Quantitative evaluation of the combined effects of drugs
Studying the effectiveness of combined action of drugs on the body is a very difficult task, because it often does not change the qualitative characteristics of efficiency, and quantitative indicators of their actions. To evaluate the combined effect of drugs most frequently used in the literature the following characteristics of the final results of their efficiency.
Synergism – sobiratelynыy term, designating a simultaneous action in one direction two or more drug substances, providing a higher final effect, than each of them alone.
If joint or sequential use of two or more drugs force their action is the sum of the effects of each substance separately, such action is called totalizer.
EABOUT E =A + EB
For Example, application ibuprofen and Paracetamol while arthralgia. Typically, such drugs cause effect, having the same mechanism of action and direction. The combination of substances, the therapeutic effect of which is summed up, to reduce the dose and reduce the likelihood of complications.
Additionally, sometimes used the concept of "Allergenic and additive effect".
Allergenic effects - When one substance, for various reasons without interfering with the mechanism of action, enhances the effect of another. For Example, insulin and glucose stimulate cell infiltration potassium; Ascorbic acid in combination with drugs increasing iron concentration in blood plasma; clofibrate increases inotropic effect of digitoxin, etc.. d.
Additive effect - When the effectiveness of the combination of drugs is more pronounced, than one of the components, but less than the sum of their effects. For Example, the combined use of furosemide and thiazides; nitroglycerin and β-blockers in coronary heart disease; теофиллина и b2-agonists in asthma.
If concurrent or sequential use of two or more drug substances there is a significant enhancement of the effect of one of them under the influence of the other and the final effect greater than the sum of effects, caused by each separately, this effect is called the potentiation, or synergistic supraadditivnym:
EABOUT > EA + EB
The phenomenon of potentiation of the combined use of drugs while developing, when they act in a common direction, but the mechanisms, as well as the localization of different substances action (They operate on different body tissues or different parts of the cell). Potentiation may be used to obtain optimum desired effect. For Example, the application of chlorpromazine (chlorpromazine), which inhibits the reticular formation of the brain, with alcohol or barbiturates, inhibiting the sensitive areas of the brain. Simultaneous inhibition of various parts of the brain leads to a stronger overall inhibition of the CNS and can be achieved by the use of reduced doses of substance, of the combination.
The phenomenon of potentiation (sinergizma) widely used in medical practice, as the desired therapeutic effect can be achieved using low doses of several drugs, acting in one direction. This combination reduces the toxic effect, as the individual substances, having different structures of molecules, can be rendered harmless in the body in different ways.
The phenomenon of developing synergies and, in cases, when drugs act on different parts of the functional system. For Example, blood pressure in hypertension quite effectively reduced using sedatives (CNS depression vasoconstrictor centers), antispasmodics and diuretics ("Adelfan-ezidreks"), b-адреноблокаторов и салуретиков («Tenorik»), ACE inhibitors and saluretics («Энап HL») and etc.
Phenomenon, when the combined use of drugs action of one of them under the influence of another decreases or disappears completely, It called antagonizmom:
EABOUT < EA + EB
The phenomenon of antagonism used in toxicology (antidotnaya therapy), and to prevent or eliminate the side effects of drugs in clinical practice (When antagonists, eliminating the unwanted effects, It does not affect or even increase the beneficial effect). For Example, b-адреноблокаторы подавляют тахикардию, caused by vasodilators; amiloride blocks kaliyuretichesky effect of thiazide diuretics.
In some cases, in medical practice, the term "antagonist" is used to drugs, that interfere with the action of vitamin, hormones, ions, metabolites. For example - vitamin K antagonists, aldosterone, calcium ions, hormones, etc..
Recently found, that, when administered to two or more drug substances can occur qualitatively new effect, which has neither one substance, used alone. In this case, the term antagonism of drugs used to indicate distortion effects, advancing their use in combined. Therefore, to analyze the causes of antagonism of drugs requires consideration of many circumstances in each case. The phenomenon of antagonism - the most common cause of pharmacological interactions of drugs.
Besides, emit a special form of antagonism - disensitizaciû, where one substance combination, not possessing activity, reduces the effect of the other. However, this classification results of the interaction of substances in their combined use is rarely used.
Interest in the study of the interaction of drugs with all due primarily to its influence on the quantitative impact of drug therapy of various diseases. Studying the mechanisms of interaction of components of medical systems is very complex, because of the large range of medicines and auxiliary substances and factors, influencing these processes. By difficulties in studying this problem is the absence of a unified standard approaches to evaluating the interaction of drugs.
The accumulated scientific and practical potential, relating to pharmaceutical, medical and biological aspects of drugs, It allows you to specify and offer more affordable classification of interaction between the components of the components at all stages of their use (applications).
From a practical standpoint drug interactions can be divided into pharmaceutical and pharmacological. In the pharmaceutical interactions should be allocated physicochemical and biopharmaceutical interaction. With regard to the pharmacological interactions, which are implemented with the participation of various functional systems of the human body, they should be divided into pharmacokinetic and pharmacodynamic interaction.
