How Drugs Act

Factors Affecting Bioactivity

The biochemical systems encountered by a drug molecule are extremely complex. Therefore, it should not be surprising that the factors affecting the drug's interactions and contributing to its final effect are also manyfold. The factors may be divided into three categories 1. Physicochemical properties such as solubility, partition coefficients, and ionization. 2. Chemical structure parameters such as resonance, inductive effect, oxidation potentials, types of bonding, and isosterism. 3. Spatial...

Enzyme Stimulation

Enzymes frequently require coenzymes for optimum activity. The coenzymes are usually vitamins and cofactors, invariably electrolytes such as mono- and divalent metallic ions (e.g., K+, Na+, Ca+2, Mg+2, Zn+2, and Fe+2). These coenzymes activate different enzymes by various means of complexation and stereochemical interactions. A detailed consideration of the mechanisms involved is not within the scope of this discussion. It can be stated, however, that such ions may affect enzymes in one of two...

Carcinolytic Antibiotics

A clinically important group of anticancer drugs are certain cytotoxic antibiotics that inhibit DNA and or RNA synthesis by complexing with DNA via an interposing reaction called intercalation. The process is now understood to be one by which the planar, poly-cyclic portions of some drugs can slide into the double helical DNA structure in a horizontal manner by interposing between the base layers of DNA, which are stacked at distances of 3.36 A above each other. Interactions between the purine...

Topliss Decision Tree In Drug Designing

Square brackets indicate alternates. Asterisk indicates compared with 4-H compound. Figure 1-10. Topliss decision tree. M, more active E, equiactive L, less active. equations can be rapidly calculated.8 This procedure gives useful correlations by both methods in most situations and has been shown to give comparable results. No doubt other refinements and approaches will be made to quantify structure-activity relationships of drugs to help design new agents...

Mitotic Inhibitors

Compounds known to inhibit the mitotic phase of the cell cycle offer potential usefulness in the treatment of cancer. Few such drugs, however, have reached clinical application either because of unacceptable toxicity or ineffectiveness. Two antimitotic agents are used for other purposes. The antibiotic griseofulvin is utilized for its antifungal properties. The alkaloid colchicine, although having antitumor activity, is used in the treatment of gout. Colchicine, obtained from the seeds of...

Ergosterol Biosynthesis Of Squalene

CH2 CH- CH2 COOH Undecylenic Acid and salts CH3- CH2 -COOH Caprylic Acid and salts CH3 -CH2-COOH Propionic Acid and salts Figure 7-10. Synthetic antifungal drugs. A number of fatty acids possess antifungal properties limited to dermatophytes Fig. 7-10 . Their mechanism of action is not understood. Acetic acid, as glyceryl triacetate Triacetin , is used in cream form against tinea pedis. It apparently acts as a pro-drug, slowly releasing the acetic acid on hydrolysis, and is presumably catalyzed...

Hypolipidemic Hypocholesterolemic Drugs

The fact that even young men can develop atherosclerosis was reported following autopsies of German soldiers during World War I. However, it was a U.S. Armed Forces Institute of Pathology report toward the end of the Korean War (Enos et al., 1953) showing that young men (average age 22) had evidence of coronary heart disease (CHD) that made the medical profession take note of the epidemic that was CHD. The problem is still extensive in spite of considerable, but slow, progress since the 1950s....

Indirect Sympathomimetics

Indirect sympathomimetics are drugs capable of actively entering the adrenergic neuron and its vesicles to displace NE from its binding sites. Thus the sympathetic effects observed with such compounds are actually elicited as a result of receptor recognition of NE, and not because of any affinity for these drugs. This is particularly true the more unrelated the compounds are to catecholamines or phenylethylamines in structure. Such agents may retain partial direct activity because they have...

Doxaprost Si Em F

16-Methy 1-18,18-19,19-tetradehydrocarbacyclin Ciloprost 16-Methy 1-18,18-19,19-tetradehydrocarbacyclin Ciloprost Cardiopulmonary bypass surgery hemoperfusion for kidney patients peripheral vascular disease, preinfarction angina, and stroke Extracorporeal circulation, treat coronary or vascular occlusions Marketed or experimental. b Trade names in parentheses. Actual or potential. Among the effects of PGs to be considered are the following 1. Effects on inflammation and pain E- and F-series PGs...

Quantitative Aspects of Drug Action An Overview

The decade of the 1930s was the beginning of attempts to introduce mathematical methods to gain increased understanding of chemical processes such as reaction rates, mechanisms, and certain processes, and to apply these techniques to the art and intuition of prediction. The scientific impetus was the then relatively new discipline of physical organic chemistry pioneered by chemists such as Hammett 1940 . These scientists elucidated the SARs of the electronic and steric effects of various...