Growth Factors and Receptor Mechanisms Quiz

Pharmacology Fundamentals

• Pharmacology is the study of substances that interact with living systems through chemical processes.
• Medical pharmacology focuses on substances used to prevent, diagnose, and treat diseases.
• Toxicology studies substances with undesirable effects on living systems.

Pharmacodynamics (PD)

• Pharmacodynamics describes the drug's actions on the body.
• This includes biochemical and physiological effects, and Mechanism of Action (MOA) of drugs.
• Drug Classes are crucial in understanding pharmacodynamics.

Pharmacokinetics (PK)

• Pharmacokinetics describes the body's action on the drug.
• This encompasses absorption, distribution, metabolism, and excretion (ADME).
• ADME studies are integral to understanding how the body processes drugs.

Receptors

• A receptor is a macromolecule within an organism or cell that interacts with a ligand (either a drug or endogenous molecule) sparking a chain of biochemical events.
• Agonists are drugs that bind to and activate a receptor.
• Antagonists bind to a receptor but prevent agonist binding, and do not activate the receptor.
• They are also known as "blockers".

Receptor Types

• Ion channels (ligand-gated, voltage-gated, second messenger gated)
• G-protein coupled receptors
• Receptor tyrosine kinases
• Intracellular hormone receptors

Partial Agonist

• A partial agonist binds to a receptor and activates it.
• Its effect is less than that of a full agonist.
• Buprenorphine is an example for opioid addiction treatment.

Inverse Agonist

• Binds to a receptor and stabilizes it in the inactive conformation.
• This model accounts for constitutive activity (receptor activity in the absence of ligands).
• Constitutive activity exists in some receptors.

Receptors without Constitutive Activity

• Inverse agonists do not apply to receptors without inherent constitutive activity

Receptors for Various Ligands

• Benzodiazepines
• Opiates
• Serotonin
• Cannabinoids
• Histamine
• Receptors for these populations undergo conformational changes and activate G proteins.

Dose-Response Curves

• Graded dose-response curves relate drug concentration to the magnitude of the response.
• EC50 represents the concentration required for 50% maximal effect.
• Maximal efficacy refers to the upper limit of the response.

Receptor Occupancy

• Receptor occupancy (B) is proportional to drug concentration (C).
• Higher Kd means lower affinity, and smaller B.
• Lower Kd means higher affinity, and higher B.

Spare Receptors

• Spare receptors allow maximal response at less-than-100% receptor occupancy.
• This increase sensitivity to drugs.
• This phenomenon is especially important for drugs (including many hormones) which exert their effect through spare receptors in tissues.

Receptor-Effector Coupling

• This describes the process where an agonist activates a receptor causing a biological response.
• There are linear and non-linear responses.

Drug Receptor Function

• Relationship between drug concentration (dose) and pharmacologic response.
• Signaling mechanisms of drug action.
• Relationship between dose and clinical response.

Intracellular Receptors

• Lipophilic hormones (e.g., steroids, thyroid hormones) pass through membranes.
• These medications cause alterations in gene transcription and subsequent protein synthesis within the target cell.

Ligand Regulatory Transmembrane Enzymes

• Similar to tyrosine kinases in their action and function.
• Ligand binding impacts enzymatic activity, primarily within the cytoplasmic domain of the receptor.

Receptor Tyrosine Kinases

• These are receptors with enzymatic activity.
• The ligand binding portion activates the receptor, and this activation leads to phosphorylation of tyrosines on the cytoplasmic domains.

Cytokine Receptors

• These receptors have kinase domains (JAKs).
• Cytokine binding causes activation of the kinase domains, resulting in downstream signaling cascades to effect change.

Ligand-Regulated Ion Channels

• Examples include receptors for acetylcholine, serotonin, GABA, and glutamine.
• These channels regulate ion flow across the cellular membrane.
• The channels respond quickly to agonists.

G Protein-Coupled Receptors

• "Serpentine receptors" with seven transmembrane regions are essential.
• Ligand binding prompts intracellular changes in G proteins.
• G proteins utilize secondary messengers.

Cholera Toxin and G-Proteins

• Cholera toxin permanently activates G protein signaling, resulting in constant water and electrolyte secretion.

Receptor Desensitization

• This is the waning response to an agonist that is still present in the system.
• Agonist binding over time causes GRK (receptor kinase) to be activated leading to phosphorylation of the receptor which eventually leads to attenuation of cell function.

Chemical Antagonists

• These are substances that bind to another substance, often a drug, which then reduces the effect of the agonist.
• Heparin and protamine sulfate are examples of this mechanism.

Physiological Antagonists

• Act on different receptor-effector systems.
• They oppose the effects of other substances, such as insulin opposing the effect of glucocorticoids on blood glucose.

Cyclic AMP (cAMP)

• A crucial second messenger.
• It's involved in various cellular processes, including glycogenolysis, adipocyte lipolysis, and protein synthesis.

Ca2+ and Phosphoinositides

• Ca2+ and phosphoinositides are involved in various cellular signal transduction pathways.

Cyclic GMP (cGMP)

• cGMP is a crucial signaling molecule, and is involved in functions such as the relaxation of smooth muscle cells in the vasculature.

Variations in Drug Responsiveness

• Idiosyncratic drug response
• Hyperreactive drug response
• Hyporeactive drug response
• Tolerance
• Tachyphylaxis

Mechanisms of Variations in Drug Responsiveness

• Alterations in drug concentration at the receptor.
• Variation in concentration of endogenous receptors.
• Alterations in number of receptors.
• Change in responsiveness distal to receptor.
• Differences in pharmacokinetics.
• Differences in drug metabolism and transport.

Clinical Selectivity

• Drugs often have both beneficial and toxic effects.
• Similar mechanisms can result in different effects.
• Differences in receptor types/tissues also lead to differences in effects and consequences.