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By M. Bram. Brooks Institute.

It and its derivatives are a group of drugs that possess the most rapid action against the disease buy hyzaar 50 mg without a prescription heart attack warnings. Artemisinin-based combination therapy: A combination of artemisinin or one of its derivatives with an antimalarial drug or drugs of a different class cheap 50 mg hyzaar amex arrhythmia recognition. Beta-lactam antibiotics: A broad class of antibiotics hyzaar 12.5mg for sale blood pressure up and down all day, consisting of all antibi- otic agents that contain a beta-lactam nucleus in their molecular structure hyzaar 50 mg low price heart attack stent. This includes penicillin derivatives, cephalosporins, monobactams, and carbapenems. Most beta-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Bioavailability: Bioavailability is a subcategory of absorption and is the fraction of an administered dose of unchanged drug that reaches the sys- temic circulation, one of the principal pharmacokinetic properties of drugs. By defnition, when a medication is administered intravenously, its bioavail- ability is 100 percent. However, when a medication is administered via other routes (such as orally), its bioavailability generally decreases due to incomplete absorption and frst-pass metabolism. Bioequivalent: The absence of a signifcant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equiva- lents becomes available at the site of drug action, when administered at the same molar dose under similar conditions in an appropriately designed study. Black market: A market of goods or services that operates outside the for- mal market, not supported by an established state power. Blockbuster drugs: Popular drugs that generate at least $1 billion in annual sales for the company that creates them. British Pharmacopoeia: Established in 1864, the British Pharmacopoeia provides authoritative offcial standards for pharmaceutical substances and medicinal products in the United Kingdom and many other countries that have adopted it. For example, density is a bulk property because it does not depend on the amount of substance tested. Central medical store: Primarily found in developing countries, it is the Ministry of Health’s procurement arm and national medical store. Central medical stores are generally responsible for the procurement, quality assur- ance, storage and distribution of drugs, vaccines, disinfectants, dressings, and related medical supplies for government health facilities and some nongovernment organizations. Chain of custody: A document intended to guarantee the integrity of a drug product along the distribution chain. Chromatography: A method for separating a mixture into its constituent substances. The separation is based on differential partitioning between a mobile and stationary phase. Subtle differences in a compound’s partition- ing result in differential retention on the stationary phase, thus effecting Copyright © National Academy of Sciences. This method is used to separate mixtures such as drugs for accurate and precise analysis. Civil liability: The potential responsibility for payment of damages or other court enforcement in a lawsuit. Colorimetry: The experimental measurement of the amount of color pro- duced by a colorimetric reagent and a sample. Compounding: The creation of a particular pharmaceutical produce to ft the unique needs to a patient. To do this, compounding pharmacists combine or process appropriate ingredient using various tools. This may be done for medically necessary reasons, such as to change the form of the medication from a solid pill to a liquid, to avoid a nonessential ingredi- ent that the patient is allergic to, or to obtain the exact dose(s) needed of particular active pharmaceutical ingredient(s). It may also be done for more optional reasons, such as adding favors to a medication or otherwise altering taste or texture. Compulsory license: Also known as statutory license of mandatory collec- tive management, provides that the owner of a patent or copyright licenses the use of their rights against payment either set by law or determined through some form of arbitration. In essence, under a compulsory license, an individual or company seeking to use another’s intellectual property can do so without seeking the rights holder’s consent, and pays the rights holder a set fee for the license. Contract manufacturing: The manufacturing of a product by an organiza- tion or company other than the marketing company. Convenience sample: A type of nonprobability sampling which involves the sample being drawn from the part of the population that is close to hand. That is, a sample population selected because it is readily available and convenient. The researcher using such a sample cannot scientifcally make generalizations about the total population from this sample because it would not be fully representative. Crude active ingredients: Chemicals that have not undergone the appropri- ate purifcation steps required to meet pharmacopeial standards or manu- facturer’s dossier requirements. It can be a result of high temperatures exceeding label requirements, resulting in decreased potency and effcacy. Developing country: A nation with a low living standard, undeveloped in- dustrial base, and low human development index relative to other countries. Development bank: A national or regional fnancial institution designed to provide medium- and long-term capital for productive investment, often accompanied by technical assistance in developing countries. Diffusion-ordered proton nuclear magnetic resonance spectroscopy: A type of nuclear magnetic resonance spectroscopy that can identify the various types of ingredients in a mixture by taking advantage of differences in mo- lecular mass. It separates the nuclear magnetic resonance signals of different components according to their diffusion coeffcient. Direct ionization: The impulses alpha and beta particles apply to orbital electrons to ionize, or completely remove an electron from an atom follow- ing the transfer of energy from a passing charged particle. Specifc ioniza- tion, the number of ion pairs formed per unit path length for a given type of radiation, is a measure of the intensity of ionization. Because of their double charge and relatively slow velocity, alpha particles have a high spe- cifc ionization and a relatively short range in matter (a few centimeters in air and only fractions of a millimeter in tissue). Beta particles have a much lower specifc ionization than alpha particles and, generally, a greater range. Direct-to-pharmacy: A supply chain model where manufacturers sell di- rectly to pharmacies. It has been recognized as a highly effcient and cost-effective strategy to control the disease. Disintegration: The process of breaking up a solid dosage form in water or simulated gastric solution. Distribution chain: A series of businesses or organizations involved in trans- porting, storing, and selling goods from the manufacturer to consumers. Diversion: The unlawful channeling of products from a legitimate, parallel marketed, subsidized supply chain into other, unsubsidized markets. Doha Declaration: A declaration adapted by World Trade Organization members in 2001. It affrms the right of all countries to protect public health and enhance access to medicines for poor countries. Drug pedigree: A statement of origin that identifes each prior sale, pur- chase, or trade of a drug, including the date of those transactions and the names and addresses of all parties to them. Drug potency: The extent to which a drug product contains the specifed amount of active ingredient. Drug resistance: The reduction in effectiveness of a drug in curing a disease or condition due to mutations in the target organism. Economies of scale: Factors that cause the average cost of production to fall as the volume of output increases. Electromagnetic spectrum: The entire range of wavelengths or frequencies of electromagnetic radiation extending from gamma rays to the longest radio waves, including visible light. This technique is used to ionize small amounts of large or labile molecules such as peptides, proteins, organometallics, and polymers.

Interestingly buy discount hyzaar 12.5mg online blood pressure medication make you cough, the four fragment miners mentioned above have been made available as 17 a single package named ParMol (Parallel Molecular Mining) purchase hyzaar 12.5 mg blood pressure pills kidney failure. Other algorithms for frequent fragment mining that are more database-centric include 18 19 18 Molfea and Warmr generic 50 mg hyzaar fast delivery arteria dorsalis pedis. Molecules are encoded as basic facts order hyzaar 50mg with visa pulse pressure aortic regurgitation, and queries result in a combination of facts. The fragments that can be searched for or result from queries, are linear sequences of non-hydrogen atoms and bonds. The fact that Molfea only finds chains of atoms limits its usefulness 19 since almost all molecules have rings or branching points. It has been successfully applied to chemical data, for instance to find frequent substructures in carcinogenic compounds. Examples and background knowledge are encoded as a facts and rules in a relational database. Logic programming is used to represent examples, background knowledge, and hypotheses, in a uniform way. Warmr searches the available patterns in a breadth-first manner, starting from the most general relations, and gradually increasing the level of complexity, to find patterns that are more specific. Candidates that are more specific are generated by pruning non-frequent patterns from the next level. Second, the complexity of relations queried, places high demands on computing 19 resources 2. For a pair of molecules, a number of substructures/fragments may exist that occur in both structures. Corresponding atoms should have the same atom type and the same topological distance to other common atoms, in both molecules. The topological distance is the number of bonds that form the shortest path between two atoms. Scores are based on the number of common atoms, and are corrected with a penalty for discontinuous pieces. Despite the high level of detail of these approaches, exhaustive study of all possible fragments can be costly, however. A more restrictive, still sensible, approach may be to focus on chemically meaningful fragments only, instead of including every single fragment in a study. This method splits molecules into non-overlapping structural parts according to a predefined set of breaking rules. This approach yields (chemically) more intuitive fragments such as rings/ring systems, linkers, side chains, functional groups, etc. A typical compound (Figure 6-a) is fragmented into 28 molecular parts, according to the method described by Bemis et al. Three ring systems (Figure 6-d) are at the core of this compound, which are connected by two linkers (Figure 6-e). Attached to this framework are the five side chains (Figure 6-b), yielding the complete molecule. There are many variations to this method; most methods differ in the precise definition of building blocks. By removing (b) the side chains from this structure, (c) the molecular framework is revealed. The connection point to the framework or rings is indicated by a rectangular label composed of the letter B and the atom type that it is connected to. Bonds that are typically formed by one of these reactions, are cleaved, essentially reversing synthesis. The resulting fragments are precursors from which the molecule can be synthesized using the set of chemical reactions. Although this approach might seem useful from a chemical point of view, it is not so appropriate for precise analysis. Moreover, there are indications that 24 actual synthesis may not be reflected very well (e. For a general 25 overview of retro-synthesis, the reader is referred to a recent review by Todd. Furthermore, a recent application of this synthetic approach was described by Vieth 26 and Siegel. The authors investigated four sets of bioactive molecules, fragmented these, and analyzed fragment distribution within a single set, and between the four sets. An interesting example is the distribution of the β-lactam framework within antibiotics. This may reflect the problem of the developing resistance observed against older antibiotics. Another example is the absence of amino acid scaffolds and side chains in marketed oral drugs. Fragments which have low abundance might indicate barely explored parts of chemical 41 Chapter 2 27 space, potentially interesting for designing new compounds. Insight can be obtained in preferences regarding chemistry as well as in differences among databases. In the next paragraphs, we will further expand on this, discussing analysis and evaluation of such databases (sections 2. Two types of representation were used, in order to analyze structures at different levels of detail. Since the same graph may represent multiple molecules of similar shape, the common structure classes are revealed. For example, benzene, hexane, and pyridine are all represented by the same hexagonal graph. In a more detailed analysis, the authors also considered atomic properties such as atom type, hybridization, and bond order. The authors defined four non-overlapping structural units that form a hierarchical description of the molecule: ring systems, linkers, frameworks, and side chains as discussed in section 2. The authors justified their choice of this classification scheme by highlighting its useful features. For example, most frequent frameworks are easily identified, which may guide future drug design. Moreover, ring systems and linkers can serve as input for combinatorial library generation. In addition, the simple building blocks in existing drugs are already useful to check the overlap between compound libraries. However, a small set of only 32 frameworks accounted for 50% of the drug molecules in the database. Analysis that also considered atomic properties logically resulted in a more diverse set of frameworks. Not surprisingly, a small set of 41 frameworks accounted for 1,235 drug molecules (24%) in the database. When we think of molecules as a common framework decorated with side chains, phenyl and other small rings may be considered side chains just as well, as in peptides. In this study, however, they were not; the few rings present in a small molecule are needed to derive a reasonable framework. The total number of side chains was 18,664, on average four side chains per scaffold. Since oxygen atoms double-bonded to a ring system have a profound effect on the ring’s electronic properties, it may be reasonable to consider these as part of the ring. The authors reasoned that the substructures and the combinations they occur in, provide insight into synthetic feasibility and “chemical habits”.

For all practical purposes buy generic hyzaar 12.5 mg line arrhythmia for dummies, steady state will be reached after approximately four or five half-lives; the concentrations at steady state may be abbreviated as Css buy hyzaar 50mg on-line supine blood pressure normal value. For a drug such as gentamicin generic 12.5mg hyzaar with amex blood pressure chart jpg, with a 1- to 4-hour half-life in patients with normal renal function hyzaar 12.5mg low cost heart attack single, steady-state concentration is achieved within 10-20 hours. For agents such as digoxin and phenobarbital, however, a week or longer may be needed to reach steady state. With multiple drug doses (Figure 4-8), steady state is reached when the drug from the first dose is almost entirely eliminated from the body. At this point, the amount of drug remaining from the first dose does not contribute significantly to the total amount of drug in the body. After a single dose, approximately four or five half-lives are required for the body to eliminate the amount of drug equivalent to the one dose. However, at steady state, the amount of drug equivalent to one dose is eliminated over one dosing interval. This apparently faster elimination is a result of accumulation of drug in the body. Although the same percentage of drug is eliminated per hour, the greater amount of drug in the body at steady state causes a greater amount to be eliminated over the same time period. The average times to reach steady-state for some commonly used drugs are shown in Table 4-2. These values may vary considerably between individuals and may be altered by disease. However, administration of a loading dose for drugs that take many hours to reach steady state is commonly used to achieve a concentration approximately equal to the eventual actual steady-state concentration. When equivalent doses are given, a drug with a low elimination rate constant and small volume of distribution should achieve higher steady-state plasma concentrations than an otherwise similar agent with a high elimination rate constant and large volume of distribution. Steady-state concentrations are commonly increased in two ways: • Method 1 Increase the drug dose but maintain the same dosing interval (τ), as shown in Figure 4-9, which results in wider fluctuations between the maximum (peak) and minimum (trough) concentrations after each dose. For example, the patient is not receiving maximal benefits because the steady-state concentrations are relatively low or the steady- state levels are high, causing the patient to experience toxic effects. Remember from earlier in this lesson that repeated doses of drug require approximately four or five half-lives to reach steady state. Clinically, this means that each time a dose or dosing interval is changed, four or five half-lives are needed to reach a new steady state. Of course, a drug with a long half-life will require a longer time to achieve the new steady state than a drug with a relatively short half-life. For example, Drug A has a half-life of 6 hours therefore if the dose or dosing interval is changed, steady state will not be reached for 24-30 hours after the change. If Drug B has a half-life of 3 hours, steady state will be reached only after 12-15 hours after a change in the dose or dosing interval. In deciding on a specific dosing regimen for a patient, the goal is to achieve a certain plasma concentration of drug at steady state. Ideally, peak and trough concentrations will both be within the therapeutic range (Figure 4-11). At steady state, the time required to eliminate one dose of drug is one dosing interval. As multiple drug doses are administered, n increases and approaches infinity (abbreviated as n →∞). As n becomes a large number, e approaches e , -nKτ -nKτ which approaches zero, so 1 - e approaches 1. When n (the number of doses given) is sufficiently large (>4 or 5 doses), the equation above simplifies to: We can estimate the minimum or trough concentration at steady state. The trough concentration occurs just before the administration of the next dose (at t = τ). In this situation, the general equation for the equation for Cn(t) becomes: Note the similarity between the equations for Cpeak(steady state) and Ctrough(steady state). The expression for -Kt Ctrough(steady state) simplifies to Cpeak(steady state) times e. An almost identical equation (below) can be used to calculate the concentration at any time after the peak. The only difference is that t is replaced by the time elapsed since the peak level. Clinical Correlate In most clinical situations it is preferable to wait until a drug concentration is at steady state before obtaining serum drug concentrations. Use of steady-state concentrations are more accurate and make the numerous required calculations easier. If two drug concentrations and the time between them are known, K can be calculated. Because is independent of any pharmacokinetic model, it is helpful to the practicing clinician (model assumptions do not have to be made). Several mathematical methods may be used to calculate the average drug concentration, but only one is presented here. Therefore: and since: The equation: 4-3 is very useful, particularly with drugs having a long half-life, in which the difference between peak and trough steady-state levels may not be large. It is important to recognize from the equations that at steady state is determined by the clearance and drug dose (dose/τ). Also, changes in V or K that are not related to a change in clearance would not alter. With multiple drug dosing at steady state, changes in τ, K, or V (with no change in clearance) would alter the observed peak and trough drug concentrations but not. In dealing with such equations, it is helpful to remember that the units of measure on both sides must be the same. For example, in the equation above, should be in micrograms per milliliter, milligrams per liter, or similar concentration units. Therefore, the right side of the equation must have the same units, as is the case when: • dose is in a consistent mass unit, such as milligrams, • clearance is in liters per hour or milliliters per minute, and • dosing interval is in hours. So dose/(Cl × τ) has the following units: Then, as both hour terms cancel out, we see that amount per volume (concentration) is left. For example, most patients with normal renal function will have a gentamicin V of 0. A patient receives 500 mg of drug X intravenously every 6 hours until steady state is reached. Just after the dose is injected, a blood sample is drawn to determine a peak plasma concentration. Using the two plasma concentrations, we first calculate K, as described previously: Then we insert the known Cpeak, K, X0, and τ values in the equation for Cpeak. By rearranging the equation to isolate the only remaining unknown variable, we can then use it to calculate V: Now we know the values of all the variables in the equation (V, K, Cpeak, X0, and τ) and can use this information to calculate a new Cpeak if we change the dose (e. For example, if we want the peak level to be higher and wish to calculate the required dose to reach this new peak level, we can rearrange our equation: -Kτ X0 = V × Cpeak(steady state)(1 - e ) and substitute our calculated V and K and the desired Cpeak. Or we can choose a new dose (X0) and calculate the resulting Cpeak by inserting the calculated K and V with τ into the original equation: Remember that each time we calculate a peak plasma level (Cpeak), the trough plasma level also can be calculated if we know K and τ: -Kτ Ctrough = Cpeake If the dosing interval is not changed, new doses and concentrations are directly proportional if nothing else changes (i. What is the maximum concentration after 15 doses if the dose (X0) is 800 mg and the volume of -1 distribution (V) is 20 L? When multiple drug doses are given and steady state is reached, the amount of drug eliminated during one dosing interval (τ) is equal to the drug dose. A drug with a relatively small K (long T1/2) takes a longer time to reach steady state than a drug with a large K. If a drug with a T1/2 of 12 hours is given every 6 hours and a peak concentration at steady state is 10 mg/L, what will be the approximate peak concentration just after the fifth dose is administered? Which patient (A or B) is likely to achieve higher steady-state plasma concentrations?

Continu- ous infusion order 12.5mg hyzaar amex blood pressure 140 over 90, initiate infusion of 10mg/h and increase by 5mg/h to 15 mg/h purchase hyzaar 12.5 mg free shipping prehypertension stage 2. When increasing the infusion dose cheap 12.5mg hyzaar mastercard hypertension level 2, administer for less than 24 hours at a rate of less than 15 mg/h Conversion from I buy generic hyzaar 50mg on line heart attack xi. Contraindications Severe hypotension, second- or third-degree heart block or sinus node dys- function, and acute myocardial infarction with pulmonary congestion are con- traindications for diltiazem use. Dubin Precautions/Warnings Use of diltiazem with β-blockers or digoxin can result in conduction abnor- malities. Drug-Drug Interactions Cimetidine use may increase diltiazem serum concentrations. The risk of bradycardia or heart block is increased with β-blocker or digoxin use. Diltiazem may decrease metabolism of cyclosporine, carbamazepine, digoxin, lovastatin, midazolam, and quinidine. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis, and hyperglycemia. Compatible Diluents/Administration The final concentration for infusion of diltiazem should be 1 mg/mL. Antiarrhythmic Medications 183 Mechanism of Action Adenosine is an endogenous purinergic agent. Contraindications Second- or third-degree heart block or sinus node dysfunction, unless a pace- maker is in place, are contraindications for adenosine use. The initial dose of adenosine should be decreased in patients receiving dipyridamole. Atropine has a half-life in children younger than 2 years of 7 hours; in children older than 2 years, of 2. Precautions/Warnings Psychosis can occur with atropine use in sensitive individuals. Drug-Drug Interactions Atropine has additive effects when administered with other anticholinergic drugs. Dubin Mechanism of Action Magnesium sulfate suppresses early after-depolarizations that can trigger tor- sade de pointes. Contraindications Heart block, serious renal impairment, and coma are contraindications for magnesium sulfate use. Precautions/Warnings Use magnesium sulfate with caution in patients with renal dysfunction and those receiving digoxin. Compatible Diluents/Administration Magnesium sulfate is incompatible when mixed with fat emulsions, calcium gluceptate, clindamycin, dobutamine, hydrocortisone, polymyxin B, procaine hydrochloride, nafcillin, tetracyclines, and thiopental. Effect of acetyla- tor phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. Mexiletine: an effective antiarrhythmic drug for treatment of ventricular arrhythmias in congenital heart disease. Control of late post- operative ventricular arrhythmias with phenytoin in young patients. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. Usefulness of propafenone for supraven- tricular arrhythmias in infants and children. Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: results of a multicenter, baseline-controlled safety and efficacy study in 160 patients. Double-blind titrated-dose comparison of metoprolol and pro- pranolol in the treatment of angina pectoris. Efficacy and safety of intravenous and oral nadolol for supraventricular tachycardia in children. Intravenous amiodarone for life-threatening tachyarrhythmias in children and young adults. Amiodarone in the treatment of cardiac arrhythmias in children: one hundred thirty-five cases. Pediatric use of intravenous amiodarone: efficacy and safety in critically ill patients from a multicenter protocol. Bretylium tosylate: a newly available antiarrhythmic drug for ventricular arrhythmias. Cardiac decompensation following verapamil ther- apy in infants with supraventricular tachycardia. Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem. The addition of these agents reduces early acute rejection events and may improve long-term graft and patient outcomes. The most controversial issue is whether corticos- teroids should be routinely added to form a “triple therapy. Finally, there is no agreement on whether intravenous anti- body induction therapy should be routinely used. A summary of the options for induction and maintenance therapy is shown in Table 8-1. It should be noted that there have been no large-scale randomized controlled tri- als of any immunosuppressive therapy in pediatric thoracic transplantation. Corticosteroids (Methylprednisolone and Prednisone) Indication Corticosteroids have broad immunosuppressive and anti-inflammatory effects. Many pediatric heart transplant centers are using steroid-avoidance regimens or early steroid withdrawal to avoid the many side effects and complications associated with long-term steroid use in children. High-dose steroids remain the standard therapy for treatment of acute rejection episodes. Mechanism of Action Corticosteroids decrease inflammation through the suppression of the migration of polymorphonuclear leukocytes and the reversal of increased 8. Corticosteroids prevent immune activation by inhibiting antigen presentation, cytokine production, and proliferation of lymphocytes. Some centers use moderate-dose oral steroids for less severe episodes of acute rejection (e. Maintenance Therapy Those centers that use long-term maintenance therapy typically use prednisone in doses of 0. Webber prednisone indefinitely, whereas others wean to discontinuation in the first few months if the rejection history is benign. Increasing evidence suggests that complete steroid avoidance beyond the intraoperative period is possible in many children, especially infants. Pharmacokinetics The peak and duration are dependent on the route of administration of the drug. Oral: peak effect occurs within 1 to 2 hours, and the duration is 30 to 36 hours Intramuscular: peak effect is 4 to 8 days, and the duration is 1 to 4 weeks Corticosteroids are metabolized in the liver to inactive glucuronide and sulfate metabolites. Monitoring Parameters Blood pressure, weight, height, serum electrolytes, and glucose should be monitored. Phenytoin, phenobarbital, and rifampin increase clearance of methylpred- nisolone; potassium-depleting diuretics (furosemide) enhance potassium depletion. Permanent diabetes mellitus may be precipitated when corticosteroids are used in combination with cyclosporine or tacrolimus. Cyclosporine was the most commonly used agent 5 years ago, but, currently, almost half of pediatric heart transplant recipients are receiving tacrolimus. Cyclosporine and tacrolimus have not been compared in large randomized tri- als in children after transplantation of thoracic organs. One small (26 children), single-center randomized trial in pediatric heart transplantation has been per- formed but was not powered to identify differences between immunosuppres- sive regimens.

Methylene Blue (Methylthioninium Chloride)* Pregnancy Category-C Indicatons Acute methaemoglobinaemia purchase hyzaar 50mg without a prescription prehypertension journal. Dose Intravenous injecton Methaemoglobinaemia caused by high dosage of prilocaine infusion: 1-2 mg/kg intravenously over 5 minutes purchase 12.5mg hyzaar with visa blood pressure medication hold parameters, followed immediately by a fuid fush of 15-30 ml to minimize local pain cheap hyzaar 12.5 mg overnight delivery hypertension life expectancy. Contraindicatons Severe renal impairment; methaemoglo- binaemia due to chlorate or induced by sodium nitrite in treatment of cyanide poisoning; afects ability to drive machinery hyzaar 12.5 mg without a prescription heart attack signs and symptoms. Naloxone* Pregnancy Category-B Schedule X Indicatons Opioid overdosage; postoperatve respiratory depression. Once response occurs start infusion of naloxone at 2/3rd the total loading dose given every hour with contnous monitoring for reccurence of respiratory depression. Precautons Physical dependence on opioids or other situatons where acute withdrawal syndrome may be precipitated (see above); lactaton; cardiovascular disease; pregnancy (Appendix 7c). Contraindicatons Carbamate poisoning and organophosphates without antcholinesterase actvity; hypersensitvity to the drug. Precautons Impaired renal functon; large doses can cause neuromuscular blockade, myasthenia gravis; atropinizaton occur faster on concurrent use with atropine; paediatrics; allergies; pregnancy (Appendix 7c). Sodium Nitrite* Pregnancy Category-C Indicatons Cyanide poisoning (together with Sodium thiosulphate). Note: Prepare as 3% soluton of Sodium nitrite in Water for Injectons (30 mg/ml) at the tme of administraton. Precautons Monitor plasma methaemoglobin levels; severe cardiovascular or cerebrovascular dis- ease; hypotension; pregnancy (Appendix 7c). Adverse Efects Nausea, vomitng and abdominal pain, vasodilataton resultng in syncope, hypotension, tachycardia, fushing, headache; methaemoglobinaemia; cyanosis, dyspnoea, tachypnoea. Child- 500 mg/kg intravenously over 10-30 minutes may be repeated at half the inital dose at 1-2 hours (12. They are typically used to treat moton sickness and the side efects of opioid analgesics, general anaesthetcs and chemo- therapy induced nausea and vomitng in cancer patents either alone or in combinaton. Some medicatons act on the gut by speeding up the rate at which the stomach emptes and help to facilitate the quick transit of food through intestne (prokinetc acton). Metoclopramide has antemetc propertes and also stmu- lates upper gastrointestnal motlity. It is efectve against nausea and vomitng associated with gastrointestnal disor- ders or migraine, following surgery and chemotherapy and is also efectve against radiaton-induced nausea and vomitng. Combining metoclopramide with cortcosteroids (such as dexamethasone) can improve its antemetc efect in chemo- therapy-induced nausea and vomitng. Metoclopramide may be useful in the management of gastro-oesophageal refux and gastroparesis, as well as preoperatvely in the preventon of aspiraton syndromes. It is also used to facilitate intubaton of the small bowel during radiographic examinatons. Metoclopramide may cause acute dystonic reactons with facial and skeletal muscle spasms and oculogyric crisis. These reac- tons are most common in the young (especially girls and young women) and the elderly; they occur shortly afer the start of treatment and subside within 24 h of drug withdrawal. Promethazine may be useful in the preventon and treatment of postoperatve and drug-induced nausea and vomitng. Domperidone* Schedule H Indicatons Nausea and vomitng from any cause in adult, epigastric senses of fullness; upper abdominal distress; non ulcer dyspepsia; migraine. Contraindicatons Hypersensitvity; prolactnoma, hepatc impairment; where increased gastro- intestnal motlity harmful; pregnancy; gastro intestnal haemorrhage; intestnal obstructon. Precautons Children; renal impairment, interactons (Appendix 6c); history of breast cancer; allergies; pheochromocytoma; i. Adverse Efects Rarely, gastro-intestnal disturbances (including cramps) and hyperprolactnaemia; very rarely, extrapyramidal efects and rashes; headache; dizziness; dry mouth; nervousness; fushing. Dose Oral or intramuscular injecton or Slow intravenous injecton Adult- Nausea and vomitng, gastro- esophageal refux, gastroparesis: (over 1 to 2 min for slow intravenous injecton), 10 mg 3 tmes daily. Aid to gastrointestnal intubaton: 20 mg as a single dose 5 to 10 min before examinaton; Adolescent (15 to 19 years), 10 mg. Child- Up to 1 year (up to 10 kg) 1 mg twice daily; 1 to 3years (10 to 14 kg) 1 mg 2 to 3 tmes daily; 3 to 5 years (15 to 19 kg) 2 mg 2 to3 tmes daily; 5 to 9 years (20 to 29 kg) 2. Contraindicatons Gastrointestnal obstructon, haemorrhage or perforaton, 3-4 days afer gastrointestnal surgery; convulsive disorders; pheochromo- cytoma; hypersensitvity. Precautons Elderly, children and young adults; hepatc impairment (Appendix 7a); renal impairment (Appendix 7d); pregnancy (Appendix 7c); may mask underlying disorders such as cerebral irritaton; avoid for 3-4 days afer gastrointestnal surgery; lactaton (Appendix 7b); interactons (Appendix 6a); Parkinson’s disease; epilepsy; depression; porphyria; driving or operatng machines; hypertension; cirrhosis; congestve heart failure. Dose Oral Preventon of post-operatve nausea and vomitng: Adult 16 mg, 1 h before inducton of anaesthesia. Nausea and vomitng associated withcancer chemotherapy: Adult- 24 mg as a single dose taken 30 min before start of single day chemotherapy. Child (4-11 yrs)- 4 mg tablets 3 tmes a day; contnue for 1-2 days afer completon of chemotherapy. Adverse Efects Headache, constpaton or diarrhoea, dizziness; fushing, hypersensitvity reacton, anaphylaxis/anaphylactoid reactons, angioedema; bronchospasm, hypotension, laryngeal edema, urtcaria, hiccups, oculagyric crisis. Dose Oral and intravenous injecton Adult- Nausea, vomitng acute atack: initally 20 mg then 20 mg every 2 h. Adult- Labyrinthine disorder: 5 mg 3 tmes daily increased to 30 mg daily in divided doses that decrease afer meal to 5 to 10 mg daily. Most antpsychotcs are best avoided during pregnancy; hypersensitvity; prolactn dependant tumors. Cauton is also required in severe respiratory disease and in patents with a history of jaundice or who have blood dyscrasias (perform blood counts if unexplained infecton or fever develops). Cauton should be taken in elderly, who are partcularly susceptble to postural hypotension and to hyper- or hypothermia in very hot or cold weather. Serious consideraton should be given before prescribing these drugs for elderly patents. As photosensitsaton may occur with higher dosages, patents should avoid direct sunlight; extrapyramidal syndrome; pregnancy (Appendix 7c); interactons (Appendix 6a). Adverse Efects Less sedatng; extrapyramidal symptoms, partcularly dystonias, more frequent; respiratory depression may occur in suscep- tble patents; amenorrhoea; blurred vision; cholestatc jaundice; neuroleptc malignant syndrome; leucopenia; agranulocytosis. Moton sickness, preventon: 20 to 25 mg at bedtme on night before travel, repeated on day of travel if necessary. Child- Moton sickness, preventon; 2 to 5 years: 5 mg at night and on day of travel, if necessary. Precautons Prostatc hypertrophy; urinary retenton; glaucoma; hepatc disease (Appendix 7a); epilepsy; elderly and children (more susceptble to adverse efects); lactaton (Appendix 7b); pregnancy (Appendix 7c); interactons (Appendix 6a). May impair ability to perform skilled tasks, for example operatng machinery, driving. Adverse Efects Drowsiness, dizziness, sedaton (but para- doxical stmulaton may occur, especially with high doses or in children and eld- erly); headache, psychomotor impairment; urinary retenton, dry mouth, blurred vision, gastrointestnal disturbances; hypersensitv- ity reactons, rashes, photosensitvity reac- tons; jaundice; blood disorders; cardiovas- cular adverse efects-afer injecton; venous thrombosis at site of intravenous injecton; pain on intramuscular injecton; somnolence; tortcollis; tnnitus; leucopenia; thrombocy- topenia, agranulcytosis; apnoea; angioneu- rotc edema. It is transmited by the faeco-oral route and infecton is usually caused by ingeston of cysts from contaminated food and drink. In non-endemic areas, sympto mless carriers should be treated with a luminal amoebicide which will reduce the risk of transmission and protect the patent from invasive amoe- biasis. Diloxanide furoate is most widely used, but other compounds, including clefamide, etofamide and teclozan, are also efectve. Treatment with diloxanide furoate is regarded as successful if stools are free of E. Symptomatc (invasive) amoebiasis may be classifed as intestnal or extra-intestnal. Intestnal amoebiasis is either amoebic dysentery or non-dysenteric amoebic colits.

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