Aciclovir

Thomas K.F. Foo, PhD

• Assistant Professor
• Department of Radiological Sciences
• Uniformed University of the Health Sciences
• Bethesda, Maryland
• Manager, MRI Lab
• GE Global Research
• Niskayuna, New York

Carvedilol is a nonselective ОІ-adrenoreceptor antagonist that also blocks О±-adrenoreceptors hiv infection from dried blood purchase 200 mg aciclovir, whereas metoprolol is a ОІ1-selective antagonist hiv infection neutropenia 800 mg aciclovir free shipping. Treatment should be started at low doses and gradually titrated to effective doses based on patient tolerance anti viral ear drops 200 mg aciclovir purchase otc. Obviously the hiv infection process order aciclovir 800 mg line, the patient who also is hypertensive will obtain additional benefit from the ОІ-blocker. These agents are also useful in reducing the symptoms of volume overload, including orthopnea and paroxysmal nocturnal dyspnea. Diuretics decrease plasma volume and, subsequently, decrease venous return to the heart (preload). Diuretics may also decrease afterload by reducing plasma volume, thus decreasing blood pressure. Thiazide diuretics are relatively mild diuretics and lose efficacy if patient creatinine clearance is less than 50 mL/min. Loop diuretics are used for patients who require extensive diuresis and those with renal insufficiency. Direct Vasodilators Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing the venous capacitance; arterial dilators reduce systemic arteriolar resistance and decrease afterload. Inotropic Drugs Positive inotropic agents enhance cardiac muscle contractility and, thus, increase cardiac output. Although these drugs act by different mechanisms, in each case the inotropic action is the result of an increased cytoplasmic calcium concentration that enhances the contractility of cardiac muscle. Digitalis the cardiac glycosides are often called digitalis or digitalis glycosides, because most of the drugs come from the digitalis (foxglove) plant. Like the antiarrhythmic drugs described in Chapter 17, the cardiac glycosides influence the sodium and calcium ion flows in the cardiac muscle, thereby increasing contraction of the atrial and ventricular myocardium (positive inotropic action). The digitalis glycosides show only a small difference between a therapeutically effective dose and doses that are toxic or even fatal. Regulation of cytosolic calcium concentration: Free cytosolic calcium concentrations at the end of contraction must be lowered for cardiac muscle to relax. The Na+/Ca2+-exchanger plays an important role in this process by extruding Ca2+ from the myocyte in exchange for Na+ (Figure 16. The concentration gradient for both ions is a major determinant of the net movement of ions. By inhibiting the ability of the myocyte to actively pump Na+ from the cell, cardiac glycosides decrease the Na+ concentration gradient and, consequently, the ability of the Na+/Ca 2+-exchanger to move calcium out of the cell. Further, the higher cellular Na+ is exchanged by extracellular Ca2+ by the Na+/Ca2+-exchanger increasing intracellular Ca2+. Because more Ca2+ is retained intracellularly, a small but physiologically important increase occurs in the free Ca2+ that is available at the next contraction cycle of the cardiac muscle. It follows that if the Na+/K+в"adenosine triphosphatase is extensively inhibited, the ionic gradient becomes so disturbed that dysrhythmias can occur. Increased contractility of the cardiac muscle: Administration of digitalis glycosides increases the force of cardiac contraction, causing the cardiac output to more closely resemble that of the P. Increased myocardial contraction leads to a decrease in end-diastolic volume, thus increasing the efficiency of contraction (increased ejection fraction). The resulting improved circulation leads to reduced sympathetic activity, which then reduces peripheral resistance. Vagal tone is also enhanced, so the heart rate decreases and myocardial oxygen demand diminishes. Pharmacokinetics: All digitalis glycosides possess the same pharmacologic actions, but they vary in potency and pharmacokinetics (Figure 16. Digoxin is very potent, with a narrow margin of safety and long half-life of around 36 hours. Digoxin is mainly eliminated intact by the kidney, requiring dose adjustment based on creatinine clearance. Adverse effects: Digitalis toxicity is one of the most commonly encountered adverse drug reactions. Side effects often can be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels (decreased K+ enhances potential for cardiotoxicity), and if indicated, giving potassium supplements. In general, decreased serum levels of potassium predispose a patient to digoxin toxicity.

Syndromes

• Eye that appears red or bloodshot
• 1 - 3 years: 3 g/day
• The gastrointestinal tract begins to develop.
• Babbling by 12 months
• Cough that has lasted more than 3 months without any other explanation
• Use of certain medications, such as acetazolamide, amphotericin B, and triamterene

The islets of Langerhans make up only about 1­2% of the total cells of the pancreas hiv infection photos 200 mg aciclovir order overnight delivery. Metabolic Effects of Insulin and Glucagon important hormone coordinating the use of fuels by tissues antiviral cream for genital herpes buy aciclovir 800 mg free shipping. Its metabolic effects are anabolic antiviral juicing purchase 200 mg aciclovir overnight delivery, favoring hiv infection oral risk order aciclovir 400 mg with visa, for example, synthesis of glycogen, triacylglycerols, and protein. Structure of insulin Insulin is composed of 51 amino acids arranged in two polypeptide chains, designated A and B, which are linked together by two disulfide bridges (Figure 23. When used in humans for the treatment of diabetes, antibodies to these foreign proteins develop. Note that the biosynthesis involves two inactive precursors, preproinsulin and proinsulin, which are sequentially cleaved to form the active hormone plus the connecting or C-peptide (see Figure 23. Also, because of its longer half-life in the plasma, the C-peptide is a good indicator of insulin production and secretion. This short duration of action permits rapid changes in circulating levels of the hormone. Stimulation of insulin secretion: Insulin secretion by the cells of the islets of Langerhans of the pancreas is closely coordinated with the release of glucagon by pancreatic cells. The relative amounts of insulin and glucagon released by the pancreas are regulated so that the rate of hepatic glucose production is kept equal to the use of glucose by peripheral tissues. Glucose: the cells are the most important glucose-sensing Meal 120 100 Glucose 80 120 U/ml 80 Insulin 40 0 cells in the body. Ingestion of glucose or a carbohydrate-rich meal leads to a rise in blood glucose, which is a signal for increased insulin secretion (as well as decreased glucagon synthesis and release, Figure 23. Amino acids: Ingestion of protein causes a transient rise in 120 pg/ml Glucagon 110 100 90 60 0 60 120 180 Minutes 240 c. The intestinal peptides cholecystokinin and gastric-inhibitor y polypeptide (glucose-dependent insulinotropic peptide) increase insulin secretion in response to oral glucose, and so are referred to as "incretins. This may account for the fact that the same amount of glucose given orally induces a much greater secretion of insulin than if given intravenously. Glucose-dependent release of insulin into blood is mediated through a rise in calcium concentration in the cell. These effects are mediated primarily by epinephrine, which is secreted by the adrenal medulla in response to stress, trauma, or extreme exercise. Under these conditions, the release of epinephrine is controlled largely by the nervous system. Epinephrine has a direct effect on energy metabolism, causing a rapid mobilization of energy-yielding fuels, including glucose from the liver (produced by glycogenolysis or gluconeogenesis, see p. In addition, epinephrine can override the normal glucose-stimulated release of insulin. Effects on carbohydrate metabolism: the effects of insulin on 3 glucose metabolism promote its storage and are most prominent in three tissues: liver, muscle, and adipose. The intravenous administration of insulin thus causes an immediate decrease in the concentration of blood glucose. Activation of multiple signaling pathways 4 utes to administration of insulin, which causes a significant reduction in the release of fatty acids. Insulin acts by promoting the dephosphorylation and, hence, inactivation of the enzyme (see p. Increased triacylglycerol synthesis: Insulin increases the Biologic effects of insulin: Glucose uptake Glycogen synthesis Protein synthesis Fat synthesis transport and metabolism of glucose into adipocytes, providing the substrate glycerol 3-phosphate for triacylglycerol synthesis. Effects on protein synthesis: In most tissues, insulin stimulates Gluconeogenesis Glycogenolysis Lipolysis Altered gene expression the entry of amino acids into cells, and protein synthesis. This is the first step in a cascade of reactions ultimately leading to a diverse array of biologic actions (Figure 23. Metabolic Effects of Insulin and Glucagon Glucose transporter 3 Cell membrane Glucose transporters increase insulinmediated uptake of glucose into cell. Glucose Fission + Vesicle Glucose transporter 2 Activated receptor promotes recruitment of glucose transporters from intracellular pool to cell membrane. Signal transduction: the binding of insulin to the subunits of the Active transport Insulinsensitive Facilitated transport Skeletal and cardiac muscle, and adipose tissue (together account for largest tissue mass) insulin receptor induces conformational changes that are transduced to the subunits. This promotes a rapid auto phosphorylation of specific tyrosine residues on each subunit (see Figure 23. Membrane effects of insulin: Glucose transport in some tissues, Insulininsensitive Epithelia of intestine Renal tubules Choroid plexus Erythrocytes Leukocytes Lens of eye Cornea Liver Brain Figure 23.

This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood hiv infection statistics south africa order aciclovir 800 mg. Both ezetimibe and ezetimibe-glucuronide are slowly eliminated from plasma natural factors antiviral purchase 200 mg aciclovir fast delivery, with a half-life of approximately 22 hours hiv infection rate swaziland 200 mg aciclovir mastercard. Ezetimibe has no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A hiv infection statistics uk generic aciclovir 400 mg with amex, D, and E. Patients with moderate to severe hepatic insufficiency should not be treated with ezetimibe. Combination drug therapy It is often necessary to employ two antihyperlipidemic drugs to achieve treatment goals in plasma lipid levels. However, the clinical value of ezetimibe either alone or in combination with statins is uncertain. Until this discrepancy is resolved, many experts recommend clinicians maximize statin dosages and use niacin, fibrates, and resins before considering ezetimibe, Figure 21. These agents are inhibitors of renal ion transporters that decrease the reabsorption of Na+ at different sites in the nephron. As a result, Na+ and other ions, such as Cl-, enter the urine in greater than normal amounts along with water, which is carried passively to maintain osmotic equilibrium. Diuretics thus increase the volume of urine and often change its pH as well as the ionic composition of the urine and blood. The efficacy of the different classes of diuretics varies considerably, with the increase in Na+ secretion varying from less than two percent for the weak, potassium-sparing diuretics to over 20 percent for the potent loop diuretics. In addition to these ion-transport inhibitors, there are osmotic diuretics that prevent water reabsorption, as well as aldosterone antagonists and a carbonic anhydrase inhibitor. The major clinical uses of diuretics are in managing disorders involving abnormal fluid retention (edema) or treating hypertension in which their diuretic action causes a decreased blood volume, leading to reduced blood pressure. The filtrate, although normally free of proteins and blood cells, does contain most low-molecular-weight plasma components in approximately the same concentrations as are found in the plasma. These include glucose, sodium bicarbonate, amino acids, and other organic solutes as well as electrolytes, such as Na+, K+, and Cl-. The kidney regulates the ionic composition and volume of urine by the active reabsorption or secretion of ions and/or the passive reabsorption of water at five functional zones along the nephronв"namely, the proximal convoluted tubule, the descending loop of Henle, the ascending loop of Henle, the distal convoluted tubule, and the collecting tubule and duct (Figure 22. Proximal convoluted tubule In the extensively convoluted proximal tubule located in the cortex of the kidney, almost all the glucose, bicarbonate, amino acids, and other metabolites are reabsorbed. If not for the extensive reabsorption of solutes and water in the proximal tubule, the mammalian organism would rapidly become dehydrated and lose its normal osmolarity. Carbonic anhydrase in the luminal membrane and cell of the proximal tubule modulates the reabsorption of bicarbonate (see acetazolamide below). Water follows salt reabsorption; thus, the presence of substances like mannitol and glucose would tend to become concentrated. This condition results in a higher osmolarity of the tubular fluid and prevents further water reabsorption, resulting in osmotic diuresis. Acid and base secretory systems: the proximal tubule is the site of the organic acid and base secretory systems (Figure 22. The organic acid secretory system is saturable, and diuretic drugs in the bloodstream compete for transfer with endogenous organic acids, such as uric acid. This explains the hyperuricemia seen with certain of the diuretic drugs, such as furosemide or hydrochlorothiazide. The organic base secretory system is responsible for the secretion of creatinine, choline, and so on, and it is found in the upper and middle segments of the proximal tubule. Descending loop of Henle the remaining filtrate, which is isotonic, next enters the descending limb of the loop of Henle and passes into the medulla of the kidney. The osmolarity increases along the descending portion of the loop of Henle because of the countercurrent mechanism that is responsible for water reabsorption. Ascending loop of Henle the cells of the ascending tubular epithelium are unique in being impermeable to water. Active reabsorption of Na+, K+, and Cl- is mediated by a Na+/K+/2Cl- cotransporter. Because the ascending loop of Henle is a major site for salt reabsorption, drugs affecting this site, such as loop diuretics (see Figure 22.

Theophylline is well absorbed by the gastrointestinal tract hiv infection in korea aciclovir 400 mg purchase mastercard, and several sustained-release preparations are available an antiviral agent quizlet discount 200 mg aciclovir fast delivery. Previously the mainstay of asthma therapy hiv infection diagram order aciclovir 800 mg without prescription, theophylline has been largely replaced with ОІ2 agonists and corticosteroids due to a narrow therapeutic window hiv infection rates in heterosexuals aciclovir 400 mg order without prescription, high side-effect profile, and potential for drug interactions. This leads to decreased binding of IgE to the high-affinity IgE receptor on the surface of mast cells and basophils. Reduction in surface-bound IgE limits the degree of release of mediators of the allergic response. Omalizumab may be particularly useful for treatment of moderate to severe allergic asthma in patients who are poorly controlled with conventional therapy. Due to the high cost of the drug (approximately $600 for a 150-mg vial), limitations on dosage, and available clinical trial data, it is not presently used as first-line therapy. Drugs Used to Treat Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease is a chronic, irreversible obstruction of airflow. These drugs increase airflow, alleviate symptoms, and decrease exacerbation of disease. Combinations of an anticholinergic plus a ОІ2 agonist may be helpful in patients for whom a single inhaled bronchodilator has failed to provide an adequate response. Addition of a long-acting ОІ2 agonists such as salmeterol, improves lung function compared to either a short-acting ОІ2 agonist or steroid alone. Drugs Used to Treat Allergic Rhinitis Rhinitis is an inflammation of the mucous membranes of the nose and is characterized by sneezing, itchy nose/eyes, watery rhinorrhea, and nasal congestion. An attack may be precipitated by inhalation of an allergen (such as dust, pollen, or animal dander). The foreign material interacts with mast cells coated with IgE generated in response to a previous allergen exposure (Figure 27. The mast cells release mediators, such as histamine, leukotrienes, and chemotactic factors, that promote bronchiolar spasm and mucosal thickening from edema and cellular infiltration. Combinations of oral antihistamines with decongestants are the first-line therapies for allergic rhinitis. Systemic effects associated with these oral preparations (sedation, insomnia, and, rarely, cardiac arrhythmias) have prompted interest in topical intranasal delivery of drugs. Antihistamines (H1-receptor blockers) Antihistamines are the most frequently used agents in the treatment of sneezing and watery rhinorrhea associated with allergic rhinitis. H1-histamine receptor blockers, such as diphenhydramine, chlorpheniramine, loratadine, and fexofenadine, are useful in treating the symptoms of allergic rhinitis caused by histamine release. Ocular and nasal antihistamine delivery devices are available over-the-counter for more targeted tissue delivery. Combinations of antihistamines with decongestants (see below) are effective when congestion is a feature of rhinitis. Antihistamines differ in their ability to cause sedation and in their duration of action. In general, anticholinergic side effects of the first-generation antihistamines (dry eyes/mouth, difficulty urinating and/or defecating) are transient and may resolve in 7 to 10 days. Constipation associated with chronic use of the first-generation antihistamines is not P. О±-Adrenergic agonists Short-acting О±-adrenergic agonists (вoenasal decongestantsв), such as phenylephrine, constrict dilated arterioles in the nasal mucosa and reduce airway resistance. When administered as an aerosol, these drugs have a rapid onset of action and show few systemic effects. Oral administration results in longer duration of action but also increased systemic effects. The О±-adrenergic agonists should be used no longer than several days due to the risk of rebound nasal congestion (rhinitis medicamentosa). О±-Adrenergic agents have no place in the long-term treatment of allergic rhinitis.

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References

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