnant.
• In addition, pregnancy increases folic acid needs
by 5 to 10 fold and deficiencies are common.
*They can act directly on the fetus, causing damage,
abnormal development (leading to birth defects), or
death.
*They can alter the function of the placenta, usually
by causing blood vessels to narrow (constrict) and
thus reducing the supply of oxygen and nutrients to
the fetus from the mother. Sometimes the result is
a baby that is underweight and underdeveloped.
*They can cause the muscles of the uterus to contract
forcefully, indirectly injuring the fetus by reducing
its blood supply or triggering preterm labor and
delivery
Some of the fetus's blood vessels are
contained in tiny hairlike
projections (villi) of the placenta
that extend into the wall of the
uterus. The mother's blood passes
through the space surrounding the
villi (intervillous space). Only a
thin membrane (placental
membrane) separates the mother's
blood in the intervillous space from
the fetus's blood in the villi. Drugs
in the mother's blood can cross this
membrane into blood vessels in the
villi and pass through the umbilical
cord to the fetus
•
Drug Categories in Pregnancy
The Food and Drug Administration (FDA) created the
following rating system in 1979 to categorize the
potential risk to the fetus for a given drug.
Category A: Controlled human studies have
demonstrated no fetal risk
Category B: Animal studies indicate no fetal risk,
but no human studies
OR adverse effects in animals , but
adequate studies in pregnant women have not
demonstrated a risk to the fetus during the first
trimester of pregnancy and there is no evidence of
risk in the last two trimester
Category C:
studies,
No adequate human or animal
•
OR adverse fetal effects in animal
studies, but no available human data..The benefits
from the use of the drug in pregnant women may
be acceptable despite its potential risks.
Category D: Evidence of fetal risk, but benefits
outweigh risks.
Category X: Evidence of fetal risk. Risks outweigh
any benefits
Pregnancy-Associated Problems
• Anemia
• Constipation
• Gastroesophageal Reflux
• Gestational Diabetes
• Nausea & Vomiting
• Pregnancy-Induced Hypertension
Anemia
• Three types of anemia are common during
pregnancy:
Results from expanded blood
volume
• Iron preparations should
be given with food to
decrease gastric irritation.
• Citrus juices enhance
absorption
Physiologic –
Iron- deficiency –
Megaloblastic –
Caused by folic acid deficiency
Constipation
Constipation occurs from decreased •
peristalsis.
Preferred treatment, if effective, is to •
increase exercise and intake of fluids and
high-fiber foods.
If a laxative is required, a bulk forming •
agent is the most physiologic because it is
not absorbed.
A stool softener or an occasional saline •
laxative (milk of magnesia) may also be
Constipation
(Cont,d)
Mineral oil should be avoided because it
interferes with absorption of fat-soluble
vitamins.
Reduced absorption of vitamin K can lead to
bleeding in newborns.
Castor oil should be avoided because it can
cause uterine contractions.
Strong laxatives or any laxative used in excess
may initiate uterine contractions and labor.
•
•
•
•
Gastroesophageal Reflux
Often occurs in the later months of •
pregnancy.
Nonpharmacologic interventions (eating •
small meals; avoiding gas producing food
and drinks) are recommended.
Antacids may be used if necessary. •
Because little systemic absorption occurs.
Cimetidine, ranitidine, or sucralfate may •
also be used.
Gestational Diabetes
Some women first show signs of diabetes during
pregnancy. This is called gestational diabetes.
•
Women without risk factors, or whose initial test
was normal, should be tested between 24 and
28 weeks of gestation.
•
Initial management includes nutrition and
exercise interventions and calorie restriction for
obese women.
•
If drug is necessary, recombinant human insulin
is needed to keep blood sugar levels as nearly
normal as possible.
•
Gestational Diabetes
(Cont,d)
Oral antidiabetic drugs are generally
contraindicated, although acarbose, metformin,
and miglitol are almost safe.
•
These women may revert to a nondiabetic state
when pregnancy ends.
•
They are at increased risk for development of
overt diabetes within 5 to 10 years.
•
Gestational diabetes usually subsides within 6
weeks after delivery.
•
Nausea & Vomiting
Dietary management and maintaining fluid and
electrolyte balance are recommended.
•
Antiemetic drugs should be given only if nausea
and vomiting are severe enough to threaten the
mother’s nutritional status.
•
Dimenhydrinate, 50 mg every 3 to 4 hours, are
thought to have low teratogenic risks.
•
Pyridoxine (vitamin B6) also may be helpful 10
to 25 mg daily.
•
Pregnancy-Induced Hypertension
Pregnancy-induced hypertension includes •
preeclampsia and eclampsia.
They endanger the lives of mother and •
fetus.
Preeclampsia occurs during the last 10 •
weeks of pregnancy, during labor, or
within the first 48 hr after delivery.
It is manifested by edema, hypertension, •
and proteinuria.
Pregnancy-Induced Hypertension
(Cont,d)
Drug therapy includes IV hydralazine or •
labetalol for blood pressure and
magnesium sulfate for seizures.
Eclampsia, occurs if preeclampsia is not •
treated effectively.
Delivery of the fetus is the only known •
cure for preeclampsia or eclampsia.
A Folic acid Category*
dednemmocer ADR gnideecxe esod C/A(Vitamin A Category*
)esod
dednemmocer ADR gnideecxe esodC/A yrogetaC Vitamin C*
)esod
dednemmocer ADR gnideecxe esod C/A yrogetaC Vitamin E*
)esod
dednemmocer ADR gnideecxe esodC/A Vitamin B Category*
)esod
Vitamin D CategoryC*
C yrogetaC Vitamin K*
Drug Effects In Lactation
Most drugs have not been tested in •
nursing women and their effect on infant
is unknown.
Maternal drug use during lactation should •
be cautious.
There is some degree of risk with any •
systemic medication ingested by the
mother.
Drug Effects In Lactation
(Cont,d)
The dose reaching the infant is proportional •
to the mother’s drug concentration.
In many instances, the infant may not •
receive sufficient drug to produce adverse
effects.
Most OTC and prescription drugs taken only •
when needed, are thought to be safe.
Drug Effects In Lactation
(Cont,d)
Safe Drugs In Lactation (NOT In Pregnancy):
Antibacterials (Penicillins And Cephalosporins) –
Anticoagulants (Heparin Or Warfarin) –
Antihypertensives (ACE Inhibitors, Ca2+ Blockers) –
Caffeine (In Moderate Amounts) –
Corticosteroids (Prednisolone or Inhaled Products) –
Decongestants (Nose Drops or Spray) –
Acetaminophen –
Cromolyn –
•
Drug Effects In Lactation
(Cont,d)
Safe Drugs In Lactation (NOT In Pregnancy):
Digoxin –
Famotidine –
Ibuprofen –
Insulin –
Levothyroxine –
Mini-pill OCPs –
Antiepileptics –
Antihistamines –
•
Drug Effects In Lactation
(Cont,d)
Drugs to be used with caution in lactation:
Aspirin
Beta blockers (acebutolol, atenolol)
Corticosteroids (systemic drugs may suppress growth
and interfere with endogenous corticosteroid
production)
Diuretics
Dyslipidemics (cholestyramine [may cause severe
constipation in the infant],statins)
Methadone
Metoclopramide
Theophylline
–
–
–
–
–
–
–
–
•
Drug Effects In Lactation
(Cont,d)
Drugs to be used with caution in lactation:
Alcohol (within 2 hours of breast-feeding)
Aluminum-containing antacids
Amantadine
Antianxiety agents (benzodiazepines)
Antibacterials (chloramphenicol, metronidazole,
nitrofurantoin, sulfonamides)
Antidepressants (bupropion, tricyclics, and selective
serotonin receptor inhibitors)
Antihistamine (clemastine)
Antipsychotics (older or typical agents)
–
–
–
–
–
–
–
–
•
Drug Effects In Lactation
(Cont,d)
Contraindicated drugs in lactation (if they •
are required, breast feeding should be
stopped):
Amiodarone –
Antibacterials (fluoroquinolones, tetracyclines, –
trimethoprim [interfere with folic acid
metabolism in the infant])
Antineoplastics –
Bromocriptine (decreases milk production) –
Drug Effects In Lactation
(Cont,d)
Contraindicated drugs in lactation
(Cont,d)
Cyclosporine –
Drugs of abuse (amphetamines, cocaine, heroin, –
marijuana, phencyclidine, nicotine)
Ergotamine –
Isotretinoin –
Lithium –
Phenytoin –
Caffeine (large amounts) –
•
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