Pharmacokinetics is the branch of pharmacology that focuses on the body’s absorption, distribution, metabolization, and excretion of a particular drug. Pharmacokinetic interactions may change the concentration of a drug in the plasma and the availability of a drug being present at the site of action. Pharmacokinetic interactions are often called ADME (absorption, distribution, metabolism, and excretion) interactions.
The three main factors that govern interactions at the absorptive site are as follows:
Gastrointestinal pH, Chelation, and Gastrointestinal motility.
Since the administration of most drugs follows the oral route, the gut plays a significant role in the absorption of a particular drug. Therefore, precipitants (agents that alter the effect of the primary administered drug) that alter the gut pH can interfere with object drugs (the drug affected by a precipitant) that gets absorbed at a particular pH environment in the gut.
Interactions at the distribution level depend on the mechanism of action of the precipitant and the object drug. For example, a change in protein-drug binding may occur due to the presence of precipitants that bind to the same protein/receptor as the object drug. In such cases, a competition between the drugs occurs at the binding site, which may change the desired effects of the object drug.
Interactions at the metabolic pathway depend on a process known as enzyme induction (stimulation of the activity of hepatic microsomal by certain drugs) which increases the metabolism and excretion of the object drug and hence, reduces the effectiveness. Interactions at the elimination/excretion site depend on competition at active transport sites, changes in glomerular filtration, active secretion or passive reabsorption in the renal tubules, and urine pH.
Pharmacodynamics of Drug Interactions
Pharmacodynamic interactions occur at the site of action of the object drug is altered by the precipitant. Such interactions can be direct or indirect.
Direct interactions can be of three types: Antagonism, addition, and synergism.
Antagonism occurs when the drugs have opposite actions towards the body.
For example, Noradrenaline and Acetylcholine have opposing effects on the heart rate.
Addition or summation occurs when the drugs have similar actions, like central nervous system depressants such as sedatives and hypnotics.
Synergism occurs when a drug enhances the effects/actions of another drug. For example, alcohol enhances the analgesic effect of aspirin.
When the object drug and the precipitant have no related effects on each other, but somehow the precipitant alerts the activity of the object drug, it is called indirect interaction. For instance, salicylates decrease platelet aggregation ability, thus hampering the body’s homeostasis if warfarin is responsible for internal bleeding to occur.
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