History of Pharmacology and Drug-Receptor Interactions

History of Pharmacology

• François Magendie published an influential formulary in the early 1800s.
• Spanish physician Orfila made significant contributions to toxicology in 1813.
• Claude Bernard determined the action of digitalis on the heart in the mid-1800s.
• Rudolph Buchheim established the first laboratory dedicated to experimental pharmacology.
• He published numerous contributions on drug actions and classified drugs in his textbook.
• He insisted on demonstrating the actions of drugs in a laboratory setting.
• Oswald Schmiedeberg, a student of Buchheim, further developed pharmacology.
• He transformed pharmacology into an independent scientific discipline.
• Schmiedeberg explored the relationship between chemical structure and drug efficacy.
• He oversaw the publication of the inaugural pharmacology journal in 1975.
• Schmiedeberg's influence on pharmacology extended throughout Europe and America.

Drug-Receptor Interactions

• Drugs exhibit specific interactions with target molecules within the body.
• The molecular shape of a drug influences its binding affinity to receptors.
• Drug receptors are molecules that interact with drugs to produce effects.
• Receptors comprise a ligand-binding site and an effector site.
• Most drug receptors are proteins.
• Drug receptors can be broadly classified as receptors, enzymes, carriers, and ion channels.
• Agonists are drugs that mimic the effects of endogenous compounds.
• Antagonists block the actions of agonists by competing for the same binding sites.
• Not all drugs require receptors to exert their effects.

Drug Activity

• Drug activity refers to the molecular-level interactions of drugs with receptors.
• Drug action describes the physiological effects resulting from drug activity.
• Drug-receptor complexes form when drug molecules interact with receptors.
• Affinity refers to the drug's tendency to bind with a specific receptor.
• Intrinsic activity, or efficacy, describes the capacity of a drug to produce an effect.
• Covalent bonds are strong and often irreversible drug-receptor interactions.
• Ionic bonds occur from electrostatic interactions between oppositely charged ions.
• Hydrogen bonds, weaker than covalent bonds, form between proton donors and acceptors.
• Van der Waals forces are very weak interactions that arise from dipole-dipole or dipole-induced dipole interactions.
• Non-specific receptors do not result in drug effects.

Drug Interactions

• Additive interactions: the combined effect of two drugs equals the sum of their individual effects.
• Synergism: the combined effect of two drugs is greater than the sum of their individual effects.
• Potentiation: a drug with no intrinsic activity enhances the effect of another drug.
• Chemical interactions occur when drugs chemically interfere with each other.
• Intra-articular drug administration may result in difficulties targeting the joint space and potential irritation.
• Oral administration is safe, convenient, and cost-effective.
• Absorption of orally administered drugs is complex and influenced by multiple factors.
• Topical application provides local effects and absorption varies depending on lipid solubility and skin characteristics.

Oral Drug Administration

• Drugs may be destroyed by digestive enzymes or gut flora.
• Absorption and bioavailability are variable due to physiological factors and food presence.
• The first-pass effect involves liver metabolism before drugs reach the bloodstream.
• Oral administration can affect normal gut flora and cause irritation.
• Anticholinergics and narcotics may delay gastric emptying and prolong drug onset.
• Increased gut motility can shorten drug contact time and reduce absorption.
• Different species have varied gastrointestinal compartments and characteristics impacting drug absorption.

Topical Drug Administration

• Topical application can be painless and useful for both systemic and local treatments.
• Application frequency depends on the specific disease, drug, and formulation.
• Topical application can be used for eyes and ears to address various issues.