Drug antagonism
Drug antagonism refers to a medicine stopping the action or effect of another substance, preventing a biological response.
[1][2] The stopping actions are carried out by four major mechanisms, namely chemical, pharmacokinetic, receptor and physiological antagonism.
Receptors bind with endogenous ligands to produce a physiological effect and regulate the body and cellular homeostasis.
In a ligand-receptor interaction, the ligand binds with the receptors to form a drug-receptor complex, producing a biological response.
The amount to which the competitive antagonist causes the agonist log concentration–effect curve to shift to the right while maintaining its maximum slope is a measure of the dosage ratio.
These variations can be evaluated regarding effectiveness, indicating the agonist-receptor complex's "strength" in causing a tissue response.
It is used to block the activity of alpha receptors in sympathetic pathway and is used in the treatment of paroxysmal hypertension and sweating resulting from pheochromocytoma and benign prostate hyperplasia.
[8] In chemical antagonism, the receptors are not involved in the process, and the antagonist directly binds with or removes the ligand.
[12] The common types of chemical antagonism include chelating agents, neutralising antibodies and salt aggregation.
Dimercaprol is a common chelating agent to treat toxic exposure to arsenic, mercury, gold, and lead.
[14] The action antagonises the toxic metal ions and helps remove them from body circulation.
[14] Neutralising antibodies block pathogen entry into cells to prevent further infection and replication.
[15] Infliximab is a monoclonal antibody binding with tumour necrosis factor-alpha (TNF-alpha), inhibiting its pro-inflammatory action.
Strongly anionic unfractionated heparin reacts with the positive cationic protamine arginine peptide to generate a salt aggregation.
[19] For example, proton-pump inhibitors (PPIs) are enteric coated to protect them from decomposition under an acidic environment.
These types of pharmacokinetics antagonism should be carefully avoided to prevent loss of drug efficacy.
For example, warfarin, a commonly-used anticoagulant drug in atrial fibrillation, is metabolised by an enzyme called CYP2C9.
Phenytoin, a CYP2C9 inducer, would increase its activity and the rate of warfarin breakdown, thereby reducing its efficacy.
Both insulin and glucagon are synthesised naturally in the human body to regulate blood glucose levels at homeostasis.
In cases of insulin-induced hypoglycaemia, glucagon injection could help increase blood glucose levels.
Pharmacodynamics (PD) is the core principle of quantifying the effects of antagonists by measuring the drug’s efficacy and safety.
PD emphasises the relationship between the dose and response of a certain drug, which can be illustrated using a dose-response curve.
A narrow TI indicates that either excess or lack of insulin can cause significant risks.
[28] On one hand, lack of insulin may result in high blood glucose levels and kidney or cardiovascular damage.
[34] Abrupt discontinuation of β-blocker may potentially aggravate coronary artery disease, tachycardia, or even sudden cardiac death.
In addition to lowering the amount of free or active poison present, antidote delivery may also lessen the toxin's effects on organs through competitive inhibition, receptor blockage, or direct antagonistic interaction.
Activated charcoal is the non-specific binding agent most frequently utilised as it has strong adsorption capacity and could prevent the toxin's enterohepatic recirculation.
[39] Antidotes can be employed to either mop up hazardous metabolites or change them into less toxic forms once they have developed.
