By I. Roy. Lakeland College. 2018.
Activation of 1-adrenoceptors bacco plant best levothroid 200mcg thyroid symptoms puffy face, on autonomic ganglia and the adrenal on cardiac tissue produces an increase in the heart rate medulla buy 200mcg levothroid with mastercard thyroid cancer weight gain. Norepinephrine and epinephrine are thus potent ceptor agonists; thus, all three can stimulate the heart vasoconstrictors of vascular beds that contain predomi- (Table 9. This observation raises the possi- adrenoceptor agonists; norepinephrine is a relatively bility that eventually therapeutic drugs may selectively weak 2-adrenoceptor agonist. Isoproterenol and epi- alter lipid metabolism and therefore provide therapeu- nephrine produce vasodilation in skeletal muscle, but tic management of obesity. The 3-receptor and the re- norepinephrine does not; rather it produces vasocon- cently identiﬁed subtypes within the 1- and 2-receptor striction through the 1-adrenoceptors. One exception is tam- and thereby diminishing the amount of transmitter re- sulosin, an antagonist with some selectivity for 1A- leased per impulse. Presynaptic Receptors Adrenoceptors of the 2 subclass also occur presynap- tically, and activation of these receptors leads to en- Presynaptic or prejunctional receptors are located on hanced norepinephrine release. The physiological and the presynaptic nerve endings and function to control pharmacological importance of these presynaptic the amount of transmitter released per nerve impulse -receptors is less certain than it is for presynaptic - 2 2 and in some instances to affect the rate of transmitter receptors. In this case, the ac- PHARMACOLOGICAL INTERVENTION tivation of the presynaptic receptor would be part of a IN NEUROTRANSMISSION negative feedback mechanism. These and many ther by preventing the transmitter from reaching the other drugs that alter transmission are discussed in sub- presynaptic receptor, thus causing excessive transmitter sequent chapters. All of the following structures have a signiﬁcant the autonomic nervous system EXCEPT: cholinergic innervation EXCEPT: (A) Smooth muscle of blood vessels (A) Ventricular wall (B) Skeletal muscle (B) Sinoatrial node (C) Sinoatrial node (C) Atrioventricular node (D) Salivary glands (D) Bladder (E) Intestinal smooth muscle (E) Ileum 9 General Organization and Functions of the Nervous System 95 3. It does not re- (B) Primarily sympathetic cholinergic neurons spond to muscarine; that is, it is not a muscarinic re- (C) Primarily parasympathetic noradrenergic ceptor. Intestinal relaxation occurs as spond to: a result of stimulation of 1- and 1-receptor stimu- (A) Acetylcholine and muscarine lation. Smooth muscle relaxation is primarily under (C) Acetylcholine, muscarine, and nicotine the inﬂuence of the sympathetic nervous system. All other choices are tissues that Compendium of Receptor Characterization and are innervated by the autonomic nervous system. Stimulation of the sympathetic noradrenergic neurons to the iris causes contraction of the radial smooth muscle and dilation of the pupil (mydriasis). Stitzel DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Albuterol 105 Isoproterenol 102 Amphetamine 106 Metaraminol 105 Dobutamine 105 Methoxamine 105 Dopamine 103 Norepinephrine 101 Ephedrine 105 Phenylephrine 105 Epinephrine 101 Terbutaline 105 The adrenomimetic drugs mimic the effects of adren- tal structure of the catecholamines is shown in Figure ergic sympathetic nerve stimulation on sympathetic 10. The adrenergic transmitter norepineph- of epinephrine and norepinephrine and possess consid- rine and the adrenal medullary hormone epinephrine erably greater pharmacological effects than do the also are included under this broad heading. Throughout most of the world, epinephrine adrenomimetic drugs are an important group of thera- and norepinephrine are known as adrenaline and nora- peutic agents that can be used to maintain blood pres- drenaline, respectively. They are also present in many over- the basic catecholamine structure primarily by having the-counter cold preparations because they constrict substitutions on their benzene ring. MECHANISM OF ACTION CHEMISTRY Many adrenomimetic drugs produce responses by inter- The adrenomimetic drugs can be divided into two ma- acting with the adrenoceptors on sympathetic effector jor groups on the basis of their chemical structure: the cells. The cate- thetic effectors have activity at 1-, 2-, 1-, or 2- cholamines include norepinephrine, epinephrine, and adrenoreceptors or in some cases, combinations of these dopamine, all of which are naturally occurring, and sev- adrenoceptors. Adrenomimetic drugs vary in their afﬁni- eral synthetic substances, the most important of which ties for each subgroup of adrenoceptors. The skele- nephrine, have a high afﬁnity for all of the adrenocep- 96 10 Adrenomimetic Drugs 97 An important characteristic of indirectly acting OH (para) adrenomimetic drugs is that repeated injections or pro- longed infusion can lead to tachyphylaxis (gradually di- OH (meta) Catechol minished responses to repeated administration). This is a result of a gradually diminishing availability of re- leasable norepinephrine stores on repeated drug ad- C ministration. Ethylamine The actions of many indirectly acting adreno- N mimetic drugs are reduced or abolished by the prior ad- ministration of either cocaine or tricyclic antidepressant FIGURE 10. Nor- Destruction or surgical interruption of the adrener- epinephrine has a high afﬁnity for - and 1-adrenocep- gic nerves leading to an effector tissue renders indirectly tors but a relatively low afﬁnity for 2-receptors. Also, patients being ity of the drug, the response characteristics of the effector treated for hypertension with reserpine or guanethidine, cells, and the predominant type of adrenoceptor found on which deplete the norepinephrine stores in adrenergic the cells. For example, the smooth muscle cells of many neurons (see Chapter 20), respond poorly to administra- blood vessels have only or predominantly -adrenocep- tion of indirectly acting adrenomimetic drugs. The interaction of compounds with these adreno- Some adrenomimetic drugs act both directly and in- ceptors initiates a chain of events in the vascular smooth directly; that is, they release some norepinephrine from muscle cells that leads to activation of the contractile storage sites and also directly activate tissue receptors. Since bronchial smooth muscle contains 2- adrenoceptors, the response in this tissue elicited by the Structure–Activity Relationships Among action of 2-adrenoceptor agonists is relaxation of Adrenomimetic Drugs smooth muscle cells. Epinephrine and isoproterenol, which have high afﬁnities for 2-adrenoceptors, cause re- The nature of the substitutions made on the basic laxation of bronchial smooth muscle.
The point of contact (synapse) duplicate the time course of intrasynap- between the first and second neurons tic agonist concentration required for occurs mainly in ganglia; therefore trusted 50mcg levothroid thyroid cancer vs hypothyroid, the appropriate high-frequency ganglionic first neuron is referred to as pregan- activation cheap levothroid 100 mcg with visa thyroid symptoms weight loss. The concentration of nico- glionic and efferents of the second as tine in the synaptic cleft can neither postganglionic. ACh stimulates receptors locat- The ganglionic effects of ACh can be ed on the subsynaptic membrane of the blocked by tetraethylammonium, hexa- second neuron. Activation of these re- methonium, and other substances (gan- ceptors causes the nonspecific cation glionic blockers). The resulting influx of trinsic activity, that is, they fail to stim- Na+ leads to a membrane depolariza- ulate ganglia even at low concentration; tion. Normally, not all preganglionic im- Certain sympathetic preganglionic pulses elicit a propagated response in neurons project without interruption to the second neuron. The ganglionic syn- the chromaffin cells of the adrenal me- apse acts like a frequency filter (A). The latter are embryologic homo- effect of ACh elicited at receptors on the logues of ganglionic sympathocytes. Ex- ganglionic neuronal membrane can be citation of preganglionic fibers leads to imitated by nicotine; i. If a with a release of epinephrine into the small dose of nicotine is given, the gan- blood (D). The ducing a partial depolarization of adre- membrane depolarizes partially, but nomedullary cells, are effective in liber- fails to reach the firing threshold. At a low concentration, nicotine acts as a gan- glionic stimulant; it alters the filter function of the ganglionic synapse, al- lowing action potential frequency in the second neuron to approach that of the first (B). Simultaneous activation of many nicotinic cholinoceptors depolarizes the ganglionic cell membrane to such an ex- tent that generation of action potentials Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Nicotine 109 First neuron Preganglionic Second neuron postganglionic -70 mV Acetylcholine Impulse frequency A. Ganglionic transmission: normal state -55 mV Persistent depolarization Low concentration Ganglionic activation Nicotine B. Ganglionic transmission: excitation by nicotine -30 mV Depolarization High concentration Ganglionic blockade Nicotine C. Ganglionic transmission: blockade by nicotine Adrenal medulla Nicotine Excitation Epinephrine D. Adrenal medulla: epinephrine release by nicotine Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Sensitivity to arterial pCO2 increases; increased afferent input At a low concentration, the tobacco al- augments respiratory rate and depth. Sensitivity to the corre- via activation of ganglionic cholinocep- sponding stimuli is enhanced. Sensitization of at diverse other neural sites, considered chemoceptors leads to excitation of the below in more detail. Ganglionic At low concentration, nicotine is al- stimulation occurs in both the sympa- so able to augment the excitability of thetic and parasympathetic divisions of the motor endplate. Para- manifested in heavy smokers in the sympathetic activation results in in- form of muscle cramps (calf muscula- creased production of gastric juice ture) and soreness. Nico- would tend to lower heart rate, this re- tine increases vigilance and the ability sponse is overridden by the simultane- to concentrate. The effect reflects an en- ous stimulation of sympathetic cardio- hanced readiness to perceive external accelerant neurons and the adrenal me- stimuli (attentiveness) and to respond dulla. On the one hand, release of epinephrine elicits cardiovas- cular effects, such as increases in heart rate und peripheral vascular resistance. On the other, it evokes metabolic re- sponses, such as glycogenolysis and li- polysis, that generate energy-rich sub- strates. The metabolic state corre- sponds to that associated with physical exercise – “silent stress”. Partial depolariza- tion of baroreceptors enables activation of the reflex to occur at a relatively smaller rise in blood pressure, leading to decreased sympathetic vasoconstric- tor activity.
Although the term parasitology (par-ah-si-TOL-o-je) is the study Microorganisms of parasites in general cheap 200mcg levothroid overnight delivery thyroid cancer blood results, in practice discount 100mcg levothroid mastercard thyroid follicular adenoma, it usually refers to Microorganisms are simple, usually single-cell forms of the study of protozoa and worms (helminths). The organisms included These organisms rarely cause diseases and will not be de- in the study of microbiology along with their scientific scribed any further in this chapter. Others produce the fer- Table 5•1 Organisms Studied in Microbiology TYPE OF NAME OF CHARACTERISTICS OF REPRESENTATIVE ORGANISM STUDY ORGANISMS EXAMPLES Bacteria Bacteriology Simple, single-cell organisms. These cells will use oxy- gen if it is present but are able to grow without oxygen if Checkpoint 5-9 What are the categories of organisms studied it is not available. Some bacteria produce resistant forms, called en- Checkpoint 5-10 What term refers to the microorganisms that dospores, that can tolerate long periods of dryness or normally live in or on the body? Because these en- dospores become airborne easily and are resistant to or- Bacteria dinary methods of disinfection, pathogenic organisms that form endospores are particularly dangerous. They are unique in that “spore,” but these structures are totally different in struc- their genetic material is not enclosed in a membrane, that ture and purpose from the reproductive spores produced is, they do not have a true nucleus. They can be botulism (a deadly form of food poisoning), and anthrax seen only with a microscope; from 10 to 1000 bacteria (de- are examples of spore-forming species. Many types of bacteria are capable of swimming rap- Staining of the cells with dyes helps make their structures idly by means of threadlike appendages called flagella more visible and reveals information about their properties. Some surfaces, such as to the surface of a liquid to get oxygen, are capable of carrying out photosynthesis, as do green and to attach bacteria to each other for exchange of ge- plants; others must take in organic nutrients, as do ani- netic information in a process called conjugation. Among the diseases caused by diplococci are gonorrhea and meningitis; streptococci and staphylococci are re- sponsible for a wide variety of infections, including pneumonia, rheumatic fever, and scarlet fever. C Staphylococci D Streptococci, ◗ Spirochetes (SPI-ro-ketes) are similar to the spirilla, but photomicrograph are capable of waving and twisting motions (see Fig. For our purposes, a convenient and sim- KET-se-ah) and the genus Chlamydia (klah-MID-e-ah) ple grouping is based on the shape and arrangement of are classified as bacteria, although they are considerably these organisms as seen with a microscope: smaller than other bacteria. They are the causative organisms in trachoma (a serious eye in- fection that ultimately causes blindness), parrot fever or A Bacilli B Bacilli, photomicrograph psittacosis, the sexually transmitted infection lym- phogranuloma venereum, and some respiratory diseases Figure 5-4 Bacilli. More specific cause of their small size and the difficulties associated with information is conveyed by adding names for subgroups growing them in the laboratory, viruses were not studied such as type, subtype, strain, variety, etc. They are very slow- growing and hard to destroy, producing spongy degenera- tion of brain tissue, described as spongiform encephalopa- Figure 5-7 Virus structure. Viruses have some of the fundamental properties of Viroids (VI-royds), in contrast, are composed of RNA living matter, but they are not cellular, and they have no alone with no protein coat. They are composed of a core of nucleic parasites, but so far, they have been linked only to dis- acid, either DNA or RNA, surrounded by a coat of protein eases in plants. Fungi Viruses are classified according to the type of nucleic acid they contain—DNA or RNA—and whether that nu- The true fungi (FUN-ji) are a large group of simple plant- cleic acid is single stranded (ss) or double stranded (ds). Al- They are further grouped according to the diseases they though fungi are much larger and more complicated than cause, of which there are a considerable number— bacteria, they are a simple form of life. Molds reproduce in lated (Hanta, Ebola, West Nile), the symptoms they cause several ways, including by simple cell division and by (yellow fever virus, which causes jaundice; hepatitis production of large numbers of reproductive spores. Tinea Table 5 in Appendix 5 presents a list of typical patho- capitis (TIN-e-ah KAP-ih-tis), which involves the scalp, genic protozoa with the diseases they cause. This is a normal inhabitant of the mouth and ◗ Parasitic Worms digestive tract that may produce skin lesions, an oral in- fection called thrush, digestive upset, or inflammation of Many species of worms, also referred to as helminths, are the vaginal tract (vaginitis) as an opportunistic infection parasites with human hosts. Whereas invasion by any form of organism is eases they cause are very dangerous and may be difficult usually called an infection, the presence of parasitic worms to cure. In the United States, it is found most frequently among chil- Although protozoa are also single-cell organisms, they are dren (ages 4 to 12 years) in rural areas with warm climates. It may infest the lungs or the intestines, producing in- in almost any body of water from moist grass to mud pud- testinal obstruction if present in large numbers. An ameba (also spelled amoeba) in soil during either freezing or hot, dry weather and can- is an irregular mass of cytoplasm that propels itself by not be destroyed even by strong antiseptics. New worms de- extending part of its cell (a pseudopod, or “false foot”) velop within the eggs and later reach the digestive system of and then flowing into the extension. This type of protozoon is covered Another fairly common infestation, particularly in with tiny hairs called cilia that produce a wave action to children, is the seat worm, or pinworm (Enterobius ver- propel the organism. They are dangerous because they suck blood from 88 ✦ CHAPTER FIVE Cysts (inactive Red blood cells forms) (ingested) Active form A Amebas B Entamoeba histolytica Tsetse fly (vector)Tsetse fly (vector) Blood vessel Trypanosome C Flagellates D Trypanosoma gambiense Asexual forms Red blood cell Anopheles mosquitoAnopheles mosquito (vector)(vector) Blood vessel Sexual forms E Sporozoa F Plasmodium vivax Figure 5-9 Some parasitic protozoa.
It is the next stage—the tant to note order levothroid 100 mcg free shipping thyroid and weight gain, however buy levothroid 100mcg on-line thyroid symptoms knee pain, that not everyone exposed to Bb nymph—that causes most cases of Lyme disease. Nymphs are very active from spring through early sum- mer, at the height of outdoor activity for most people. Lyme disease is usually described in terms of length Because they are still quite small (less than 2 mm in of infection (time since the person was bitten by a tick length), they are difficult to spot, giving them ample op- infected with Bb) and whether Bb is localized or dissem- portunity to transmit Bb while feeding. Although far inated (spread through the body by fluids and cells carry- more adult ticks than nymphs carry Bb, the adult ticks ing Bb). Furthermore, when and how symptoms of Lyme 1252 GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 The first sign of lyme disease is usually an itchy rash around the site of the tick bite. Late disseminated disease and chronic Lyme People who experience recurrent bouts of symptoms disease over time are said to have chronic Lyme disease. Weeks, months, or even years after an untreated tick bite, symptoms can appear in several forms, including: Early localized Lyme disease • fatigue, forgetfulness, confusion, mood swings, irri- The most recognizable indicator of Lyme disease tability, numbness is a rash around the site of the tick bite. Often, the tick • neurologic problems, such as pain (unexplained and not exposure has not been recognized. The rash—erythema usually one-sided but may be on both sides), and a mim- migrans (EM)—generally develops within 3–30 days icking of the inflammation of brain membranes known and usually begins as a round, red patch that expands. The rash may look like a bruise on and other musculoskeletal complaints individuals with dark skin. Of those who develop Less common effects of Lyme disease are heart ab- Lyme disease, about 50% notice the rash; about 50% normalities (such as irregular rhythm or cardiac block) notice flu-like symptoms, including fatigue, and eye abnormalities (such as swelling of the cornea, headache, chills and fever, muscle and joint pain, and tissue, or eye muscles and nerves). However, a rash at the site can also be an allergic reaction to the tick saliva rather Diagnosis than an indicator of Lyme disease, particularly if the rash appears in less than 3 days and disappears only A clear diagnosis of Lyme disease can be difficult, days later. Sharp, intense pain may be ease may mimic other conditions, including chronic fa- relieved by applying an ice pack to the affected area. The patient may treat Lyme disease by visual- other diseases with many symptoms involving multiple izing Bb as looking like ticks swimming in the blood- body systems. Differential diagnosis (distinguishing stream being killed by the flame of a candle. Lyme disease from other diseases) is based on clinical evaluation with laboratory tests used for clarification, • Probiotics. A two-test approach is common to con- ficial microbes either by ingestion or through a sup- firm the results. Probiotics can restore a healthy balance of results (false-positive and false-negative), laboratory bacteria to the body in cases where long-term antibi- tests alone cannot establish the diagnosis. Yo- gurt or Lactobacillus acidophilus preparations may Doctors generally know which disease-causing or- be ingested. The most helpful piece of information is whether a tick bite or rash • Supplements. Use calcium and magnesium for aches, was noticed and whether it happened locally or while chlorophyll to aide healing, vitamin C for bacterial in- traveling. Doctors may not consider Lyme disease if it is fection and inflammation, bioflavonoids for joint in- rare locally, but will take it into account if a patient men- flammation and to boost the immune system, diges- tions vacationing in an area where the disease is com- tive enzyme for digestive problems, vitamin B com- monly found. Treatment While antibiotics are essential in treating Lyme dis- Allopathic treatment ease, many alternative therapies may minimize symp- toms, improve the immune response, and help treat late For most patients, oral antibiotics (doxycycline or disseminated or chronic disease. The doctor may guidelines include drinking plenty of fluids and eating have to adjust the treatment regimen or change medica- cooked whole grains and fresh vegetables. Antibiotics can sugar, fat, refined carbohydrates, and dairy products kill Bb only while it is active, rather than while it is dor- should be reduced. When symptoms indicate nervous system involve- Lyme disease include: ment or a severe episode of Lyme disease, intravenous antibiotic (ceftriaxone) may be given for 14–30 days. Formulae used to treat systemic bac- Some physicians consider intravenous ceftriaxone the terial infections include Wu Wei Xiao Du Yin (Five-In- best therapy for any late manifestation of disease, but gredient Decoction to Eliminate Toxin), Yin Hua Jie Du treatments for late Lyme disease are still controversial Tang (Honeysuckle Decoction to Relieve Toxicity), and as of 2003. Inflammation at the site of infection may be treated externally with Yu Lu San (Jade Dew Extract) or Expected results Jin Huang San (Golden Yellow Powder). Specific Chi- nese herbs and treatments can be used for specific If aggressive antibiotic therapy is given early, and symptoms. For examples, for systemic bacterial infec- the patient cooperates fully and sticks to the medica- tion, one may use honeysuckle flower, forsythia, isa- tion schedule, recovery should be complete. Acupuncture and small percentage of Lyme disease patients fail to re- ear acupuncture treatments are also utilized. Co-infection with other nacea species) to clear infection and boost the immune infectious organisms spread by ticks in the same areas system, goldenseal ( Hydrastis canadensis) to clear in- as Bb (babesiosis and ehrlichiosis, for instance) may fection and boost the immune system, garlic to clear be responsible for treatment failures or more severe bacterial infection, and spilanthes (Spilanthes species) symptoms.
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