Pharmacology Quiz

Pharmacology I Drug Receptors & Pharmacodynamics

• Receptors are specific molecules in a biological system that drugs interact with to produce changes in the system's function.
• Receptors must be selective in their ligand-binding characteristics and modifiable when they bind a drug molecule.
• Most receptors are proteins, and the receptor site for a drug is the specific binding region with high and selective affinity for the drug molecule.
• Effectors translate the drug-receptor interaction into a change in cellular activity and can be enzymes or a part of the receptor molecule.
• Graded dose-response curve graphs increasing response to increasing drug concentration or dose, and the response is continuous and gradual.
• Potency denotes the amount of drug needed to produce a given effect and is determined mainly by the affinity of the receptor for the drug and the number of receptors available.
• Efficacy, or maximal efficacy, is the greatest effect an agonist can produce and is determined mainly by the nature of the drug and the receptor and its associated effector system.
• Graded dose-binding relationship measures the percentage of receptors bound by a drug, and the concentration of drug required to bind 50% of the receptor sites is denoted as Kd.
• Spare receptors exist if the maximal drug response is obtained at less than maximal occupation of the receptors and increase sensitivity to the agonist.
• Quantal dose-response curve graphs the fraction of a population that shows a specified response at progressively increasing doses.
• Median effective dose (ED50) and median toxic dose (TD50) are determined from quantal dose-response curves and provide information about the variation in sensitivity to the drug in a given population.
• The therapeutic index is the ratio of the TD50 (or LD50) to the ED50 and represents an estimate of the safety of a drug, while the therapeutic window describes the dosage range between the minimum effective therapeutic concentration or dose, and the minimum toxic concentration or dose.

Cell Signaling Mechanisms and Receptor Regulation

• Receptors for membrane ion channels can either directly cause the opening of the channel or modify its response to other agents.
• Acetylcholine at the nicotinic receptor causes the opening of the ion channel, leading to Na+ influx and localized excitatory postsynaptic potential.
• G protein-coupled receptors bind to a large number of drugs and are linked to intracellular or membrane-bound effectors.
• When G-coupled receptors bind agonist, the G protein is activated, involving replacement of GDP with GTP and dissociation of the trimeric G protein complex.
• Cyclic adenosine monophosphate (cAMP) mediates various physiological processes such as energy mobilization and heart muscle function.
• Phospholipase C (PLC) splits phosphatidylinositol-4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3), leading to calcium release and activation of protein kinase C.
• Elevated cytoplasmic Ca+2 concentration resulting from IP3-promoted opening of channels promotes the binding of Ca+2 to calmodulin, regulating activities of other enzymes.
• IP3 is inactivated by dephosphorylation, DAG is either phosphorylated or deacylated, and Ca+2 is actively removed from the cytoplasm by Ca+2 pumps.
• Cyclic guanosine monophosphate (cGMP) is produced by membrane-bound guanylyl cyclase and acts by stimulating a cGMP-dependent protein kinase.
• Receptors are dynamically regulated in number, location, and sensitivity over short and longer periods.
• Continuous exposure to agonists can result in short-term diminution of the receptor response, due to mechanisms such as intracellular protein blocking access of a G protein and internalization of agonist-bound receptors by endocytosis.
• Removal of the agonist results in the restoration of the full receptor response after a few minutes or hours.

Pharmacological Principles in Drug Response

• Quantal dose-response curve is obtained by plotting the percentage of the population showing a response at each dose versus the log of the dose administered.
• Median effective dose (ED50) is the dose at which 50% of individuals exhibit the specified effect, while the median toxic dose (TD50) is the dose required to produce a toxic effect in 50% of animals.
• The ED50 determined by quantal dose-response measurements has no direct relation to the ED50 determined from graded dose-response curves.
• Quantal dose-response data provide information about the variation in sensitivity to the drug in a given population, with a small variation resulting in a steep curve.
• The therapeutic index is the ratio of the TD50 (or LD50) to the ED50, representing an estimate of the safety of a drug.
• The therapeutic window describes the dosage range between the minimum effective therapeutic concentration or dose, and the minimum toxic concentration or dose.
• Full agonists fully activate the effector system when they bind to the receptor, while partial agonists produce less than the full effect even when saturated.
• Inverse agonists induce a pharmacological response opposite to that of an agonist, and neutral antagonists have no activity in the absence of an agonist but can block the activity of either.
• Competitive antagonists bind to the agonist receptor site in a reversible way without activating the effector system for that receptor.
• Irreversible antagonists cause a downward shift of the maximum effect, with no shift of the curve on the dose axis unless spare receptors are present.
• Physiological antagonists bind to a different receptor molecule, producing an effect opposite to that produced by the drug it antagonizes, differing from pharmacological antagonists.
• Understanding these principles is crucial for determining drug potency, efficacy, and safety, as well as for developing effective pharmacological interventions.