By F. Zapotek. University of South Dakota. 2018.

These are too small to be counted individually discount eskalith 300mg on-line, so the mole is the unit used by chemists to make counting and measuring a lot easier buy eskalith 300 mg on-line. Just as the word ‘dozen’ represents the number 12 generic 300mg eskalith otc, the mole also represents a number – 6 × 1023. The atomic mass of potassium is 39; so 1 mole of potassium has a mass of 39 g (which is the same as saying that 6 × 1023 atoms of potassium have a total mass of 39g). For 96 Moles and millimoles example, one hundred 1p coins weigh 356 g; it is quicker to weigh 356g of 1p coins than to count a hundred coins. Now consider a single molecule of sodium chloride (NaCl) which consists of one sodium ion (Na+) and one chloride ion (Cl–). NaCl = molecule Na+ Cl– = ions Since moles can refer to ions as well as molecules, it can be seen that one mole of sodium chloride contains one mole of sodium ions and one mole of chloride ions. From tables (see the end of this section), the relative ionic masses are: sodium (Na) 23 chloride (Cl) 35. The ‘2’ after the ‘Cl’ means two ions of chlorine: CaCl2 = molecule Ca2+ Cl– +Cl– = ions The molecular mass of calcium chloride is 147. The reason why the molecular mass does not always equal the sum of the atomic masses of the individual ions is because water forms a part of each calcium chloride molecule. From the molecular formula and knowledge of the atomic weights it can be seen that calcium chloride contains: 1moleofCa=40g 2 moles of Cl = 71g 2 moles of H2O, each mole of water = 18g; 2 × 18 = 36g What are moles and millimoles 97 So adding everything together: (40 + 71 +36) = 147 i. One millimole is equal to one- thousandth of a mole One micromole is equal to one- thousandth of a millimole It follows that: 1 mole contains1,000 millimoles (mmol) 1 millimole contains1,000 micromoles (mcmol) So, in the above explanation, you can substitute millimoles for moles and 98 Moles and millimoles milligrams for grams. For our purposes: Sodium chloride would give sodium + chloride 1 mole or 1 mole or 1 mole or 1 millimole 1 millimole 1 millimole 58. It is unlikely that you will encounter these types of calculations on the ward, but it is useful to know how they are done and they can be used for reference if necessary. So it follows that the amount (in milligrams) equal to 1 millimole of sodium chloride will give 1 millimole of sodium. In this case, calculate the total amount (in milligrams) of sodium chloride and convert this to millimoles to find out the number of millimoles of sodium. Calculations involving moles and millimoles 99 So 1 millimole of sodium chloride (NaCl) will weigh 58. First work out the number of millimoles for 1 mg of sodium chloride, and then the number for the total amount. Alternatively, a formula can be used: mg/mL total number of millimoles = × volume(mL) mg of substtance containing 1mmol where, in this case mg/mL = 1. Conversion of percentage strength (% w/v) to millimoles Sometimes it may be necessary to convert percentage strength to the number of millimoles. All you need to do is to convert the percentage strength to the number of milligrams in the required volume, then follow the steps as before. So, the amount (in milligrams) equal to 1 millimole of sodium chloride will give 1 millimole of sodium. A formula can be devised: percentage strength (% w/v) mmol = × 10 × volume (mL) mg of substance ccontaining 1mmol In this example: percentage strength (% w/v) = 0. When moles of substances are dissolved in water to make solutions, the unit of concentration is molarity and the solutions are known as molar solutions. When one mole of a substance is dissolved in one litre of solution, it is known as a one molar (1M) solution. If 2 moles of a substance are made up to 1 litre (or 1 mole to 500mL), the solution is said to be a two molar (2M) solution. To do this, you need to calculate the equivalent number of moles per litre (1,000mL). Alternatively, a formula can be derived: number of moles concentration (mol/L or M) = volume in litres The number of moles is calculated from the weight (in g) and the molecular mass: weight (g) moles = molecular mass Molar solutions and molarity 103 To convert the volume (in mL) to litres, divide by 1,000: volume in litres = Putting these together gives the following formula: number of moles concentration (mol/L or M)= = volume in litres Re-writing this gives: concentration (mol/L or M)= In this example: weight (g) = 18 molecular mass = 294 volume (mL) = 200 Substitute the figures into the formula: concentration = = 0. Alternatively, a formula can be derived: number of moles concentration (mol/L or M) = volume in litres so: number of moles = concentration (mol/L or M) × volume in litres We want to go a step further and calculate a weight (in grams) instead of number of moles. The number of moles is calculated from the weight (in grams) and the molecular mass: weight (g) moles = molecular mass To convert the volume (in mL) to litres, divide by 1,000: volume in litres = Putting these together gives the following formula: weight (g) moles = = concentration (mol/L or M)× molecular mass Re-writing this gives: concentration (mol/L or M) × molecular mass ×× final volume (mL) weight (g) = 1,000 Molar solutions and molarity 105 In this example: concentration (mol/L or M) = 0. Conversion of Dosages to mL/hour • In this type of calculation, it is best to convert the dose required to a volume in millilitres. Conversion of mL/hour Back to a Dose • Sometimes it may be necessary to convert mL/hour back to the dose in mg/min or mcg/min and mg/kg/min or mcg/kg/min. Drip rate calculations (drops/min) 107 • If doses are expressed in terms of milligrams, then there is no need to multiply by 1,000. The first (drops/min) is mainly encountered when infusions are given under gravity as with fluid replacement. The second (mL/hour) is encountered when infusions have to be given accurately or in small volumes using infusion or syringe pumps – particularly if drugs have to be given as infusions. The drip rate of the giving set is always written on the wrapper if you are not sure. To do this, multiply the volume of the infusion by the number of ‘drops per mL’ for the giving set, i.

Stopping drug treatment Figure 18: Stopping drug treatment For drugs with first-order elimination kinetics the plasma concentration decreases by 50% each half-life period buy eskalith 300mg lowest price, if no more of the drug is taken (Figure 18) buy eskalith 300mg free shipping. The effect of the drug stops when the concentration falls below the therapeutic threshold discount eskalith 300mg visa. For example, if the initial plasma concentration is 300 ug/ml, the therapeutic threshold 75 ug/ml and the half-life 8 hours, this will take 16 hours (2 half-lives). For example, 100 mg is eliminated per day, regardless of whether the total amount in the body is 600 mg or 20 grams. This also means that the Cp/time curve never levels off to a certain maximum: the plasma concentration can rise forever if more of the drug is administered than the body can eliminate. To maintain a steady state you will have to administer exactly the amount that the body eliminates. The dosage of drugs in this category requires great care because of the increased risk of accumulation. Special features of the curve In commonly used dosage schedules with identical doses taken at regular intervals, the required steady state is reached after 4 half-lives, and plasma concentration drops to zero when the treatment is stopped. In Figure 19: Loading dose steady state the total amount of drug in the body remains constant. If you want to reach this state quickly you can administer at once the total amount of drug which is present in the body in steady state (Figure 19). Theoretically you will need the mean plasma concentration, multiplied by the distribution volume. In the majority of cases these figures can be found in pharmacology books, or may be obtained from the pharmacist or the manufacturer. The first reason is when a drug has a narrow therapeutic window or a large variation in location of the therapeutic window in individuals. This means that you should not raise the dose before this time has elapsed and you have verified that no unwanted effects have occurred. Table 7 in Chapter 8 lists drugs in which slowly raising the dose is usually recommended. Tapering the dose Sometimes the human body gets used to the presence of a certain drug and physiological systems are adjusted to its presence. To prevent rebound symptoms the treatment cannot be abruptly stopped but must be tailed off to enable the body to readjust. To do this the dose should be lowered in small steps each time a new steady state is reached. Table 8 in Chapter 11 lists the most important drugs for which the dosage should be decreased slowly. These are essential tools in your prescribing, as they indicate which drugs are recommended and available in the health system. In many cases they are used by countries when developing their national treatment guidelines. London: British Medical Association & The Pharmaceutical Society of Great Britain. Although revised every six months, old issues remain a valuable source of information and may be available to you at no or very low cost. Published fortnightly; offers comparative assessments of therapeutic value of different drugs and treatments. Published quarterly; provides English translations of selected articles on clinical pharmacology, ethical and legal aspects of drugs, which have appeared in La Revue Prescrire. Published fortnightly; provides comparative drug profiles and advice on the choice of drugs for specific problems. This booklet also contains the criteria for the selection of essential drugs and information on applications of the model list. A quarterly journal that provides an overview of topics relating to drug development and regulation. This book contains an updated cumulative list of officially approved generic names in Latin, English, French, Russian and Spanish. Essential Drugs Monitor, Geneva: World Health Organization, Action Programme on Essential Drugs. Free of charge and published three times per year; contains regular features on issues related to the rational use of drugs, including drug policy, research, education and training, and a review of new publications. This annex contains step by step guidance on how to administer different dosage forms. This information is included because, as a doctor, you are ultimately responsible for your patient’s treatment, even if that treatment is actually administered by a colleague, such as a nurse, or by patients themselves. You will often need to explain to patients how to administer a treatment correctly. The instructions have been presented in such a way that they can be used as a self-standing information sheet for patients. If you have access to a photocopy machine you might consider making copies of them as they are. You might also wish to adapt them to your own situation or translate them into a national language.

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The artemisinin component rapidly clears parasites from the blood (reducing parasite numbers by a factor of approximately 10 000 in each 48-h asexual cycle) and is also active against the sexual stages of parasite that mediate onward transmission to mosquitos purchase 300 mg eskalith otc. The longer-acting partner drug clears the remaining parasites and provides protection against development of resistance to the artemisinin derivative proven eskalith 300 mg. Partner drugs with longer elimination half-lives also provide a period of post-treatment prophylaxis order 300 mg eskalith otc. Other considerations The guideline development group considered that 3 days of artemisinin derivative are necessary to provide suffcient effcacy, promote good adherence and minimize the risk of drug resistance resulting from incomplete treatment. Shorter courses (1–2 days) are therefore not recommended, as they are less effective, have less effect on gametocytes and provide less protection for the slowly eliminated partner drug. It is essential to achieve effective antimalarial drug concentrations for a suffcient time (exposure) in all target populations in order to ensure high cure rates. The dosage recommendations below are derived from understanding the relationship between dose and the profles of exposure to the drug (pharmacokinetics) and the resulting therapeutic effcacy (pharmacodynamics) and safety. Some patient groups, notably younger children, are not dosed optimally with the “dosage regimens recommended by manufacturers, which compromises effcacy and fuels resistance. In these guidelines when there was pharmacological evidence that certain patient groups are not receiving optimal doses, dose regimens were adjusted to ensure similar exposure across all patient groups. While age-based dosing may be more practical in children, the relation between age and weight differs in different populations. Age-based dosing can therefore result in under- dosing or over-dosing of some patients, unless large, region-specifc weight-for-age databases are available to guide dosing in that region. Factors other than dosage regimen may also effect exposure to a drug and thus treatment effcacy. The drug exposure of an individual patient also depends on factors such as the quality of the drug, the formulation, adherence and, for some drugs, co-administration with fat. Poor adherence is a major cause of treatment failure and drives the emergence and spread of drug resistance. Fixed-dose combinations encourage adherence and are preferred to loose (individual) tablets. Prescribers should take the time necessary to explain to patients why they should complete antimalarial course. Target dose range: A total dose of 5–24 mg/kg bw of artemether and 29–144 mg/ kg bw of lumefantrine Recommended dosage regimen: Artemether + lumefantrine is given twice a day for 3 days (total, six doses). As these target populations may be at increased risk for treatment failure, their responses to treatment should be monitored more closely and their full adherence ensured. Therefore, their response to artesunate + amodiaquine treatment should be closely monitored. Concomitant use of efavirenz increases exposure to amodiaquine and hepatotoxicity. Additional comments: • No signifcant changes in the pharmacokinetics of amodiaquine or its metabolite desethylamodiaquine have been observed during the second and third trimesters of pregnancy; therefore, no dosage adjustments are recommended. Few data are available on the pharmacokinetics of amodiaquine in the frst year of life. To reduce acute vomiting and optimize absorption, the total mefoquine dose should preferably be split over 3 days, as in current fxed-dose combinations. Target dose and range: A target dose (range) of 4 (2–10) mg/kg bw per day artesunate given once a day for 3 days and a single administration of at least 25 / 1. Fortunately, molecular markers of resistance to antifols and sulfonamides correlate well with therapeutic responses. These showed lower exposure in younger children with higher risks of treatment failure. The revised dose regimens are predicted to provide equivalent piperaquine exposures across all age groups. The subgroup also reviewed preliminary results from an unpublished study using doses similar to those now recommended in this guidelines (n=100). The effect of dosing regimens on the antimalarial effcacy of dihydroartemisinin–piperaquine: a pooled analysis of individual patient data. Formulations: Currently available as a fxed-dose combination in tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine and paediatric tablets contain 20 mg dihydroartemisinin and 160 mg piperaquine. Target dose and range: A target dose (range) of 4 (2–10) mg/kg bw per day dihydroartemisinin and 18 (16–27) mg/kg bw per day piperaquine given once a day for 3 days for adults and children weighing ≥ 25 kg. Children in this age group have signifcantly lower plasma piperaquine concentrations than older children and adults given the same mg/kg bw dose. As this does not affect primary effcacy, no dosage adjustment is recommended for pregnant women. There has been no evidence of piperaquine-related cardiotoxicity in large randomized trials or in extensive deployment. Treatment failure may result from drug resistance or inadequate exposure to the drug due to sub-optimal dosing, poor adherence, vomiting, unusual pharmacokinetics in an individual or substandard medicines. It is important to determine from the patient’s history whether he or she vomited the previous treatment or did not complete a full course of treatment.

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