Master Drug-Receptor Interaction

Key Concepts in Drug-Receptor Interaction

• Signal amplification is a characteristic of GPCRs and enzyme-linked receptors that allows for the amplification of signal intensity and duration via a signal cascade effect.
• Spare receptors are unoccupied receptors that exist due to signal amplification and are used only in case of receptor damage or blockage.
• Signal counteraction can occur through different mechanisms such as tachyphylaxis, down-regulation, up-regulation, super sensitization, and tolerance.
• Tachyphylaxis is the desensitization of a receptor following excessive agonist stimulation to minimize the agonist response.
• Down-regulation is the decrease in the number of receptors due to repeated exposure to the agonist.
• Up-regulation is the increase in the number of receptors available due to repeated exposure to an antagonist.
• Super sensitization is the increase in the response of the receptor to agonists and/or making the receptor more resistant to the antagonist.
• Tolerance is the diminished response to the same dose of a drug over days or weeks and occurs by tachyphylaxis or down-regulation.
• Refractory receptors require a finite time following stimulation before they can be activated again and are unresponsive during this recovery phase.
• Efficacy is the intrinsic activity of a drug, which is the ability of an agonist to activate its specific receptor, and depends on the number of drug-receptor complexes and the intrinsic activity of the drug.
• Receptors are present in an equilibrium between active and inactive states, with unbounded receptors being inactive and requiring an agonist to be active.
• Constitutive activity is the spontaneous conversion from Rinactive to Ractive in the absence of an agonist and is a characteristic of some receptors.

Comparison of Parasympathetic and Sympathetic Nervous System

• The Parasympathetic Nervous System originates from craniosacral nerves, while the Sympathetic Nervous System originates from thoracolumbar nerves of the spinal cord.
• The Parasympathetic Nervous System has long pre-ganglionic fibers and short post-ganglionic fibers, while the Sympathetic Nervous System has short pre-ganglionic fibers and long post-ganglionic fibers.
• The ganglia of the Parasympathetic Nervous System is near or on the effector organ, while the ganglia of the Sympathetic Nervous System is in the paravertebral chain on either side of the spinal cord.
• The Parasympathetic Nervous System uses Ach as the NT in ganglia and post-ganglia, while the Sympathetic Nervous System uses Ach in ganglia and NA & A in post-ganglia.
• Both systems have cholinergic receptors (nicotinic and muscarinic) and adrenergic receptors (alpha and beta).
• Cholinergic and adrenergic drugs can act as agonists or antagonists on the receptors of the ANS.
• The Parasympathetic Nervous System maintains essential functions such as digestion and elimination, while the Sympathetic Nervous System prepares the body for stress conditions.
• Most organs are innervated by both systems, but they usually oppose each other in action.
• Exceptions to dual innervation include the salivary glands, constrictor pupillae muscle, dilator pupillae muscle, most blood vessels, pilomotor muscle, sweat glands, and adrenal medulla.
• The adrenal medulla is considered a modified sympathetic ganglion that releases NA and A directly into the blood.
• The Enteric Nervous System is the third division of the ANS that innervates the GIT, pancreas, and gallbladder and functions independently of the CNS.
• The Enteric Nervous System is modulated by both the sympathetic (inhibits it) and parasympathetic (stimulates it) nervous systems.