How Drugs and Receptors Interact - Essay Example

 HOW DRUGS AND RECEPTORS INTERACT Introduction Receptors are components of a cell that interact with drugs leading to a myriad of effects of the drug (Arkin and Whitty, 2009, p. 284). There are five primary channels through which a drug can interact with the body. They include: ligand gated ion channels; cytokine receptors; ligand-mediated transmembrane enzymes; intracellular receptors for lipid soluble agents as well as G proteins and second messengers (Ciccone, 2015, p. 5). Therefore, this paper principally addresses these drug-receptor interactions, including their mechanism of action and binding processes. In addition, the paper looks into the impacts of potency, specificity, affinity, antagonist, agonists and partial agonist to interaction. Discussion Drug Interaction Channels a) Ligand-gated ion channels Ligand-gated ion channels (LGICs) are types of transmembrane ion proteins which permit ions such as Cl-, K+, Na+, and Ca2+ to pass through in response to binding of a ligand or any other chemical agent like a neurotransmitter (Bakker et al., 2008, p. 267). These proteins are composed of two principal domains: an extracellular domain that includes the allosteric binding site (ligand binding location) and an ion pore which is a transmembrane domain. Some examples of ligand-gated ion channels are: serotonin receptor, acetylcholine receptors, Glutamate receptor, and GABAA. Serotonin receptors are located in the peripheral and central nervous system. The kinetics of LGICs is simple in nature (Stimmel, 2014, p. 5). They trigger both inhibitory and excitatory neurotransmission and are mediated by serotonin. They mediate the production of hormones such as epinephrine, nor-epinephrine, and many others. GABAA receptors are also ligand-gated and ionotropic channels. Upon binding of the drug such hormones are automatically triggered. Examples of drugs that bind through this mechanism include bicuculline, muscimol, and gaboxadol. b) Ligand-Regulated Transmembrane Enzymes Ligand-Regulated Transmembrane Enzymes are receptor molecules that mediate the early steps of signalling by insulin, growth factor, epidermal growth factor, platelet-derived, transforming growth factor, atrial natriuretic peptide, and many more trophic hormones. They are a type of receptors that are polypeptides in nature and comprise of extra-cellular-hormone-binding domains that bind to a cytoplasmic enzyme (Vardhini, 2014, p. 34). The enzyme can be a tyrosine kinase, a guanylate cyclase or serine. In all these receptors, the two are linked by a polypeptide, a hydrophobic domain that cuts across the lipid layers (Dubois et al., 2010, p. 1119). Upon binding of the drug (ligand) to the extracellular receptor, the receptor activates monomers to dimmers and the two receptor polypeptides bind strongly to the membrane. The cytoplasmic domains are then phosphorylated on tyrosine residues and their particular enzymatic activities or effects are activated. The tyrosine kinase receptor signalling pathway begins with binding of the drug or ligand to the external domain of the receptor. For example, monoclonal antibodies that act as antagonists of the tyrosine kinase receptors are effective in the management of breast cancer-related with over-expression of the growth factor receptor (Silverman and Holladay, 2014, p. 24). c) Intracellular Receptors for Lipid Soluble Agents Intracellular receptors are characteristically located in the cytoplasm that is located inside the cell. Therefore, it means that drugs or other ligands that use this avenue are sufficiently soluble in lipids to across the cell membrane to act on intracellular receptors. They activate the receptors and the aftermath is the transcription of genes through binding to particular DNA sequences or fragments near the target gene to be regulated. As such, binding of the drug to the receptor relieves the inhibition constraint on the process of transcription and stimulation of the receptor. A good example of the drug that uses this technique is aspirin (Sam, Waheed and Fakhreddin, 2014). d) G proteins and second messengers G-protein receptors are transmembrane receptors that stimulate G proteins (GTP-biding signal transducer proteins) that eventually regulate the production of intracellular second messengers. A majority of extracellular ligands and drugs act by enhancing intracellular concentrations of second messengers like cAMP (with adenylyl cyclases as the effectors), phosphoinositides, or calcium ion. The kinetics of these receptors is as follows. First, the drug is specifically detected by a cell-surface receptor that causes a sudden change in information. Secondly, the change in the structural conformation of the receptor activates a G protein on the cytoplasmic side of the membrane. Consequently, the activated G protein alters the activity of the effector substance, usually an ion channel or enzyme. The activity change of the effector material affects the concentration of the second messenger in the intracellular space. G protein receptors employ similar mechanisms that involve hydrolysis and binding of GTP. A good example of a drug that uses the G protein receptor is morphine, a painkiller that acts as an agonist (Dustin, Christopher and Sam, 2014). e) Cytokine receptors Cytokines are proteins that critically fight infections and other pathogens, even though they can cause diseases. As such, cytokine associated drugs act by either blocking or stimulating their activities (Zhou, 2014, p. 469). Cytokines such as interferons (IFN) and interleukins (IL) carry inter- and intra-cellular signals that control the immune response that is critical in regulating pathogens and other pathological conditions. There are several theories that suggest how cytokine-mediated receptor activation works. One idea proposes that the receptors are pre-assembled on the cell surface, and activation results from structural changes inside the receptors upon drug or ligand attachment. Examples of such drugs that inhibit cytokine action include Cyclosporin A and Pentamidine (Jenei et al., 2011, pp. 3-8). Impacts of Potency Potency is an evaluation of how much of a medicine is needed to trigger a certain response or produce a certain effect. A highly potent drug requires a less dosage to produce the desired effects. i) Affinity: Affinity refers to how tightly a drug binds or holds on to its receptors. If the drug binds well, its potency is high and the action of the drug will be felt for a very long time. For example, Antihistamine and noxalone are antagonists with very high affinity. ii) Specificity Specificity is very decisive and most companies invest significantly to ensure that drugs designed are specific to particular receptors. Non-specific medicines are very detrimental and sometimes cause more side effects. For instance, acetylcholine, a parasympathetic nervous system drug used to activate muscarinic receptors, receives competition from nicotine and muscarine. As such, more specific drugs have higher potency (Glennon and Young, 2011, p. 20). iii) Agonist, Antagonist and Partial Agonist Agonists are drugs that produce a pharmacologic effect when interacting with a receptor. They shift the equilibrium from the inactive to the active form. A good illustration is the insulin drug used to treat diabetes. They produce a maximal effect and cause higher affinity. On the other hand, partial agonist produces an incomplete or partial response when bound to a specific receptor. As such, their affinity is slightly higher. An example is Buspirone drug used to treat anxiety. Antagonists are drugs that inhibit agonists. They have high affinity, but do not activate the receptor when bound. Therefore, they do not initiate any process since they depend on the presence of an agonist. Diphenhydramine, an antihistamine, is just effective in histamine activated-receptors (Mitra, 2013, p. 4). References Arkin, M. R and Whitty, A., 2009. 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