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By D. Angir. Northwest Nazarene University. 2018.

Thyroid hormones are used in hypothyroidism (myxoedema) and also in difuse non-toxic goitre buy 4mg cyproheptadine with mastercard, Hashimoto thyroidits (lymphadenoid goitre) and thyroid carcinoma cyproheptadine 4 mg amex. Levothyroxine Sodium (thyroxine Sodium) is the treatment of choice for maintenance therapy. It is almost completely absorbed from the gastrointestnal tract but the full efects are not seen for up to 1 to 3 weeks afer beginning therapy; there is a slow response to dose change and efects may persist for several weeks afer withdrawal. Dosage of levothy- roxine in infants and children for congenital hypothyroidism and juvenile myxoedema should be ttrated according to clinical response, growth assessment and measurement of plasma thyroxine and thyroid-stmulatng hormone. Antthyroid Drugs: Antthyroid drugs such as propylthiouracil and carbimazole are used in the management of thyrotoxicosis. They are usually well- tolerated, with mild leukopenia or rashes developing in a few percent of cases, usually during the frst 6-8 weeks of therapy. During this tme the blood count should be checked every 2 weeks or if a sore throat or other signs of infecton develop. The drugs are generally given in a high dose in the frst instance untl the patent becomes euthyroid, the dose may then be gradually reduced to a maintenance dose which is contnued for 12-18 months, followed by monitoring to identfy relapse. There is a lag tme of some 2 weeks between the achievement of biochemical euthyroidism and clinical euthyroidism. Beta- adrenoceptor antagonists (beta-blockers) (usually propranolol) may be used as a short-term adjunct to antthyroid drugs to control symptoms but their use in heart failure associated with thyrotoxicosis is controversial. Treatment can be given, if neces- sary, in pregnancy but antthyroid drugs cross the placenta and in high doses may cause fetal goitre and hypothyroidism. The lowest dose that will control the hyperthyroid state should be used (requirements in Graves disease tend to fall during preg- nancy). If surgery (partal thyroidectomy) is contemplated, it may be necessary to give iodine for 10 to 14 days in additon to antthyroid drugs to assist control and reduce vascularity of the thyroid. Iodine should not be used for long-term treat- ment since its antthyroid acton tends to diminish. In patents in whom drug therapy fails to achieve long-term remissions defnitve treatment with surgery or (increasingly) radioactve iodine is preferable. Carbimazole* Pregnancy Category-D Schedule H Indicatons Thyrotoxicosis; Grave’s disease. Contraindicatons Nodular goitre; subacute thyroidits, postpartum painless thyroidits. Adverse Efects Nausea, mild gastro-intestnal disturbances; headache; rashes and pruritus, arthralgia; rarely, myopathy, alopecia, bone marrow suppression (including pancytopenia and agranulocytosis); vasculits; cholestatc jaundice, hepatc necrosis. Storage Store protected from light and moisture at a temperature not exceeding 30⁰C. Contraindicatons Lactaton (Appendix 7b), tuberculosis, bron- chits, asthma, hyperkalaemia, acne vulgaris. Adverse Efects Hypersensitvity reactons including coryza- like symptoms; headache; lacrimaton; conjunctvits, pain in salivary glands; laryngits, bronchits, rashes; on prolonged treatment depression, insomnia, impotence; goitre in infants of mothers taking iodides; eosinophilia, hypothyroidism, abdominal pain, arrhythmia. Storage Store in ground glass stoppered container or earthenware container with waxed bungs. Dose Oral Adult- Hypothyroidism: Initally 50 to 100 µg daily (25 to 50 µg for those over 50 years) before breakfast, increased by 25 to 50 µg every 3 to 4 weeks untl normal metabolism maintained (usual maintenance dose, 100 to 200 µg daily); where there is cardiac disease, initally 25 µg daily or 50 µg on alternate days, adjusted in steps of 25 µg every 4 weeks. Child- Congenital hypothyroidism and juvenile myxoedema; Up to 1 month: initally 5 to 10 µg/kg daily. Over 1 month: initally 5 µg/kg daily, adjusted in steps of 25 µg every 2 to 4 weeks, untl mild toxic symptoms appear, then reduce dose slightly. Immunologicals Actve Immunity: Actve immunity may be induced by the administraton of micro-organisms or their products which act as antgens to induce antbodies to confer a protectve immune response in the host. Vaccinaton may consist of (a) a live atenuated form of a virus or bacteria, (b) inactvated preparatons of the virus or bacteria, or (c) extracts of or detoxifed exotoxins. Live atenuated vaccines usually confer immunity with a single dose which is of long duraton. Inactvated vaccines may require a series of injectons in the frst instance to produce an adequate antbody response and in most cases, require reinforcing (booster) doses. Extracts of or detoxifed exotoxins require a primary series of injectons followed by reinforcing doses. Passive Immunity: Passive immunity is conferred by injectng preparatons made from the plasma of immune individuals with adequate levels of antbody to the disease for which protecton is sought. This immunity lasts only a few weeks but passive immunizaton can be repeated where necessary. Sera and Immunoglobulins Antbodies of human origin are usually termed immunoglob- ulins. Because of serum sickness and other allergic-type reactons that may follow injectons of antsera, this therapy has been replaced wherever possible by the use of immunoglobulins. Contraindicatons and Precautons Anaphylaxis, although rare, can occur and epinephrine (adrenaline) must always be immediately available during immunizaton.

With an aim to avoid signifi- cant product loss due to nanoparticulate adhesion on to the interior wall of the spray dryer discount 4mg cyproheptadine visa, as well as to prevent the aggregation of the nanoparticles cheap cyproheptadine 4mg on line, a double- nozzle spray-drying method has been developed together with the use of manni- tol as an antiadherent (75). In this process, the surface of the spray-dried nanoparticles gets coated with mannitol and the degree of agglom- eration is reduced. Supercritical Fluid Spraying This technology is advantageous in that the use of an organic solvent/surfactant can be avoided or minimized, thus producing nanoparticles that are free from toxic impurities. The rates of two-way mass transfer are much faster than those for conventional organic antisolvents. This causes the solvent concentration to be significantly lowered, resulting in the precipitation of the drug inside the poly- mer matrix. A major challenge of this process is the need to filter the precipitate from the organic solvent solution without particle growth and aggregation. Various parameters that affect the resulting particle size and morphology are the pre- and postexpansion temperature and pressure, noz- zle geometry, and solution concentration (77,82). The disadvantages of this method include the use of higher temperatures to form homogenous precipitates (thus degrading thermally labile drugs) and the limited solubility of the polymers and drugs that result in low drug loading (83). In general, they possess several poten- tial advantages, such as better oral bioavailability for poorly water-soluble drugs, formulating intravenous injections, and targeting of drugs to specific tissues, thus reducing general toxicity. The nanoparticulate mode of drug delivery using biodegradable polymers is viewed as one of the most promising approaches for (i) improving the bioavailability of the drug with the possibility of reduction of the effective dose, thus reducing the chance of potential toxicity and the adverse effects of the drug, (ii) passive drug targeting to specific tissues, and (iii) effective stabi- lization of the drug in the polymer matrix, protecting from enzymes and other nor- mal defense mechanisms of the body. Besides nanoparticles, other colloidal carriers such as emulsions for the administration of drugs and parenteral nutrition offer the advantage of reduction of adverse effects such as pain and inflammation at the injec- tion site. Successful commercial products include Diazemuls r , Diazepam-Lipuro r , Etomidate-Lipuro r , and Diprivan r. However, a major disadvantage of this sys- tem is the critical, physical instability caused by the incorporated drug, which leads to a decrease in the zeta-potential and thus promotes agglomeration, drug expul- sion, and, finally, breaking of the emulsion (85). The expensive toxicity studies associated with the search for new oils with improved solubility properties present a challenge to the further development of this delivery system (86). Another particulate carrier system, lipo- somes, have been introduced to reduce the toxic adverse effects of the highly potent drugs and thereby enhance the efficacy of the system. However, low physical stability, drug leakage, nonspecific tumor targeting, nonspecific phagocytosis, problems in up- scaling and their high cost limit the total number of products in the market (87,88). The polymeric nanoparticulate carrier system consisting of either biodegradable or nonbiodegradable polymers are thus advantageous in terms of site-specific target- ing and controlled release of the encapsulated drug molecules (89). While both for- mulation stability and in vivo stability are big advantages of nanoparticles, their disadvantage arises from the cytotoxicity of polymers after being internalized by the cells such as macrophages and their subsequent degradation as in the case of polyester polymers (90). Thus far, the lack of a suitable large-scale production method that would be cost-effective and lead to an acceptable product by the reg- ulatory authorities has lead to very few marketed nanoparticle preparations. The major challenges faced by the pharmaceutical industry in the manufacturing of nanoparticles are controlling batch-to-batch variation of the particle size and drug loading. The formation of uniform sized microdrops of solvated polymer by the use of piezoelectric transducers have been reported. Although the size distribution of the particles were narrow, the average size was larger than 10 μm. In addition, the freeze-drying of the nanoparticles with bioactive cryoprotectants and the pro- cessing of sterile products offer major challenges. The aggregation of nanoparticles in the biological medium poses another challenge, as the aggregate size and not the individual particle size determines the transport of the drug and the cellular uptake. Regardless of these challenges, given the potential of nanoparticulate poly- meric drug delivery systems in improving dug therapy, it appears to be a promising strategy for the drug delivery industry to allocate R&D initiatives in this area. More- over, a number of drugs that were previously removed from the pipeline owing Polymeric Nanoparticles for Small-Molecule Drugs 31 to unfavorable biopharmaceutic properties could now be potentially revisited by using the nanoparticle carrier systems. Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer’s disease. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavail- ability. The antihypertensive effect of orally adminis- tered nifedipine-loaded nanoparticles in spontaneously hypertensive rats. Biodegradation of and tissue reaction to 50:50 poly(d,l-lactide-co-glycolide) microcapsules. Biodegradable polymers for use in surgery: Poly(glycolic)/ poly(lactic acid) homo- and copolymers; part 1. Aliphatic polyesters; part 2: The degradation of poly(d,l-lactide), poly(E-caprolactone) and their copolymers in vivo. Structure–property relationships in the case of the degradation of massive aliphatic poly( -hydroxy acids) in aqueous media; part 1. Structure–property relationships in the case of the degradation of massive aliphatic poly( -hydroxy acids) in aqueous media; part 3. Polymers for biodegradable medical devices; part I: The potential of polyesters as controlled macromolecular release system. Microencapsulation using poly(l-lactic acid); part I: Microcapsule prop- erties affected by the preparative techniques. In vitro and in vivo degradation of poly(dl- lactide/glycolide) type microspheres made by solvent evaporation method.

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Contraindicatons Pregnancy (Appendix 7c); hypersensitvity; myelosuppression; lactaton order 4 mg cyproheptadine mastercard. Adverse Efects Nausea discount 4mg cyproheptadine amex, vomitng, oral mucosits, hyperuricaemia, bone marrow suppression, alopecia, thromboembolism, leucopenia; menstrual irregularites; haemolytc anaemia. Contraindicatons See notes above and consult literature; hypersensitvity; pregnancy (Appendix 7c) and lactaton (Appendix 7b). Precautons See notes above and consult literature; monitor blood count; uric acid levels; renal impairment and hepatc impairment (Appendix 7a); interactons (Appendix 6c). Dose Oral Choriocarcinoma: 15 to 30 mg daily for 5 days repeat 3 to5 full courses afer 1 week. Intramuscular route 15 to 30 mg daily for 5 days, repeat 3 to5 courses afer 1 week. Leukaemia, maintenance afer remission: 30 mg/m2 body surface area (max upto 15 mg twice a week). Contraindicatons See notes above and consult literature; severe renal and hepatc impairment; alcohol liver disease; severe leucopenia; thrombocytopenia; pregnancy (Appendix 7c) and lactaton (Appendix 7b). Precautons See notes above and consult literature; bone marrow depression; renal and hepatc impairment (Appendix 7a); interactons (Appendix 6a, 6c, 6d). Mitomycin* Pregnancy Category-D Indicatons Adrenocarcinoma, lymphosarcoma and seminoma, superfcial bladder cancer (adjuvant therapy). Contraindicatons Pregnancy (Appendix 7c); bone marrow depression; severe anaemia; thrombocyto- penia; lactaton. Precautons It causes delayed bone-marrow toxicity and therefore it is usually administered at 6-weekly intervals. Cauton in handling because it is irritant to tssues, thrombocytopenia; necrosis; leucopenia. Note: Irritant to tssues Paclitaxel* Pregnancy Category-D Schedule H Indicatons Metastatc ovarian and breast cancer. Dose Intravenous infusion Adult- 175 mg/m2 body surface area over 3 h, repeat every 3 weeks. Anthistamines, cortcosteroids or H2 antago- nist may be required during treatment. Contraindicatons Hypersensitvity; severe hepatc impairment; lactaton; pregnancy (Appendix 7c). Dose Oral 50 mg daily to start with initally, increased to 250 to 300 mg individual doses. Contraindicatons See notes above and consult literature; hypersensitvity; pregnancy (Appendix 7c) and lactaton (Appendix 7b). Precautons See notes above and consult literature; ulceraton; haemorrhage; leucopenia: renal and hepatc impairment (Appendix 7a); interactons (Appendix 6a). Adverse Efects See notes above and consult literature; leucopenia; anaemia; thrombocytopenia; hypotension; retnal haemorrhage. Thalidomide is adminis- tered in combinaton with dexametha- sone in 28-day treatment cycles. Dexamethasone is 40 mg daily adminis- tered orally on days 1-4, 9-12, and 17-20 every 28 days. Dosing with thalidomide should contnue untl signs and symptoms of actve reacton have subsided, usually a period of at least 2 weeks. Tapering of medicaton should be atempted every 3 to 6 months, in decre- ments of 50 mg every 2 to 4 weeks. Contraindicatons Hypersensitvity, pregnancy (Appendix 7C) and lactaton, interactons (Appendix 6c). Adverse Efects Teratogenicity, Drowsiness/somnolence, peripheral neuropathy, constpaton, dizziness, bradycardia, orthostatc hypoten- sion, hypersensitvity, and neutropenia. Vinblastne* Pregnancy Category-D Schedule H Indicatons Disseminated Hodgkin’s and Non-Hodgkin’s lymphomas; advanced testcular carcinoma, breast carcinoma; palliatve treatment of Kaposi’s sarcoma; trophoblastc tumours; Leterer-Siwe disease; Histolytc lymphoma. Contraindicatons See notes above and consult literature; hypersensitvity; severe granulocytopenia; lactaton (Appendix 7b). Note: Irritant to tssues Vincristne* Pregnancy Category-D Schedule H Indicatons Acute lymphoblastc leukaemia; neuroblas- toma, Wilm’s tumour, Hodgkin’s and Non- Hodgkin’s lymphomas; rhabdomyosarcoma, Ewing’s sarcoma; mycosis fungoides. Precautons See notes above and consult literature; uric acid neuropathy; branchospasm; hepatc impairment (Appendix 7a); pregnancy (Appendix 7c). Specifc expertse, diagnostc precision, individualizaton of dosage or special equipment are required for their proper use Immunosuppressive drugs are used in organ transplant recipi- ents to suppress rejecton; they are also used as second-line drugs in chronic infammatory conditons. Careful monitoring of blood counts is required in patents receiving immunosuppressive drugs and the dose should be adjusted to prevent bone- marrow toxicity.

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