What is an Antagonist Drug?

The term antagonist can refer to both pharmaceuticals (drugs) and also to literary concepts.

What is a drug antagonist?

A drug antagonist is any drug that binds with a specific chemical receptor within the body, and in doing so, precludes another drug from binding to such a receptor and therefore stops the original drug from having an affect on the body.
 

Examples of antagonists

Competitive Antagonists: Distinguishing between the antagonists naloxone and flumazenil.

Naloxone is an opiate antagonist, which ‘binds to opiate receptor sites and competes with opiate agonists for their spaces on opiate receptor sites’ (MIMS Annual 2003 p. 4-433). Flumazenil, like naloxone is an antagonist drug, but unlike naloxone, which acts on opiate receptor sites, it acts on benzodiazapine (BZ) receptor sites. Flumazenil binds to the ‘BZ receptor sites and blocks the agonists through competitive inhibition’(Bryant and Knights 2003, p271). By binding to gamma-aminobutyric acid (GABA) gated chloride channels flumazenil blocks the Cl flow, where BZs open the Cl flow.

A proportion of all drug molecules entering into the blood stream bind to proteins to form drug-protein complexes. ‘Acidic drugs bind mainly to albumin, while basic drugs bind to acid glyco-proteins contained in the blood’ (Bryant and Knight 2003, p.108). Because of the size of the molecules formed by plasma protein drug complexes, drugs which are bound to proteins cannot pass through the plasma membrane of the vascular system, and are therefore are unable to cause their desired effect on their target cells or organ. Galbraith states that ‘because protein-drug-complexes are large they cannot diffuse into the target cells or tissues and act on the body’ (Galbraith 1998, p. 79). ‘The stronger the protein binding, the less of the free drug that will be present in the plasma and the longer the drug will remain within the vascular system increasing the drugs ½ life’ (Galbraith 1998, pp.1081).

If a drug, such as the BZ midazalam has a 95% plasma protein bound concentration, only 5% of it is actually having an effect on the desired cell or organ. Because drugs bind with proteins and then release and bind with new proteins, the entire concentration of a drug will eventually pass through the plasma membrane and into the interstitial space. Therefore, the concept of plasma protein binding becomes of clinical importance, as paramedics by considering a drugs half-life. If it has a large percentile protein bound, it will take longer for the drug to release from the proteins and take effect on the desired cells or organs. When giving an antagonist, such as the BZ antagonist flumazenil, which is only ‘50% bound to protein’(MIMS Annual 1997, p. 20-1123) as opposed to midazalam which is ‘95% bound to protein’ (MIMS Annual 2003 p. 4-433) the drug ½ life will be much longer for the midazalam as opposed to flumazenil. It is for this reason that repeated doses of the antagonist may have to be given, as the antagonist may be completely out of the system while large percentages of the agonist remain within the intravenous space as protein-drug complexes. According to the Australian Medicines Handbook the ‘1/2 life of flumazenil is about one hour which is much shorter than that of all BZ; therefore repeated doses of flumazenil are required to maintain effect’ (Australian Medicines Handbook 2003).

Because albumin and other plasma proteins provide a number of binding sites, two drugs can compete with one another for the same site and displace each other (Bryant & Knights, 2003, p 109). For competitiveness antagonist have: Drug + antagonist + receptor = D and R + A and R. For a fixed total amount of receptors, the two ligands D and A compete for binding at the receptor. These two ligands compete for the same site on the receptor. Increasing the concentration of D or A displaces the equilibrium towards the formation of the corresponding receptor complex (Galbraith 1998, pp. 1081-3). Therefore, in an overdose situation, such as Heroin, large doses of the antagonist Naloxone may need to be administered to displace the equilibrium in competition of the opiate receptor sites.

A noncompetitive antagonist cannot be displaced by increasing the concentration of agonist. This is often due to different binding sites on the receptor for the agonist and antagonist. Irreversible antagonists form covalent bonds with the receptor and therefore cannot be displaced by other ligands, neither naloxone or flumazenil do this, and therefore their effects can diminish, as their agonist steal their spaces on the receptor molecules. Consequently if an opiate or BZ antagonist has a longer 1/2 than the antagonist, or has a larger plasma drug concentration, it may still occupy the receptor sites and therefore the need for repeated doses of the antagonists may be required to maintain the desired affect.

What is an antagonist in litterary terms?

In literary terms the antagonists is the person who is opposed to, or competes againsts a specific oppenent.