By Y. Gorn. Miami Christian University.
Calcium channel blockers appear to involve their interference with the calcium entry into the myocardial and vascular smooth muscle generic diltiazem 60 mg fast delivery, thus decreasing the availability of the intracellular calcium e order diltiazem 180 mg mastercard. Other therapeutic uses: hypertension, acute coronary insufficiency, tachycardia, Adverse effects: flushing nausea/vomiting, headache, Ankle swelling, dizziness, constipation, etc. Acetylsalicylic acid Acetylsalicylic acid (aspirin) at low doses given intermittently decreases the synthesis of thromboxne A2 without drastically reducing prostacylin synthesis. Thus, at the doses of 75 mg per day it can produce antiplatelet activity and reduce the risk of myocardial infarction in anginal patients. However, it is generally accepted that cardiac arrhythmias arise as the result of either of a) Disorders of impulse formation and/ or b) Disorders of impulse conduction. Pharmacotherapy of cardiac arrhythmias Antiarrhythmic drugs are used to prevent or correct cardiac arrhythmias (tachyarrhythmias). Drugs used in the treatment of cardiac arrhythmias are traditionally classified into: Class (I): Sodium channel blockers which include quinidine, lidocaine, phenytion, flecainide, etc. Lidocaine, which is used commonly as a local anaesthetic blocks both open and inactivated sodium channel and decreases automaticity. Adverse effects: excessive dose cause massive cardiac arrest, dizziness, drowsiness, seizures, etc. It is used in ventricular ectopic beats in patients with normal left ventricular function. Beta blockers may potentiate the negative inotropic action of other antiarrhythmics. Therapeutic uses: This is useful in tachyarrhythmias, in pheochromocytoma and in thyrotoxicosis crisis. It is also useful in patients with atrial fibrillation and flutter refractory to digitalis. The main adverse effects of this drug are anorexia, nausea, abdominal pain, tremor, hallucinations, peripheral neuropathy, A. It is absolutely contraindicated in patients on beta blockers, quinidine or disopyramide. Class - V drugs: Digoxin causes shortening of the atrial refractory period with small doses (vagal action) and a prolongation with the larger doses (direct action). This action is of major importance in slowing the rapid ventricular rate in patients with atrial fibrillation Diuretics Diuretics are drugs, which increase renal excretion of salt and water: are principally used to remove excessive extracellular fluid from the body. In order to understand the action of diuretics it is important to have some knowledge of the basic processes that take place in the nephron (unit structure of kidney. Approximately 180 liters of fluid is filtered from the glomerulus into the nephron per day. There are three mechanisms involved in urine formation 64 a) glomerular filtration b) tubular reabsorption c) Tubular secretion. Classification of diuretics:- Most of the diuretics used therapeutically act by interfering with sodium reabsorption by the tubules. Thiazide diuretics act by inhibiting NaCl symport at the distal convoluted tubule. Adverse effects: epigastric distress, nausea, vomiting, weakness, fatigue, dizziness, impotence, jaundice, skin rash, hypokalemia, hyperuricemia, hyperglycaemia and visual disturbance. Loop diuretics: Loop diuretics like frusemde inhibit Na - K – 2Cl symporter in the ascending limb. Adverse effects: Hypokalemia, nausea, anorexia, vomiting epigastric distress, fatigue weakness muscle cramps, drowsiness. Therapeutic uses: acute pulmonary edema, edema of cardiac, hepatic and renal disease. Hypertension, cerebral edema, in drug overdose it can be used to produce forced diuresis to facilitate more rapid elimination of drug. Potassium sparing diuretics mechanism of action: Potassium sparing diuretics (spironolactone, triamterene, amiloride) are mild diuretics causing diuresis by increasing the excretion of sodium, calcium and bicarbonate but decrease the excretion of potassium. Hyponatraemia 65 Therapeutic uses: used with conjunction with thiazides or loop diuretics in edema due to, cardiac failure nephrotic syndrome and hepatic disease. Carbonic anhydrase inhibitors: these drugs like acetazolamide inhibit the enzyme carbonic anhydrase in renal tubular cells and lead to increased excretion of bicarbonate, sodium and potassium ions in urine. Main adverse effects of these agents are drowsiness, hypokalemia, metabolic acidosis and epigastric distress. Osmotic diuretics: these drugs like mannitol and glycerine (glycerol) are freely filtered at the glomerulus and are relatively inert pharmacologically and undergo limited reabsorption by renal tubule. These are administered to increase significantly the osmolality of plasma and tubular fluid. Drugs used in hypotensive states and shock Antihypotensive drugs or agents are used to elevate a low blood pressure and may be classified as follows: I. Vasoconstrictor drugs these include: • Peripherally acting vasoconstrictors which are further divided into sympathomimetic drugs and direct vasoconstrictors. Sympathomimetics used to elevate the blood pressure include adrenaline, noradrenaline, methoxamine, phenylephrine, mephentermine and ephedrine.
Finally purchase diltiazem 60 mg on line, a general overview will be made on lipids diltiazem 180mg overnight delivery, the most peculiar metabolites of this bac- terium. Expectations were generated on the elucidation of some unique characteristics of the biology of the tubercle bacillus, such as its characteristic slow growth, the nature of its complex cell wall, certain genes related to its virulence and persistence, and the apparent stability of its genome. In turn, the few genes with particularly low (< 50 %) G+C content are those coding for transmembrane proteins or polyketide synthases. This deviation to low G+C content is believed to be a consequence of the required hydrophobic amino acids, essential in any trans- membrane domain, that are coded by low G+C content codons. The posses- sion of a single rrn operon in a position relatively distant from oriC has been pos- tulated to be a factor contributing to the slow growth phenotype of the tubercle bacillus (Brosch 2000a). Another 32 different insertion sequences were found, of which seven belonged to the 13E12 family of repetitive sequences; the other insertion sequences had not been described in other organisms (Cole 1998b). Two prophages were detected in the genome sequence; both are similar in length and also similarly organized. The second prophage, PhiRv2 has proven to be much more stable, with less variability among strains (Cole 1999). A bias in the overall orientation of genes with respect to the direction of replication was also found. It was also found that the number of genes that arose by duplication is similar to the number seen in E. The lack of divergence of duplicated genes is consistent with the hypothesis of a recent evolutionary descent or a recent bottleneck in my- cobacterial evolution (Brosch 2002, Sreevatsan 1997, see chapter 2). This flexibility is useful for survival in the changing environments within the human host that range from high oxygen tension in the lung alveolus to microaerophilic/anaerobic condi- tions within the tuberculous granuloma. In total, there are genes encoding for 250 distinct enzymes involved in fatty acid metabolism, compared to only 50 in the genome of E. These proteins are believed to play an important role in survival and multiplication of mycobacteria in different environments (Marri 2006). Pro- teins in this class contain multiple tandem repetitions of the motif Gly-Gly-Ala, hence, their glycine concentration is superior to 50 %. This gene encodes the enzyme in charge of removing oxidized guanines whose incorporation during repli- cation causes base-pair mismatching (Mizrahi 1998, Cole 1999). With the aim of making the information publicly available and the search and analysis of information easier, the Pasteur Institute (http://www. This database is freely available for use on the Internet and is known as the Tuberculist Web Server http://genolist. As more information was generated, databases grew bigger, more experimental information became available, and better and more accurate algorithms for gene identification and prediction were released. The letter C was not included since it usually stands for “comple- mentary”, which means that the gene is located in the complementary strand. As expected, the classes that exhibited the greatest numbers of changes were the un- known category and the conserved hypothetical category (Table 4-1). The re- annotation of the genome sequence allowed the identification of four sequencing errors making the current sequence size change from 4,411,529 to 4,411,532 bp (Camus 2002). Comparative genomics In recent times, new technologies have been developed at an overwhelming pace, in particular those related to sequencing and tools for genome sequence data man- agement, storage and analysis. As of April 2007, 484 microbial genomes have been finished and projects are underway aimed at the sequencing of other 1,155 micro- organisms (http://www. Mycobacteria are not an exception in this titanic genome-sequencing race; since 1998, when the first myco- bacterial genome sequence was published (Cole 1998a); many genome projects have been initiated. Until April 2007, 34 projects on the genome sequencing of different mycobacterial species are finished or in-process. For this reason, these are the strains that have been used as reference strains for comparative genomics both in vitro and in silico. The next step in comparative genomics was the use of genomic subtractive hybridi- zation or bacteria artificial chromosome hybridization for the identification of re- gions of difference among the strains under analysis (Mahairas 1996, Gordon 1999). As a result, they identified 10 regions of difference, including the three previously described (Mahairas 1996). Until 2002, most studies concerning comparative genomics were based on differ- ences among the strain type M. Some excellent reviews are available on comparative genomics, made before the publication of the second M. This strain was considered to be highly transmissible and virulent for human beings (Fleischmann 2002). With the sequence of this second strain, a first approach to the bioinformatic analysis of intraspecies variability became possible. Dark gray filled cells indicate the presence in all strains tested, light gray indicate the presence in some strains, white is absence from all strains tested. These studies have been complemented with data obtained from the genome sequence of a third organism of the M. Sequencing con- firmed the absence of 11 regions of difference, and the presence of only one inser- tion in comparison to the sequenced M. The comparison of the three genomes reflects the high degree of conservation among the members of the M.
As soon as an influenza-like illness devel- oped in one family member diltiazem 180 mg free shipping, the family received either zanamivir (10 mg zanamivir inhaled once daily for 10 days) or placebo buy diltiazem 60mg lowest price. In the zanamivir families, 4 % of fami- lies had at least one new influenza case, compared with 19 % in the placebo fami- Zanamivir 217 lies. A similar risk reduction was shown in a study where zanamivir was administered after close contact with an index case of influenza-like illness (Kaiser 2000). In a study of inhaled zanamivir for the prevention of influenza in families, 4 % of zanamivir versus 19 % of placebo households had at least 1 contact who developed symptomatic, laboratory-confirmed influenza (81 % protective efficacy). The pro- tective efficacy was similarly high for individuals (82 %) and against both influenza types A and B (78 % and 85 %, respectively, for households) (Monto 2002). Children In a trial on children aged five to twelve years, zanamivir reduced the median time to symptom alleviation by 1. Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients (Hedrick 2000). Children, especially those under 8 years old, are usually unable to use the delivery system for inhaled zanamivir appropriately (not producing measurable inspiratory flow through the diskhaler or producing peak inspiratory flow rates below the 60 l/min considered optimal for the device). As a lack of measurable flow rate is related to inadequate or frankly undetectable serum concentrations, prescribers should carefully evaluate the ability of young children to use the delivery system when considering prescription of zanamivir. When zanamivir is prescribed for children, it should be used only under adult supervision and with attention to proper use of the delivery system (Relenza 2003). Special Situations Special settings in which zanamivir has been used include acute lymphoblastic leu- kemia (Maeda 2002) and allogeneic stem cell transplantation (Johny 2002). The second report found no toxicity attributable to zanamivir and rapid resolution of influenza symptoms. Avian Influenza Strains In a study performed on mice in 2000, zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1, and H5N1 transmissible to mammals (Leneva 2001). To date, no virus resistant to zanamivir has been isolated from immunocompetent individuals after treatment. Known resistance mutations are both influenza virus subtype and drug specific (McKimm-Breschkin 2003). There is evidence for different patterns of susceptibility and cross-resistance be- tween neuraminidase inhibitors (Mishin 2005, Yen 2005), but no studies have so far evaluated the risk of emergence of cross-resistance in clinical practice. Zanamivir is not metabolised, and the potential for clinically rele- vant drug-drug interactions is low (Cass 1999b). There is no theo- retical basis for expecting metabolic interactions between zanamivir and other co- administered compounds (Daniel 1999). Each Relenza Rotadisk contains 4 double-foil blisters and each blister contains 5 mg of zanamivir (plus 20 mg of lactose which contains milk proteins). Here, a blister is pierced and zanamivir is dispersed into the air stream when the patient inhales through the mouthpiece. The amount of drug delivered to the respi- ratory tract depends on patient factors such as inspiratory flow. Patients should be instructed in the use of the delivery system, and instructions should include a demonstration – which may be difficult in daily medical practice. When prescribed for children, zanamivir should only be used under adult supervi- sion and instruction. A study of 73 patients (aged 71 to 99 years) from wards providing acute elderly care in a large general hospital found that most elderly people could not use the inhaler device and that zanamivir treatment for elderly people with in- fluenza was unlikely to be effective (Diggory 2001). Dosage The recommended dose of zanamivir for the treatment of influenza in adults and paediatric patients aged 7 years and older is 10 mg bid (= twice daily 2 consecutive inhalations of one 5-mg blister) for 5 days. Patients with pulmonary dysfunction should always have a fast-acting bronchodi- lator available and discontinue zanamivir if respiratory difficulty develops. Standard Dosage for Treatment: 10 mg bid (= twice daily 2 consecutive inhala- tions of one 5-mg blister) for 5 days. Standard Dosage for Prophylaxis: in most countries, zanamivir has not been ap- proved for prophylaxis. Pharmacokinetics: 10 to 20 percent of the active compound reaches the lungs, the rest is deposited in the oropharynx. Warning: zanamivir is not recommended for the treatment of patients with under- lying airways disease (such as asthma or chronic obstructive pulmonary disease). Interactions: no clinically significant pharmacokinetic drug interactions are pre- dicted based on data from in vitro studies. Side effects: zanamivir has a good safety profile and the overall risk for any respi- ratory event is low. Patient information: the use of zanamivir for the treatment of influenza has not been shown to reduce the risk of transmission of influenza to others. There is a risk of bronchospasm, especially in the setting of underlying airways disease, and patients should stop zanamivir and contact their physician if they expe- rience increased respiratory symptoms during treatment such as worsening wheez- ing, shortness of breath, or other signs or symptoms of bronchospasm. A patient with asthma or chronic obstructive pulmonary disease must be made aware of the risks and should have a fast-acting bronchodilator available.
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