Drugs pharmacodynamic phase

Drugp act in various ways in the body. Oral drugp go through three phases the pharmaceutic phase, pharmacokinetic phase, and pharmacodynamic phase Liquid and parenteral drug (drug given by injection) go through the later two phases only. 

Structural Integrity of a Drug Molecule Pharmaceutical, Pharmacokinetic and Pharmacodynamic Phases... 

When using QSAR calculations to optimize a drug for the pharmacodynamic phase, it is important to use relevant biological activities. If in vivo activities are used, the bioactivities will be influenced by pharmacokinetic and pharmaceutical factors. In order for QSAR calculations to reflect the pharmacodynamic phase, the bioactivities should be based on in vitro data — optimally, receptor binding studies. 

QSAR studies are not restricted to the optimization of biological activity at the pharmacodynamic phase. Since toxicity also arises from drug-receptor interactions, the QSAR... 

Once the lead dmg molecule has been optimized for the pharmacodynamic phase, it must next be optimized for the pharmacokinetic and pharmaceutical phases. If a dmg molecule cannot withstand the trip from the gut to the receptor microenvironment, it makes no difference whether the drug actually binds to the receptor. 

Figure 3.11 Failure of drug molecules. Many drugs that are successful in the pharmacodynamic phase ultimately fail to become useful drugs. This pie-chart presents the reasons for failure at this stage of the development process. Toxicity is an important cause of failure.

Define the terms pharmacokinetic phase and pharmacodynamic phase in the context of drug action. List the main general factors that affect these phases. 

For definitions see Section 2.7. The factors affecting the pharmacokinetic phase are ADME. The factor affecting the pharmacodynamic phase is the stereoelectronic structure of the drug molecule. 

Shape and stereochemical. These properties affect the pharmacodynamic phase of drug action and influence the drug s interaction with its target receptor. Shape and stereochemical properties describe the structural arrangement of the drug molecule s constituent atoms and influence the molecule s final approach toward the target receptor. 

Electronic. Electronic properties also affect the pharmacodynamic phase of drug action. The electronic properties of a molecule are governed by the... 

In both pharmacokinetic and pharmacodynamic considerations, an important emphasis concerns the rate at which events occur and the rate at which circumstances change. The pharmacokinetic phase covers the relationship between drug input and the concentration achieved over time. The pharmacodynamic phase covers the relationship between concentration and the therapeutic effect over time (toxicodynamics is concerned with the relationship between concentration and adverse effects over time). 

In the foregoing sections, pharmacon metabolism has been considered in relation to the pharmacodynamic, especially toxic aspects of action. Drug distribution also plays a role in the pharmacodynamic phase of drug action. Modulation of drug distribution, for instance, exclusion of penetration of particular barriers in the organism (e.g. the blood-brain barrier), or preferential bioactivation or bioinactivation in particular tissues, can modulate the spectrum of action of compounds and possibly exclude particular undesired effects. 

Pharmacodynamic Phase This is the effect the drug has on the body. 

The pharmacodynamics phase corresponds to the way in which a drug binds to receptors, transporters, and channels in order to elicit a particular action from a cell (this is called signal transduction). This is referred to as the mechanism of action. While researchers attempt to determine the mechanism of action of promising compounds in order to better predict therapeutic outcomes and unexpected effects, often times the exact mechanism remains unknown, even after the drug has been approved for use. 

Pharmacodynamic phase Quality of the drug-receptor interaction Nature and intensity of the biological response Maximal activity Maximal selectivity Minimal toxicity... 

While pharmacokinetics investigates what the body does to the drug, pharmacodynamics is concerned with what the drug does to the body. Most scientists who consider themselves to be medicinal chemists will be most comfortable with and interested in this phase. They will cooperate with biochemists and pharmacologists to elucidate mechanistic details of the interaction of the drug with its target(s), a topic we will treat in the Section III. 

The cl mg discovery process can be envisioned as four interconnected phases (see Figure 8.1). Generally, these are the acquisition of chemicals to be tested for biological activity, the determination of the activity of those chemicals on biological systems (pharmacodynamics), the formulation of the most active of these for therapeutic testing in humans (pharmaceutics), and the determination of adequate delivery of the active drug to diseased tissues (pharmacokinetics). Each of these collections of processes is interconnected with the others and failure in any one of them can halt the development process. It is worth considering each process separately, as well as the relationships between them. 

---