By L. Yokian. Ottawa University.
It is synthesized in exactly the same manner except using 1-(2-tetrahydrofuroyl)piperazine instead of 1-(2-furoyl)piperazine [48–51] tadalafil 2.5 mg on-line. In the early history of civilization and in the middle ages generic tadalafil 20 mg on-line, consumption of grain of contaminated ergot resulted in gangrene in the extremities buy tadalafil 10mg lowest price, miscarriages 10mg tadalafil with amex, and seizures. Despite the fact that the majority of ergot alkaloids exhibit α-adrenoblocking activity, their pharmacology is often different. In terms of chemistry, ergotamine and ergonovine are derivatives of lysergic acid. Adrenoblocking Drugs counterproductive in chronic diseases because of the possibility of side effects such as triggering gangrene. However, like ergota- mine, it is used in gynecological–obstetrical practice for stopping postnatal bleeding. The most likely mechanism of action is the direct spasmogenic effect on the uterus. It is isolated from the plants Corynanthe johimbe and Rauwolfia serpentina [60,61]. Being a derivative of indolylalkylamine, it selectively blocks α2-adrenergic receptors. It weakens the negative feedback mechanism of norepinephrine release in nerve endings. Additional research is evidently needed to conclusively delineate its pharmaco- logical action. These drugs can interfere with the synthesis, storage and release of norepinephrine, dopamine, and serotonin. Reserpine is one of the alkaloids isolated from a perennial shrub of the Rauwolfia family [67–72]. It weakens intracellular uptake of biogenic amines and reduces the ability if storing them in vesicles. Breakdown of catecholamines is expressed by a decreased number of intraneuronal serotonin and dopamine. Reserpine is used for treating hypertension; however, it is not the drug of choice because of a number of side effects. A number of drugs combined with other hypertensive agents— diuretics in particular—are based on reserpine. Reserpine is prescribed under a number of names, including serpasil, brinerdin, diupres, and others. Azocine is alkylated by chloracetonitrile, which forms 1-azocinylacetonitrile (12. It acts on branched ends of sympathetic peripheral nerve fibers and permeates into the neuron by the same mechanism of reverse uptake that returns norepinephrine from the synaptic cleft to neu- ron endings. Inside the neuron, guanethidine accumulates and competes with norepi- nephrine for storage space as granules. With an increase in guanethidine concentration, norepinephrine is replaced and thus the quantity of neurotransmitters capable of being released is reduced. In response to stimulation, the nerve may release guanethidine, which, however, is not an adrenergic receptor stimulant. In addition to this disturbance and the presence of stores of catecholamines in adrenergic nerve endings, guanethidine also acts on the stores of catecholamines in organs such as the heart, spleen, and aorta. Adrenoblocking Drugs Since it does not pass through the blood–brain barrier, it does not act on the central sym- pathetic neurons. Guanethidine is used for severe hypertension, where use of more universally accepted drugs is not successful. It is a very powerful and long-lasting drug, and its effects last for 2–3 days after using it. It is used for treating hypertension in patients who do not respond to thiazide diuretics. It can be used as an adjuvant drug in thiazide treatment for reaching an optimal level of blood pressure. Treating this with hydrogen iodide removes the methyl-protecting group on the phenyl hydroxyl group and the product (12. It competitively inhibits tyrosine hydroxylase action, thus reducing the formation of epinephrine and norepinephrine. It is used for treating patients with pheochromocytoma, in cases where a rise in the level of catecholamines is observed. It is known that the effect of acetylcholine in certain organs can be reproduced by the alka- loid muscarine, and in other organs by the alkaloid nicotine. The division of cholinore- ceptors into so-called mucarinic (M-cholinoreceptors) and nicotinic (N-cholinoreceptors) is based on this observation. Cholinoreceptors in certain locations have different sensitiv- ities to different drugs. There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of bio- genic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Acetylcholine is the primary neurotransmitter in the parasympathetic division of the autonomic nervous system, which mainly innervates the gastrointestinal tract, eyes, heart, respiratory tract, and secretory glands. Although its receptors are crucial for maintaining all normal functions of the body, an extremely small number of illnesses can be explained by the dysfunction of cholinergic regions of the peripheral autonomic system. Although acetylcholine itself is a substance without which normal body function would not be possible, two properties make it extremely undesirable for use as medicinal agents. First, its action is very brief because of the rapid breakdown by cholinesterases, and sec- ond—and more importantly—the diversity of action, which makes it practically impossi- ble to make its action specific in accomplishing certain tasks. However, a number of acetylcholine derivatives are more resistant to cholinesterase action and can have more selective action. Thus, cholinomimetics are those drugs that imitate action of endoge- nously released acetylcholine. Cholinergic receptors are coupled to G proteins (intramem- brane transducers that regulate second messengers). Classifications of these drugs are based on the mechanism of their action, which is exhibited either by direct stimulation of 179 180 13. Cholinomimetics cholinergic receptors by choline esters or cholinomimetic alkaloids, or in an indirect man- ner of inhibiting acetylcholinesterases, which are enzymes responsible for the chemical decomposition of acetylcholine. These, in turn, are subdivided into reversible cholinesterase inhibitors and irreversible cholinesterase inhibitors. So, parasympathetic nerves use acetylcholine as a neurotransmitter and cholinomimetic drugs mimic the action of acetylcholine at its receptors. Indirect-acting (cholinesterase inhibitors), which, in turn, can be reversible or irreversible. At the same time they selectively stimulate uri- nary and gastrointestinal tracts, facilitating emptying of neurogenic bladder in patients after surgery or parturition or with spinal cord injury. Nicotinic receptor agonists mimic the effects of acetylcholine at nicotinic receptors on autonomic ganglionic synapses and skeletal neuromuscular junctions. The single case of medical usefulness is their use as a transdermal patch or as chewing gum for cessation of smoking. These drugs are divided into drugs that stimulate muscarinic (M-cholinoreceptors) or nicotinic (N-cholinoreceptors) receptors. Drugs whose efficacy is primarily connected to stimulation of muscarinic receptors, including choline esters, i. Drugs whose action is based on stimulation of nicotinic receptors include the alkaloids nicotine and lobeline. Despite the fact that these drugs are able to directly stimu- late all cholinergic receptors, their therapeutic efficacy is mediated by reaction with mus- carinic receptors (subtypes M1 and M2). The only difference between these drugs is their duration of action, and to some extent selectivity for receptors. For example, 2-chloroethanol is reacted with trimethylamine, and the resulting N,N,N-trimethylethyl-2-ethanolamine hydrochloride (13.
Remember cheap 5mg tadalafil free shipping, we all have these imbalances proven tadalafil 5 mg, and the sooner you identify and address them purchase tadalafil 10 mg fast delivery, the sooner you’ll be on your way to freedom from pain best tadalafil 10 mg. Your Mind and Your Diet: Two Other Potential Sources of Back Pain While problems in the body tend to be the ones most doctors and health care professionals focus on, the mind and the diet play a much bigger role than most realize. In fact, I personally feel, and more and more research is suggesting, that these other areas may be keys to improving back pain. It’s quite easy to have issues with “too much,” “too little,” and blood circulation or body energy that’s “too slow” because of your emotional and dietary life. Remember, we all have these imbalances, and the sooner you identify and address them, the sooner you’ll be on your way to freedom from pain. Your Mind and Your Diet: Two Other Potential Sources of Back Pain The Mind: While problems in the body tend to be the ones most doctors and health care professionals focus on, the mind and How Emotions Cause the diet play a much bigger role than most realize. In fact, I personally feel, and more and more research is suggesting, that Physical Pain these other areas may be keys to improving back pain. It’s quite easy to have issues with “too much,” “too little,” and blood circulation or body energy that’s “too slow” because of Most of us have been conditioned to believe that if we feel your emotional and dietary life. But what we may not Don’t forget to watch my three-part video series realize is that sometimes the hidden cause of physical pain can “Why You’re Still in Pain. We can experience too much stress, anxiety, trauma, sadness, anger, and emotional pain, and too It’s free and you can find it on my website at: little relaxation, stress relief, joy, fun, security, and calm. We often experience physical symptoms of pain or discomfort because of anger, fear, anxiety, sadness, or other negative emotions. These types of emotional stressors don’t need to be catastrophic or provoke mental illness to trigger a chain of events leading to back pain. It’s important to recognize that in these cases, the pain is not imaginary or “in your head. In fact, an extensive study conducted by Stanford University on more than 3,000 employees at the Boeing Corporation found that emotions and psychological factors were the biggest indicators of back pain. You have only to imagine stepping off a bridge to feel your stomach fly up into your throat and your muscles tense. This mental thought can trigger a chain of physical reactions, including dramatic fluctuations in blood pressure, breathing rates, oxygen levels, and more. So you can see the effect your mind can have on your body, particularly if you’re thinking stressful thoughts many times throughout the day. Your muscles tighten and, if you remember from the last chapter, tight muscles cause problems. They inhibit circulation, constricting blood vessels so the blood doesn’t flow through your body like it should and creating muscle imbalances. Without adequate blood flow, the cells in your body become slightly oxygen deprived. Toxins and waste aren’t cleaned out as efficiently as they should be and can build up in certain parts of your body, creating or reactivating trigger points. These knots are often painful to the touch and, in some cases, can cause muscles to spasm or “lock up,” which can pull your spinal column out of alignment— pinching nerves and causing nerve-based back pain. And if you doubt the effects the mind can have on the body, let me tell you about a study that was done in Finland. Autopsies were performed on people who had died from non- back-pain-related causes but had reported suffering from back 47 The 7-Day Back Pain Cure The Mind: How Emotions Cause Physical Pain 48 physical conditions in your body that make it highly pain while alive. Researchers were shocked to find that the susceptible to pain—especially back pain. And remember, without fresh blood University on more than 3,000 employees at the Boeing supplying oxygen and nutrients, it’s nearly impossible to heal. Corporation found that emotions and psychological factors Stress also alters your breathing. Oxygen and nutrients don’t How Emotions Act on the Body circulate at optimum levels, again contributing to the buildup of toxins. Stress also can release hormones, such as adrenaline, The mind is inextricably connected to the body. You have which can trigger chronic tension and inflammation in your only to imagine stepping off a bridge to feel your stomach fly muscles, ligaments, and tendons. This mental flow to remove these hormones from the body, they can thought can trigger a chain of physical reactions, including linger longer than usual and create more damage. Which muscles do you tend to tense most Just thinking about a stressful event can cause all this! Shoulders usually come first, directly So you can see the effect your mind can have on your affecting the spine. The jaw, stomach, and lower back also are body, particularly if you’re thinking stressful thoughts many very common areas. Your muscles tighten and, if you some of the first parts of the body to suffer from stress. They inhibit circulation, constricting blood vessels Other Ways Emotions Affect Health so the blood doesn’t flow through your body like it should and creating muscle imbalances. Negative emotions can have other detrimental effects on Without adequate blood flow, the cells in your body our health—effects that can make back pain worse. Toxins and waste aren’t Think about an emotionally distressing episode in your cleaned out as efficiently as they should be and can build up life. You probably slept too little, depriving your body of its in certain parts of your body, creating or reactivating trigger primary healing time. These knots are often painful to the touch somehow, so that you either lost your appetite and ate too and, in some cases, can cause muscles to spasm or “lock up,” little or reverted to eating too many highly processed, low- which can pull your spinal column out of alignment— nutrient foods. You might have skipped your usual exercise pinching nerves and causing nerve-based back pain. And if you doubt the effects the mind can have on the People around you may have commented on your increased body, let me tell you about a study that was done in Finland. Too little sleep, exercise, and calm, along with too much anxiety, bad foods, and inactivity all can have profound effects on your body. Back pain, neck pain, headaches, jaw pain, and joint soreness all are just around the corner. What makes this especially difficult is that the emotional component of any painful condition often is ignored. Somehow we’re conditioned to believe that any physical manifestation of our feelings is a sign of weakness or some mental problem. On the contrary, it’s quite typical to have a mental burden impact your physical body. As a society, we accept that being diagnosed with cancer or suffering a heart attack—even having a baby—can cause emotions like depression, anger, and even guilt. What we don’t recognize as easily is that the communication works both ways—from mind to body and from body to mind. Science has proven that the brain’s messengers (neurotransmitters) communicate information in the brain and throughout the body. Since the mind itself operates on physical and chemical reactions, why wouldn’t emotions, which are communicated in physical ways inside the body, have very physical outcomes? The truth is that our thoughts and emotions, and how we handle them, all have a very large effect on our everyday health and well-being. During periods of stress, they certainly cause or exacerbate physical discomfort or injury. It’s an unfortunate thing that as children 49 The 7-Day Back Pain Cure The Mind: How Emotions Cause Physical Pain 50 All these occasions are like dominoes stacked up against we’re rarely taught how to deal with our feelings. Too little sleep, exercise, and were learning all about reading, writing, math, and science— calm, along with too much anxiety, bad foods, and inactivity unless our parents were especially gifted in teaching us—we all can have profound effects on your body. Back pain, neck learned very little about the art of mastering our own pain, headaches, jaw pain, and joint soreness all are just emotions. If we were angry and blew up, most likely we were sent to What makes this especially difficult is that the emotional our rooms, or if we were in school, to the principal’s office. On the contrary, it’s quite typical to have a mental instruction along the way may have avoided the aches and burden impact your physical body. As a society, we accept that being diagnosed with cancer or But for many of us, we never learned the art of expressing suffering a heart attack—even having a baby—can cause ourselves without hurting others, or how journaling, emotions like depression, anger, and even guilt. Science has proven that the brain’s Some of us may not even realize when a powerful emotion messengers (neurotransmitters) communicate information in has taken hold of us. Since the mind itself or turning to self-destructive habits like alcohol or drug use.
Improvement in objective phenomena is reported from a number of excellent observers discount tadalafil 10mg free shipping. The agent is also prescribed in irritable conditions of the larynx and air passages discount tadalafil 20 mg with amex, especially if evidenced by spasmodic cough buy tadalafil 2.5mg on-line. It has served a good purpose in whooping cough cheap tadalafil 5mg with mastercard, in the cough of measles, and in general bronchial or pulmonary irritation. Lambert is of the opinion that trifolium has a direct action in improving the nutrition of the brain. He thinks it is demanded when the patient is overworked; when there is general mental failure, with loss of memory of words, or when there is confusion of ideas of functional causes; also when there is weakness of the lower extremities, or of the feet from deficient capillary circulation. It soothes the cough of incipient phthisis, especially where there is a tendency to hemorrhage, over which it has a marked controlling influence. It controls uterine hemorrhage of a passive character to an excellent advantage, especially menorrhagia and metrorrhagia. Therapy—A mild nerve tonic claimed to be valuable in the treatment of sexual impotence. Some of our physicians praise it highly for its influence in sexual neurasthenia, and it is said to correct frigidity in the female. It had long enjoyed a local reputation as a stimulant tonic of the sexual apparatus among the natives of Mexico, before it attracted the attention of the profession. Besides its peculiar action on the sexual appetite and function, it is a general tonic, somewhat cathartic, and is slightly cholagogue. The midwives and women of loose morals of Western Mexico also attribute emmenagogue properties to it. Reid uses Damiana in all conditions where a general tonic is needed, especially if there be enfeeblement of the central nervous system. It is valuable in renal and cystic catarrh and in general irritation of the urinary passages, through its influence in soothing irritation of mucous membranes. This latter property renders it valuable in the treatment of respiratory disorders, especially those accompanied with profuse secretion. In the line of the action of this remedy in its influence upon the reproductive organs, Dr. Reid mentions dysmenorrhea, headache, at the menstrual epoch, bad complexion, rough or discolored patches on the skin with acne, especially of a severe type, depending upon uterine Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 440 irritation. Watkins gives as its further indications, delayed or suppressed menstruation in young girls, irregularity at the beginning of menstruation, amenorrhea in very young girls. It will certainly allay sensitiveness of the sympathetic nervous system to irritations caused by disorders of the womb and ovaries. From five to ten grains of the extract is necessary three or four times a day, and persisted in. The writer has been using it as suggested, and has been very well satisfied with it. In one most severe case of acne, with discoloration of the skin, due to uterine irritation, the results were satisfactory, both to the patient and physician. I am satisfied that it relieves hyperesthesia of the sympathetic nervous system and prevents many of the results of reflex irritation from uterine or ovarian disorder. Occurrence—Turpentine is obtained from the Pinus palustris and from other species of the pine in the form. The oleoresin is distilled, and the product is the Oil of Turpentine or the Spirits of Turpentine. Description—The oil is a thin, neutral, colorless liquid, with a specific gravity of 0. For respiratory disorders, drop from two to five drops on a square of loaf sugar to be dissolved slowly on the tongue, and swallowed with the saliva. Terpene hydrate is formed by the action of nitric acid upon the rectified oil of turpentine, and alcohol. The product is distilled; it is crystalline, Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 441 colorless, nearly odorless; slightly soluble in water, soluble in alcohol. Physiological Action—The oil of turpentine is an irritant when applied to the skin or mucous membranes in any considerable quantity. In the stomach it produces warmth, increased from an overdose to a burning pain, nausea, vomiting, purging, eructations of the oil, great gastro- intestinal irritation, amounting to gastro-enteritis. In toxic doses it causes renal hyperemia, great irritation of the urinary tract, violent hematuria and strangury, with suppression of urine and albuminuria. It stimulates the heart, increases the arterial tension for a time, increases the temperature and exalts the mental faculties. Ultimately there is a reduction of physical strength, muscular insecurity, tremblings, incoordination, great nervous irritation, wandering of the mind, incoherence, insensibility and coma, breathing stertorous and labored, from paralysis of respiration; face cyanosed or flushed, pupils dilated. While violent symptoms have often been produced by full medicinal doses of turpentine, fatal results have seldom. The agent is eliminated through the kidneys and mucous membrane, and this fact explains its immediate influence upon these organs and structures. Specific Symptomatology—In two marked conditions apparently diametrically opposite in their character, this agent is specific. In excessive secretion of mucus—catarrhal discharges from whatever cause, especially if there be relaxed, enfeebled, atonic mucous membranes. Second; in gastric or intestinal inflammation, or in persistent fevers, with dry, red, glazed tongue, dry mucous membranes—tympanites, with suppression of the secretions of all gastric and of intestinal glands. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 442 It is also indicated by a steady distress or dull grinding pain in the abdomen, a sensation of hardness across the abdomen, with tendency to constipation, with general inactivity of the entire glandular structure of the gastrointestinal tract. It increases the tone and capillary circulation of all the mucous structures, and in the abdomen of the muscular structures of the intestines also. Its antiseptic powers are great, destroying parasites and germs of disease, and inhibiting putrefaction and fermentation. In intestinal disorders of childhood it prevents the formation of lactic and butyric acids, and the irritation caused by their presence. Therapy—The specific indications suggest the use of turpentine in acute and chronic bronchitis when there is an excessive discharge of mucus. It controls the cough, allays the excessive bronchial secretion, soothes the irritation throughout the chest, relieves the diffused soreness and promotes the cure. In acute inflammations within the chest its external application is of much value, especially in pneumonitis or capillary bronchitis with diffused soreness. Soreness and tenderness in acute fevers and inflammations are relieved by the external use of turpentine, while quick, sharp, acute pain is best combated by the external use of mustard and anodyne counter-irritants. It is given internally, applied externally, and its vapors are inhaled in these cases for a short time, careful watch being kept for evidences of its irritating influence upon the kidneys. In some extreme cases where it has not been previously used, a single large dose of ten or fifteen drops to a child of five years or above, will apparently exercise a prompt influence. In diphtheria with occlusion of the larynx, throat or nasal passages, from the membrane, it should be dropped on the surface of hot water in a close-mouthed vessel, and the vapor inhaled for a few minutes every two or three hours. It may be used in this manner with excellent results with an equal amount of the oil of eucalyptus. It may be also used in an Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 443 atomizer for this purpose. It is a remedy for acute and chronic nasal catarrh and if given persistently it will prove most serviceable, even in stubborn, chronic cases. In gastric or intestinal catarrh it is a remedy of much value given in proper doses in palatable emulsion. Pain due to this condition is quickly relieved by turpentine, and atonic, relaxed and enfeebled mucous or muscular structures quickly restored, and normal function attained. Turpentine is a most excellent remedy in the treatment of typhoid typhus and low forms of fever, and in typhoid complications of acute inflammations. In these conditions, when the tongue is dry, glazed and dark red, the temperature persistently high, the pulse small, wiry, rapid and feeble, with distention of the abdomen from tympanites, the urine scanty and dark, the intestinal glands ulcerated and intestinal hemorrhage present, turpentine is certainly a most efficient remedy. Its antiseptic influence is exercised in conjunction with its restorative power over the mucous and intestinal glands. In peritonitis or appendicitis with any of the above phenomena with tympanites the agent is prescribed with only good results. In all conditions within the abdomen where its internal use is demanded, especially if there is distention of the abdominal parieties from the accumulation of gases, the external use of turpentine is important. A stupe may be prepared by wringing a piece of flannel out of hot water and sprinkling a few drops of turpentine over its surface as it is applied. A popular domestic method is to melt a quantity of lard and add to it an equal quantity of turpentine and apply this freely to the surface.
Tetracyclines are the drug of choice with respect to a broad number of infections order 2.5 mg tadalafil with amex, including chlamydia generic tadalafil 2.5 mg otc, Bacteria Rickettsia buy 5mg tadalafil fast delivery, and others generic tadalafil 10 mg without a prescription. Blue-pus bacillus, proteus, serracia, most strains of Bacteroides fragilis, most fungi, and small viruses are resistant to this drug. It is used for pneumonia, bronchitis, empyema of the lungs, angina, cholecystitis, whooping cough, endocarditis, endometritis, intestinal infections, prostatitis, syphilis, gonorrhea, brucellosis, osteomyelitis, purulent infections of soft tissues, and others caused by microorganisms sensitive to this drug. Antibiotics synthesized biosynthetically as a result of the activity of actinomycete S. However, it can be synthesized microbiologically using the actinomycete Streptomyces viridifaciens,as well as a certain mutant S. It also belongs to the group of short-lasting tetracyclines, and is used for the same indications as chlorotetracycline. Synonyms of oxytetracycline are acromycin, bicyclin, cyclopar, sarco- cyclin, and many others. As a result, an antibiotic is synthesized that is more resistant to acids and bases in comparison with the methyl homologs [215–221]. Demeclocycline is used for the same indications as other antibiotics of the tetracycline series. Simultaneous sulfonation gives a naphthacen–sulfotetrahydrofuran derivative intermediate (32. Doxycycline can be formally viewed as the result of transferring the C6 hydroxyl group of tetracycline to C5. One of the ways suggests dehydrating oxytetracycline at C6 by reducing the tertiary hydroxyl group with hydrogen using a rhodium on carbon catalyst [226,227]. Reductive dechlorination of this product using sodium thiosulfate forms the intermediate methacycline (32. This prod- uct is reduced by hydrogen over a Raney nickel catalyst, during which reductive desulfu- rization takes places, giving doxycycline [225,228–230]. In some cases it is more active with respect to a number of organisms, and is better tolerated than other tetracyclines. This under- goes diazotization when reacted with butylnitrate in sulfuric acid, and the resulting diazo derivative (32. During this, the product is deazotized, while the nitro group is simultaneously reduced to an amino group, which undergoes exhaustive methylation by formaldehyde into minocycline (32. In a few cases, it is tolerated worse than other tetracyclines, and in particular, it has an effect on the vestibular apparatus. In addition, as seen already from the synthesis scheme, it is much more expensive than other tetracyclines, which are synthesized in a purely microbiological manner. The six-membered aminocyclitol ring is either streptidine (1,3-diguanidino-2,4,5,6-tetrahydroxycyclohexane), as in streptomycin, or 2-deoxystreptamine (1,3-diamino-4,5,6-trihydroxycyclohexane), as in all other amino- glycosides. Thus, neomycines, including neomycin itself and paro- momycin, have three sugar residues (two aminohexoses and one non-amino sugar pentose) bound to 2-deoxystreptamine. Analogs of kanamycin (kanamycin, tobramycin, amikacin) and gentamicin (gentamicin, sysomycin, netilmicin) each have two aminohexoses bound to the central aglycon. For a number of canamycines this is kanosamine, and for a number of gentamicines this is garosamine. Variations inside the aminoglycoside series themselves are caused by differences in the amino sugars and aglycon side chains. Of the eight aminoglycosides that are currently used, five are synthesized from differ- ent versions of Streptomyces: streptomycin (isolated from Streptomyces griseus), neomycin (isolated from Streptomyces fradiae), paromomycin (isolated from S. Gentamicin is isolated from Micromonospora purpurea, and it consists of a mixture of approximately equal amounts of three compounds: gentamicines C1,C1a, and C2. Netilmicin is a semisynthetic derivative of schizomycin, which is isolated from Micromonospora inyoensis. The common element in the process leading to the lethal outcome of bacteria is the active transfer of the drug from the surrounding medium into the bacterial cell, which leads to a large accumulation of medicine inside the cell exceeding that of the surroundings. Aminoglycosides easily diffuse through the outer membrane of the bacteria and enter the periplasmic space. The initial intracellular region of aminoglycoside action is the bacterial ribosome. There is evidently a minimum of two different types of ribosomal binding: one is specific to streptomycin, and the other acts by binding with other aminoglycosides. Other aminoglycosides bind to different regions of 30 S and 50 S ribosomal subunits, and cannot compete with streptomycin for binding with 30 S ribosomes. However, none of these effects fully explains the bactericidal effect of aminoglycosides. Aminoglycosides are drugs used predominantly against aerobic and a few Gram-negative microorganisms, S. Bacterial resistance with respect to aminoglycosides can be explained by changes in binding regions on ribosomes, decline in intracellular transport, and deactivation of drugs by microbial enzymes. A change in this protein as a result of a mutation makes the ribosomes unable to bind with strepto- mycin, which makes the organism resistant. Gentamicin, tobramycin, netilmicin, and amikacin bind with many regions on both subunits of the ribosomes, and therefore mutational resistance to them is not common. The second mechanism of resistance makes transport into the cell more difficult, which leads to resistance to all aminoglycosides. This type of resistance is not common among Gram-negative, aerobic, and a few other microorganisms. Since the transport of amino- glycosides through the cytoplasmic membrane is an oxygen-requiring process, anaerobic bacteria always exhibit resistance with respect to these bacteria. The most important mechanism of resistance is the enzyme production by plasmids, which phosphorylate, adenylate, or acetylate specific amino or hydroxyl groups in the aminoglycoside molecules. As soon as the drug passes through the outer membrane and reaches the perplasmic space, it undergoes a change by enzymes. The altered drug (along with the unchanged drug) competes for entrance into the cell, but it turns out that they are unable to bind with ribosomes. In turn, amino- glycosides differ in terms of their ability to resist enzymatic inactivation. Gentamicin, tobramycin, netilmicin, and amikacin are effective in treating aerobic infections and other Gram-negative bacilli. Streptomycin is the drug of choice for treating rabbit fever, plague, and brucellosis (in combination with tetracycline ). It is not used for treating other Gram-negative bacterial infections because of the high likelihood of developing resistance, which can develop as a result of only one mutation. However, it should be especially noted that practically all antibiotics of the aminoglycoside series are not metabolized in the body, but build up in the kidneys and have a certain oto- and nephrotoxicity. It is effective with respect to most Gram-negative and a few Gram-positive bacteria; staphylococci, streptococci, pneu- mococci, gonococci, meningococci, stimulus of dysentery, brucellosis, tuberculosis, rabbit fever, plague, and others. It is used for various diseases caused by microorganisms that are sensitive to it in bacterial endocarditis, periotonitis, meningitis, infections of the urinary tract, gastric infections, and so on. Neomycin: Neomycin is a complex mixture of antibiotics (neomycins A, B, C, D, E, and F), that is formed by the actinomycete S. Neomycin A, also called neamine, is 2-deoxy-4-O-(2,6-diamino-2,6-dideoxy-α-D-glucopyranosyl)-D-streptamine (32. At the same time, neomycin B, O-2,6-diamino- 2,6-dideoxy-α-D-glucopyranosyl(1→4)-O-[O-2,6-diamino-2,6-dideeoxy-β-L-idopyra- nosyl-(1→3)-β-D-ribofuranosyl-(1→5)]-2-deoxy-D-streptamine (32. It is effective with respect to the majority of Gram-negative and a few Gram-positive bacteria; staphylo- cocci, pneumococci, gonococci, meningococci, and stimulants of dysentery. The antibiotic effect of neomycin with respect to many types of bacteria is higher than that of streptomycin. At the same time, microorganisms sensitive to neomycin become resistant to a lesser degree than streptomycin. It is used for various gastrointestinal diseases caused by microorganisms sensitive to it, including enteritis, which is caused by microbes that are resistant to antibiotics. However, because of its high oto- and nephrotoxicity, its local use is preferred for infected skin dis- eases, infected wounds, conjunctivitis, keratitis, and others. Paromomycin: From a chemical point of view, paromomycin, O-2-amino-2-deoxy-α- D-glucopyranosyl(1→4)-O-[O-2,6-diamino-2,6-dideoxy-β-L-idopyranoxyl-(1→3)-β-D- ribofuranosyl-(1→5)]-2-deoxy-D-streptamine (32. In addition, it is recommended for treating severe and chronic forms of gastric amebiasis.