PHARMACODYNAMICS

Pharmacodynamics is the study of the physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect.

Effects on the body

The majority of drugs either

 (a) mimic or inhibit normal physiological/biochemical processes or inhibit pathological processes in animals    (b) inhibit vital processes of endo- or ectoparasites and microbial organisms.

There are 5 main drug actions:

depressing

stimulating

destroying cells (cytotoxicity)

irritation

replacing substancesDesired activity

The desired activity of a drug :

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).In principle, a pharmacologist would aim for a target 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 concentrations 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.

Undesirable effects

Undesirable effects of a drug

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

PHARMACOKINETICS

Pharmacokinetics is the study of drug absorption, distribution, metabolism, and excretion . A fundamental concept in pharmacokinetics is drug clearance, that is, elimination of drugs from the body, analogous to the concept of creatinine clearance. In clinical practice, clearance of a drug is rarely measured directly but is calculated as either of the following:

AUC, the area under the curve, represents the total drug exposure integrated over time and is an important parameter for both pharmacokinetic and pharmacodynamic analyses. As indicated in equation 1, the clearance is simply the ratio of the dose to the AUC, so that the higher the AUC for a given dose, the lower the clearance. If a drug is administered by continuous infusion and a steady state is achieved, the clearance can be estimated from a single measurement of the plasma drug concentration (Css) as in equation 2.

Clearance can conceptually be considered to be a function of both distribution and elimination. In the simplest pharmacokinetic model,

V is the volume of distribution, and K is the elimination constant. V is the volume of fluid in which the dose is initially diluted, and thus the higher the V, the lower the initial concentration. K is the elimination constant, which is inversely proportional to the half-life, the period of time that must elapse to reach a 50% decrease in plasma concentration. When the half-life is short, K is high and plasma concentrations decline rapidly. Thus both a high V and a high K result in relatively low plasma concentrations and a high clearance.