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By N. Dudley. Huston-Tillotson College.

In large doses purchase gyne-lotrimin 100mg amex, it may cause methae- moglobinaemia and therefore methaemoglobin levels should be monitored during treatment buy cheap gyne-lotrimin 100 mg line. Cyanide Poisoning: Cyanide poisoning may be treated with Sodium nitrite followed by Sodium thiosulphate order gyne-lotrimin 100 mg with visa. Following that infusion of atropine at 10-20 % of total inital dose required/hour; may require boluses during infusion. Contraindicatons In myasthenia gravis (but may be used to decrease muscarinic side-efects of antcholinesterases), paralytc ileus, pyloric stenosis and prostatc enlargement; refux oesophagits; unstable cardiac rhythm. Precautons Elderly, Down syndrome; angle-closure glaucoma; myasthenia gravis; prostatc enlargement; pyrexia; lactaton (Appendix 7b); interactons (Appendix 6a); pregnancy (Appendix 7c). Adverse Efects Constpaton, transient bradycardia (followed by tachycardia, palpitaton and arrhythmias), reduced bronchial secretons, urinary urgency and retenton, dilataton of the pupils with loss of accommodaton, photophobia, dry mouth, fushing and dryness of the skin. Occasionally, confusion (partcularly in the elderly), nausea, vomitng and giddiness; very rarely, angle-closure glaucoma may occur. Desferrioxamine Mesylate* Pregnancy Category-C Indicatons Acute iron poisoning; chronic iron overload; aluminium overload; primary hemochromatosis. Afer 1 to 2 h reduce to 3-4 mg/kg/h for the next 22-23 hrs (max dose is 100 mg/kg over 24 hrs). Precautons Renal impairment; eye and ear examinatons before and at 3-month intervals during treatment; aluminium encephalopathy (may exacerbate neurological dysfuncton); children under 3 years (may retard growth); lactaton; interactons (Appendix 6c). Adverse Efects Anaphylaxis; fushing, urtcaria, hypotension, shock (especially if given by too rapid intravenous infusion); gastrointestnal disturbances; fever, headache, arthralgia, myalgia; arrhythmias; renal impairment; blood disorders; neurological disturbances including neuropathy, paraesthesia and dizziness; convulsions; Yersinia and mucormycosis infectons; visual disturbances (including lens opacity and retnopathy) and hearing loss; rash; rarely, growth retardaton (in young children); rarely, acute respiratory distress syndrome; pain on intramuscular or subcutaneous injecton; local irritaton on prolonged subcutaneous infusion; reddish- brown discolouraton of urine. Precautons Hypertension; renal impairment (discontnue or use with extreme cauton if renal failure occurs during treatment); any abnormal reacton such as hyperpyrexia should be assessed; elderly; pregnancy (Appendix 7c); lactaton, alkalinize urine to pH of 7. Adverse Efects Hypertension, tachycardia; malaise, nausea, vomitng, abdominal pain, salivaton, lacrimaton, sweatng, burning sensaton in the mouth, throat and eyes; feeling of constricton in throat and chest; headache, muscle spasms, tngling of the extremites; fever in children; local pain and abscess at injecton site, iron toxicity potentaton. Child- 20 mg/kg/day administered in 3-4 divided doses, initatng treatment at 25% of this dose and gradually increasing to full dose over 2-3 weeks to minimize adverse reactons. Precautons Monitor throughout treatment including blood counts and urine tests; renal impairment; immunosuppressive treatment; avoid oral iron within 2 h of a dose; hepatc impairment; pregnancy (Appendix 7c). In Wilson’s disease, consider withdrawal if platelet count falls below 120 000/mm3 or white blood cells below 2500/mm3 or if 3 successive falls within reference range (can restart at reduced dose when counts return to reference range but permanent withdrawal necessary if neutropenia or thrombocytopenia recur). In Wilson’s disease warn patent to tell doctor immediately if sore throat, fever, infecton, non-specifc illness, unexplained bleeding and bruising, purpura, mouth ulcers or rashes develop. Adverse Efects Initally nausea (less of a problem if taken with food and on retring), anorexia, fever; taste loss (mineral supplements not recommended); blood disorders including thrombocytopenia, neutropenia, agranulocytosis and aplastc anaemia; proteinuria, rarely, haematuria (withdraw immediately); haemolytc anaemia, nephrotc syndrome, lupus erythematosus- like syndrome, myasthenia gravis-like syndrome, polymyosits (rarely, with cardiac involvement), dermatomyosits, mouth ulcers, stomatts, alopecia, bronchiolits and pneumonits, pemphigus, Goodpasture syndrome and Stevens-Johnson syndrome also reported; male and female breast enlargement reported; rash early in treatment (usually allergic-may need temporary withdrawal), late rashes (reduce dose or withdraw treatment). Flumazenil* Pregnancy Category-C Indicatons Antdote for benzodiazepine overdose, reversal of sedatve efects produced by benzodiazepenes administered during general anaesthesia or diagnostc or therapeutc procedures. Contraindicatons Epilepsy, neuromuscular blockade, hypersensitvity to benzodiazepines, patents of suspected tricyclic antdepressant overdose, raised intracranial pressure. Precautons History of seizures, panic atack, alcohol drug dependence, bleeding disorder, liver disease, head injury, respiratory depression, pregnancy (Appendix 7c). Adverse efects Convulsions, fatgue, injecton site pains, increased sweatng, facial erythema, raised intracranial pressure, agitaton, dizziness, abnormal vision, may cause complete heart block, fushing, transient increase in blood pressure and heart-rate. Methylene Blue (Methylthioninium Chloride)* Pregnancy Category-C Indicatons Acute methaemoglobinaemia. Dose Intravenous injecton Methaemoglobinaemia caused by high dosage of prilocaine infusion: 1-2 mg/kg intravenously over 5 minutes, followed immediately by a fuid fush of 15-30 ml to minimize local pain. Contraindicatons Severe renal impairment; methaemoglo- binaemia due to chlorate or induced by sodium nitrite in treatment of cyanide poisoning; afects ability to drive machinery. 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.

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Colloidal bioadhesives Bioadhesive microspheres composed from a variety of materials such as starch generic gyne-lotrimin 100 mg without a prescription, carbomer buy gyne-lotrimin 100mg on-line, hyaluronan esters trusted gyne-lotrimin 100mg, dextrans have been used to prolong the retention time of the drug within the nasal cavity. The clearance half-life of microspheres can be in the order of 3–4 hours, in comparison with 15 minutes for a simple solution. Improved bioavailabilities have been seen for gentamicin, insulin and desmopressin. A temporary widening of the tight junctions of cultured cells, which coincided with an increase in the rate of absorption of the applied drug, insulin, has been observed in the presence of starch microspheres. It is likely that the dry starch microspheres took up water from the cells causing them to dehydrate and “shrink” resulting in a separation of the intercellular junctions. Should this be the case, it provides evidence for the paracellular absorption of insulin. This can be achieved by including an excipient in the formulation with a reversible ciliostatic effect; such agents include certain preservatives. However, it is important that the chosen strategy does not permanently compromise mucociliary clearance, which would adversely affect airway homeostasis and defense. However the long-term effects of even a temporary impediment to the mechanism of nasal clearance is unknown and such an approach should be used with caution. For instance, cytochrome P450-dependent monooxygenase metabolizes nasal decongestants, nicotine, cocaine and progesterone. With respect to the degradation of peptides and proteins, a variety of protease inhibitors have been studied including bestatin, diprotinin A and aprotinin, which inhibit leucine aminopeptidase, dipeptidyl peptidase and trypsin respectively (Table 9. Some inhibitors are active against more than one peptidase, for example leupeptin inhibits both cathepsin and trypsin. The choice of inhibitor depends upon the peptide, for instance inhibitors having a trypsin- inhibitory effect have been shown to enhance the nasal absorption of salmon calcitonin in rats. Interestingly, compounds which have been investigated for their penetration-enhancing effect at the absorbing membrane have also been shown to decrease the metabolism of certain peptides. By denaturing leucine aminopeptidase and preventing enzyme-substrate complex formation, the bile salt sodium glycocholate has been shown to protect insulin from proteolysis in the rat nasal mucosa. In addition to formulation additives, peptides can be chemically modified to improve their stability to proteases, as described in Chapter 1 (Section 1. However, altering the tonicity of the formulation had no effect on the absorption of human granulocyte colony-stimulating factor (molecular weight 19 kDa). In another study, decreasing the pH of the formulation was shown to enhance absorption. Alterations of osmotic pressure and pH beyond a certain range might be expected to result in damage to the epithelium and hence increase its permeability to xenobiotics. Delivering the drug as a dry powder 243 A further approach has been to deliver drugs in the form of a powder (but without a bioadhesive carrier). For example, freeze-dried insulin has been shown to be better absorbed as a powder than in solution, although the absorption of glucagon and dihydroergotamine, when delivered from liquid or powder formulations, was equivalent. However, problems which require resolving include developing absorption promoters with minimal toxicity and overcoming adverse nasal pathology to ensure accurate and reproducible dosing. List the mechanisms by which the permeability of the nasal epithelium may be increased to improve the efficacy of nasal drug delivery. Delivery of anti-asthmatic and other locally acting drugs directly 245 to their site of action reduces the dose needed to produce a pharmacological effect, while the low concentrations in the systemic circulation may also reduce side-effects. The lung may additionally be employed as a route for delivery of drugs into the systemic circulation, and onward to an effect site located elsewhere in the body. A product containing ergotamine tartrate is available as an aerosolized dosage inhaler for the treatment of migraine. Volatile anesthetics, including, for example, halothane, are also given via the pulmonary route. In recent years, the possibility of utilizing the pulmonary route for the systemic delivery of peptides and other molecules which are not absorbed through the gastrointestinal tract has also been explored. Pulmonary drug delivery for both local and systemic effects will be discussed in this chapter. There are a number of schemes for categorizing the different regions of the respiratory tract. With respect to pulmonary drug delivery, division into the following three regions is useful (Figure 10. Every branching of the tracheobronchial tree leads to a new “generation” of airways; for example, the trachea (“generation 0”) bifurcates into two main bronchi (“generation 1”) and then follows sequential branching into lobar bronchi (“generation 2”), segmental bronchi (“generation 3”), intrasegmental bronchi, bronchioles, secondary bronchioles and ultimately the terminal bronchioles (“generation 16”). The terminal bronchioles mark the limit of the tracheobronchial region, beyond which lies the alveolar region (“generations 17 to 23”). Progression from the trachea to the extremities of the tracheobronchial tree is characterized by decreases in both the diameter and length of the tubules with each branching, but the geometrically increasing number of airways results in dramatic increases in surface area. It should be borne in mind, however, that in humans, the left and right lungs are not identical and each contains irregular dichotomous and trichotomous branching patterns. Additionally, while the average path length from trachea to terminal bronchioles is 16 branches, short paths of only 8 to 10 branches may also exist. The alveolar region begins at the respiratory bronchioles, where alveoli begin to appear in the airway walls. Further branching of the respiratory bronchioles is associated with increasing frequency of alveoli appearing until the airway terminates at a respiratory unit, which contains alveolar ducts, atria and about 20 alveoli. The alveoli are packed tightly with adjacent alveoli separated by a common alveolar septum. The diversity of pulmonary epithelia can be illustrated by examining its structure at three principal levels (Figure 10. Some serous cells, brush cells and Clara cells are also present with few Kulchitsky cells. The frequency of goblet and serous cells decreases with progression along the airways while the number of Clara cells increases.

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