Pharmacodynamics is the study of the biochemical and physiological effects of drugs and the mechanisms of drug action and the relationship between drug concentration and effect. It is often summarily stated that pharmacodynamics is the study of what a drug does to the body, whereas pharmacokinetics is the study of what the body does to a drug. Biochemistry is the chemistry of life. ... Physiology (in Greek physis = nature and logos = word) is the study of the mechanical, physical, and biochemical functions of living organisms. ... It has been suggested that Blockbuster drug be merged into this article or section. ... Pharmacokinetics (in Greek: pharmacon meaning drug, and kinetikos meaning putting in motion) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. ...

Pharmacodynamics is sometimes abbreviated as "PD", and when referred to in conjunction with pharmacokinetics can be referred to as "PK/PD."

Drug action

Effects on the body

There are 4 main drug actions:

• depressing
• stimulating
• destroying cells
• replacing substances

is what happens when the shit hits the fan ...

Desired activity

The desired activity of a drug is mainly due to one of the following:

• Cellular membrane disruption
• Chemical reaction
• Interaction with enzyme proteins
• Interaction with structural proteins
• Interaction with carrier proteins
• Interaction with ion channels
• Ligand binding to receptors:
  • Hormone receptors
  • Neuromodulator receptors
  • Neurotransmitter receptors

General anesthetics were once thought to work by disordering the neural membranes, thereby altering the Na⁺ influx. Antacids and chelating agents combine chemically in the body. Enzyme-substrate binding is a way to alter the production or metabolism of key endogenous chemicals, for example aspirin irreversibly inhibits the enzyme prostaglandin synthetase (cyclooxygenase) thereby preventing inflammatory response. Colchicine, a drug for gout, interferes with the function of the structural protein tubulin, while Digitalis, a drug still used in heart failure, inhibits the activity of the carrier molecule, Na-K-ATPase pump. The widest class of drugs act as ligands which bind to receptors which determine cellular effects. Upon drug binding, receptors can elicit their normal action (agonist), blocked action (antagonist), or even action opposite to normal (inverse agonist). Drawing of a cell membrane A component of every biological cell, the selectively permeable cell membrane (or plasma membrane or plasmalemma) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Vapours of hydrogen chloride in a beaker and ammonia in a test tube meet to form a cloud of a new substance, ammonium chloride A chemical reaction is a process that results in the interconversion of chemical substances. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... The structure of a thing is how the parts of it relate to each other, how it is put together. This contrast with process, which is how the thing works; but process requires a viable structure. ... Carrier proteins are membrane proteins that transport a specific substance or group of substances in the blood or across the cell membrane. ... Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... Structural genomics or structural bioinformatics refers to the analysis of macromolecular structure particularly proteins, using computational tools and theoretical frameworks. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... A neuromodulator is a substance other than a neurotransmitter, released by a neuron at a synapse and conveying information to adjacent or distant neurons, either enhancing or damping their activities. ... Chemical structure of D-aspartic acid, a common amino acid neurotransmitter. ... A general anaesthetic drug is an anaesthetic (or anesthetic AE) drug that brings about a reversible loss of consciousness. ... A bottle of antacid tablets An antacid is any substance, generally a base, which counteracts stomach acidity. ... Chelation (from Greek, claw like) describes the reversible binding of an organic ligand, the chelator or chelating agent, to a metal ion, forming a metal complex, the chelate. ... The word endogenous means arising from within. Compare exogenous. ... Aspirin, or acetylsalicylic acid (IPA: ), (acetosal) is a drug in the family of salicylates, often used as an analgesic (to relieve minor aches and pains), antipyretic (to reduce fever), and as an anti-inflammatory. ... Cyclooxygenase (COX) is an enzyme (EC 1. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... Colchicine is a highly deadly poisonous alkaloid, originally extracted from plants of the genus Colchicum (Autumn crocus, also known as the Meadow saffron). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. ... Tubulin is the protein which makes up microtubules. ... Species About 20 species, including: Digitalis cariensis Digitalis ciliata Digitalis davisiana Digitalis dubia Digitalis ferruginea Digitalis grandiflora Digitalis laevigata Digitalis lanata Digitalis leucophaea Digitalis lutea Digitalis obscura Digitalis parviflora Digitalis purpurea Digitalis thapsi Digitalis trojana Digitalis viridiflora Digitalis is a genus of about 20 species of herbaceous biennials, perennials and... Flow of ions. ...

In principle, a pharmacologist would aim for a certain plasma concentration of the drug for a desired level of response. In reality, there are many factors affecting this goal. Pharmacokinetic factors determine peak concentrations, and levels cannot be maintained with absolute consistency because of metabolic breakdown and excretory clearance. Genetic factors may exist which would alter metabolism or drug action itself, and a patient's immediate status may also affect indicated dosage. Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... DNA, the molecular basis for inheritance. ...

Undesirable effects

Undesirable effects of a drug include:

• Increased probability of cell mutation (carcinogenic activity)
• A multitude of simultaneous assorted actions which may be deleterious
• Interaction (additive, multiplicative, or metabolic)
• Induced physiological damage, or abnormal chronic conditions

In biology, a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) of an organism and thus increases the number of mutations above the natural background level. ... The hazard symbol for carcinogenic chemicals in the Globally Harmonized System. ...

Receptor binding

The binding of ligands (drug) to receptors is governed by the law of mass action which relates the large-scale status to the rate of numerous molecular processes. The rates of formation and un-formation can be used to determine the equilibrium concentration of bound receptors. Although the receptors are fixed to a 2-dimensional membrane, an arbitrary control volume can be used to calculate the dissociation constant, The Law of Mass Action, first expressed by Waage and Guldberg in 1864 [1], states (in modern language) that the rate of a chemical reaction is proportional to probability that the reacting molecules will be found together in a small volume. ...

where L=ligand, R=receptor, square brackets [] denote concentration. The fraction of bound receptors is found as (1+[R]/[L·R])^-1 , which can then be expressed using K_d as,

Semi-log plots of two agonists with different K_d.

This expression is one way to consider the efficacy of a drug, in which the response may be directly proportional to the fraction of bound receptors. Often the response is determined as a function of log[L] to consider many orders of dosage range. It is useful to note that 50% of the receptors are bound when [L]=K_d . Image File history File links DoseResponse000. ... Image File history File links DoseResponse000. ...

A plot of the function for the bound fraction of receptors forms a typical model for the dose response of a drug. The graph shown represents the dose-response for two hypothetical receptor agonists, plotted in a semi-log fashion. The curve toward the left represents a higher potency (potency arrow does not indicate direction of increase) since lower concentrations are needed for a given response. The efficacy increases as a function of concentration. A dose-response curve is a simple X-Y graph with Y usually being the measured dose (usually in milligrams, micrograms, or grams per kilogram of body-wieght) and X being the response. ...

Multicellular pharmacodynamics

The concept of pharmacodynamics has been expanded to include Multicellular Pharmacodynamics (MCPD). MCPD is the study of the static and dynamic properties and relationships between a set of drugs and a dynamic and diverse multicellular 4 dimensional organization. It is the study of the workings of a drug on a minimal multicellular system (mMCS), both in vivo and in silico. Networked Multicellular Pharmacodynamics (Net-MCPD) further extends the concept of MCPD to model regulatory genomic networks together with signal transduction pathways, as part of a complex of interacting components in the cell. For a fuller explanation of these concepts see the articles:

• Jackson, R.C. (2003) Predictive software for drug design and development. Pharmaceutical Development and Regulation 1 ((3)), 159-168.

• Werner, E., In silico multicellular systems biology and minimal genomes, DDT vol 8, no 24, pp 1121-1127, Dec 2003. (Introduces the concepts MCPD and Net-MCPD)

A good source for further information and posting to experts can be found courtesy of Dr. David W. A. Bourne, OU College of Pharmacy [1].

See also

• Dose-response relationship
• Pharmacokinetics
• ADME
• Pharmaceutical company
• Schild regression