Nifedipine

Pharmacokinetic interactions

Medicines that affect the metabolism of nifedipine

Nifedipine is metabolized by isoenzymes CYP3A3, CYP3A4, CYP3A5, which are located in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may affect the first pass effect through the liver (after oral administration) or the clearance of nifedipine.

Inducers of the CYP3A4 isoenzyme

Rifampicin

Rifampin is a potent inducer of the CYP3A4 isoenzyme. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness is reduced. Therefore, the simultaneous use of nifedipine with rifampicin is contraindicated.

Antiepileptic drugs that induce CYP3A4 (eg, phenytoin, carbamazepine, phenobarbital)

Phenytoin induces the CYP3A4 isoenzyme. With the simultaneous use of nifedipine and phenytoin, the bioavailability of nifedipine is reduced and its effectiveness is reduced. When using this combination simultaneously, it is necessary to monitor the clinical response to nifedipine therapy and, if necessary, increase its dose. If the dose of nifedipine is increased with simultaneous use of both drugs, the dose of nifedipine should be reduced after discontinuation of phenytoin. Clinical studies examining the potential interaction between nifedipine and carbamazepine or phenobarbital have not been conducted. Since both drugs reduce the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of a decrease in the concentration of nifedipine in the blood plasma and a decrease in its effectiveness cannot be excluded.

CYP3A4 isoenzyme inhibitors

Macrolide antibiotics (for example, erythromycin)

Clinical studies on the interaction of nifedipine and macrolide antibiotics have not been conducted. Some macrolides are known to inhibit the CYP3A4 isoenzyme. As a result, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and macrolide antibiotics.

Azithromycin, a macrolide antibiotic, does not inhibit the CYP3A4 isoenzyme.

HIV protease inhibitors (eg, ritonavir)

Clinical studies examining the interaction of nifedipine and HIV protease inhibitors have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. In addition, drugs of this class have been shown to suppress the metabolism of nifedipine mediated by the CYP3A4 isoenzyme in vitro.

When used simultaneously with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma cannot be ruled out due to a decrease in the effect of “first pass” through the liver and slower elimination.

Azole antifungals (eg, ketoconazole)

Clinical studies examining the interaction of nifedipine and azole antifungals have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. When used simultaneously with nifedipine, a significant increase in the systemic bioavailability of nifedipine is possible by reducing the effect of “first pass” through the liver.

Cimetidine and ranitidine

It has been established that cimetidine and ranitidine inhibit the CYP3A4 isoenzyme and cause an increase in the concentration of nifedipine in the blood plasma (by 80% and 70%, respectively), thereby enhancing its antihypertensive effect.

Diltiazem

Diltiazem reduces the clearance of nifedipine. This combination should be used with caution. A dose reduction of nifedipine may be required.

Fluoxetine

Clinical studies examining the interaction of nifedipine and fluoxetine have not been conducted. It is known that fluoxetine in vitro

suppresses the metabolism of nifedipine mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and fluoxetine.

Nefazodone

Clinical studies examining the interaction between nifedipine and nefazodone have not been conducted. Nefazodone is known to inhibit the metabolism of other drugs mediated by the CYP3A4 isoenzyme. Therefore, the possibility of increased plasma concentrations of nifedipine cannot be excluded with simultaneous use of nifedipine and nefazodone.

Quinidine

Increased plasma concentrations of nifedipine have been reported when administered concomitantly with quinidine. Therefore, careful monitoring of blood pressure is necessary when using quinidine and nifedipine simultaneously. If necessary, the dose of nifedipine should be reduced.

Quinupristin/dalfopristin

Concomitant use of quinupristin/dalfopristin may lead to increased plasma concentrations of nifedipine.

Valproic acid

Clinical studies examining the interaction of nifedipine and valproic acid have not been conducted. Since valproic acid increases the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of increasing the concentration of nifedipine in the blood plasma and enhancing its effectiveness cannot be excluded.

Grapefruit juice

Grapefruit juice inhibits the CYP3A4 isoenzyme and suppresses the metabolism of nifedipine. The simultaneous use of nifedipine with grapefruit juice leads to an increase in the concentration of nifedipine in the blood plasma and a prolongation of its action due to a decrease in the effect of “primary passage” through the liver and a decrease in clearance. This may enhance the antihypertensive effect of nifedipine. With regular consumption of grapefruit juice, this effect can last for 3 days after the last consumption of the juice. Consumption of grapefruit/grapefruit juice during treatment with nifedipine is contraindicated.

CYP3A4 isoenzyme substrates

Substrates of the CYP3A4 isoenzyme (for example, cisapride, tacrolimus, benzodiazepines, imipramine, propafenone, terfenadine, warfarin), when used simultaneously with nifedipine, may act as CYP3A4 inhibitors and increase the concentration of nifedipine in the blood plasma.

Cisapride

Concomitant use of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.

Effect of nifedipine on other drugs

Quinidine

Nifedipine causes a decrease in the concentration of quinidine in the blood plasma. After discontinuation of nifedipine, a sharp increase in the concentration of quinidine in the blood plasma may occur. Therefore, when using nifedipine as additional therapy or discontinuing nifedipine, the concentration of quinidine in the blood plasma should be monitored and, if necessary, its dose should be adjusted.

Digoxin

The simultaneous use of nifedipine and digoxin may lead to a decrease in the clearance of digoxin and, consequently, to an increase in the concentration of digoxin in the blood plasma. The patient should be carefully monitored for symptoms of glycoside overdose and, if necessary, reduce the dose of digoxin, taking into account its concentration in the blood plasma.

Theophylline

Nifedipine increases plasma concentrations of theophylline, and therefore the concentration of theophylline in blood plasma should be monitored. The clinical effect of both drugs when used together does not change.

Tacrolimus

Tacrolimus is metabolized with the participation of the CYP3A4 isoenzyme. Recently published data indicate the possibility of increased tacrolimus concentrations in selected cases when administered concomitantly with nifedipine. When using tacrolimus and nifedipine simultaneously, the concentration of tacrolimus in the blood plasma should be monitored and, if necessary, its dose should be reduced.

Vincristine

Nifedipine slows down the elimination of vincristine from the body and may cause increased side effects of vincristine. If simultaneous use is necessary, reduce the dose of vincristine.

Drugs that bind to blood proteins

Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, non-steroidal anti-inflammatory drugs, quinine, salicylates, sulfinpyrazone), as a result of which their concentration in the blood plasma may increase .

Cephalosporins

With the simultaneous use of cephalosporins (for example, cefixime) and nifedipine in probands, the bioavailability of the cephalosporin increased by 70%.

Pharmacodynamic interactions

Medicines that lower blood pressure

The antihypertensive effect of nifedipine may be enhanced when used simultaneously with antihypertensive drugs, such as diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARA II), other BMCCs, alpha-blockers, phosphodiesterase-5 inhibitors, methyldopa.

When using nifedipine and beta-blockers simultaneously, it is necessary to carefully monitor the patient's condition, since in some cases the course of chronic heart failure may worsen.

The severity of the decrease in blood pressure increases with the simultaneous use of inhalational anesthetics and tricyclic antidepressants.

Nitrates

When used simultaneously with nitrates, tachycardia increases.

Antiarrhythmic drugs

BMCCs can enhance the negative inotropic effect of antiarrhythmic drugs such as amiodarone and quinidine. Nifedipine should be co-administered with disopyramide and flecainide with caution due to a possible increase in negative inotropic effect.

Magnesium sulfate

It is necessary to carefully monitor blood pressure in pregnant women while using nifedipine with intravenous magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which poses a danger to both the mother and the fetus.

Fentanyl

The simultaneous use of nifedipine and fentanyl can lead to severe arterial hypotension. If possible, it is recommended that nifedipine be discontinued at least 36 hours before fentanyl-based anesthesia.

Calcium preparations

Reduced effectiveness of nifedipine.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs reduce the antihypertensive effect of nifedipine due to suppression of prostaglandin synthesis, sodium and fluid retention in the body.

Sympathomimetics

Sympathomimetics reduce the antihypertensive effect of nifedipine.

Estrogens

Estrogens reduce the antihypertensive effect of nifedipine due to fluid retention in the body.

Lithium preparations

When BMCC is used together with lithium drugs, it is possible that the neurotoxicity of the latter may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

How to relieve pain yourself

Rinsing with a soda solution (1 teaspoon of soda per glass of warm water) will help temporarily relieve toothache during pregnancy. You need to rinse your mouth more often, every 2 hours. In addition to soda, you can use Furacilin solution, decoctions of medicinal herbs - chamomile, oak bark, yarrow.

Not recommended

use herbs containing essential oils (sage, eucalyptus, peppermint, cloves, etc.), they can cause severe uterine cramps.

Severe dental pain during pregnancy can be treated with a suitable anesthetic. Steroid-based drugs and drugs that penetrate the placental barrier are contraindicated.

Decoding the results

Signs indicating that the fetus has chromosomal abnormalities:

The thickness of the collar space exceeds 2.8 mm. This indicates that the volume of fluid accumulating in the subcutaneous fold in the neck area exceeds normal values. On ultrasound, the fold appears white, and the fluid underneath appears darker.
Absence or small size of the nasal bone. This sign indicates Down syndrome.
Short upper jaw.
Heart rate exceeds permissible norms, heart defects.

Anomalies in the development of the musculoskeletal system, pathologies of internal organs, unformed ears - all these signs are characteristic of a chromosomal developmental abnormality.

Diagnosis of the first trimester

The first fetal ultrasound is performed between 11 and 14 weeks. In addition to an ultrasound examination, a woman must take a blood test for hCG. Only a comprehensive diagnosis will help conduct high-quality screening and exclude any developmental anomalies.

During an ultrasound, the doctor evaluates the following fetal indicators:

chorion structure;
coccyx-parietal length;
collar space thickness;
heart rate.

If the results of ultrasound screening do not correspond to generally accepted standards, the woman is prescribed a repeat, more in-depth diagnostic study.

Why are children born with Down syndrome?

No couple is immune from the development of Down syndrome in the fetus. This genetic abnormality occurs spontaneously. It does not depend in any way on the physical and mental health of the parents. However, women aged 18–35 years are more likely to give birth to a healthy baby. Scientists have proven that women who become pregnant after 35 years of age have a much greater risk of developing a chromosomal mutation than at a younger age. This is due to the aging of eggs. Another reason, which is very rare, is hereditary predisposition. If there are relatives in the family with Down syndrome, the chances of giving birth to an unhealthy baby increase significantly. In addition, doctors tracked the connection between the age of the grandmother who gave birth to her daughter and the chance of getting a grandson with a genetic anomaly. The older the grandmother was at the time of her daughter’s birth, the higher the risk of grandchildren being born with an extra 21 chromosome. The age of the father plays an important role. The risk group for conceiving a sick baby includes men over 45 years of age.

Is it possible to do x-rays?

Contrary to popular belief, X-rays can be taken during pregnancy. For this purpose, computer radiovisiographs are used. The radiation dose received by the patient when using a visiograph is minimal. If possible, the study should be carried out in the 2nd trimester

, excluding cases where urgent help is required - severe, acute pain in the teeth during pregnancy. X-ray examination is carried out observing all possible means of protecting the fetus.

“Fighting” radiation on the visiograph, women calmly fly south to eat fruit and bask in the sun. Not knowing that during a 2-3 hour flight a person receives 20-30 μSv. This is a radiation dose equivalent to 10-15 images on a visiograph. Ionizing radiation differs from light rays only in wavelength and has a damaging effect only under certain conditions.