Which medicines can not be taken together: the pharmacist answers

Medicines should help fight the disease, and not harm the human body. To prevent the latter from happening, it is important to strictly observe the frequency of administration, not to take more than the required dose, to take into account the effect of food on the absorption of a particular drug. But most importantly, you need to understand that some drugs cannot be taken together, since they are able to interact with each other, changing the therapeutic effect of each other, in some cases negatively affecting the body.

What is the interaction of drugs, what it can be

The term “drug interaction” is used to refer to situations where, when two or more drugs are taken simultaneously, the specific effect of at least one of them changes significantly. The risk of its occurrence is directly proportional to the amount of funds used: the more drugs enter the body together, the higher the likelihood of negative consequences.

There are two main types of interactions:

• pharmacodynamic (concerning the mechanism of action and the effect of the drug);
• pharmacokinetic (affect the absorption, distribution, excretion of drugs from the body). ^[1]

Pharmacodynamic interaction

Taking multiple drugs can cause two types of interactions related to their pharmacodynamics in the body:

1. Synergism, which can manifest itself as a potentiation of the action of one drug or the summation of the effects of two drugs. For example, the simultaneous intake of iron preparations with ascorbic acid increases their absorption and, accordingly, increases the concentration in the blood. As an example of the summation of effects, we can cite the interaction of two drugs from the group of non-steroidal anti-inflammatory painkillers – paracetamol and acetylsalicylic acid (aspirin). Their simultaneous reception can cause symptoms, as with an overdose: dizziness, loss of orientation in space, nausea, diarrhea, bleeding in the digestive tract. ^[2]
2. Antagonism is a type of interaction in which one drug eliminates the effect of the second. It leads to the complete disappearance of the therapeutic effect of the drug or to its weakening. In some situations, antagonism can be a useful form of interaction – for example, when it is necessary to use antidotes. But in most cases, the incorrect prescription of several drugs with antagonistic action to each other leads to treatment failure. A striking example of antagonism is the neutralization of sulfanilamide drugs (for example, streptocid, biseptol, sulfadimezin, phthalazol) with para-aminobenzoic acid (group B vitamins, novocaine, dicaine, procaine, benzocaine). Their simultaneous administration leads to a significant decrease in the antimicrobial properties of such drugs. ^[3]

Pharmacokinetic interaction

Some drugs should not be taken together, not only because of the change in their therapeutic effect, but also because of the pharmacokinetic interaction. Both absorption and transportation, metabolism, distribution and even excretion of one or both drugs can change, that is, all the processes that take place with the drug after it enters the body. The end result of such transformations can be a change in the concentration of the active substance in the body, which is a key moment of treatment.

What can happen if you do not take into account the possible pharmacokinetic interaction:

• a change in the motility of the gastrointestinal tract, as a result of which the absorption of certain drugs occurs differently. For example, taking laxatives reduces the absorption of the drug. Cholinolytics, prokinetics and anticholinesterase agents – increase its absorption;
• a decrease or increase in the acidity of the stomach, as a result of which the absorption of the active substance of certain drugs changes. There are products that require an acidic environment for complete absorption and reaching a certain concentration in the body. There are also drugs that need an alkaline pH, so it is necessary to take into account the possible change in acidity under their action. For example, if antacids are prescribed, you should not take them along with antiviral agents: zalcibatin or tipranavir. It is for these funds that a low pH is needed, otherwise absorption will slow down; ^[2]
• competitive binding to plasma proteins, which leads to an increase in the blood concentration of one of the drugs. This mechanism is explained by the fact that some drugs are 90-98% bound to plasma proteins, and when the patient takes drugs simultaneously with them, which have a high degree of similarity to the same proteins, the former are replaced by the latter. One example: the antiarrhythmic drug quinidine is able to displace digoxin. Due to this, the concentration of digoxin in the blood increases, as if the patient had taken a dose several times more than usual. This leads to the appearance of unpleasant symptoms and increased side effects: nausea, vomiting, headache, decreased heart rate, dizziness;
• change in the activity of cytochrome P-450. With its increase, there is a decrease in the concentration of drugs and insufficient effectiveness of treatment, with a decrease in activity, on the contrary. Inhibitors of enzyme activity, for example, are antifungal drugs (ketoconazole, fluconazole), antibiotics (erythromycin, clarithromycin). Examples of inducers are carbamazepine, ritonavir, rifabutin, and others. ^[4]

Unwanted and dangerous “pairs” of drugs

The interaction of drugs is usually divided into four classes:

1. A – this class includes combinations in which the interaction is not clinically significant (for example, the combination of phenobarbital and ranitidine);
2. B – this class contains pairs of agents whose interaction has not yet been described
3. C is a class of interacting drugs that change the therapeutic effect of each other. May be corrected by dose adjustment (cimetidine and theophylline)
4. D – this class includes pairs of drugs, the use of which at the same time can be dangerous and unacceptable.^[5] It is these combinations that are worth talking about.

Contraceptive hormones and antibiotics

To prevent an unplanned pregnancy, a doctor may prescribe oral contraceptives to a woman. These are hormonal drugs, the mechanism of action of which is based on the suppression of ovulation. Thus, even if the most “active” spermatozoa enter the cervix, fertilization will not occur, because the egg does not mature.

Antibiotics can also be part of the treatment regimen for infectious diseases. They destroy bacteria, but at the same time they “kill” the beneficial microflora. It is this side effect of antibacterial agents that is the reason for the decrease in the level of hormones in the body. Due to a violation of the microflora in the intestine, hormones are practically not absorbed, and therefore cease to act. As a result, a woman can become pregnant if she does not take additional protection. Such a combination of drugs is not dangerous for the body, but if pregnancy is not planned, it must be taken into account. ^[6]

Anticoagulants and painkillers

Drugs from the group of anticoagulants are used to thin the blood and prevent blood clots. The main danger of an overdose of such drugs is the occurrence of internal bleeding.

Painkillers have a completely different purpose and mechanism of action. They stop pain of various origins, but their additional effect is to reduce blood clotting. For this reason, the simultaneous use of these two groups of drugs can lead to bleeding in the internal organs. This condition is dangerous, first of all, blood loss. It is important not to overuse painkillers while constantly taking anticoagulants, or to stop their use, if possible, during therapy with drugs from the NSAID group. ^[7]

Calcium channel blockers and beta blockers

Medicines that belong to calcium blockers are intended for the treatment of arterial hypertension and angina pectoris. They act by blocking calcium, which constricts blood vessels, thereby expanding them. Due to this, blood pressure decreases, and blood flow to the heart makes it work better. At the same time, calcium channel blockers also affect the heart itself, so when they are used, bradycardia and intracardiac blockades are possible.

Beta-blockers are used for ischemic heart disease, arrhythmia, arterial hypertension, chronic heart failure. They reduce heart rate and conduction of the heart. The imposition of such effects from two drugs at once can cause sudden cardiac arrest. With the simultaneous appointment of beta-blockers and calcium channel blockers, you need to carefully monitor the heart rate. With severe bradycardia – less than 50 beats per minute, you should immediately consult a doctor.

Anti-allergic and anti-cold drugs

At the first symptoms of a cold, many people choose sachets of powder to prepare a hot drink. They really do a pretty good job of dealing with headaches, body aches, nasal congestion. And all because the composition contains paracetamol, as well as antihistamine components. If you combine these bags with allergy medications, you may encounter an overdose of the latter. The result is high drowsiness, which is very dangerous for drivers or those who work with mechanisms that require concentration.

The same danger is posed by mixing antihistamines with motion sickness and motion sickness remedies.

Antidiarrheals and calcium preparations

The dangerous combination of these two groups of drugs primarily concerns diarrhea remedies based on loperamide. Such a remedy reduces intestinal motility, thereby reducing the frequency of bowel movements. It cannot be taken with intestinal infections, since the pathogenic microflora will not be excreted from the body, which will lead to an increase in intoxication.

Calcium is a mineral that helps strengthen bones. It is often prescribed for fractures, for the prevention of osteoporosis in women during menopause. Also, calcium can be part of the means to reduce the acidity of gastric juice. In addition to strengthening bone tissue, it also affects intestinal motility, just like loperamide. The simultaneous use of two of these drugs can lead to prolonged constipation. That is why it is worth abandoning calcium supplements during the treatment of diarrhea with loperamide. ^[8]

Antifungals and statins

To lower cholesterol levels and prevent atherosclerosis, drugs from the statin group are used. They disrupt the process of cholesterol production by the liver, so it “takes” the processing of what is already in the blood. Such drugs are often prescribed in the complex therapy of arterial hypertension. Antifungal agents are used to treat dermatomycosis, oral candidiasis, vaginal candidiasis, onychomycosis.

The cytochrome P-450 enzyme takes part in the metabolism of both one and the other drugs, so the simultaneous use of antifungal and statins can lead to an increase in the level of the latter in the blood and their accumulation in skeletal muscles. The result of this penetration of cholesterol-lowering agents is a high risk of developing rhabdomyolysis.

Also, do not take statins along with anticoagulants, as bleeding is possible. ^[9]

An inhibitor of APF is spironolactone

ACE inhibitors are a fairly popular group of drugs for the treatment of arterial hypertension.

The mechanism of their action is based on blocking the production of angiotensin, which constricts blood vessels. Thus, the vessels dilate and the pressure decreases.

Spironolactone is an active ingredient in medicines prescribed for heart failure. It reduces blood volume by removing excess fluid and salt, thereby reducing the workload on the heart.

Both drugs increase the level of potassium in the blood, which can lead to hyperkalemia. The danger of such a condition is that the rhythm of the heart and its conduction are disturbed. ^[10]

How to avoid negative consequences for the body

The most important rule to avoid the dangerous consequences of taking two or more drugs at the same time is not to self-medicate.

It is better to entrust the appointment of drugs to doctors. It is in this case that you can get the maximum benefit from the treatment. In extreme cases, you need to carefully study the instructions to find out with what it is worth taking the remedy, and with what it is strictly prohibited.

The second thing that every patient should remember is that it is important to strictly observe the dosage and time intervals. If there is a need to take two or more medicines, it is advisable to take them separately. The minimum interval between different drugs should be 30 minutes.

And the last thing – when undergoing treatment at the same time by several specialists, it is imperative to warn them about all the prescribed medicines, otherwise you may encounter an unexpected or even health-threatening result of such therapy.

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