Pharmacodynamics

Flashcards covering the foundational principles of pharmacodynamics, drug-receptor interactions, dose-response terminology, and mechanisms of tolerance and sensitization.

Pharmacology

The branch of medicine that deals with the uses, effects, and modes of actions of drugs.

Pharmacokinetics

Subfield of pharmacology dealing with the absorption, distribution, biotransformation and excretion of drugs.

Pharmacodynamics

Subfield of pharmacology dealing with the study of the biochemical effects of drugs and their mechanism of action.

Agonists

Drugs that bind to receptors and cause a biological response; they are said to have intrinsic activity.

Receptor

Receptors are specialized protein molecules located on cell membranes or within cells that interact with drugs (ligands) to initiate a series of biological effects. Each receptor type is designed to specifically bind to certain ligands, which may include endogenous substances like hormones or neurotransmitters, as well as exogenous compounds such as pharmaceuticals and toxins. The binding of a ligand to a receptor induces a conformational change in the receptor, triggering intracellular signaling pathways that result in physiological responses. Receptors can be classified into various families, such as G-protein coupled receptors (GPCRs), ion channels, and nuclear receptors, each playing distinct roles in cell communication and function.

Types of receptors in pharmacodynamics

There are several major types of receptors in pharmacodynamics, each playing unique roles in the body's response to drugs:

1. G-Protein Coupled Receptors (GPCRs)
      - The largest and most diverse group of receptors. These receptors transmit signals inside the cell through the activation of G-proteins. GPCRs are involved in various physiological processes including vision, taste, and olfactory senses, as well as responses to hormones and neurotransmitters.

2. Ion Channels
      - Membrane proteins that regulate the flow of ions across the cell membrane. They can be ligand-gated (opening in response to the binding of a ligand) or voltage-gated (opening in response to changes in membrane potential). Ion channels play critical roles in electrical signaling in neurons and muscle contraction.

Endogenous ligands

Naturally occurring substances in the body that receptors are designed to mediate the effects of, rather than drugs.

Affinity

The strength of attraction between a drug and its receptor, often represented by the inverse of the dissociation constant $Kd$.

$Kd$ (Dissociation Constant)

A value representing the rate of dissociation; lower values indicate low dissociation and high affinity.

Law of Mass Action

The principle that the magnitude of drug effect is proportional to the number of receptors occupied, and a drug produces maximal effect when all receptors are occupied.

Dose-Response Curve

A graph, typically sigmoid in shape, describing the relationship between the increase in drug dose and the resulting cellular and behavioral response.

ED50 (Effective Dose)

The dose that produces a response in $50\%$ of subjects.

TD50 (Toxic Dose)

The dose that produces a given toxic effect in $50\%$ of subjects.

LD50 (Lethal Dose)

The dose that kills $50\%$ of subjects.

Therapeutic Index (TI)

A measure of drug safety calculated as $\frac{TD50}{ED50}$.

Safety margin

The difference between the lethal dose and effective dose, calculated as $LD50 - ED50$.

Potency

How much of a drug is needed to produce a specific effect, determined by pharmacokinetic profile and receptor affinity.

Efficacy

The maximum effect that can be produced by a drug; it is determined by the drug's intrinsic activity.

Antagonists

Drugs that bind to receptors (having affinity) but have no intrinsic activity, acting by blocking the action of agonists or endogenous ligands.

Competitive Antagonists

Drugs that bind to the same receptor site as an agonist and shift the dose-response curve to the right, an effect that can be overcome by increasing the agonist dose.

Non-Competitive Antagonists

Drugs that do not compete with the agonist for the same binding site and cause a decrease in maximum effect that cannot be overcome by increasing the agonist dose.

Irreversible Antagonists

Drugs that form a long-lasting bond with receptors, where recovery of function only occurs after new receptors are synthesized.

Partial Agonists

Drugs with intermediate levels of intrinsic activity that can act as weak agonists or behave as competitive antagonists in the presence of full agonists.

Inverse Agonists

Drugs that produce a descending dose-effect curve by initiating a biological effect opposite to that produced by an agonist or endogenous ligand.

Tolerance

A phenomenon where a drug effect gets smaller with chronic administration, resulting in a shift to the right in the dose-response curve.

Sensitisation

A phenomenon where a drug effect gets bigger with repeated administration, resulting in a shift to the left in the dose-response curve.

Tachyphylaxis (Acute Tolerance)

The rapid decrease in drug effect within a single session.

Cross-tolerance

The decrease in a drug's effect resulting from the repeated administration of a different drug.

Pharmacokinetic Tolerance

Tolerance arising from metabolic changes, such as enzyme induction (e.g., increased alcohol dehydrogenase in chronic drinkers).

Pharmacodynamic Tolerance

Tolerance arising from changes to receptors and their signaling pathways, such as a decrease in receptor number.

Dependence

A pharmacological state characterized by the development of tolerance such that ceasing drug use results in withdrawal symptoms.

Withdrawal symptoms

Physical or psychological symptoms that are typically opposite to the acute effects of a drug, occurring upon cessation of use in dependent individuals.