Theophyllin in Asthma Patient

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Asthma is a serious public health problem throughout the world, affecting people of all ages. When uncontrolled, asthma can place severe limits on daily life, and is sometimes fatal.

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  • Asthma is a serious public health problem throughout the world, affecting people of all ages. When uncontrolled, asthma can place severe limits on daily life, and is sometimes fatal.
  • Theophyllin in Asthma Patient

    1. 1. THEOPHYLLINE (Nuelin) for ASTHMA ANTONIO B. JIMENO JR.,MD
    2. 2. Definition of Asthma <ul><li>A chronic inflammatory disorder of the airways </li></ul><ul><li>Many cells and cellular elements play a role </li></ul><ul><li>Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing </li></ul><ul><li>Widespread, variable, and often reversible airflow limitation </li></ul>
    3. 3. Source: Peter J. Barnes, MD Asthma Inflammation: Cells and Mediators
    4. 4. Source: Peter J. Barnes, MD Asthma Inflammation: Cells and Mediators
    5. 5. Mechanisms: Asthma Inflammation Source: Peter J. Barnes, MD
    6. 6. Burden of Asthma <ul><li>Asthma is one of the most common chronic diseases worldwide with an estimated 300 million affected individuals </li></ul><ul><li>Prevalence increasing in many countries, especially in children </li></ul><ul><li>A major cause of school/work absence </li></ul>
    7. 7. Burden of Asthma <ul><li>Health care expenditures very high </li></ul><ul><li>Developed economies might expect to spend 1-2 percent of total health care expenditures on asthma. Developing economies likely to face increased demand </li></ul><ul><li>Poorly controlled asthma is expensive; investment in prevention medication likely to yield cost savings in emergency care </li></ul>
    8. 8. Risk Factors for Asthma <ul><li>Host factors: predispose individuals to, or protect them from, developing asthma </li></ul><ul><li>Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist </li></ul>
    9. 9. Factors that Influence Asthma Development and Expression <ul><li>Host Factors </li></ul><ul><li>Genetic </li></ul><ul><li>- Atopy </li></ul><ul><li>- Airway hyperresponsiveness </li></ul><ul><li>Gender </li></ul><ul><li>Obesity </li></ul><ul><li>Environmental Factors </li></ul><ul><li>Indoor allergens </li></ul><ul><li>Outdoor allergens </li></ul><ul><li>Occupational sensitizers </li></ul><ul><li>Tobacco smoke </li></ul><ul><li>Air Pollution </li></ul><ul><li>Respiratory Infections </li></ul><ul><li>Diet </li></ul>
    10. 10. Factors that Exacerbate Asthma <ul><li>Allergens </li></ul><ul><li>Respiratory infections </li></ul><ul><li>Exercise and hyperventilation </li></ul><ul><li>Weather changes </li></ul><ul><li>Sulfur dioxide </li></ul><ul><li>Food, additives, drugs </li></ul>
    11. 11. Is it Asthma? <ul><li>Recurrent episodes of wheezing </li></ul><ul><li>Troublesome cough at night </li></ul><ul><li>Cough or wheeze after exercise </li></ul><ul><li>Cough, wheeze or chest tightness after exposure to airborne allergens or pollutants </li></ul><ul><li>Colds “go to the chest” or take more than 10 days to clear </li></ul>
    12. 12. Asthma Diagnosis <ul><li>History and patterns of symptoms </li></ul><ul><li>Measurements of lung function </li></ul><ul><li>- Spirometry </li></ul><ul><li>- Peak expiratory flow </li></ul><ul><li>Measurement of airway responsiveness </li></ul><ul><li>Measurements of allergic status to identify risk factors </li></ul><ul><li>Extra measures may be required to diagnose asthma in children 5 years and younger and the elderly </li></ul>
    13. 13. Classification of Asthma <ul><li>Etiology </li></ul><ul><li>Asthma Severity </li></ul><ul><ul><li>Classification by clinical features prior to treatment </li></ul></ul><ul><li>Asthma Control </li></ul>
    14. 14. Clinical Control of Asthma <ul><li>No (or minimal)* daytime symptoms </li></ul><ul><li>No limitations of activity </li></ul><ul><li>No nocturnal symptoms </li></ul><ul><li>No (or minimal) need for rescue medication </li></ul><ul><li>Normal lung function </li></ul><ul><li>No exacerbations </li></ul><ul><li>_________ </li></ul><ul><li>* Minimal = twice or less per week </li></ul>
    15. 15. Characteristic Controlled (All of the following) Partly controlled (Any present in any week) Uncontrolled Daytime symptoms None (2 or less / week) More than twice / week 3 or more features of partly controlled asthma present in any week Limitations of activities None Any Nocturnal symptoms / awakening None Any Need for rescue / “reliever” treatment None (2 or less / week) More than twice / week Lung function (PEF or FEV 1 ) Normal < 80% predicted or personal best (if known) on any day Exacerbation None One or more / year 1 in any week
    16. 16. ASTHMA MANAGEMENT <ul><li>Controllers -medications taken daily on a long-term basis to keep asthma under clinical control chiefly through their antiinflammatory effects. </li></ul><ul><li>Relievers –medications used on an as-needed basis that act quickly to reverse bronchoconstriction and relieve its symptoms. </li></ul>
    17. 17. Factors Involved in Non-Adherence <ul><li>Medication Usage </li></ul><ul><li>Difficulties associated with inhalers </li></ul><ul><li>Complicated regimens </li></ul><ul><li>Fears about, or actual side effects </li></ul><ul><li>Cost </li></ul><ul><li>Distance to pharmacies </li></ul><ul><li>Non-Medication Factors </li></ul><ul><li>Misunderstanding/lack of information </li></ul><ul><li>Fears about side-effects </li></ul><ul><li>Inappropriate expectations </li></ul><ul><li>Underestimation of severity </li></ul><ul><li>Attitudes toward ill health </li></ul><ul><li>Cultural factors </li></ul><ul><li>Poor communication </li></ul>
    18. 18. Asthma Management and Prevention Program: Five Interrelated Components 1. Develop Patient/Doctor Partnership 2. Identify and Reduce Exposure to Risk Factors 3. Assess, Treat and Monitor Asthma 4. Manage Asthma Exacerbations 5. Special Considerations
    19. 19. Goals of Long-term Management <ul><li>Achieve and maintain control of symptoms </li></ul><ul><li>Maintain normal activity levels, including exercise </li></ul><ul><li>Maintain pulmonary function as close to normal levels as possible </li></ul><ul><li>Prevent asthma exacerbations </li></ul><ul><li>Avoid adverse effects from asthma medications </li></ul><ul><li>Prevent asthma mortality </li></ul>
    20. 20. . Asthma Management and Prevention Program <ul><li>Asthma can be effectively controlled in most patients by intervening to suppress and reverse inflammation as well as treating bronchoconstriction and related symptoms </li></ul><ul><li>Early intervention to stop exposure to the risk factors that sensitized the airway may help improve the control of asthma and reduce medication needs. </li></ul>
    21. 21. Asthma Management and Prevention Program <ul><li>Although there is no cure for asthma, appropriate management that includes a partnership between the physician and the patient/family most often results in the achievement of control </li></ul>
    22. 22. Component 1: Develop Patient/Doctor Partnership <ul><li>Guidelines on asthma management should be available but adapted and adopted for local use by local asthma planning teams </li></ul><ul><li>Clear communication between health care professionals and asthma patients is key to enhancing compliance </li></ul>
    23. 23. Component 2: Identify and Reduce Exposure to Risk Factors <ul><li>Measures to prevent the development of asthma, and asthma exacerbations by avoiding or reducing exposure to risk factors should be implemented wherever possible. </li></ul><ul><li>Asthma exacerbations may be caused by a variety of risk factors – allergens, viral infections, pollutants and drugs. </li></ul><ul><li>Reducing exposure to some categories of risk factors improves the control of asthma and reduces medications needs. </li></ul>
    24. 24. Component 3: Assess, Treat and Monitor Asthma <ul><li>The goal of asthma treatment, to achieve and maintain clinical control , can be achieved in a majority of patients with a pharmacologic intervention strategy developed in partnership between the patient/family and the health care professional </li></ul>
    25. 25. Component 3: Assess, Treat and Monitor Asthma <ul><li>Depending on level of asthma control, the patient is assigned to one of five treatment steps </li></ul><ul><li>Treatment is adjusted in a continuous cycle driven by changes in asthma control status. The cycle involves: </li></ul><ul><li>- Assessing Asthma Control </li></ul><ul><li>- Treating to Achieve Control </li></ul><ul><li>- Monitoring to Maintain Control </li></ul>
    26. 26. <ul><li>A stepwise approach to pharmacological therapy is recommended </li></ul><ul><li>The aim is to accomplish the goals of therapy with the least possible medication </li></ul><ul><li>Although in many countries traditional methods of healing are used, their efficacy has not yet been established and their use can therefore not be recommended </li></ul>Component 3: Assess, Treat and Monitor Asthma
    27. 27. <ul><li>The choice of treatment should be guided by: </li></ul><ul><li>Level of asthma control </li></ul><ul><li>Current treatment </li></ul><ul><li>Pharmacological properties and availability of the various forms of asthma treatment </li></ul><ul><li>Economic considerations </li></ul>Component 3: Assess, Treat and Monitor Asthma
    28. 28. Characteristic Controlled Partly controlled (Any present in any week) Uncontrolled Daytime symptoms None (2 or less / week) More than twice / week 3 or more features of partly controlled asthma present in any week Limitations of activities None Any Nocturnal symptoms / awakening None Any Need for rescue / “reliever” treatment None (2 or less / week) More than twice / week Lung function (PEF or FEV 1 ) Normal < 80% predicted or personal best (if known) on any day Exacerbation None One or more / year 1 in any week
    29. 29. Component 3: Asthma Management and Prevention Program: Controller Medications <ul><li>Inhaled glucocorticosteroids </li></ul><ul><li>Leukotriene modifiers </li></ul><ul><li>Long-acting inhaled β 2 -agonists </li></ul><ul><li>Systemic glucocorticosteroids </li></ul><ul><li>Theophylline (SR) </li></ul><ul><li>Cromones </li></ul><ul><li>Long-acting oral β 2 -agonists </li></ul><ul><li>Anti-IgE </li></ul><ul><li>Systemic glucocorticosteroids </li></ul>
    30. 30. Component 3: Asthma Management and Prevention Program: Reliever Medications <ul><ul><li>Rapid-acting inhaled β 2 -agonists </li></ul></ul><ul><ul><li>Systemic glucocorticosteroids </li></ul></ul><ul><ul><li>Anticholinergics </li></ul></ul><ul><ul><li>Theophylline (short acting) </li></ul></ul><ul><ul><li>Short-acting oral β 2 -agonists </li></ul></ul>
    31. 31. controlled partly controlled uncontrolled exacerbation LEVEL OF CONTROL maintain and find lowest controlling step consider stepping up to gain control step up until controlled treat as exacerbation TREATMENT OF ACTION TREATMENT STEPS REDUCE INCREASE STEP 1 STEP 2 STEP 3 STEP 4 STEP 5 REDUCE INCREASE
    32. 34. <ul><li>Step 1 – As-needed reliever medication </li></ul><ul><li>Patients with occasional daytime symptoms of short duration </li></ul><ul><li>A rapid-acting inhaled β 2 -agonist is the recommended reliever treatment ( Evidence A ) </li></ul><ul><li>When symptoms are more frequent, and/or worsen periodically, patients require regular controller treatment ( step 2 or higher) </li></ul>Treating to Achieve Asthma Control
    33. 36. <ul><li>Step 2 – Reliever medication plus a single controller </li></ul><ul><li>A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages ( Evidence A ) </li></ul><ul><li>Alternative controller medications include leukotriene modifiers ( Evidence A ) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids </li></ul>Treating to Achieve Asthma Control
    34. 38. <ul><li>Step 3 – Reliever medication plus one or two controllers </li></ul><ul><li>For adults and adolescents, combine a low-dose inhaled glucocorticosteroid with an inhaled long-acting β 2 -agonist either in a combination inhaler device or as separate components ( Evidence A ) </li></ul><ul><li>Inhaled long-acting β 2 -agonist must not be used as monotherapy </li></ul><ul><li>For children, increase to a medium-dose inhaled glucocorticosteroid ( Evidence A ) </li></ul>Treating to Achieve Asthma Control
    35. 39. <ul><li>Additional Step 3 Options for Adolescents and Adults </li></ul><ul><li>Increase to medium-dose inhaled glucocorticosteroid ( Evidence A ) </li></ul><ul><li>Low-dose inhaled glucocorticosteroid combined with leukotriene modifiers ( Evidence A ) </li></ul><ul><li>Low-dose sustained-release theophylline ( Evidence B ) </li></ul>Treating to Achieve Asthma Control
    36. 41. <ul><li>Step 4 – Reliever medication plus two or more controllers </li></ul><ul><li>Selection of treatment at Step 4 depends on prior selections at Steps 2 and 3 </li></ul><ul><li>Where possible, patients not controlled on Step 3 treatments should be referred to a health professional with expertise in the management of asthma </li></ul>Treating to Achieve Asthma Control
    37. 42. <ul><li>Step 4 – Reliever medication plus two or more controllers </li></ul><ul><li>Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β 2 -agonist ( Evidence A ) </li></ul><ul><li>Medium- or high-dose inhaled glucocorticosteroid combined with leukotriene modifiers ( Evidence A ) </li></ul><ul><li>Low-dose sustained-release theophylline added to medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β 2 -agonist ( Evidence B ) </li></ul>Treating to Achieve Asthma Control
    38. 44. Treating to Achieve Asthma Control <ul><li>Step 5 – Reliever medication plus additional controller options </li></ul><ul><li>Addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A) </li></ul><ul><li>Addition of anti-IgE treatment to other controller medications improves control of allergic asthma when control has not been achieved on other medications (Evidence A) </li></ul>
    39. 45. Treating to Maintain Asthma Control <ul><li>When control as been achieved, ongoing monitoring is essential to: </li></ul><ul><li>- maintain control </li></ul><ul><li>- establish lowest step/dose treatment </li></ul><ul><li>Asthma control should be monitored by the health care professional and by the patient </li></ul>
    40. 46. Component 4: Manage Asthma Exacerbations <ul><li>Exacerbations of asthma are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness </li></ul><ul><li>Exacerbations are characterized by decreases in expiratory airflow that can be quantified and monitored by measurement of lung function (FEV 1 or PEF) </li></ul><ul><li>Severe exacerbations are potentially life-threatening and treatment requires close supervision </li></ul>
    41. 47. Component 4: Manage Asthma Exacerbations <ul><li>Treatment of exacerbations depends on: </li></ul><ul><li>The patient </li></ul><ul><li>Experience of the health care professional </li></ul><ul><li>Therapies that are the most effective for the particular patient </li></ul><ul><li>Availability of medications </li></ul><ul><li>Emergency facilities </li></ul>
    42. 48. Component 4: Manage Asthma Exacerbations <ul><li>Primary therapies for exacerbations: </li></ul><ul><li>Repetitive administration of rapid-acting inhaled β 2 -agonist </li></ul><ul><li>Early introduction of systemic glucocorticosteroids </li></ul><ul><li>Oxygen supplementation </li></ul><ul><li>Closely monitor response to treatment with serial </li></ul><ul><li>measures of lung function </li></ul>
    43. 49. Component 5: Special Considerations <ul><li>Special considerations are required to </li></ul><ul><li>manage asthma in relation to: </li></ul><ul><li>Pregnancy </li></ul><ul><li>Surgery </li></ul><ul><li>Rhinitis, sinusitis, and nasal polyps </li></ul><ul><li>Occupational asthma </li></ul><ul><li>Respiratory infections </li></ul><ul><li>Gastroesophageal reflux </li></ul><ul><li>Aspirin-induced asthma </li></ul><ul><li>Anaphylaxis and Asthma </li></ul>
    44. 50. <ul><li>Asthma can be effectively controlled in most patients by intervening to suppress and reverse inflammation as well as treating bronchoconstriction and related symptoms </li></ul><ul><li>Although there is no cure for asthma, appropriate management that includes a partnership between the physician and the patient/family most often results in the achievement of control </li></ul>Asthma Management and Prevention Program: Summary
    45. 51. Asthma Management and Prevention Program: Summary <ul><li>A stepwise approach to pharmacologic therapy is recommended. The aim is to accomplish the goals of therapy with the least possible medication </li></ul><ul><li>The availability of varying forms of treatment, cultural preferences, and differing health care systems need to be considered </li></ul>
    46. 53. Nuelin TM Syrup 26.7mg/5mL Nuelin TM SR 125mg & 250mg
    47. 54. Formulation <ul><li>Nuelin SR Tablets: Anhydrous theophylline in a sustained release formulation </li></ul><ul><li>Nuelin Syrup: Each 5mL contains theophylline 26.7mg </li></ul><ul><ul><ul><li>Also contains methyl and propyl Hydroxybenzoate and sugar 50g/100mL </li></ul></ul></ul>
    48. 55. Pharmacology <ul><li>Theophylline has a direct relaxant effect on the smooth muscle of bronchial airways and pulmonary blood vessels, serving as a bronchodilator and pulmonary vasodilator </li></ul><ul><li>Exhibits activities typical of xanthines such as CNS stimulation including the respiratory center, cardiac stimulation, coronary vasodilation, diuresis and increase gastric secretion </li></ul>
    49. 56. Pharmacology <ul><li>Mechanism of action in vivo is not fully elucidated </li></ul><ul><li>Mediates smooth muscles relaxation by inhibition of phosphodiesterase thus reducing intracellular cyclic of AMP </li></ul><ul><li>Theophylline also acts additively with B 2 -adrenoceptor such as catecholamines. These increase intracellular levels of cyclic AMP by stimulation of adenyl cyclase </li></ul>
    50. 57. Pharmacology <ul><li>The clinical significance of this interaction should be considered when theophylline is used concurrently with sympathomimetic agents. </li></ul><ul><li>No evidence that tolerance develops with continued use of theophylline </li></ul>
    51. 58. Pharmacokinetics - Absorption <ul><li>Nuelin tablets and Nuelin Syrup contains theophylline in a form which affords complete bio-availability without the addition of organic bases as in aminophylline or choline theophylline </li></ul><ul><li>The tablet dissolves rapidly in water to produce a neutral solution </li></ul><ul><li>Nuelin Syrup contains theophylline in an alcohol-free vehicle </li></ul>
    52. 59. Absorption <ul><li>Peak plasma theophylline level occurs 1 1/2 to 2 hours after a dose of Nuelin tablets or Nuelin Syrup </li></ul>
    53. 60. Absorption <ul><li>Nuelin SR </li></ul><ul><li>Bio-availability of theophylline from Nuelin SR tablet is approximately 100% </li></ul><ul><li>Peak levels are found usually 4 to 6 hours after administration </li></ul><ul><li>Steady-sate conditions are usually found after 4 days of appropriate therapy </li></ul>
    54. 61. Absorption <ul><li>Nuelin SR </li></ul><ul><li>From the results of a single dose studies it appears as that the rate of theophylline absorption from Nuelin SR tablets is slowed by food intake, especially in children </li></ul><ul><li>Extent of absorption is affected by food </li></ul><ul><li>In multiple dosing situations a slower rate of theophylline absorption leads to lower peak-trough fluctuation </li></ul>
    55. 62. Distribution <ul><li>50% - 70% of the circulating theophylline is bound to the plasma proteins </li></ul><ul><li>Theophylline partitions into saliva, breast milk and crosses the placental barrier </li></ul>
    56. 63. Metabolism <ul><li>Theophylline is metabolized in the liver </li></ul><ul><li>1.3-dimethyluric acid with other minor metabolites being 3-methylxanthine and 1-methyluric acid </li></ul><ul><li>3-methylxanthine has some pharmacological activity but less than theophylline </li></ul>
    57. 64. Excretion <ul><li>Theophylline and its metabolites are excreted by the kidney </li></ul><ul><li>About 10% of the administrated dose is excreted unchanged </li></ul>
    58. 65. Half-Life <ul><li>The elimination half-life of theophylline varies considerably. </li></ul><ul><li>In healthy adults it ranges from 3 to 12 hours. </li></ul><ul><li>Half-life is shortened by smoking and is prolonged by cardio-respiratoy or hepatic disease and other drugs </li></ul><ul><li>In children ages 1 to 9 years the half-life is usually significantly less than adults </li></ul>
    59. 66. Indications <ul><li>For the relief of reversible bronchospasm associated with bronchial asthma, bronchitis, emphysema and related conditions </li></ul>
    60. 67. Contraindications <ul><li>Not be used where hypersensitivity to its constituents, or to xanthines generally, is known or has been demonstrated </li></ul>
    61. 68. Precautions <ul><li>As there is correlation between plasma levels of theophylline and therapeutic effect, and as patient response can vary considerably due to variable rates of elimination, monitoring plasma levels in individual patients is recommended. </li></ul><ul><li>Dosage must be individualized if ideal therapeutic effects is to be achieved. </li></ul>
    62. 69. Precautions <ul><li>Theophylline should be administered with caution to patients with cardiac disease, severe hypertension or hyperthyroidism </li></ul>
    63. 70. Precautions <ul><li>Theophylline clearance decreases in patients with congestive heart failure, impaired renal function, acute pulmonary oedema, chronic obstructive pulmonary disease, pneumonia and acute febrile episodes </li></ul><ul><li>Clearance is markedly decreased in patients with hepatic cirrhosis </li></ul>
    64. 71. Precautions <ul><li>There is some evidence that theophylline exhibits dose-dependent kinetics, at least in sick and elderly patients. </li></ul><ul><li>Care should be exercised by titration of dosage requirements in small increments and by monitoring serum theophylline levels </li></ul>
    65. 72. Precautions <ul><li>Theophylline clearance is increased in smokers and dosage may need to be adjusted accordingly. </li></ul><ul><li>Should not be administered concurrently with other xanthine medications and caution should be exercised when sympathomimetic agents are also part of the regimen </li></ul><ul><li>Xanthine containing beverages (e.g. tea, coffee, cola, cocoa) may interfere with some serum theophylline assays </li></ul>
    66. 73. Drug Interaction <ul><li>Theophylline clearance may be significantly reduced by erythromycin and other macrolide antibiotics </li></ul><ul><li>Cimetidine may significantly decrease theophylline clearance by inhibition of the metabolising enzyme systems with a resulting increase in serum theophylline levels </li></ul><ul><li>Theophylline level should be monitored and dose adjustment be made if concomitant therapy is necessary with these drugs. </li></ul>
    67. 74. Use During Pregnancy <ul><li>Nuelin is a drug which has been taken by a large number of pregnant women and women of childbearing age, without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus have been observed </li></ul>
    68. 75. Use During Lactation <ul><li>Theophylline is excreted in breastmilk, and is slowly eliminated by infant, particularly if premature </li></ul><ul><li>Dosage to the mother should be minimized to avoid toxicity to the infant </li></ul>
    69. 76. Adverse Reaction <ul><li>Most common adverse reactions are gastric irritation, nausea, vomiting, epigastric pain, tachycardia, palpitations and tremor </li></ul><ul><li>Usually early signs of toxicity </li></ul><ul><li>More serious signs of high serum levels (usually above 30 mg/L) such as cardiac arrhythmias and convulsions may appear rarely without prior warning </li></ul><ul><li>As these effects are mostly dose-related the frequency and severity are usually decreased by dose reduction </li></ul>
    70. 77. Overdose <ul><li>Early symptoms of toxicity such as anorexia, nausea, vomiting, headache, irritability and tachycardia may progress to sensory disturbances, confusion, hyperthemia, ventricular arrhythmias, extreme thirst, delirium and convulsion </li></ul><ul><li>Treatment: </li></ul><ul><ul><li>No specific antidote </li></ul></ul><ul><ul><li>Symptomatic support is indicated </li></ul></ul><ul><ul><li>Gastric lavage should be considered and if necessary Haemodialysis or peritoneal dialysis </li></ul></ul>
    71. 78. Dosage and Administration <ul><li>Therapeutic plasma levels usually associated with optimal benefit without adverse effects are considered to be between 10 and 20 mg/L (55 to 110 micromol/L) </li></ul><ul><li>Variable rates of elimination may necessitate considerable variation in dosage needed to achieve therapeutic levels. </li></ul><ul><li>Dosage should be individualized, and monitoring of theophylline plasma levels is recommended if side effects appear or if high doses are needed. </li></ul>
    72. 79. Dosage and Administration <ul><li>Adults: </li></ul><ul><li>Syrup: 25 mL every 6 hours </li></ul><ul><li>SR 125mg & 250mg: 1 tablet of appropriate strength every 12 hours </li></ul>
    73. 80. Dosage and Administration <ul><li>Children: </li></ul><ul><li>Under 2 years: Not to be given except on the advice of a physician </li></ul><ul><li>Over 2 years: 1mL/kg body weight (up to a maximum of 25mL) every 6 hours </li></ul><ul><li>Children 2 to 12 years: </li></ul><ul><ul><li>1 tablet SR 125mg every 12 hours or as advised by a physician </li></ul></ul><ul><ul><li>1/2 tablet SR 250mg every 12 hours or as advised by a physician </li></ul></ul>
    74. 81. Dosage and Administration <ul><li>As a guideline for optimizing therapy, the daily dose should be adjusted according to body weight, usually on the basis of up to 10mg/kg body weight every 12 hours </li></ul><ul><li>As a guideline, a child from 12 kg to 25kg body weight (2 - 7 years) usually requires 125mg bid and a child over 25 kg usually requires 250mg bid. </li></ul><ul><li>Nuelin SR is not recommended for child under 2 years of age </li></ul>
    75. 82. Theophylline Monitoring <ul><li>If side effects appear or if unusually high doses are required, plasma theophylline should be monitored </li></ul><ul><li>Blood samples for monitoring should be drawn immediately before administration of the morning dose when the plasma theophylline level is lowest. </li></ul><ul><li>Another sample should be drawn 4-6 hours after administration of the sustained-release preparation when the theophylline level is at a maximum </li></ul>
    76. 83. Factors Affecting Metabolism of Theophylline <ul><li>clearance </li></ul><ul><li>Elderly </li></ul><ul><li>Liver Disease </li></ul><ul><li>Macrolides </li></ul><ul><li>Allopurinol </li></ul><ul><li>Caffeine </li></ul><ul><li>Ciprofloxacin </li></ul><ul><li>Heart Disease </li></ul><ul><li>Infection </li></ul><ul><li>Cimetidine </li></ul><ul><li>Contraceptives </li></ul><ul><li>Rifampicin </li></ul><ul><li>Propranolol </li></ul><ul><li>↑ </li></ul><ul><li>clearance </li></ul><ul><li>Smoking </li></ul><ul><li>Cystic Fibrosis </li></ul><ul><li>Phenytoin </li></ul><ul><li>Phenobarbital </li></ul><ul><li>Corticosteroid </li></ul>
    77. 84. Presentation <ul><li>Nuelin Syrup: 26.7mg/5mL (berry flavored): 60ml, 120ml </li></ul><ul><li>Nuelin SR tablets: </li></ul><ul><ul><li>125mg (White marked 1 25, and N/L reverse): 100 </li></ul></ul><ul><ul><li>250mg (White marked 3M 250, and N/L reverse): 100 </li></ul></ul>
    78. 85. Theophylline <ul><li>Bronchodilator Action </li></ul>NUELIN SR
    79. 86. Theophylline <ul><li>Cost Effective </li></ul>NUELIN SR
    80. 87. Theophylline <ul><li>Easily Administered </li></ul>NUELIN SR
    81. 88. Theophylline <ul><li>Better Compliance </li></ul>NUELIN SR
    82. 89. Theophylline <ul><li>Long Duration of Effect </li></ul>NUELIN SR
    83. 90. Theophylline <ul><li>Steroid Sparing Effect </li></ul>NUELIN SR
    84. 91. Asthma Rx <ul><li>“ Two breakfast cups of strong coffee… given on an empty stomach” </li></ul>1860 Henry Hyde Salter
    85. 92. THANK YOU!!!

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