It was introduced by the scientists in pharmacology and biochemistry fields in the process of understanding the synergistic interaction between drugs and chemicals over the century.
For example, aspirin, paracetamol, and caffeine are formulated together to treat pain caused by tension headaches and migraine.
For example, co-administration of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids increases the risk of gastric bleeding.
Thus, the origin of additive effect dates back to the early twentieth century when the search for synergy started.
Hence, Loewe additivity and Bliss independence were developed to determine whether an effect of a drug combination is synergistic or antagonistic.
During the construction of these models, the concept of additive effect was introduced as the baseline for the determination of synergy and antagonism.
For example, the calcium carbonate, magnesium, and aluminium salts are all antacids with the mechanism of using the negative ion to neutralize the acid in the stomach.
[12] The mechanism of action of curcumin remains largely unknown, but the antiparasitic effect is believed to be associated with the potentiation of innate and adaptive immunological responses.
[15] Drugs with the same target in different sites that produce additive effects are also considered as independent action.
[18] A recent study has shown that doxorubicin and trabectedin do not hinder each other and could produce an additive anticancer effect.
[22] The combination of angiotensin II receptor antagonist (ARB), Candesartan-cilexetil, and angiotensin-converting enzyme inhibitor (ACEI), Ramipril, demonstrates a synergistic effect in reducing systolic blood pressure.
The combination of acetylsalicylic acid and ibuprofen demonstrates an antagonistic effect in relieving pain and inflammation.
An example of combination therapy demonstrating additive effect is the use of β-2 adrenergic receptor agonists together with inhaled corticosteroids.
The corticosteroids also reverse and restore the function and number of β-2 adrenergic receptors in patients’ lungs in vivo.
Meanwhile, the combined activity of two drugs resolves the problem of reduced sensitivity in some patients with chronic obstructive pulmonary disease towards inhaled corticosteroids.
CCBs are vasodilators inhibiting L-type voltage-operated calcium channels in the blood vessels to alleviate vasoconstriction resulting in a decrease in peripheral vascular resistance.
[26] This combination, with ARB, valsartan, and CCB, amlodipine, is a common treatment in high-risk hypertensive patients, especially the elderly.
There are controlled, double blind clinical trials and studies involving patients with preserved left ventricular function demonstrating that the combination of calcium channel blocker and beta blocker has an additive cardio depressant effects when comparing with either drug class alone.
Since hyperkalemia has the potential to cause arrhythmia and metabolic acidosis, the combination of ACEI and potassium-sparing diuretics is avoided.
[32][33] As a result, the concomitant use of NSAIDs and glucocorticoids increases the risk of gastric bleeding and worsens peptic ulcer disease.