CELL BIOLOGY AND BIOCHEMISTRY

DIGITAL ASSIGNMENT 3

RIVIEW ARTICLE

PROJECT REPORT SUBMITTED TO :

DR. GAYATHRI M.

BY:

MANASWINI MAHALA (18BCB0060)

SHUBHANGI SINGH ( 18BCB0018)

SUCHARITA PAUL ( 18BCB0078)

ANUPAMA GAUTAM (18BCB0019)

EFFECT OF DIFFERENT TYPES OF DRUGS IN
PREGNANCY

ABSTRACT
Pregnancy is a special physiological condition where drug treatment presents a special concern because
the physiology of pregnancy affects the pharmacokinetics of medications used and certain medications
can reach the fetus and cause harm. Total avoidance of pharmacological treatment in pregnancy is not
possible and may be dangerous because some women enter pregnancy with medical conditions that
require ongoing and episodic treatment (e.g. asthma, epilepsy, hypertension). Also during pregnancy
new medical problems can develop and old ones can be exacerbated (e.g. migraine, headache) requiring
pharmacological therapy. The fact that certain drugs given during pregnancy may prove harmful to the
unborn child is one of the classical problems in medical treatment. In 1960's pregnant ladies who
ingested thalidomide gave birth to children with phocomelia. Various other examples of teratogenic
effects of drugs are known. It has been documented that congenital abnormalities caused by human
teratogenic drugs account for less than 1% of total congenital abnormalities. Hence in 1979, Food and
Drug Administration developed a system that determines the teratogenic risk of drugs by considering
the quality of data from animal and human studies. FDA classifies various drugs used in pregnancy into
five categories, categories A, B, C, D and X. Category A is considered the safest category and category X
is absolutely contraindicated in pregnancy. This provides therapeutic guidance for the clinician.

MECHANISM :

CAFFEINE AND NICOTINE :

"Pregnant women who take painkillers could be harming the fertility of their unborn sons," states the
Mail Online's report on a new study about the potential effects of exposure to painkillers during
pregnancy.They found that foetal human tissue exposed to paracetamol and ibuprofen for a week had
reduced numbers of germ cells – the cells that develop into sperm and eggs.

The researchers said their results "raise concerns" about the use of painkillers during pregnancy, as they
could cause the unborn child to have fertility problems.Prolonged use of paracetamol and other
painkillers during pregnancy may pose a health risk to baby boys, warn experts.
Danish research suggests the drugs raise the risk of undescended testicles in male babies, a condition
linked to infertility and cancer in later life.

Current guidelines advise that paracetamol is usually safe to take during pregnancy but at the lowest
effective dose for the shortest possible time. Ibuprofen should be avoided during pregnancy unless you
have been specifically advised to take it by your doctor.

Non steroidal anti-inflammatory drugs like ibuprofen are also very effective but these are best avoided
in early pregnancy and may upset your stomach,’ says Dr Roger Marwood, co-founder of The Doctor and
Daughter's Guide to Pregnancy.

It’s best to steer clear of any stronger medication while you’re pregnant so your baby’s development
isn’t affected in any way.

The Department of Health also advises against taking ibuprofen in the third trimester of pregnancy as
there is a risk of heart problems that cause high blood pressure in your unborn baby’s lungs and may
reduce the amount of amniotic fluid in which your baby floats.

Prescription painkillers, or opioids, are commonly used to treat pain. Opioid painkillers include drugs
such as hydrocodone (Vicodin), oxycodone (OxyContin), codeine, and morphine. In addition to their
inclusion in the many opioid analgesic formulations, opioids are also found in some prescription cough
medicines 1.

Opioids exert their painkilling effects by binding to opioid receptors in the brain. For many people, the
pain relief experienced after taking opioids is often accompanied with euphoric or rewarding sensations
that promote continued use. However, these pleasurable effects come with some serious dangers as use
increases. Too-high or too-frequent doses can result in respiratory depression, coma, and even death.

A developing fetus who is exposed to opioid painkillers in utero is at a higher risk for complications.

A population-based study led by the CDC found a link between birth defects and opioid painkillers taken
during pregnancy. The CDC study found an association between the following conditions in babies and
opioid painkiller use by the mother 1:

Spina bifida.

Hydrocephaly (excessive fluid in the baby’s brain).

Glaucoma.

Gastroschisis (a hole in the abdominal wall from which the baby’s intestines stick out).
Congenital heart defects.

Ventricular and atrial septal defects.

Tetralogy of Fallot.

Pulmonary valve stenosis.

In this study, researchers noted a significant increase in the number of heart defects a baby had,
including hypoplastic left heart syndrome 1. Hypoplastic left heart syndrome is a condition in which the
left side of the heart doesn’t develop correctly.

One study found that when women used opioid painkillers right before they got pregnant or during the
first trimester of their pregnancy, they were twice as likely to have a baby born with a heart defect 1.

Taking opioids during pregnancy might also cause 3:

Preterm birth (before 37 weeks’ gestation).

Neonatal abstinence syndrome (NAS).

Neonatal Abstinence Syndrome (NAS)

When a woman uses opioid painkillers during pregnancy, it can cause her baby to develop neonatal
abstinence syndrome (NAS)—essentially, opioid withdrawal.

NAS can occur when a pregnant woman takes opioids, such as 5:

Codeine.

Oxycodone (OxyContin, Percocet).

Methadone.

Hydrocodone (Lortab, Norco, Vicodin).

NAS symptoms can begin 1-3 days after the baby is born. If doctors believe that the baby may be at risk
for more complications, they may have the baby stay at the hospital for up to a week for medical
supervision and monitoring.

Symptoms of NAS might include 5:

Blotchy skin coloring (mottling).

Rapid breathing.

Stuffy nose and/or sneezing.

Sweating.

Vomiting.

Diarrhea.

Excessive crying or high-pitched crying.

Irritability.

Sleep problems.

Excessive sucking.

Fever.

Hyperactive reflexes.

Hypertonicity (pathologically increased muscle tone).

Trembling (tremors).

Seizures.

Convulsions.

THALIDOMIDE - AFFECTING EMBRYO

• The mechanisms behind birth defects induced by thalidomide involve its teratogenic ability to bypass
an intrinsically important embryonic defense system that is responsible for preventing toxic substances
from entering embryonic cells as well as escorting tagged toxicants out of the cell.

• These crucial homeostatic cellular functions are carried out by efflux transporters found in the
cytoplasmic membrane.

• Efflux transporters are members of the ATP-binding cassette (ABC) protein family, which use primary
active transportation by means of ATP hydrolysis to provide energy for the translocation of toxic
compounds out of the cell.
• Although the transport system is usually quite effective, it is entirely dependent upon these proteins
to recognize and interact with the introduced chemical.

• Thalidomide is not, however, recognized by the transporters and therefore binding does not occur,
allowing the chemical to remain within the cell.

• Once thalidomide evades the efflux transportation system, it is capable of inducing oxidative stress to
reactive oxygen species (ROS) dependent signaling pathways in the apical ectodermal ridge (AER),
responsible for limb bud growth, as well as in the zone of polarizing activity (ZPA), responsible for the
establishment of the anterior-posterior axis in the limb bud.

• The mechanisms of thalidomide’s teratogenicity were identified through an experiment

conducted by Jürgen Knobloch and Ulrich Rüther in 2007 on human skin cells and chick
embryos.

PAIN-KILLERS:
• Prescription painkillers, or opioids, are commonly used to treat pain. Opioid painkillers include drugs
such as hydrocodone (Vicodin), oxycodone (OxyContin), codeine, and morphine. In addition to their
inclusion in the many opioid analgesic formulations, opioids are also found in some prescription cough
medicines 1.

• Opioids exert their painkilling effects by binding to opioid receptors in the brain. For many people, the
pain relief experienced after taking opioids is often accompanied with euphoric or rewarding sensations
that promote continued use. However, these pleasurable effects come with some serious dangers as use
increases. Too-high or toofrequent doses can result in respiratory depression, coma, and even death.

COCAINE:
• Cocaine hydrochloride is usually sold as a crystalline powder that is taken
intravenously or intranasally. Crack cocaine, the second form, is created by mixing
cocaine with either ammonia or sodium bicarbonate with water and then heating the
mixture. Crack cocaine is water-insoluble and is smoked, spreading more rapidly in the
human body than cocaine hydrochloride.
• Cocaine works as a central nervous system stimulant by interfering with the nervous
cells' reuptake of norepinephrine and dopamine, which are chemicals involved in the
transmission of neurological signals, or neurotransmitters; slowed reuptake causes
levels of such neurotransmitters to increase in the user.

• Dopamine accumulation leads to a sense of ecstasy, increased alertness and energy,

heightened sexual stimulation, and reduced fatigue. At the same time, increased levels
of norepinephrine enable cocaine to accumulate at nerve terminals, which in pregnant
women results in the constriction of maternal blood vessels (vasoconstriction) and in
high blood pressure (hypertension) at the site where the uterus and placenta attach
together.

• This disruption of blood flow to the uterus and placenta may also result in maternal
tachycardia, a condition that manifests in an abnormally high heart rate, an increased
risk for ventricular arrhythmias, and amnion rupture, which in turn causes limb defects in
the foetus.

Most women who are addicted to cocaine are of childbearing age. Estimates suggest
that about 5 percent of pregnant women use one or more addictive substances,and
there are around 750,000 cocaine-exposed pregnancies every year. Most women who
are addicted to cocaine are of childbearing age. Estimates suggest that about 5 percent
of pregnant women use one or more addictive substances,25 and there are around
750,000 cocaine-exposed pregnancies every year.

Cocaine use during pregnancy is associated with maternal migraines and seizures,
premature membrane rupture, and separation of the placental lining from the uterus
prior to delivery. Pregnancy is accompanied by normal cardiovascular changes, and
cocaine use exacerbates these—sometimes leading to serious problems with high
blood pressure (hypertensive crises), spontaneous miscarriage, preterm labor, and
difficult delivery.

Babies born to mothers who use cocaine during pregnancy are often prematurely
delivered, have low birth weights and smaller head circumferences, and are shorter in
length than babies born to mothers who do not use cocaine.Dire predictions of reduced
intelligence and social skills in babies born to mothers who used crack cocaine while
pregnant during the 1980s—so-called "crack babies"—were grossly exaggerated.
However, the fact that most of these children do not show serious overt deficits should
not be over interpreted to indicate that there is no cause for concern.
Using sophisticated technologies, scientists are now finding that exposure to cocaine
during foetal development may lead to subtle, yet significant, later deficits in some
children. These include behaviour problems (e.g., difficulties with self-regulation) and
deficits in some aspects of cognitive performance, information processing, and
sustained attention to tasks—abilities that are important for the realization of a child’s
full potential.Some deficits persist into the later years, with prenatally exposed
adolescents showing increased risk for subtle problems with language and
memory. Brain scans in teens suggests that at-rest functioning of some brain regions—
including areas involved in attention, planning, and language—may differ from that of
non-exposed peers.More research is needed on the long-term effects of prenatal
cocaine exposure.

Using substances like cocaine during pregnancy may also impact a mother’s likelihood
of carrying her baby to full-term . “Full-term” is defined as birth between 37 and 41
weeks. The last few weeks of pregnancy are important stages in a baby’s brain
development; a baby’s brain at 35 weeks is only two-thirds the weight of what it will be
at 39 or 40 weeks . A shorter pregnancy could negatively affect a baby’s final growth
spurt.

The impact of maternal cocaine use during pregnancy on infant development has been
widely researched during the past two decades. Many investigators have focused on
the possible physical and cognitive effects of prenatal exposure to cocaine on the
development of infants and young children.

The findings of studies examining potential cognitive outcomes among cocaine-exposed

children have been mixed and somewhat inconsistent (Lester, LaGasse, & Brunner,
1997) with recent reviews and meta-analyses suggesting that cocaine’s effects on these
outcomes may be subtle (Lester, LaGasse, &Seifer 1998).

At the same time, there is increasing recognition that cocaine may have significant
influences on regulatory behaviors. For instance, in their review, Lester et al.
(1997) reported that of 9 studies focusing on regulatory processes among cocaine-
exposed infants, seven reported significant group differences.
These regulatory difficulties include poorer state regulation, increased arousal from
sleep, and differential physiological responding to sensory challenges, as measured by
both heart rate (HR) and cortisol levels, beginning in the neonatal period and persisting
throughout the first year of life (Bendersky& Lewis, 1998a,b; Brown, Bakeman, & Coles,
1998; DiPietro, Suess, Wheeler, Smouse, &Newlin, 1995; Gingras et al., 1995; Karmel&
Gardner, 1996; Mayes, Bornstein, Chawarska, & Granger, 1995; Mayes, Bornstein,
Chawarska, & Granger, 1996; Regalado, Schechtman, Del Angel, & Bean,
1995; Regalado, Schechtman, Del Angel, & Bean, 1996).

These findings are particularly significant when considering the fact that achievement of
self-regulation is an important precursor to normal development.

In fact, managing arousal in order to respond appropriately to environmental demands

is among the earliest skills to develop during infancy. Thus, problems in this area may
have implications for later functioning.

Although prenatal exposure to cocaine has increasingly been linked to poorer regulation
during infancy, the association between prenatal exposure to cocaine and infant
regulatory processes may not always be simple or direct.

Arousal and regulatory processes during infancy are complex developmental

phenomena that are influenced by a variety of endogenous and exogenous factors.

In fact, the neural regulation of autonomic functioning is sensitive to a range of perinatal

factors that may disrupt the development of self-regulatory skills (Porges, 1996)
including a range of substances used during pregnancy as well as other infant and
maternal risk variables.

For example, heart rate (HR) is believed to reflect autonomic function and neurological
integrity in young infants. Specifically, HR is predictive of later cognitive development
and may impact reactivity to external stressors.

An elevated resting HR is indicative of a higher level of physiological arousal which

impacts both the quality and quantity of infant responsiveness to stimulation. Infants
who are more highly aroused prefer less intense stimulation (e.g., Karmel, Gardner,
&Magnano, 1991). Because an infant’s approach toward or withdrawal from stimulation
may reflect the infant’s attempts to regulate its own level of arousal, HR functions as an
important index of physiological regulation during early infancy.
CONCLUSIONS
The unique nature of physiology of pregnancy presents challenges for pharmaceutical treatment of
chronic and acute disorders and for symptom management of many complaints associated with
pregnancy. It is the responsibility of all clinicians including pharmacists to counsel patients with
complete, accurate and current information on the risks and benefits of using medications during
pregnancy. Counselling women who have had exposure to drugs about risk of teratogens involves
accurately identifying exposure and quantifying the magnitude of exposure. This may be straightforward
for prescribed drugs but it can be much more difficult with ethanol or other illicit substances or OTC
drugs. Also, when selecting drugs to be used in pregnancy effectively, drugs that have been in use for a
long time are often preferable because fetal safety has been established even though newer alternatives
may be available
REFERENCES:
1.scopus journals

2.elziver