Pharmadipine
Pharmadipine is used as an emergency aid in case of hypertensive crisis. In this form, the medication should not be used for course use.
Pharmacodynamics
Pharmadipine has pronounced hypotensive as well as antianginal properties. It prevents the entry of Ca ions into cardiomyocytes and smooth muscle cells of peripheral and coronary arteries through slow potential-dependent calcium channels of cell membranes. It helps to relax smooth vascular muscles, and besides it eliminates various spasms, reducing the strength of peripheral resistance of blood vessels and blood pressure after a load, as well as the oxygen demand of the myocardium. In addition, it slightly reduces aggregation of platelets and slightly reduces myocardial contractility.
Pharmacokinetics
After oral intake is well absorbed from the digestive system. Bioavailability indicators are 40-60%. The therapeutic effect is most quickly achieved with a sublingual method of administration - after 5-10 minutes. Peak efficiency reaches 30-40 minutes. The rate of absorption of the drug does not depend on the intake of food.
The haemodynamic effect lasts about 4-6 hours. About 90% of the substance nifedipine binds to plasma blood proteins. Metabolism occurs in the liver, and from the body the medicine is excreted mainly in the form of inactive exchange products. The overall cleansing factor of nifedipine is 0.4-0.6 liters / kg / h. The half-life of T1 / 2 is 2-4 hours. This figure can increase approximately 2-fold in older people, and in addition, in patients suffering from cirrhosis, as they experience a slowing down of the cleavage of nifedipine. Therefore, in such situations, you should lower the dosage and increase the break between taking drugs.
Nifedipine is not accumulated in the body. A small amount of the drug can pass through the placenta and the blood-brain barrier, and also get into the mother's milk.
Contraindications
Among the contraindications:
- Unstable angina;
- Allergic reaction to the components of the drug;
- Condition of cardiogenic shock;
- Acute stage of myocardial infarction;
- Narrowing of the mitral valve and aorta in severe form;
- Hypotension or tachycardia;
- Lactation period;
- Children under 18 years.
Side effects Pharmadipine
If you comply with medical recommendations, adverse reactions will be insignificant and short-lived, and if they occur, you do not generally need to stop using drugs.
Frequent uncontrolled use of the drug can lead to the development of side effects, which are typical for drugs that are part of this pharmacological category.
Cardiovascular system: often vasodilation and swelling, occasionally - hypotension, increased heart rate, tachycardia, and also syncope.
CNS and PNS: mainly headache; more rarely are migraines, a sense of anxiety, problems with sleep, tremor, vertigo, and dizziness; very rarely - a state of arousal, short-term vision problems, and in addition to dysesthesia, as well as paresthesia.
Endocrine system: development of hyperglycemia (this fact should be taken into account in patients with diabetes mellitus).
Digestion system: mostly constipation; rather rarely due to excess dosage observed - dyspepsia, flatulence, abdominal pain, nausea, vomiting, a feeling of dryness in the oral cavity, hyperplasia of the gums (in case of prolonged use) and transient increase in liver enzymes.
Urinary system: occasionally dysuria or polyuria.
Circulatory system: leukopenia or anemia or thrombocytopenia is rare.
Allergies: sometimes allergic swelling / edema of Quincke (including edema of the larynx); rarely rashes on the skin, itching and hives; extremely rare - anaphylactic / anaphylactoid shock.
Other: mostly poor health; sometimes there is nasal congestion or bleeding from it, as well as erythema; rarely - muscle cramps, edema of the lower leg or joints, nonspecific pain, dyspnoea, fever, impotence.
Dosing and administration
In the case of a sharp strong jump in blood pressure, the initial single-dose dosage for an adult will be 3-5 drops. (2-3.35 mg), and for the elderly patient - a maximum of 3 drops. (2 mg), while keeping the medicine under the tongue, or dropping on a slice of sugar or breadcrumb, and then hold in your mouth. If the desired effect can not be achieved, you should increase the dosage until there are improvements in the patient's condition. Further, when the blood pressure level is raised, this dosage should be taken as a guide.
If necessary (if the blood pressure rises to 190 in 100/220 per 110 mm of mercury), a single dose can sometimes be gradually increased to 10-15 drops. (6.7-10 mg), taking into account individual changes in blood pressure in the patient.
Interactions with other drugs
Nifedipine, when used simultaneously with receptor antagonists of AT-1 nerve endings and other calcium antagonists, diuretics, ACE inhibitors and PDE5, alpha-adrenoreceptor blockers, alpha-methyldopa, and β-blockers, can increase their antihypertensive properties.
In the case of simultaneous use with β-blockers, in addition to increasing the strength of the antihypertensive effect, there is sometimes a risk of heart failure.
Diltiazem reduces the rate of excretion of nifedipine, so when this happens, the dosage of nifedipine is lowered.
Amiodarone, together with quinidine, can increase the negative inotropic effect of the active drug component. Sometimes, when combined with oral administration of nifedipine with quinidine, the saturation of the latter in the blood plasma decreases.
Simultaneous use of nifedipine with theophyllines, and in addition cardiac glycosides in patients occasionally increases the level of theophylline, as well as digoxin in the blood plasma (which is why you need to carefully monitor their performance).
Nifedipine helps to increase the level of blood serum saturation with carbamazepine, as well as phenytoin. The combination of nifedipine with cimetidine can increase the level of the first in the blood plasma.
Rifampicin enhances the activity of enzymes, increasing the rate of nifedipine cleavage, thereby reducing the strength of the clinical effects of nifedipine (so this combination is contraindicated).
Treatment with nifedipine should be completed 36 hours before the planned use of fentanyl. Nifedipine has good compatibility with radiopaque contrasts.
As a result of the simultaneous use of the active ingredient of Pharmadipine with magnesium sulfate, administered intravenously, a neuromuscular transmission disorder may occur in women during childbearing.
Nifedipine is cleaved by cytochrome P450 3A4, which is located in the intestinal and hepatic mucosa. Therefore, drugs that contribute to the suppression or enhancement of this system of enzymes, can affect the effect of the so-called "first pass" (with oral administration) or the cleansing factor of nifedipine.
When combined with nifedipine macrolide antibiotics (for example, erythromycin), substances, HIV protease inhibitors (such as ritonavir), azole antimycotics (eg, ketaconazole), fluoxetine, as well as nefazodone and in addition cimetidine with quinupristin or dalfopristine, and also cisapride, an increase in the saturation of the active substance of the drug in plasma is possible.
Since valproic acid, due to a slowing of enzyme activity, increases the plasma saturation of nimodipine-like nimodipine (a blocker of calcium channels), an increase in the saturation of the former, together with an increase in the effectiveness of the effect, can also be observed.
Ticrolimus is also cleaved by the cytochrome of the P450 3A4 group. Therefore, in some cases, taking it together with nifedipine, you need to reduce dosage. Also, during the application, you should monitor the saturation of tacrolimus in the plasma and, if necessary, reduce its dosage.
Grapefruit juice slows the activity of cytochrome P450 3A4, so the use in combination with nifedipine causes an increase in the level of saturation of this substance in the plasma, and also lengthens the duration of its action (because the metabolic process slows down at the moment of the first passage or lowering of the cleansing factor). As a result, the antihypertensive properties of the drug may increase. If you drink grapefruit juice regularly, a similar effect can continue for 3 days after the last use. That is why juice should be avoided on the basis of this citrus or grapefruit, while treatment with the active drug component continues.