What are “Contraindications” ? Why is any drug considered as a contraindication?
There are people in different physiological conditions such as pediatrics, geriatrics, pregnant and lactating women, and people suffering from various disease conditions. Because their pharmacokinetic and pharmacodynamics characteristics are altered from typical people their body reactions for certain drugs can be vary. If any drug overweighs the Risk than its benefits (Risk>Benefit), these types of drugs are considered as “Contraindications”.
Why pregnant women are specially considered?
Pregnant women get medications for various health problems such as diabetes, morning sickness, high blood pressure. Some women tend to get over-the-counter medications for these issues without consulting a physician. This is unacceptable, because these drugs can affect the mother as well as the fetus really bad! The reason is, within this period, the physiology of the mother’s body is changed, and also these drugs can pass through the placenta and affect the fetus!
Does every drug pass through the placenta?
No. If the drug particle size is smaller, it has a more tendency to pass through. And if the drug is uncharged at the physiological PH, it has more tendency to pass through (charged drugs pass less). Furthermore, the higher the lipid solubility, the more its likely to pass through.
How can these drugs affect the mother and the fetus?
When the drugs pass through the placenta to the fetus, it may cause toxicity to the fetus. Specially during the organogenesis period, it’s more likely to cause teratogenicity to the fetus. Drugs reaching the embryo during this stage may result in spontaneous abortion, a sub lethal gross anatomic defect, or covert embryopathy.
In mother’s aspect, she also has altered pharmacokinetic and pharmacodynamics physiology in her body. During pregnancy, the cardiac output increases by 40%; the drug dosage requirements may increase; the plasma volume increases. Because of this, the serum albumin concentration decreases. Many plasma protein binding sites are occupied by hormones that are specially increased due to pregnancy. Therefore, the free drug concentration available in the plasma rises up. And this may cause several adverse effects on her.
Due to these issues, the Food and Drug Authority (FDA), has categorized the drugs that are used in pregnancy into 5 categories as A, B, C, D, and X. They range from the lowest risk category A to the highest risk category X. Category A, B, C consist of the drugs that do not show harmful effects on human fetus experimentally, but the animal studies have revealed some adverse effects to the fetus by category C drugs.
Category D drugs have evidence of human fetal risk, but the benefits to the mother may be acceptable despite the risk to the fetus. (ex: life threatening situations or a serious disease for which safer medications can’t be used).
🔹 Tetracycline- Cause Hypospadias (at 1st trimester), Inguinal hernia, limb hypoplasia, teeth discoloration (2nd, 3rd trimesters), cataracts, cleft palates, spina bifida, polydactyly to the fetus. And liver toxicity, irreversible shock to the mother.
🔹 Phenytoin- cause congenital abnormalities, hemorrhage at birth, and neuro development abnormalities to the fetus. And folic acid deficiency to the mother.
Among these categories the category “X” consists of the contraindications. These drugs experimentally overweigh the risk than the benefits desired from it. (Risk> Benefit).
🔹 Warfarin- It is a teratogen which is responsible of the inhibition of clotting factors, that can lead to internal bleeding of the fetus while the inhibition of osteocalcin causes lower bone growth. Also it can induce spontaneous abortion.
🔹 Cytotoxic drugs (Methotrexate)- Can lead to birth abnormalities that affect in child’s physical and mental development. It can cause neural tube defects that affect the brain, spine or spinal cord.
🔹 Lithium- Taking lithium in 1st trimester of pregnancy may increase the risk of the heart development of the baby, and heart defects may occur. Also congenital malformations may occur.
🔹 Radiopharmaceuticals-The possible effects associated with prenatal radiation exposure include immediate effects or increased risk for cancers later in life. The 1st trimester is the stage that the rate of growth is rapid, and the fetus is at its most radiation sensitive stage.
This issue also happens to lactation women. Because the drugs can pass through the breast milk, the toxicities can occur in baby. Therefore, it’s always better to consult a physician before taking any medication specially if you are a pregnant or a lactating woman.