Directorate of Technical Education
KERALA (Government of Kerala)



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By: M. Ali, M.B. B.A.O., M.B.B.Ch., Ph.D.

Assistant Professor, Chicago Medical School of Rosalind Franklin University of Medicine and Science

Disease exacerbations may be caused by decreased theophylline concentrations allergy testing wichita ks cheap 200 mcg entocort visa, and a dosage increase may be warranted in some patients allergy nebraska cheap entocort 100mcg amex. Phenytoin allergy testing wiki generic 100mcg entocort otc, carbamazepine, phenobarbital, rifampin, and moricizine all increase theophylline clearance. It allows individualized target serum concentrations to be chosen for a patient, and each pharmacokinetic parameter can be customized to reflect specific disease states and conditions present in the patient. Literature- based recommended dosing is a very commonly used method to prescribe initial doses of theophylline. Doses are based on those that commonly produce steady-state concentra- tions in the lower end of the therapeutic range, although there is a wide variation in the actual concentrations for a specific patient. Pharmacokinetic Dosing Method The goal of initial dosing of theophylline is to compute the best dose possible for the patient given their set of disease states and conditions that influence theophylline pharma- cokinetics and the pulmonary disorder being treated. In order to do this, pharmacokinetic parameters for the patient will be estimated using average parameters measured in other patients with similar disease state and condition profiles. Unfortunately, there is no good way to estimate the elimination characteristics of liver metabolized drugs using an endogenous marker of liver function in the same manner that serum creatinine and esti- mated creatinine clearance are used to estimate the elimination of agents that are renally eliminated. Because of this, a patient is categorized according to the disease states and conditions that are known to change theophylline half-life, and the half-life previously measured in these studies is used as an estimate of the current patient’s half-life. To produce the most conservative theo- phylline doses in patients with multiple concurrent disease states or conditions that affect theophylline pharmacokinetics, the disease state or condition with the longest half-life should be used to compute doses. For instance, for a patient with asthma who currently smokes tobacco-containing cigarettes and has severe liver disease, an estimated theophylline half- life of 24 hours would be used to compute initial dosage requirements. Once the correct half-life is identified for the patient, it can be converted into the theophylline elimination rate constant (k) using the following equation: k = 0. For obese patients (>30% above ideal body weight), ideal body weight is used to compute theophylline volume of distribution. For a 150-kg obese patient with an ideal body weight of 60 kg, the esti- mated theophylline volume of distribution is 30 L: V = 0. When oral therapy is required, most clinicians utilize a sustained-release dosage form that has good bioavail- ability (F = 1), supplies a continuous release of theophylline into the gastrointestinal tract, and provides a smooth theophylline serum concentration/time curve that emulates an intravenous infusion after once or twice daily dosing. Because of this, a very simple pharmcokinetic equation that computes the average theophylline steady-state serum con- centration (Css in μg/mL = mg/L) is widely used and allows maintenance dosage calcula- tion: Css = [F ⋅ S (D/τ)]/Cl or D = (Css ⋅ Cl ⋅τ)/(F ⋅ S), where F is the bioavailability frac- tion for the oral dosage form (F = 1 for most oral theophylline sustained-release products), S is the fraction of the theophylline salt form that is active theophylline (S = 1 for theo- phylline, S = 0. The steady-state serum concentration (Css) expected from an equivalent theophylline or aminophylline continuous infusion is shown by the dotted line in the steady-state concentrations. When intravenous therapy is required, a similar pharmacokinetic equation that com- putes the theophylline steady-state serum concentration (Css in μg/mL = mg/L) is widely used and allows dosage calculation for a continuous infusion: Css = [S ⋅ k0]/Cl or k0 = (Css ⋅ Cl)/S, where S is the fraction of the theophylline salt form that is active theo- phylline (S = 1 for theophylline, S = 0. Cl is theo- phylline clearance in liters per hour and is computed using estimates of theophylline elimination rate constant (k) and volume of distribution: Cl = kV. The steady- state serum concentration (Css) expected from an equivalent theophylline or aminophylline contin- uous infusion is shown by the dotted line in the steady-state concentrations. Recent guidelines suggest that for initial treatment of pulmonary disease, clinical response to theophylline concentrations between 5–15 μg/mL should be assessed before higher concentrations are used. However, theophylline therapy must be individualized for each patient in order to achieve optimal responses and minimal side effects. Suggest an initial theophylline dosage regimen designed to achieve a steady-state theophylline concentration equal to 8 μg/mL.

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Sodium fusidate is a narrow- spectrum product that is indicated in penicillin-resistant staphylococci infections such as osteomyelitis and in staphylococcal endocarditis allergy shots philippines purchase entocort in india. The pathophysiology of pain in terminal carcinoma may be multiple because of the varied factors leading to its occurrence allergy testing jackson wy discount entocort 100 mcg without prescription. The pharmacist could monitor the use of drugs to maintain the patient as pain free as possible and to manage other problems such as the nausea that may arise allergy symptoms uk discount entocort. Tramadol is an opioid analgesic that is associated with fewer side-effects compared with other opioid drugs. Opioids may cause nausea and vomiting especially during the initial doses, constipa- tion and drowsiness. A56 B Tamoxifen is an oestrogen-receptor antagonist available as an oral formulation that is administered daily. It is used in adjuvant treatment of early breast Test 2: Answers 105 cancer, in the palliative treatment of advanced disease and for prophylaxis in women at increased risk. Paroxetine should be administered in the morning to minimise insomnia, anxiety and nervousness during the night. The occurrence of dependence results in withdrawal symptoms, should the drug be discontinued abruptly. The advantage of using diazepam as an anxio- lytic outweighs the disadvantages of tolerance and dependence. A complication of diabetes mellitus is vascular disease in the peripheries, which predisposes patients to the development of an infection following trauma to the area. For this reason diabetics are advised to take good care of their feet, avoid injuries and foot maceration from footwear. Diabetics should immediately seek advice about injuries to the feet to avoid development of infections in the area. It is included in the therapeutic regimen, together with cefuroxime, to expand the spectrum of activity of the anti-infectives used. Questions 61–62 Morphine is an opioid analgesic that is widely used in the management of moderate to severe pain. Morphine may be administered as standard tablets, modified-release tablets, oral solution and injections. This gives the least number of tablets required to be taken by the patient to achieve the required dose. In the majority of cases this is caused by the organism Helicobacter pylori and a triple-therapy eradication regimen is recommended in these cases. Iron salts should be administered by the oral route, unless this has been unsuccessful because of non-compliance, intolerance to side- effects, malabsorption and continued blood loss. Iron is absorbed mostly as the ferrous state in an acidic environment and hence absorption takes place mostly in the stomach. Absorption may be reduced by food; however, many patients experience nausea and diarrhoea when iron is administered on an empty stomach. He should be advised to take regular small meals, avoid strong tea, coffee and spicy food and limit food intake late at night as this increases nocturnal gastric secretion. She is taking perindopril (angiotensin-converting enzyme inhibitor), digoxin (cardiac glycoside), bumetanide (loop diuretic), metformin (biguanide), amitriptyline (tricyclic antidepressant) and ranitidine (H2-receptor antagonist). Risk of dehydration increases with environmental factors that Test 2: Answers 109 support fluid and electrolyte loss, such as heat exposure caused by hot temper- atures and inadequate ventilation at home.

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It does not appear to induce systemic immunosuppression of other α4β7 integrin-binding antibodies such as natalizumab because it does not bind to the majority of α4β7 integrin on lymphocytes allergy shots preventive care cheap 200mcg entocort fast delivery. It is indicated as an adjunct to percutaneous coronary intervention in combination with aspirin and heparin for the prevention of cardiac ischemic complications allergy shots lupus buy entocort 100 mcg on line. Denosumab is indicated for treatment of postmenopausal women with osteoporosis at high risk for fracture allergy symptoms vs flu buy 100 mcg entocort fast delivery. Eculizumab is a humanized IgG monoclonal antibody that binds the C5 complement component, inhibiting its cleavage into C5a and C5b thereby inhibiting the terminal pore-forming lytic activity of complement. Clinicians must be aware of increased risk of meningococcal infection in patients receiving this anti-C5 monoclonal antibody. It is used in neonates at risk for this viral infection and reduces the frequency of infection and hospitalization by about 50% (see Chapter 49). Ranibizumab is approved for intravitreal injection in patients with neovascular age-related macular degeneration, diabetic macular edema, and sudden blurring or vision loss secondary to macular edema following retinal vein occlusion. Raxibacumab is approved for the treatment or prophylaxis of adults and children with inhalational anthrax in combination with appropriate antibacterial drugs. Interestingly, raxibacumab was not tested in humans because exposing a control cohort to inhalational anthrax is unethical and there are too few naturally infected persons to conduct a proper clinical trial. The agents used differ somewhat for the specific disorders treated (see specific agents and Table 55–1), as do administration schedules. Because autoimmune disorders are very complex, optimal treatment schedules have yet to be established in many of them. Close histocompatibility matching reduces the likelihood of graft rejection and may also reduce the requirements for intensive immunosuppressive therapy. Prior to transplant, patients may receive an immunosuppressive regimen, including antithymocyte globulin, daclizumab, or basiliximab. Four types of rejection can occur in a solid organ transplant recipient: hyperacute, accelerated, acute, and chronic. Hyperacute rejection is due to preformed antibodies against the donor organ, such as anti-blood group antibodies. Hyperacute rejection occurs within hours of the transplant and cannot be stopped with immunosuppressive drugs. Accelerated rejection is mediated by both antibodies and T cells, and it also cannot be stopped by immunosuppressive drugs. Reversal of acute rejection is usually possible with general immunosuppressive drugs such as azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, glucocorticoids, cyclophosphamide, methotrexate, and sirolimus. It is characterized by thickening and fibrosis of the vasculature of the transplanted organ, involving both cellular and humoral immunity. Allogeneic hematopoietic stem cell transplantation is a well-established treatment for many malignant and nonmalignant diseases. The conditioning regimen is used not only to kill cancer cells in the case of malignant disease, but also to totally suppress the immune system so that the patient does not reject the donor stem cells. As patients’ blood counts recover (after reduction by the conditioning regimen) they develop a new immune system that is created from the donor stem cells. Rejection of donor stem cells is uncommon, and can only be treated by infusion of more stem cells from the donor.

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Vasospasm caused by ergot is refractory to most vasodilators allergy medicine itchy skin order entocort uk, but infusion of large doses of nitroprusside or nitroglycerin has been successful in some cases allergy medicine names purchase 100mcg entocort overnight delivery. Chronic therapy with methysergide was associated with connective tissue proliferation in the retroperitoneal space allergy testing kingwood tx buy entocort 100mcg low price, the pleural cavity, and the endocardial tissue of the heart. These changes occurred insidiously over months and presented as hydronephrosis (from obstruction of the ureters) or a cardiac murmur (from distortion of the valves of the heart). Other toxic effects of the ergot alkaloids include drowsiness and, in the case of methysergide, occasional instances of central stimulation and hallucinations. Contraindications to the use of ergot derivatives consist of the obstructive vascular diseases, especially symptomatic coronary artery disease, and collagen diseases. Use to deliberately cause abortion is contraindicated because the high doses required often cause dangerous vasoconstriction. Preuss H et al: Constitutive activity and ligand selectivity of human, guinea pig, rat, and canine histamine H2 receptors. Ergot Alkaloids: Pharmacology Dahlöf C, Van Den Brink A: Dihydroergotamine, ergotamine, methysergide and sumatriptan—Basic science in relation to migraine treatment. Fortunately, neither patient in this episode of food poisoning had significant laryngeal edema or bronchospasm. Certain types of fish, if improperly preserved, contain large quantities of histamine, due to the conversion—by bacteria contaminating the muscle tissue— of histadine to histamine. If consumed in sufficient amount, enough histamine can be absorbed to cause the clinical picture described. Treatment with maximal doses of histamine blockers, especially H blockers, is usually sufficient to control the symptoms. Because this is not an allergic reaction,1 administration of epinephrine is not necessary unless hypotension or airway obstruction is severe. His physician initially prescribed hydrochlorothiazide, a diuretic commonly used to treat hypertension. Although his blood pressure was reduced by hydrochlorothiazide, it remained at a hypertensive level (145/95 mm Hg), and he was referred to the university hypertension clinic. Your evaluation revealed that the patient had elevated plasma renin activity and aldosterone concentration. Hydrochlorothiazide was therefore replaced with enalapril, an angiotensin-converting enzyme inhibitor. What other drugs could be used to inhibit renin secretion or suppress the renin-angiotensin system, and decrease blood pressure, without the adverse effects of enalapril? As noted in Chapters 6 and 21, they play important roles as transmitters in the autonomic and central nervous systems. This chapter focuses on the smooth muscle actions of the peptides and on drugs that alter their biosynthesis or actions. It is synthesized as a prepromolecule that is processed to prorenin, which has poorly understood actions, and then to active renin, a glycoprotein consisting of 340 amino acids. Enzymes with renin-like activity are present in several extrarenal tissues, including blood vessels, uterus, salivary glands, and adrenal cortex, but no physiologic role for these enzymes has been established. Specialized granular cells called juxtaglomerular cells are the site of synthesis, storage, and release of renin. The macula densa is a specialized segment of the nephron that is closely associated with the vascular components of the juxtaglomerular apparatus. The vascular and tubular components of the juxtaglomerular apparatus, including the juxtaglomerular cells, are innervated by the sympathetic nervous system.

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