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Uncovering drug synergy: How to determine whether a drug is achieving optimal efficacy?
In pharmacology, the additive effect of a drug means that when two drugs act together, their effect is equal to the sum of the effects of the two drugs acting independently. This concept originated from the synergy between drugs and developed with scientists' understanding of the interaction of drugs and chemical substances. Additive effects usually occur when two similar drugs are taken together, aiming to achieve the same therapeutic effect while reducing the side effects of a particular drug. For example, a combination of aspirin, acetaminophen, and caffeine is often used to treat the pain of tension headaches and migraines.
The additive effect can also be used to detect synergy, as it can be considered a baseline effect in methods of determining whether a drug is synergistic.
In addition to the additive effect, there is also a synergistic effect. Its combined effect exceeds the additive effect and can show the effect of "2+2 > 4". If the combined effect of two drugs is less than the sum of the two drugs' independent effects, a so-called antagonistic effect, such a combination of drugs is usually not prescribed together. In drug combinations, even drugs with additive effects may trigger adverse effects. For example, the combined use of nonsteroidal anti-inflammatory drugs (NDAIDs) and corticosteroids can increase the risk of gastric bleeding.
Historical background
The concept of additive effect originated from drug synergy. The concept dates back to the early 20th century, when scientists began to explore the synergistic effects of drugs. During this process, Loewe additivity and Bliss independence models were successively proposed. These models can help measure the effect of drug combinations and thereby confirm the synergistic or antagonistic effects of drugs.
Types of bonus effects
Additive effects can be divided into two main types, including equivalent or overlapping effects and independent effects.
Equivalent or overlapping effects
Many similar drugs exhibit additive effects because they share similar therapeutic mechanisms. For example, calcium carbonate, magnesium and aluminum salts are all antacids, which reduce discomfort by neutralizing acidity in the stomach. These antacids do not interact with each other and therefore may be considered to have an additive effect when taken together. Even drugs of the same type with different targets can achieve additive effects by interacting with different targets in the same pathway.
Independent function
When two drugs work in unrelated pathways against different targets, they are said to have additive effects acting independently. For example, both artemisinin and curcumin exhibit antimalarial effects. The former produces reactive oxygen species (ROS) through metabolism to generate reactive metabolites, leading to the death of parasites, while curcumin exhibits antimalarial effects by promoting innate and adaptive immune responses. Antiparasitic effect.
Common misunderstandings
Although the concept of additive effect is similar to simple addition in mathematics, in most cases additive effect does not amount to simply adding up the effects of the drug. For example, the inhibitory effect of Drug A and Drug B is 20%, but the additive effect is not equal to 40%.
Clinical significance
Detecting synergy
A typical application of additive effects is the detection of synergy, which can be used as a baseline effect to confirm synergy between two drugs.
Detection of antagonism
Similarly, additive effects can also be used to detect antagonism. Pharmacists can confirm the presence of antagonism when the combined effect of a drug is less than additive, such as the antagonism known as pain and inflammation relief when aspirin is combined with ibuprofen.
Combination therapy
In clinical use, the most common application of additive effects is combination therapy, usually two or more drugs used together to treat a single disease.
Adverse reactions
Although additive effects are widely used clinically, the potential adverse reactions of these drug combinations cannot be ignored. Similarly, the side effects of different drugs may worsen when used together, thereby affecting the patient's health.
How can we ensure that our medication choices do not produce unintended side effects or effects when our understanding of drug interactions is limited?
