Pharmacology: Drug Categories and Actions

• Drugs are categorized (scheduled) based on safety concerns and abuse potential.
• The scheduling of drugs dictates how the drug is obtained and prescribed.
• NAPRA I drugs require a prescription for sale (e.g., narcotics).
• NAPRA II drugs do not require a prescription but must be dispensed by a pharmacist (e.g., insulin).
• NAPRA III drugs can be obtained at a pharmacy without a pharmacist's assistance (e.g., Zantac).
• Unscheduled drugs can be obtained at retail stores and pharmacies
• A drug (or ligand) is a substance that causes a biological change through chemical actions
• Pharmacodynamics refers to the actions of drugs on the body whereas pharmacokinetics refers to actions of the body on drugs
• Useful drugs should be inactivated and excreted at a reasonable rate to avoid prolonged action
• At room temperature, most drugs are solids.
• Most drugs are small organic molecules that interact with macromolecules (receptors).
• Proteins are the most important type of receptor for drugs.
• Physiological receptors normally respond to endogenous regulatory ligands
• The signal transduction pathway involves the receptor, its cellular target, and intermediary molecules.
• Some drugs do not act on receptors.
• Antacids directly neutralize HCl in the stomach.
• Osmotic diuretics promote increased urine formation via osmotic forces in renal tubules.
• Drug and receptor structure and chemical properties dictate drug selectivity.
• Proteins consist of a sequence of amino acids determined by DNA.
• Proteins' amino acids interact, forming secondary structures.
• Hydrogen bonds are a key component of secondary structures.
• Alpha-helices, beta-barrels, and beta-pleated sheets exemplify secondary structures.
• Tertiary structures involve interactions of more distant amino acids, including hydrogen, ionic, and covalent bonds.
• Quaternary structures form from the interaction of multiple polypeptides.

Drug-Receptor Interactions

• The receptor binding site has unique properties that enable the drug to interact and bind.
• Affinity dictates favourability of a drug-receptor binding interaction
• Drugs need adequate size, charge, shape, and composition to interact selectively with receptors.
• The ideal drug would interact only with a molecular target producing desired therapeutic effects but not with molecular targets producing adverse effects

Size

• Drug size ranges from 100-1000 Daltons (Da).
• The lower limit of 100 Da facilitates specificity of action and receptor binding.
• The upper limit of 1000 Da allows reasonable movement in the body.
• Large drugs, such as protein therapeutics, are administered directly into compartments for effect.

Charge

• Chemical forces or bonds mediate drug and receptor interactions.
• Drugs binding through multiple weak bonds are more selective due to the requirement of a more precise fit.
• Most drugs use a combination of covalent, ionic, hydrogen, and Van der Waals interactions.
• Covalent bonds are usually irreversible, requiring cells to synthesize new receptors.

Shape and Atomic Composition

• A drug's shape and atomic makeup must allow binding to its receptors (lock-and-key interaction).

Stereochemistry

• Enantiomers (optical isomers) can exist for drugs with chiral centers and are named S (left-handed) and R (right-handed).
• One enantiomer is typically more potent due to a better receptor fit.
• A racemic mixture contains a 50:50 mix of both enantiomers.
• Enantiomers may exhibit differing pharmacokinetics and pharmacodynamics.
• Left rotation is sinister, right rotation is rectinsum

Selectivity

• The ideal drug would interact only with desired molecular target, producing therapeutic effects while avoiding other molecular targets that would produce adverse effects
• Restricted cell-type distribution enhances drug selectivity.
• Ranitidine (H2 receptor antagonist) treats gastroduodenal ulcers with limited effects due to H2 receptor restriction in the stomach.
• Lidocaine (Na+ channel blocker) is a local anesthetic, but can have widespread adverse effects if it reaches systemic circulation due to broad Na+ channel expression.

Explore drug categorization based on safety and abuse potential, including NAPRA schedules. Understand pharmacodynamics and pharmacokinetics, focusing on drug actions and the body's response. Many drugs are small, organic solids interacting with protein receptors.