Pharmacodynamics (PD) is the study of the biochemical, physiological, and molecular effects of drugs on the body and involves receptor binding (including receptor sensitivity), post receptor effects, and chemical interactions. Pharmacodynamics is also described as what drug does to the body. It include physiological and biochemical effects of drugs and their mechanism of action at organ system/sub-cellular/macromolecular levels. Modification of the action of one drug by another drug is also an aspect of pharmacodynamics.
Factors Affecting Drug’s Pharmacodynamics
A drug’s pharmacodynamics can be affected by physiologic changes due to:
- A disorder or disease
- Aging process
- Other drugs
Disorders that affect pharmacodynamic responses include genetic mutations, thyrotoxicosis, malnutrition, myasthenia gravis, Parkinson disease, and some forms of insulin-resistant diabetes mellitus. These disorders can change receptor binding, alter the level of binding proteins, or decrease receptor sensitivity. Aging tends to also affect pharmacodynamic responses through alterations in receptor binding or in post receptor response sensitivity.
Mechanism of Drug’s Pharmacodynamic Effects
Majority of drugs produce their effects by interacting with a discrete target biomolecule, which usually is a protein. Such mechanism confers selectivity of action to the drug. Functional proteins that are targets of drug action can be grouped into four major categories; viz. enzymes, ion channels, transporters, and receptors.
Receptors
The largest number of drugs do not bind directly to the effectors, viz. enzymes, channels, transporters, structural proteins, template biomolecules, etc. but act through specific regulatory macromolecules which control the above listed effectors. These regulatory macromolecules or the sites on them which bind and interact with the drug are called ‘receptors’.
Functions of receptors can be summarized into:
- To propagate regulatory signals from outside to inside the effector cell when the molecular species carrying the signal cannot itself penetrate the cell membrane.
- To amplify the signal.
- To integrate various extracellular and intracellular regulatory signals.
- To adapt to short term and long-term changes in the regulatory milieu and maintain homeostasis.
Dose-Response Relationship
When a drug is administered systemically, the dose-response relationship has two components; the dose-plasma concentration relationship and the plasma concentration-response relationship. The former is determined by pharmacokinetic considerations and ordinarily, descriptions of dose-response relationship refer to the latter, which can be more easily studied in vitro.
Understanding the exposure-response relationship between Pharmacokinetics and Pharmacodynamics is key to the development and approval of every drug. Pharmacokinetics and Pharmacodynamics data contribute much of what is on a drug package insert. A well-characterized Pharmacokinetics Pharmacodynamics studies are an important tool in guiding the design of future experiments and trials.
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