Ibuprofen and alcohol, or Alcohol vs NSAIDs

Despite the fact that everyone knows about the harm of alcohol, some are interested in whether it is possible to combine alcohol with… medications, and, for example, what painkillers can be taken with alcohol for headaches or muscle pain, 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

Let us note right away: alcohol is a multi-organ xenobiotic, and Ibuprofen is a drug from a large group of non-steroidal anti-inflammatory drugs (NSAIDs), derivatives of arylalkanoic acid (including derivatives of arylacetic, propionic, heteroarylacetic and indoleacetic acids), which not only have a therapeutic effect, but, unfortunately, can also cause side effects that are quite serious from a clinical point of view.

First of all, irritation of the mucous membrane of the stomach and small intestine with the formation of ulcers and the threat of gastrointestinal bleeding is noted, 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 adhesion of platelets during the formation of a blood clot that stops bleeding. This property is also inherent in alcohol, so the risk of prolonged bleeding increases in those who take Ibuprofen after or before drinking alcoholic beverages.

Side effects may also include functional renal disorders and liver failure; increased heart rate and blood pressure; decreased platelet and leukocyte levels in the blood, etc. Headaches and dizziness, hyperhidrosis, sleep and psychomotor disorders, depressive states, etc., associated with the side effects of these drugs at the level of the nervous system (central and peripheral). And if this is supplemented by the effects that occur when drinking alcohol...

Why is it impossible to combine Ibuprofen and alcohol, and why can't you drink, say, a shot of vodka with lunch (as they say, "to whet your appetite") and take a pill after eating? Pay attention to the section "Drug and other interactions" in the instructions for the drugs: everything is clearly stated there. [ 2 ]

The interaction of all types of NSAIDs with alcohol, as with other drugs, can be pharmacodynamic, in which ethanol weakens or nullifies their therapeutic effect, and pharmacokinetic, when the alcohol consumed (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 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 (PGE2, PGD2, PGF2α, PGI2) that transmit inflammatory and pain signals.

Alcohol, on the contrary, induces COX-2, and the expression of the enzyme reaches its highest level 15-16 hours after 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 can activate TLR4 and IL-1RI receptors, transmitting 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 should not take 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 these tablets contain Paracetamol and Ibuprofen, which are NSAIDs.

Alcohol, Ibuprofen and other NSAIDs: pharmacokinetic interactions

When alcoholic drinks enter the stomach, they increase blood flow to it, which causes an increase in gastric secretion. But blood flow to muscle tissues is noticeably weakened, which can cause muscle weakness and painful sensations.

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

Pharmacokinetic interactions between alcohol, Ibuprofen and other NSAIDs usually occur in the liver, where both the drugs taken orally and the 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, aldehyde dehydrogenase (ALDH), is needed to break down ethanol.

Since the load on the liver and its enzymatic apparatus increases, the negative impact of alcohol on the liver metabolism of these drugs is beyond doubt. More information in the material - Metabolism of drugs in the liver

And more about the liver. Due to overload, its ability to neutralize and remove everything unnecessary from the body decreases with the help of the antioxidant enzyme glutathione produced by it, which prevents damage to cells by free radicals. And when the breakdown of alcohol and the drug taken is combined, not only does additional reactive oxygen form, but also the amount of glutathione in the mitochondria of liver cells decreases. As a result, the cells are subject to oxidative stress.

Researchers have found that in people who rarely drink alcohol, the CYP2E1 enzyme breaks down a small portion of ethanol. But in those who drink regularly, the activity of this enzyme increases almost tenfold, which is why the side effects of Ibuprofen and other NSAIDs occur more often and are more severe.

Part of the consumed alcohol (no more than 10%) is transformed by the first-pass metabolism through the liver, the rest from the liver enters the systemic bloodstream and is distributed throughout all tissues of the body, and then ends up in the liver again. First, alcohol is oxidized by the ALDH enzyme, as a result of which hydrogen is split off from ethanol and ethane aldehyde is obtained, that is, the most toxic metabolite - acetaldehyde; in the second stage, acetaldehyde is converted into ethane (acetic) acid, and it is broken down into carbon dioxide and H2O. This process takes 8-12 hours, and ethanol is detected in urine longer than in blood. Based on these parameters, you can calculate how long you can take Ibuprofen after alcohol. [ 7 ]

NSAIDs are broken down into hydroxylated and carboxylated metabolites and acyl glucuronides, and the drugs have to “compete” with alcohol, so their elimination is delayed. In this regard, the risk of a cumulative effect with the development of complications cannot be ruled out.

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

Alcohol and antipyretics

Even weak alcohol and antipyretics 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, as it affects the reticular formation of the brainstem and the autonomic nuclei of the medulla oblongata.

When blood flow to the skin increases, a person initially turns red and sweats, but sweating causes a dose-dependent loss of heat and a decrease in core body temperature (sometimes much lower than the physiological norm). Therefore, doctors do not recommend taking alcohol and antipyretics at the same time. [ 9 ]

The analgesic and antipyretic Paracetamol and alcohol interact pharmacokinetically. Almost 97% of this drug is transformed by cytochrome C reductases in the liver: 80% by conjugation with sulfates and glucuronic acid (with the formation of inactive metabolites), and the rest by hydroxylation, which results in the formation of several active substances. Their final metabolism and deactivation also involves a combination, but with the previously mentioned antioxidant enzyme glutathione. If there is a deficiency of it - in cases of alcohol consumption - these metabolites have a hepatotoxic effect. [ 10 ]

Read also – Antipyretic drugs

Citramon 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% Aspirin (which is an NSAID) and also contains Paracetamol and caffeine. [ 11 ], [ 12 ]

The interaction of NSAIDs and Paracetamol with alcohol was discussed above, and caffeine, which has a stimulating effect on the brain and promotes vasodilation, in combination with ethanol has a negative effect on brain cells and the cardiovascular system, which can be expressed in increased headaches 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

Tolperisone (other trade names: Tolizor, Calmirex, Mydocalm), a centrally acting muscle relaxant used in the symptomatic treatment of muscle hypertonia and spastic conditions of skeletal muscles, is an aromatic ketone and relaxes muscles by blocking ion channels of nerve fibers. In addition, this drug, acting on peripheral nerve endings, helps reduce pain in radiculitis, sciatica and lumbago. [ 14 ]

According to the DrugBank database, the exact mechanism of the drug's active ingredient, 2-methyl-1-(4-methylphenyl)-3-(1-piperidinyl)-1-propanone, has not been fully studied. And the official instructions for the drug note that the clinical data available today allow us to state that Tolperisone and alcohol do not interact. [ 15 ]