Assessment of the knowledge of analgesic drug utilization among pregnant

women in Pakistan.
Introduction
Analgesic drug use is fairly frequent all around the world. The majority of
analgesics, such as paracetamol, and NSAIDs such as aspirin, diclofenac,
ibuprofen, and naproxen, are available without a prescription1, 2. These
medications are often used by people of all ages and genders, including women of
reproductive age, pregnant and breastfeeding women on the basis of self-
prescription3. Pregnancy is a unique physiological condition in which medication
intake offers a difficulty and a worry due to changed drug pharmacokinetics and
drugs potentially crossing the placenta and causing damage to the fetus3. Despite
the high safety profile that most over-the-counter medications have, some have
unknown safety or are documented to have harmful effects on fetuses 4. Certain
analgesics may increase the risk for adverse fetal and pregnancy outcomes, while
poorly managed pain can result in adverse maternal outcomes such as depression
and hypertension5. The majority of antacids, acetaminophen and other frequently
used over-the-counter drugs have an excellent safety track record. It is advisable
to use caution when using NSAIDs and other high-risk medications6. Paracetamol
is considered as the most safest analgesic and is available as over the counter
drug. But some studies have mentioned that even this can have some sort of risk
to fetus and should be used by pregnant women in lowest possible doses7, 8.
NSAIDs are used to reduce symptoms of inflammation as well as pain9. They
inhibit COX (cyclooxygenase) and ultimately their effects and side effects depend
upon their selective or non-selective inhibition pattern6. They have teratogenic
effects in animal studies while they have not shown any risk in human studies to
fetuses in first trimester10. All NSAIDs have the potential to cause premature
closure of the ductus arteriosus Botalli as well as nephrotoxicity, causing in
oligohydramnios11. Aspirin have dose-dependent side effects on the fetus. Both
aspirin and its metabolite, salicylate, are physiologically active in the fetus. Higher
doses of it can lead to toxicity while it is safer in low dose i.e. 150g/day5. It
effectively treats preeclampsia during pregnancy. Its recommended dose is 75-
150mg starting from 12th week of gestation till birth generally12. Diclofenac is most
commonly used NSAID. Its use in early and middle pregnancy has not shown
significant adverse effects but its use in late pregnancy can put in danger to both
mother and fetus. Also it can lead to higher risk of miscarriage and low birth
weight of infant13. However animal studies of diclofenac showed it to be high risk
drug14. Ibuprofen is also not advised during the latter trimester of pregnancy prior
to 30 weeks gestation because it may cause congenital malformations to fetus 15.
Similarly in case of naproxen limited research exists which suggests that it is not
harmful in first trimester11.
FDA has classified the drugs utilized in pregnancy into five categories based on
the risk factors in pregnancy. Categories include A,B,C,D, and X. Category A drugs
are considered highly safe drugs ,since evidence of safety exists. Category B drugs
are safe but there is no evidence of safety or risk of drugs in human studies. Risk
has been reported in animal studies in case of category C. Medicines in category D
have a definite record of endangering human fetuses but they can be used in
severe conditions where both mother and fetus are at risk as in instance of
epilepsy seizures. Category X is totally contraindicated due to its obvious
teratogenic toxicity16, 17.

Medication treatment in pregnancy cannot be totally avoided since some

Pakistan is a diverse country which has varying health care practices and cultural
beliefs. It requires deep study about analgesic drug utilization in pregnancy.
Cultural and social differences play role in selection analgesic drugs in Pakistan.
Traditional and natural remedies may conflict the pharmaceutical intervention.
Also, the availability and accessibility of analgesics and other drugs pose serious
challenges20. The regulatory framework and registration processes are different as
compared to other countries. Despite very little knowledge exists about this topic
in Pakistan, this article aims to address the gaps of research and shed light on
current understanding of analgesic use in pregnancy.

Background

Pregnancy related physiological and anatomical changes in the body can lead to
several pains. Being dynamic in nature , pregnancy presents several changes
throughout the period starting from fertilization until the parturition 21. These
changes can lead to several types of pains or can even amplify the already existing
pains22. This can lead to negative quality of life, disruption of social and personal
life. Tiredness, difficulty in sleep and reduction in physical ability are associated
with pregnancy pains23.The incidence of lower back pain lie between 66% to
71.3% and that of pelvic girdle pain ranges between 20% to 64.7%. as pregnancy
progresses ,the pain symptoms worsen. Normally both these pains are taken
together because they are unable to be distinguished , even woman herself is
unable to differentiate between these pains. The root cause of these pains is not
evident but there are two contributing factors including altered posture and the
hormone relaxin. The abdominal muscles which usually maintain the posture
become unable to perform their job due to overstretching of muscles and addition
of weight. As a result, the posture become altered in pregnancy. The other factor
is relaxin hormone which is released during pregnancy to make the ligaments soft
and thus help to facilitate easy delivery of baby through birth canal. But this
hormone also act on other joints and bones and cause painful inflammation 23.
Neuropathic pains such as carpal tunnel syndrome and meralgia paresthetica are
common issues. The incidence of these pains range in between 2.3% to 35%.
Reasons behind might include electrophysiological alterations in median nerve
and edema induced due to hormonal changes22. Intercoastal neuralgia occur as a
result of lesions and stretching at the level of intercoastal nerves due to enlarging
uterus.

Some of the women are reluctant to medication use in pregnancy due to fear of
toxicity to fetus. These fears ultimately have impact on patient compliance to
medication , which can reduce quality of life24. Because they are concerned about
utilizing drugs during pregnancy, some pregnant women may decide to live with
their discomfort rather than having it addressed. As a result, these women are
likely to get insufficient or no treatment for unpleasant conditions. Chronic, severe
pain that is not well treated has been associated to hypertension, anxiety, and
depression, none of which are conducive to a healthy pregnancy. But drug therapy
in pregnancy cannot be totally diminished because of illnesses and pains. Out of
10,8 pregnant women use medication either prescription only or over the counter
drugs. Fetus is more sensitive to damaging effects caused by drugs rather than
growing children because fetus does not have ability to fight against chemical
agents. Fetal abnormalities can either occur immediately or late after few months
or after few years. Thalidomide toxicity is seen as immediate response while
clonidine and diethylstilbesterol ADRs are observed after months and years
respectively. The medication dose, method of administration, duration of
treatment, and gestational age are all factors that influence teratogenic risk during
drug exposure. One drug may be safe at a certain dose while damaging at higher
dose and frequency. Also, the route can also determine the level of toxicity e.g.,
topical usage is much safer because of reduced systemic absorption and hence
diminished placental crossing of drug. So a careful balance between risk and
benefit ratio is required while medication use in pregnancy25.

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