How Drugs Act

Mitotic Inhibitors

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

Ergosterol Synthesis

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...

Natural Stop Smoking Aids

Activation of acyclovir and 6-deoxyacyclovir. drug is more effective than acyclovir against cytomegalovirus and against some HSVs resistant to acyclovir. Ribavirin represents a drastic remodeling of the purine structure. This compound was first reported in 1972. It is a (Fig. 7-16). A broad spectrum of activity is claimed for this drug against DNA viruses (e.g., HSV, vaccinia) and RNA viruses (e.g., influenza Ab A2, and B). Later reports confirmed this. X-ray...

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...

Factors Affecting Bioactivity

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...

Theories of Drug Activity

Although there is no single uniform theory that can explain the activity of drugs, several theories have been advanced over the years in attempts to elucidate drug action. In general we may consider pharmacological action to be of two types. One type is thought to be caused solely by the physicochemical properties of the compound without discernible relationship to chemical structure. These structurally nonspecific drugs are usually administered in relatively large doses. It is presumed that...

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...

Computers as Drug Design Aids

The traditional method of drug development, at least in this century, has been to develop leads by first using, and then by isolating and identifying, the active chemical constituents from natural products, some of which may have been medicinally in use since antiquity. With the advent of modern organic chemistry some of these purified compounds were used directly (e.g., morphine, cocaine, atropine, quinine), and, once their chemical structures were ascertained, they became leads for hoped-for...

Psychoactive Drugs Chemotherapy of the Mind

It is difficult to exaggerate the complexity of the human brain's chemistry and functions, many of which are only beginning to be understood. Much is still undiscovered. Before embarking on a discussion of mental diseases and mechanistic aspects of the drugs used in their treatment, it is important to define certain terms frequently encountered. Psychosis. A mental disorder of sufficient magnitude to result in personality breakdown and loss of contact with reality. Delusions and hallucinations...

Stereochemical Aspects of Psychotropic Drugs

Dopaminergic Synapse

Stereochemical and other geometric factors are significant in determining the type of psychotropic activity obtained. It appears that planar ring systems yield optimal neuroleptic activity. The tricyclic 6-6-6 system i.e., all three rings contain six atoms of the phenoth-iazines seems to prove this. However, compounds with total rigid planarity, as in a 6-5-6 system exemplified by carbazole and fluorene derivatives, are invariably inactive. It might be postulated that neuroleptic receptors are...

BuspironeIs Anxioselectivity Possible

The question arises whether anxiolytic activity must always be accompanied by concomitant skeletal muscle relaxant and anticonvulsant activity as well as strong sedation. Can an anxioselective drug exist that will not interact significantly and additively with CNS depressant compounds, particularly alcohol More significantly, both from a medical and sociologic viewpoint, will it be possible to treat anxiety and stress without the added complication of potent sedative effects, dependency, and...

CNS Depressants

Cocaine And Biogenic Amine Transporters

In this section drugs used because of their CNS depressant properties will considered. The volatile general anesthetics (gases and low-boiling liquids), fixed general anesthetics (e.g., certain barbiturates), and sedative hypnotics (as defined earlier) will be included. In subse- Figure 12-8. Schematic relationships between synthesis and metabolic degradation of a biogenic amine. Figure 12-8. Schematic relationships between synthesis and metabolic degradation of a biogenic amine. Table 12-4....

Iupac Name Of Leucanthone

CH,0 P CH CO, CHj O OH Metrifonate The acetylcholinesterase in schistosomes acts as an inhibitory neurotransmitter so that inhibition of the enzyme results in paralysis. The suckers holding the worm to the wall of the vein let go, and the parasite is swept out (to the lungs) with the blood flow. Shortly after oral administration of the drug, serum cholinesterase levels in the patient are essentially eliminated while erythrocyte levels drop by about three fourths. These take several weeks to be...

Local Anesthetics

Local anesthetics are used to produce a loss of sensation, without a loss of consciousness, at localized areas of the body. When they are applied topically as creams, lotions, and aerosol sprays, they can be useful in alleviating pain of sunburns, severe itching, and other discomforts of the skin. This represents the relatively trivial uses of these drugs. More significant applications are by the parenteral route. Here, solutions of soluble salts such as hydrochlorides are used to alleviate, or...

Opiumand the Strong Analgetics Emanating from It

Medicines Act Images

Opium is the dried exudate of the unripe capsule of Papaver somniferum.4 Varieties of this plant have been cultivated and used for several millennia. Today, it is grown in Turkey, Iran, Afghanistan, Russia, China, Southeast Asia, and Mexico, as well as in other areas of the world, both licitly and illicitly. Crude opium is known to contain over 25 different alkaloids that can be chemically divided into two categories the phenanthrenes and the ben-zylisoquinolines (Fig. 5-7). Only morphine,...

Narcotic Antagonists

Prior to the early 1940s no satisfactory pharmacologic antidote for opiate overdoses and poisoning existed. Treatment was essentially the same as for other CNS and respiratory depressants (i.e., with CNS stimulants and supportive physical methods). Some antagonism to the respiratory depression of morphine had been achieved by replacing the N-CH3 group of codeine with an allylic function (-CH2-CH CH2) during the 1920s. This fact was subsequently utilized as a rationale for the introduction of...

Agonist Antagonist Analgetics

The disclosure that the antagonist nalorphine was a potent analgetic led to the synthesis of a number of 6,7-benzmorphans that were clinically evaluated as to analgesia, psychotomimetic effects, and the existence of other opioid effects. Phenazocine, which demonstrated high potency but no antagonism, was already mentioned. Cyclazocine, with n-propyl (subsituted) allyl propynyl cyclopropylmethyl cyclobutylmethyl n-propyl (subsituted) allyl propynyl cyclopropylmethyl cyclobutylmethyl 10 This dose...

Antidepressants

Depression, or melancholy, as it was once called, is a sense of lowering mood. It has become a mental health problem of major proportions in modern society. It has been estimated that one-fifth of our population is likely to experience at least one major depres Manic-depressive Pure depressive Pure manic Figure 12-23. Types of manic depressions. Manic-depressive Pure depressive Pure manic Figure 12-23. Types of manic depressions. sive episode in his or her lifetime. For many there will be...

JfY Mo nH

Progabide - NH2 H N N2 r-Nitrophenylisonipecotate j-Nitronipecottte Lamotrigine (Lamigtal) Lamotrigine (Lamigtal) was originally synthesized as a dihydrofolate reductase inhibitor. The compound was much better as an epileptic than it was in its original mission. Its talent is apparently in stabilizing presynaptic neuronal membranes by blocking their sodium channels as well as inhibiting excitory neurotransmitters. These features make it useful in the treatment of partial onset epilepsy....

Drugs That Act On

Compiled from Spratt, 1977 and Spratt, 1983. d A third protein identified in one study. Compiled from Spratt, 1977 and Spratt, 1983. d A third protein identified in one study. potent cell killing of many Gm-organisms. Combining this drug with other broad-spectrum P-lactam compounds e.g., ampicillin, cefamandol produces a synergistic effect. Thienamycins and clavulinic acid also have been shown to bind primarily to PBP2, resulting in the same morphological cellular changes as produced by...

Mild Analgetics

Drugs in this category have the ability to alleviate mild, and on occasion, severe pain. The agents are also quite effective in reducing fever to normal levels.2 The drugs most frequently 2 Antipyretic is the term applied to drugs that reduce fever to normal body temperatures. Compounds able to reduce temperature below normal are termed hypothermic. encountered here are acetanilid, acetophenetidin (phenacetin), and acetaminophen (p-ace-toaminophenol, paracetamol). As Eq. 5.1 illustrates, these...

The Opiate Receptor

The existence of binding sites specific to opiates had been assumed for many years. Some of the early indirect evidence leading to this receptor hypothesis included the relatively high potency of the narcotic drugs and the structural and stereospecificity exhibited by them. Even with the synthetic analgetics biological effects are usually found in those optical isomers stereochemically related to the natural (-) morphine molecule.12 The concept involved here may be understood by considering...

Endogenous Opiate Receptor Ligands

The receptor work described previously now sets the stage to answer an interesting question What are the receptors for plant alkaloids doing in the mammalian CNS A reasonable hypothesis is that opiate receptors are part of a neurotransmitter or neuromodulator system that functions through the mediation of some naturally occurring morphinelike substance (i.e., an endogenous ligand). To prove this hypothesis, it would be necessary to find and identify this ligand or ligands in the mammalian CNS...

The Qra Binds To Block

Tardive dyskinesia, once rarely encountered (e.g., Huntington's disease), has become commonplace since the introduction of antipsychotic drugs. Such drug-induced dyskinesia (rhythmic involuntary movements) can be attributed to supersensitive postsynaptic DA receptors. (Such symptoms, of course, can also result from decreased cholinergic activity.) It is doubtful whether any of the antipsychotic drugs considered are significantly lower (better) in producing these symptoms. Table 12-16 lists many...

Miscellaneous Carcinolytics

Procarbazine (Matulane), a hydrazine compound having monoamine oxidase inhibiting activity, is very active against Hodgkin's disease, especially in combination with mustar-gen, vincristine, and prednisone the MOPP protocol. The drug has activity against certain lung cancers, myeloma, melanoma, and brain tumors. The drug undergoes complex metabolic activation. In this form chromosome damage, antimitotic effects, and inhibition of proteins and nucleic acids have all been demonstrated, yet no...

Plasminogen Activators

Plasminogen activators (PAs) are serine proteases with high plasminogen specificity. Hydrolysis of the proenzyme yields an active two-chain serine protease plasmin. Plasminogen can also be physiologically activated by the intrinsic system (see earlier), specifically by prekallikrein, factor XII, and a high-molecular-weight kininogen found in the plasma. More relevant to clinical applications, however, are the enzymes of the extrinsic system the serine proteases to be considered. These enzymes,...

References

USA 12 132, 1926. Banting, G. F., Best, C. H., J. Lab. Clin. Med. 7 251, 1992. Enos, W. F., Holmes, R. H Beyer, J., J. Am. Med. Assoc. 152 1090, 1953. Goldstein, J. L., Brown, M. S., in The Metabolic Basis of Inherited Disease, Stanbury, J.B., Ed., McGraw Hill, New York, 1983, pp. 672-712. Herrick, J. B Arch. Int. Med. 6 517, 1910. Hopwood, D. A., Sci. Amer. 245 67, 1981. Kato, K Ohkawa, S., Terao, S., et al., J. Med. Chem. 28 287, 1985. Lehninger, A. L., Nelson,...

Neurochemistry of Mental Disease

Can abnormalities in the steady state of biogenic amines (NE, DA, 5-HT) and other neurotransmitters of the CNS be causative factors in mental diseases such as schizophrenia, endogenous depression, and manic behavior Only 50 years ago arguments in favor of such a notion would have elicited, at best, benign smiles of amusement from an audience of psychiatrists. It is interesting that some experiments in the 1880s had suggested a possibility of chemical factors affecting the pathology of...

Isosteric Drugs

-NH2), tolbutamide, soon replaced carbutamide in clinical practice. Finally, a third isostere Xc (-C1 for -CH3), chlorpropamide, was introduced whose attributes were both decreased toxicity, and also extended duration of activity (due to nonoxidizability of the CI atom compared to the CH3 group). Bioisosteric interchanges, of course, are not limited to univalent functions. In fact, divalent atoms and groups add the additional factor of steric similarity to the equation since the bond angles...

Histamine Antagonists

By the beginning of the twentieth century the imidazole ring was known to occur in the amino acid histidine, the alkaloid pilocarpine (Chapter 8), and histamine, all of interest to biologically oriented chemists at the time. Its synthesis was accomplished in 1907. The vascular effects of this biogenic amine were not fully recognized for another decade neither was its wide occurrence and distribution in animal tissues. In 1920 it was demonstrated that histamine stimulated secretion of gastric...

Chemistry Of Sporozotocide

Chemotherapy Malaria Cycle

The number of humans presently afflicted is staggering (e.g., malaria, schistosomiasis, roundworm, hookworm, and whipworm). Overall estimates for the world are as high as 3 billion people. That would easily make parasitic diseases the world's leading health problem. Though many of these diseases were thought of as a third world problem, this is not so anymore. The ease of air travel and large migrations of people into more temperate climates now presents...

Arsenic In Melarsopol

Cumulative renal, hepatic, and, particularly, cardiac damage were soon recognized. Pentavalent antimonials, being less toxic, are probably safer and more effective. They may be viewed as derivatives of the antimonide ion Sb(OH) . Sodium stibogluconate (Fig. 7-9) can be prepared from Sb205 and gluconic acid in the presence of solubilizing NaOH solution. The exact structure and composition are not known, but are based on tartar emetic by analogy. Polymeric properties of antimonic acid makes...

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...

Cardiovascular Diseases

Hypertension (High Blood Pressure) Hypertension is termed the silent killer since it is asymptomatic (i.e., without direct characteristic symptoms). Hypertension is a leading cause of death. It is estimated that 20 of 1 In 1900 heart disease killed 27,000 and strokes 21,000 U.S. population was about half of today's. the American population has some elevation of blood pressure. Untreated high blood pressure can result in strokes, congestive heart failure, or kidney failure. All are high...

Antipsychotic Drugs The Neuroleptics

The tricyclic compound phenothiazine, which has been known since the late nineteenth century, is a toxic compound of little therapeutic interest except as a large-animal anthelmintic at one time. An N-10 derivative, diethazine, was synthesized by French workers in the late 1940s as a possible antihistamine. The added anticholinergic properties it had I. Discrete mental disorder * (mood) with two major components

Oh Oh O O O

Chemical instabilities of tetracycline elevated temperatures, increased acidity). ATC28 has been shown to be nephrotoxic. Another degradation reaction is ring cleavage resulting in isotetracycline (ITC). Following tautomerization of TC to the 12-keto form, base catalyzes p-ketone cleavage of the 11-1 la bond followed by lactonization of the 6-OH with the 11-keto function (Fig. 6-20). It will be noted that both these degradation reactions involve the 6-OH group. The semisynthetic...

Introduction To Medicinal Chemistry

The following discussion will briefly outline two categories of macrolide (large ring system) antibiotics the lactone macrolides that include clinically useful erythromycins and several related compounds and the ansamacrolides, the most prominent members being the rifamcyins. The macrolide lactone antibiotics are isolated primarily from the genus Streptomyces. Their antibacterial activity is mostly in the Gm+ spectrum. They are classified on the basis of the size of the macrocyclic lactone...

Rhnchch2cooh

Taurine (2-aminoethanesulfonic acid) may have certain central inhibitory properties that qualify it for neurotransmitter status. At present only strychnine appears as a viable antagonist (as it is for gly), making it difficult to differentiate the central effects of these two amino acids. Glutamic and aspartic acids, which are viewed as excitatory neurotransmitter amino acids, are present in the CNS in relatively large amounts. Kainic acid, which is viewed as a rigid and therefore...

Introduction

Steroids are polycyclic hydrocarbons that can be viewed as fully saturated (i.e., perhydro) analogs of cyclopentanophenanthrene. The ring designations and numbering of the carbon skeleton are indicated earlier. In the majority of steroids the junctions between ring C D and B C are trans (i.e., the H atoms at 8 and 9), and the H at 14 and the CH3 at 13 (itself numbered 18) are one above and one below the general plane of the ring system as shown later. Substituents above the ring systems are...

Ch2ch2ch2nhch3

Second-generation antidepressants. Trade names in parentheses. *Withdrawn in 1987. monoamine, while cocaine and amphetamine which do are not particularly useful in treating depression. It may be reasoned that if the acute effect of TCAs and MAO inhibitors is to raise the amine levels and yet no symptom relief is discernible for the first 2 weeks of treatment that the amine levels per se are not really significant or that these compounds are achieving their results by a different...

Structure Of Morizicine

Comparative metabolic pathways of lidocaine and tocainide. The N-deethylated metabolite, although still bioactive, is then rapidly cleaved by microsomal amidases to inactive m-xylidine and N-ethylglycine. This readily explains the short half-life of the drug. Tocainide, on the other hand, presents a different picture. Its oral bioavailability is primarily due to slow hepatic metabolism on the first and subsequent passes. The large percentage of the drug excreted without enzymic...

Thrombolytics

Thrombolytics are agents capable of lysing thrombi in the cardiovascular system. As was seen earlier, clot formation is governed by the coagulation scheme. Understanding of that scheme has led to agents able, to a degree, to inhibit clot formation prophylactically. Anticoagulants and platelet aggregation inhibitors considered in this chapter are prime examples. Lysis of clots is regulated by another complex series of interrelated biochemical reactions referred to as the fibrinolytic system Fig....

The Nonsteroidal Antiinflammatory Drug

The ideal NSAID agent has not yet been developed. Efforts have been continuous since the introduction of aspirin in 1899. For example, the patent literature for 1966 alone reveals disclosures of more than 100 groups (not single compounds) of antiinflammatory structures. The pace of research is not likely to have abated. Unfortunately, only a small number of lead compounds emerge with sufficient potency and adequate tolerance for further development. Chronic toxicity determinations in animals...

Nh Nh Ncnhcnh2

C Active metabolite ca. 5 hours. ' Available in United States only on investigational basis (see text). The newer second generation compounds, glyburide and glypizide, have a greatly increased potency and sometime efficacy (i.e., they may produce clinical responses in patients who have failed to exhibit one with earlier agents). It is curious that the mechanism of action of the sulfonylureas is still not fully understood. It is established that the ability to secrete some endogenous insulin...

Carcinolytic Antibiotics

Pyrimldine Charge-Transfer Interactions This is a complex formation process between electron-rich donor molecules and electron-poor acceptor molecules. Energies holding the charge-transfer components rarely exceed 7 kcal mole. These forces are operative over a 3-3.5 A distance. 7t-Electron-rich heterocyclic ring compounds such as thiophene, furan, and pyrrole, or more complex structures containing them, make excellent donor species for CT complex-ation so do aromatic structures having electron...

Prostaglandins

The fact that PG-synthetase is present in the gut wall, which, therefore, also contains types E and F PGs, has been known for a long time. The gastric mucosa in particular secretes E series PGs into gastric juice. PGEs (and possibly PGAs) can inhibit histamine-stimulated HC1 secretion without diminution of mucosal flow. The ability to maintain the mucosal integrity and thus protect the gastric wall, which is a property now named cytoprotection, has been ascribed to PGEs. In fact, such...

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...

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....

Prostacyclins

Prostacyclin (PGI2) was found to be the strongest inhibitor of platelet aggregation and a smooth muscle relaxant even before its exact structure was known. In fact, it was briefly named PGX. Much has been learned about this fascinating molecule, which is now classified as a hormone, since then. It is continuously produced both in the walls of blood vessels as well as in kidneys and lung tissue. Tests of this property have demonstrated that infusion of PGI2 produces a potent antithrombotic...

Inhibition of Mediator Release

The discussion so far may have given the impression that allergic, particularly asthmatic, attacks responses are solely mediated by a sudden release of copious quantities of histamine that are stimulated to do so by some pathological event such as an autoimmune reaction, pollen exposure, or an antigen-antibody reaction. While it is true that histamine is released by mast cells and also their circulating counterparts, the basophils , causing swelling of nasal passages by affecting blood vessels...

Receptor Concept of Drug Action Mechanisms 151 Historical Development

The development of the idea that can be called a drug-receptor theory required over a century to reach its present modest level of sophistication. It expresses the understanding that a drug exerts its biological activity as a consequence of binding, or interacting in some manner, with a specific receptor in a biological system. Not that people did not wonder how the various powders, potions, and infusions worked their imagined, and occasionally real, magical effects they undoubtedly came up...

Guu Guc Gua

There are also codons for protein synthesis initiation (AUG) and polypeptide chain termination (UAG, UGA, and UAA). There are also codons for protein synthesis initiation (AUG) and polypeptide chain termination (UAG, UGA, and UAA). becoming complementary to it. The synthesis is catalyzed by RNA polymerase (transcriptase). Thus mRNA has the code transcribed onto it. The new molecule leaves the nucleus and travels to the site of protein formation after transcription, where in turn it acts as a...

Drugs Act Both As Progestins And Androgen Antagonists

Studies involving human breast cancer showed a definite relationship between estrogen uptake (i.e., binding) and the response to oophorectomy and adrenalectomy. These intracellular cytoplasmic hormone-binding proteins, now termed estrogen receptors, have since been found to exist in up to 65 of breast cancers postmenopausal women having a much higher incidence and level of receptor-positive tumors than premenopausal women. Negative receptor assays quickly identify...

Clotting Prevention and Lysis

From any viewpoint blood is chemically the most complex tissue in the body. In addition to the multitude of cells and platelets, it contains inorganic ions (electrolytes), various plasma proteins, hormones, lipids, vitamins, a large variety of enzymes, nucleic acid breakdown products, a large number and unknown types of environmentally ingested chemicals (drugs, food additives, pollutants) at varying stages of metabolic conversion, gases, and, of course, water. The list of specific entities...

Drugs Affecting Cholinergic Mechanisms

This and the next chapter on adrenergic drugs involve chemical agents that derive their therapeutic use from effects on the peripheral autonomic nervous system, primarily by mimicking or blocking, directly or indirectly, the neurotransmitters of that system acetylcholine, norepinephrine, and dopamine. Drugs affecting these transmitters centrally, rather than peripherally, will also be considered because of chemical or mechanistic similarities. It is therefore necessary to discuss some...

Proton Pump Inhibitors HKATPase

Prilosec Mechanism

Figure 13-2 implicates in simplistic form the various receptor activations of the parietal cell with H -K -ATPase the proton pump and thereby the release of H into the gastric lumen. Cyclic-AMP, and its production from ATP, which is catalyzed by adenyl cyclase, is the significant mediator system in this process. Omeprazole Fig. 13-4 emerged from a series of benzimidazoles as a compound able effectively and specifically to inhibit the pump's production of gastric acid. Cellular components of the...

Antimicrobial Drugs II

This chapter will concern itself with antimicrobial agents (as broadly defined earlier) of synthetic origin.1 Unlike the semisynthetic antibiotics, which were obtained from biological sources and then modified by one or more synthetic steps, these compounds are synthetically created. In many cases the prototype compound was discovered by a more or less random screening process (e.g., sulfanilamide, Chapter 2) and then, by first applying empirical and now more scientifically predictive SAR...

Sars Of Barbiturate Rapid Onset Alkyl Group

Onset preteen years abrupt short loss of consciousness (< 30 sec) mild clonic motions (e.g., blinking, jerking) B. Tonic-clonic seizures (grand mal) Major convulsions maximal tonic spasm (< 30 sec) then clonic phase (< 1 min) seizures last 2-5 minutes, unconsciousness variable occurrence at any age Repetitive clonic jerks (early childhood) or sudden generalized or focal contractions (myoclonic) of face, limb, or trunk a Adapted and greatly simplified from Commission on classification...

Ureids Drugs That Acts On Sedative And Hypnotics

It has been possible to produce a balanced type of anesthesia wherein low-potency N20 is combined with an opioid analgesic, usually the meperidine analog fentanyl (Fig. 5-10), or the more recent analogs sufentanil and alfentanil. When a butyrophenone-type neuroleptic (see later), particularly droperidol, is added, a state of neuroleptoanesthesia is produced where, without loss of consciousness, analgesia sufficient for surgery is achieved during which the patient still responds to commands.6...

K118614g6-vintage

Much of the work and theoretical discussions as to the intricacies of the molecular mechanism (and chemical stabilities) of P-lactam antibiotics have previously revolved 10 It can also be named as an azetidine derivative (e.g., 2-azetidinone, or 2-keto-azetidine). Cephalosporins (X-H, Y S) Ccphamycins (X OCHj,Y S) Oxaccphcm (X H, Y 0) Carbacepham (X H, Y CHj ) Cephalosporins (X-H, Y S) Ccphamycins (X OCHj,Y S) Oxaccphcm (X H, Y 0) Carbacepham (X H, Y CHj ) around the penicillins and...

Clonidine Structure In Benzene Ring Type

In the case of the protonated salt form of clonidine, using the analogy with guanidine Fig. 10-6 , in order to retain optimum molecular stability, the proton must be found on the bridge nitrogen. That way, as the following composite resonance structure shows, the electrons of the double bond can be delocalized so that the positive charge is distributed over all three nitrogens. Certain corresponding features between clonidine and NE have also been established, as both are substances that...

Meth Gbl And Candida

Gamma-aminobutyric acid metabolic interactions. GA glutaminase GABA y-aminobutyric acid GABA-T GABA a-oxaloglutarate transaminase GAD glutamic acid decarboxylase GS glutamic synthetase NAD nicotinamide adenine dinucleotide PP pyridoxal phosphate vitamin B6 SSA succinic semialdehyde SSADH succinic semialdehyde dehydrogenase GHB y-hydroxybutyric acid GBL y-butyrolactone.

Drugs and the Cardiovascular

This chapter, which is essentially a continuation of the preceding discussion, will deal with the chemotherapeutic approaches to such cardiovascular conditions as result in thrombus formation, especially by involving thrombocytes or platelets, and the control of blood lipids, particularly certain types of cholesterol-containing lipoproteins. Since diabetes ultimately involves cardiovascular pathology, some of the chemicals used to control and ameliorate the so-far inexorable diabetic processes...

Antisense Drugs

Antisense drugs is a catchy name that may make more sense with a technical term such as sequence-defined oligonucleotides (ONs). Perhaps a brief explanation of what it is we are attempting to achieve with these curiously named substances will perhaps be more useful. The first term gives a hint. It contains the word drug. Thus we are seeking a new, different, and more specific approach to therapeutics. Most drugs today have a downside in terms of adverse effects. That is, they are primarily...

Gene Therapy

Gene therapy the very name seems so futuristic, almost like science fiction. Not long ago one might have put it in the pipe dream category not any more. It is not likely to explode on the scene with cures, or even with amelioration of hundreds of genetic defects and the pathologies resulting from them, yet between 1990 and mid-1995 a total of 87 gene therapy trials were approved by the Recombinant DNA Advisory Committee to the National Institutes of Health. Of the approximately 600 patients...

Sickle Cell Disease or Anemia

This is an inherited genetic disease. It was first described by a Chicago physician (Herrick, 1910) who believed it was caused by syphilis. It affects about 60,000 Americans, the majority of whom are black. In India, Iran, and around the Mediterranean, it affects nonblacks as well. Nearly two decades after Herrick's report susceptible erythrocytes were demonstrated to change to sickle cells when deoxygenated. This reversed on oxygenation. It took another two decades before Pauling et al. (1949)...

Adrenergic Concepts and Synthesis

The biochemical properties of the sympathetic (adrenergic) system are better understood than some of the ramifications of its physiological functions. As already mentioned, postganglionic sympathetic nerve endings elaborate norepinephrine (NE), which is eliminated from storage vesicles within the nerve terminal. Another important biogenic catecholamine1 is epinephrine (EP, adrenalin), which is produced by N-methylation of NE in the adrenal medulla, a gland on top of the kidneys. Unlike NE, EP...