Pharmacology Basics Quiz

Study Notes

Pharmacology: The Study of Drugs

Pharmacology explores how drugs interact with living organisms.
Toxicology examines the harmful effects of chemicals on living systems.
A drug is any substance intended for diagnosis, prevention, or treatment of diseases in humans or animals.
Drugs can be natural, synthetic, or pharmaceutical preparations.
Xenobiotics refer to drugs produced outside the body, either synthetic or natural.
A poison is a drug that can kill.
A toxin is a poison produced by a living organism, such as plants or animals.
Receptors are macromolecules, usually proteins, that bind to drugs and trigger cellular changes.
Drug-receptor interactions are typically reversible and the response is proportional to the drug concentration.
Ligands bind to receptors, initiating biochemical reactions within the cell.
Ligands can be exogenous (drugs) or endogenous (neurotransmitters, hormones, growth factors).
Not all drugs work through receptor interactions, such as antacids neutralizing stomach acid.

Types and Locations of Receptors

Transmembrane ligand-gated ion channels (Ionotropic receptors):
- The extracellular portion of these receptors binds to drugs and regulates the opening of ion channels in cell membranes.
- These channels allow ions like Na+, K+, Ca2+, and Cl- to pass through.
- Activation by an agonist opens the channel for milliseconds.
- Binding sites are also found on voltage-gated ion channels, regulating their function.
- Local anesthetics block sodium influx by binding to voltage-gated sodium channels, reducing neural conduction.
- Ion channels are found in excitable cells like neurons and muscle cells.
Transmembrane G protein-coupled receptors (Metabotropic receptors):
- The extracellular portion of these receptors binds to ligands.
- The intracellular portion interacts with G proteins, which activate cellular effectors (enzymes or ion channels).
- Responses typically last seconds to minutes.
- Activated effectors often produce 'second messengers' that trigger further signaling cascades.
Enzyme-linked receptors:
- Receptors for insulin and other growth factors directly linked to tyrosine kinase.
- They have large extracellular and intracellular domains.
- Hormone binding activates tyrosine kinase in the intracellular domain.
- Activated tyrosine kinase activates cellular enzymes, leading to gene transcription and cellular responses.
Intracellular receptors:
- Located in the nucleus or cytoplasm, these receptors bind to steroid and thyroid hormones.
- These hormones are lipid-soluble and easily enter cells.
- After binding, the receptor undergoes conformational changes, exposing a DNA-binding domain.
- The receptor-hormone complex binds to DNA, activating specific genes and increasing protein synthesis.

Drug Actions and Antagonism

Agonist: A drug that binds to a receptor and produces a pharmacological effect.
Partial agonist: A drug that binds to a receptor but produces a weaker effect than a full agonist.
Antagonist: A drug that binds to a receptor but does not activate it, preventing agonists from binding or activating the receptor.
Antagonism can be:
- Competitive: Both agonist and antagonist bind reversibly to the same site on the receptor, and the effect can be overcome by increasing the agonist concentration.
- Noncompetitive:
  - Irreversible: The antagonist binds irreversibly to the receptor, permanently reducing available receptor sites for agonists.
  - Allosteric: The antagonist binds to a site other than the agonist-binding site, preventing receptor activation.
- Physiological (functional): Two drugs act at different receptors or through different mechanisms on the same physiological system, causing opposite effects (e.g., insulin and glucagon on blood sugar).

Dose-Response Relationships

The pharmacological effect of a drug depends on its concentration at the site of action, which is determined by the dose administered.
This relationship is called the 'dose-response relationship'.
Graded dose-response curves:
- Plot the magnitude of response against increasing drug doses.
- Reveal important drug characteristics:
  - Potency: The amount of drug required to produce a desired response. Lower doses for the same effect mean higher potency.
  - Efficacy: The maximum response a drug can produce, regardless of dose. Efficacy is more clinically useful than potency.
Quantal dose-response curves:
- Plot the proportion of a population that responds to a specific dose of a drug.
- Useful for determining doses that produce a therapeutic response in a majority of the population.
- ED50: The dose that causes a therapeutic response in 50% of the population.
Therapeutic index (TI):
- The ratio of the toxic dose (TD50) to the effective dose (ED50) of a drug.
- A large TI indicates a wide margin between effective and toxic doses, making the drug safer.
- Drugs with small TIs require careful monitoring.

Examples of Therapeutic Indices

Warfarin: A drug with a small therapeutic index, requiring careful monitoring due to the narrow margin between efficacy and toxicity.
Penicillin: A drug with a large therapeutic index, considered relatively safe because of a wide margin between effective and toxic doses.