Ibuprofen and alcohol, or Alcohol vs NSAIDs

Despite the fact that everyone knows about the dangers of alcohol, some are interested in whether it is possible to combine with alcohol... Drugs, and, for example, what kind of pain reliever can be taken with alcohol for headaches or muscle pains, joint pain or neuralgia. [1]

Doctors consider it unacceptable to take medications and drink alcohol at the same time. And this statement is not unfounded, but confirmed by pharmacologists.

Ibuprofen and other NSAIDs vs alcohol

We note right away: alcohol is a multiorgan xenobiotic, and  Ibuprofen  is a drug of a large group of non-steroidal anti-inflammatory drugs (NSAIDs), derivatives of arylalkanoic acid (including derivatives of arylacetic, propionic, heteroarylacetic and indole-acetic acids), which, unfortunately, have not only therapeutic effects, which can also cause quite serious side effects from a clinical point of view.

First of all, irritation of the mucous membrane of the stomach and small intestine is noted with the formation of ulceration and the threat of gastrointestinal bleeding, the latter is associated with a decrease in the synthesis of thromboxane (a lipid with the properties of a vasoconstrictor and platelet aggregator). It turned out that Ibuprofen and other NSAIDs inhibit the formation of thromboxane, which reduces the clumping of platelets during the formation of a blood clot that stops bleeding. This property is also inherent in alcohol, therefore, the risk of prolonged bleeding increases in those who take Ibuprofen after or before drinking alcoholic beverages.

As a side effect, functional renal disorders and malfunctions of the liver are also possible; increased heart rate and increased blood pressure; a decrease in the level of platelets and leukocytes in the blood, etc. There may be headaches and dizziness, hyperhidrosis, sleep disturbances and psychomotor reactions, depressive conditions, etc., associated with side effects of these drugs at the level of the nervous system (central and peripheral). And if this is complemented by the effects of drinking alcohol...

Why is the compatibility of Ibuprofen and alcohol impossible, and why is it impossible to drink, say, a shot of vodka at lunch (as they say, "for appetite"), and after eating take a pill? Pay attention to the section "Medicinal and other interactions" in the instructions for the drugs: everything is clearly indicated there. [2]

The interaction of all types of NSAIDs with alcohol, like other drugs, can be pharmacodynamic, in which ethanol weakens or negates their therapeutic effect, and pharmacokinetic, when consumed alcohol (even a low-alcohol drink) interferes with the metabolism of the drug.

Ibuprofen and alcohol: pharmacodynamic interaction

Briefly about how ibuprofen and alcohol interact pharmacodynamically.

The general mechanism of the analgesic, anti-inflammatory and hypothermic (antipyretic) action of all drugs related to NSAIDs is due to the inhibition of the membrane enzyme cyclooxygenase (COX-1 and COX-2), which, in turn, blocks the biosynthesis of prostaglandins transmitting inflammatory and pain signals (PGE2, PGD2, PGF2α, PGI2).

Alcohol, on the contrary, induces COX-2, and the expression of the enzyme reaches its highest level 15-16 hours after taking the last dose of alcohol (if the dose is large, then faster), and this increases its immune reactivity. Moreover, ethanol is able to activate intracellular signaling pathways with the formation of proinflammatory cytokines (IL-1, IL-6, IL-8), and by interacting with membrane lipids, it can activate TLR4 and IL-1RI receptors that transmit pain and inflammatory signals.

By the way, all synonymous drugs containing ibuprofen - Ibufen, Ibunorm, Imet, Nurofen, Ibuprex,  Ibuprom  and alcohol interact identically. [3]

For the same reasons, you cannot take the non-steroidal anti-inflammatory drugs Ketorolac, Ketorol, Ketolong or Ketanov and alcohol, Ketoprofen and its synonym Ketonal and alcohol, as well as NSAIDs, a derivative of phenylacetic acid Diclofenac and alcohol. [4],  [5], [6]

In the same way, the drugs Next or Ibuclin and alcohol are in an antagonistic relationship, since the composition of these tablets includes Paracetomol and Ibuprofen, which is an NSAID.

Alcohol, ibuprofen and other NSAIDs: pharmacokinetic interaction

Once in the stomach, alcoholic beverages increase blood flow to it, which causes an increase in gastric secretion. But the blood flow to the muscle tissue is noticeably weakened, so muscle weakness and soreness may occur.

Although alcohol is absorbed slowly in the stomach cavity, it can be detected in the blood already five minutes after consumption, and an hour is enough to reach the highest level of its content, equal to the entire dose taken.

Pharmacokinetic interactions of alcohol, ibuprofen and other NSAIDs usually occur in the liver, where both drugs taken by mouth and alcohol consumed are transformed by the same enzymes: cytochrome P450 (CYP) and cytochrome-C reductases (CYP2E1, as well as CYP2C8 and CYP2C9). However, another enzyme is needed to break down ethanol - aldehyde dehydrogenase (ALDH).

Since the load on the liver and its enzyme apparatus increases, the negative effect of alcohol on the hepatic metabolism of these drugs is beyond doubt. More information in the material -  Drug metabolism in the liver

And more about the liver. Due to overload, its ability to neutralize and remove everything unnecessary from the body is reduced with the help of the antioxidant enzyme glutathione it produces, which prevents free radicals from damaging cells. And with the combination of the breakdown of alcohol and the drug taken, not only the formation of additional reactive oxygen occurs, but also a decrease in the amount of glutathione in the mitochondria of liver cells. As a result, cells are exposed to oxidative stress.

The researchers found that in people who rarely drink alcohol, a small part of the ethanol is broken down by the CYP2E1 enzyme. But in regular drinkers, the activity of this enzyme increases almost tenfold, so the side effects of Ibuprofen and other NSAIDs occur more often and are stronger.

Part of the alcohol consumed (no more than 10%) is transformed by the metabolism of the first passage through the liver, the rest from the liver enters the systemic circulation and spreads to all tissues of the body, and then returns to the liver. First, alcohol is oxidized by the ALDH enzyme, as a result of which hydrogen is split off from ethanol and ethanaldehyde is obtained, that is, the most toxic metabolite is acetaldehyde; at the second stage, acetaldehyde is converted into ethanic (acetic) acid, and already it is split into carbon dioxide and H₂O. This process takes 8-12 hours, and ethanol is found in urine longer than in blood. According to these parameters, you can calculate how long you can take Ibuprofen after alcohol. [7]

NSAIDs are broken down into hydroxated and carboxed metabolites and acylglucuronides, and drugs have to "compete" with alcohol, so that their elimination is delayed. In this regard, the risk of a cumulative effect with the development of complications is not excluded.

How much is Ibuprofen excreted from the body? A single dose of the drug taken orally after a meal is absorbed into the blood with a maximum plasma concentration after 60-90 minutes. The drug is present in the blood serum for about 4-5 hours, and after the last dose taken, it is completely removed from the body (from all biological fluids) only after 24 hours. [8]

Alcohol and antipyretics

Even weak alcohol and antipyretic drugs are incompatible, and the combination of ethanol with antipyretic drugs can lead to the development of negative consequences for the gastric mucosa, as well as liver tissue.

Functional changes in thermoregulatory effector mechanisms during alcohol consumption have been scientifically proven, since it affects the reticular formation of the brain stem and the autonomic nuclei of the medulla oblongata.

With an increase in blood flow to the skin, a person first turns red with sweating, but sweating causes a dose-dependent loss of heat and a decrease in the core temperature of the body (sometimes much below the physiological norm). Therefore, doctors do not recommend taking alcohol and antipyretics at the same time.[9]

The pharmacokinetic interaction includes the analgesic and antipyretic Paracetamol and alcohol. Almost 97% of this drug is transformed by cytochrome-C-reductases of the liver: 80% - by conjugation with sulfates and glucuronic acid (with the formation of inactive metabolites), and the rest - by hydroxylation, as a result of which several active substances are formed. Their final metabolism and deactivation also lies in the combination, but already with the previously mentioned antioxidant enzyme glutathione. With its lack - in cases of alcohol consumption - these metabolites have a hepatotoxic effect. [10]

Read also -  Antipyretic drugs

Citramone and alcohol

The non-narcotic analgesic Citramon and alcohol - in cases of headache or fever - also cannot be taken at the same time, since this drug is 56% composed of Aspirin (which is an NSAID) and, in addition to it, contains Paracetamol and caffeine. [11], [12]

The interaction of NSAIDs and Paracetamol with alcohol was discussed above, and caffeine, which stimulates the brain and promotes vasodilation, in combination with ethanol negatively affects brain cells and the cardiovascular system, which can be expressed in increased headache and the appearance of increased nervous excitability, as well as an increase in blood pressure and heart rhythm disturbances. [13]

Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver.

Tolperisone and alcohol

Used in the symptomatic treatment of muscle hypertonia and spastic conditions of the skeletal muscles, muscle relaxant with central action Tolperisone (other trade names - Tolizor, Kalmirex, Midocalm) is an aromatic ketone and relaxes the muscles by blocking the ion channels of nerve fibers. In addition, this drug, acting on the peripheral nerve endings, helps to reduce pain in sciatica, sciatica and lumbodynia. [14]

According to the DrugBank database, the exact mechanism of the drug's active substance - 2-methyl-1- (4-methylphenyl) -3- (1-piperidinyl) -1-propanone - has not been fully understood. And in the official drug instructions it is noted that the current clinical data suggest that Tolperisone and alcohol do not interact. [15]