By H. Yasmin. Tabor College.

Onset of Action Duration Hyperprolactinemia 2 h 24 h Parkinson’s disease 30–90 min No data Acromegaly 1–2 h 4–8 h Food: Take with food or milk buy 80 mg propranolol. Contraindications: Severe ischemic heart disease purchase propranolol 40mg on line, peripheral vas- cular disease purchase 40 mg propranolol overnight delivery, sensitivity to ergot alkaloids. Warnings/precautions: Use with caution in patients with kidney disease, liver disease. Advice to patients • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Clinically important drug interactions • Drugs that increase effects/toxicity of bromocriptine: sympa- thomimetics, diuretics. Editorial comments: Alarge percentage of patients will experience mild to moderate side effects from bromocriptine, particularly with higher doses (>20 mg/d). In postpartum studies, only 3% of patients needed to discontinue therapy because of side effects. Although brompheniramine is considered compatible with breastfeeding by the American Academy of Pediatrics, it is stated to be contraindicated by one manufacturer. Warnings/precautions • Use with extreme caution in patients with active peptic ulcer, severe coronary artery disease, symptomatic prostatic hypertro- phy. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Editorial comments: This drug is available in combination with other agents, including pseudoephedrine, phenylephrine, phenyl- propanolamine, aspirin, acetaminophen. Warnings and precautions, side effects, etc, of other ingredients should be kept in mind when prescribing. Mechanism of action: Inhibits elaboration of many of the media- tors of allergic inflammation, eg, leukotrienes and other products of the arachidonic acid cascade. Maintenance: reduce initial dose to smallest amount necessary to control symptoms. Warnings/precautions • If patient is transferred from systemic corticosteroid to inhala- tion drug, symptoms of steroid withdrawal may result. Alternatively, adre- neal insufficiency may occur: weakness, fatigue, nausea, anorexia. This may minimize the development of dry mouth, hoarseness, and oral fungal infection. Parameters to monitor • Signs and symptoms of acute adrenal insufficiency, particu- larly in response to stress. If these occur, the dose of systemic steroid should be increased followed by slower withdrawal. Editorial comments • Inhaled corticosteroids are the drugs of choice for patients with refractory symptoms on prn adrenergic agonist bron- chodilators. However, there is considerable controversy with respect to the beneficial use of higher than recommended inhalation doses of these drugs. Mechanism of action: Inhibits sodium and chloride resorption in proximal part of ascending loop of Henle. Contraindications: Hypersensitivity to sulfonamides, anuria, hepa- tic coma, severe electrolyte depletion. Editorial comments • This drug is listed without detail in the Physician’s Desk Reference, 54th edition, 2000. Class of drug: Local and regional anesthetic Mechanism of action: Reversibly inhibits initiation and conduc- tion of nerve impulses near site of injection. Contraindications: Hypersensitivity for amide-type local anes- thetic (eg, lidocaine), sensitivity to sodium metabisulfate (in prepa- rations containing epinephrine), obstetrical paracervical block. Warnings/precautions • Use local anethetics plus vasoconstrictor (eg, epinephrine, nor- epinephrine) with caution in patients with the following con- ditions: peripheral vascular disease, hypertension, administration of general anesthetics. Use with extreme cau- tion for lumbar and caudal epidural anesthesia in patients with the following conditions: spinal deformities, existing neurologic dis- ease, severe uncontrolled hypotention, septicemia. Any increase in heart rate and sys- tolic pressure within 45 seconds (the epinephrine response) would indicate that the injection is intravascular. The necessary means must be avail- able to manage this condition (dantrolene, oxygen, supportive measures). Advice to patient: Be aware that there will be a loss of sensation for several hours after the injection. At the first sign of a change that suggests onset of toxicity, administer oxygen and stop drug. Establish and maintain a patent airway, begin assisted ventilation, and administer 100% oxygen. Resuscitation equipment and drugs, as well as oxygen, should be available for immediate use. Mechanism of action: Binds to opiate receptors and blocks ascending pain pathways. Adjustment of dosage • Kidney disease: creatinine clearance <30 mL/min: 50–100 mg q12h Maximum: 200 mg.

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Fludrocort- sone has glucocortcoid propertes but it has potent mineralocor- tcoid propertes and is used for its mineralocortcoid efects order propranolol 80 mg with amex. In pharmacological (high) doses purchase 80 mg propranolol mastercard, glucocortcoids decrease infammaton and suppress the immune response buy propranolol 80mg online. If suppressive doses are given for prolonged periods, the adrenal cortex may undergo atrophy and this leads to a defciency on sudden withdrawal or dosage reducton or situatons such as stress or trauma where cort- costeroid requirements are increased. Afer high dosage or prolonged therapy, withdrawal should be gradual, the rate depending on various factors including patent response, cortcosteroid dose, duraton of treatment and disease state. The suppressive acton of a cortcosteroid on cortsol secre- ton is least when given in the morning. Cortcosteroids should normally be given in a single morning dose to atempt to mini- mize pituitary-adrenal suppression. Because the therapeutc efects of cortcosteroids are of longer duraton than the metabolic efects, intermitent therapy may allow the body’s normal metabolic rhythm and the therapeutc efects to be maintained. Alternate day dosing is, however, suitable only in certain disease states and with cortcosteroids with small mineralocortcoid efects and a relatvely short duraton of acton. Hydrocortsone is used in adrenal replacement therapy and on a short-term basis by intravenous injecton for the emer- gency management of some conditons. Its mineralocortcoid actvity is too high for it to be used on a long-term basis for disease suppression. The mineralocortcoid actvity of fudro- cortsone is also high and its ant-infammatory actvity is of no clinical relevance. It is the actve metabolite of prednisone, conversion of which is vari- able and prednisone should not be used interchangeably with prednisolone. Dexamethasone has very high glucocortcoid actvity in conjuncton with insignifcant mineralocortcoid actvity making it partcularly suitable for high-dose therapy in conditons where water retenton would be a disadvantage such as cerebral oedema. It also has a long duraton of acton and this, together with its lack of mineralocortcoid actvity makes it partcularly suitable for conditons requiring suppres- sion of cortcotrophin secreton such as congenital adrenal hyperplasia. Adverse Efects of Cortcosteroids: Overdosage or prolonged use may exaggerate some of the normal physiological actons of cortcosteroids leading to mineralocortcoid and glucocortcoid adverse efects. Mineralocortcoid adverse efects include hypertension, sodium and water retenton and potassium loss. These efects are most marked with fudrocortsone but are signifcant with hydrocortsone, occur slightly with prednisolone and are negligible with dexamethasone. Glucocortcoid adverse efects include diabetes mellitus and osteoporosis which is of partcular importance in the elderly since it may result in osteoporotc fractures of the hip or vertebrae. Mental distur- bances can occur, including serious paranoid state or depres- sion with risk of suicide, partcularly in patents with a history of mental disorders; euphoria is also common. High doses may cause Cushing syndrome (typical moon face, striae and acne), which is usually reversible on withdrawal of treatment, but this should always be tapered gradually to avoid symp- toms of acute adrenal insufciency (see also Withdrawal). In children, cortcosteroids may result in suppression of growth and cortcosteroids administered during pregnancy can afect adrenal development in the fetus. Any adrenal suppression in the neonate following prenatal exposure usually resolves spontaneously afer birth and is rarely, clinically important. Healing of wounds may be impaired and infectons and thin- ning of the skin may occur; spread of infectons may result from modifcaton of tssue reactons. Abrupt withdrawal afer a prolonged period may lead to acute adrenal insufciency, hypotension or death (see Withdrawal of Systemic Cort- costeroids, below). Withdrawal may also be associated with fever, myalgia, arthralgia, rhinits, conjunctvits, painful itchy skin nodules and weight loss. Cortcosteroid Cover During Stress: To compensate for a diminished adrenocortcal response caused by prolonged cortcosteroid treatment, any signifcant intercurrent illness, trauma, or surgery requires a temporary increase in cortcosteroid dose, or if already stopped, a tempo- rary re-introducton of cortcosteroid treatment. Anaesthetsts must therefore know whether a patent is taking or has been taking a cortcosteroid, to avoid a precipitous fall in blood pres- sure during anaesthesia or in the immediate postoperatve period. A suitable regimen for cortcosteroid replacement, in patents who have taken more than 10 mg prednisolone daily (or equivalent) within 3 months of surgery, is: • Minor surgery under general anaesthesia-usual oral cortcosteroid dose on the morning of surgery or hydrocortsone 25-50 mg intravenously at inducton; the usual oral cortcosteroid dose is recommenced afer surgery. Infectons: Prolonged courses of cortcosteroids increase susceptbility to infectons and increase their severity; clinical presentaton of infectons may also be atypical. Serious infectons, for example septcaemia and tuberculosis, may reach an advanced stage before being recognised, and amoebiasis or strongyloidiasis may be actvated or exacerbated (exclude before initatng a cortcosteroid in those at risk or with suggestve symptoms). Chickenpox Unless they have had chickenpox, patents receiving oral or parenteral cortcosteroids for purposes other than replace- ment should be regarded as being at risk of severe chickenpox on exposure. Passive immunizaton with varicella-zoster immunoglobulin is needed for exposed non-immune patents receiving systemic cortcosteroids or for those who have used them within the previous 3 months; varicella-zoster immunoglobulin should preferably be given within 3 days of exposure and no later than 10 days. Topical, inhaled or rectal cortcosteroids are less likely to be associated with an increased risk of severe chickenpox. Measles Patents taking cortcosteroids should be advised to take partcular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. In life-threatening diseases, high doses may be needed because the complicatons of therapy are likely to be less serious than the disease. In long-term therapy in rela- tvely benign chronic conditons such as rheumatoid arthrits, adverse efects ofen outweigh the advantages. In order to minimize the adverse efects, the maintenance dose should be kept as low as possible and if possible, single morning doses or alternate day therapy should be used.

Most micronized drugs for inhalation will have particle densities around 1 generic 80 mg propranolol, although materials produced by freeze-drying or spray-drying methods are likely to be significantly less dense cheap propranolol 80mg with mastercard. It should not be assumed propranolol 80mg without a prescription, however, that the uptake of water vapor will always occur. If the drug is given as an aerosolized powder then the drug first needs to dissolve in the mucus layer. Although mucus has a very high water content, varying between approximately 90–95%, its viscosity may result in a slow dissolution of drugs. Thus dissolution may be a rate determining step, especially for poorly soluble drugs, such as some of the corticosteroids which are delivered as dry powder aerosols. Improvement of drug penetration into mucus has been attempted using mucolytic drugs such as N- acetylcysteine, which act to reduce mucus viscosity. Highly water-soluble drugs, given as dry powder 256 aerosols, may dissolve at the very high relative humidity (>99%) present in the airways air and impact as solution droplets. Once in solution, the drug will diffuse through the mucus layer and enter the aqueous environment of the epithelial lining fluid. The rate of diffusion through the mucus will be dependent upon such factors as: • the thickness of the mucus layer; • mucus viscosity—although it should be appreciated that it is the viscosity of the mucus gel intersticies (i. Mucus secretion may be stimulated as a response to “assault” by what the lung perceives as foreign bodies such as microorganisms and dusts or irritants such as cigarette smoke. Airways disease states such as bronchitis, cystic fibrosis and asthma are often associated with a hypersecretion of mucus. Clearly this presents a far greater barrier than is seen in the normal healthy lung. Many studies have been performed with a variety of antibiotics delivered by aerosol for the treatment of chronic lung infections. The studies have produced mixed results with delivery to the lung from the bloodstream (after oral or parenteral dosing) often producing better clinical response. A number of factors, including the efficiency of drug delivery, may be responsible for these observations, but the overproduction of mucus in these disease states also seems likely to play a major role in preventing the drug reaching its target microorganism. A detailed discussion of the structure and properties of mucus and respiratory mucins is given in Chapter 9 (Section 9. The cilia beat at approximately 1,000 beats min−1 in an organized fashion and the ciliary movement may be conceived as a form of rhythmic waving which enables hook-like structures at the ciliary tips to propel mucus along the airways to the throat (see Section 9. Mucociliary clearance is an organized, complex process which is highly dependent upon the composition and depth of the epithelial lining fluid and the viscoelastic properties of the mucus. This may cause an overloading of the ciliary transport process, resulting in 257 a debilitated mucociliary clearance and the build-up of mucus as a thick, highly viscous layer. Thus while the mucociliary clearance of particles takes hours under normal circumstances, induced coughing may result in rapid removal of mucus and any associated drug within minutes. It should be remembered, however, that aerosolized drug deposition is likely to occur over a large surface area in the healthy and mild to moderate airways diseased lung. Coughing will remove mucus from a few localized areas where build-up has occurred and thus the fraction of the deposited dose removed by coughing is likely to be small. In cases of severe lung disease, drug deposition is likely to be highly localized and the situation may be different. For example, in cystic fibrosis patients, high levels of gentamicin, representing significant proportions of the deposited dose, were found in the sputum, when the aerosolized drug was deposited in the central airways. The main route is via the mucociliary escalator, although transport from the A region to the start of the mucociliary escalator is a very slow process and may involve transport through interstitium and lymphatic tissues in addition to a transfer by random movement by macrophages. Macrophages may also be transported via lymphatic systems to lymph nodes and the bloodstream. The uptake of particles by macrophages is a fairly rapid process but the subsequent clearance of particle-laden macrophages only occurs over days or weeks. Absorption is clearly important for systemically-acting drugs since it is one element of the events leading to delivery of drug to its site of action. Absorption is equally important for locally-acting drugs since for these compounds it represents removal of drug from its site of action. Metabolism of drugs is also an important consideration since it may lead to drug inactivation or the production of active or toxic metabolites. These same features also offer great potential for the delivery of systemically-acting compounds. The surface area of the airways is approximately 140 m , slightly larger than that of the small intestine. More importantly, however, a well-2 designed aerosol system can rapidly deliver drug to a high proportion of this surface area, whereas an orally delivered drug will have its access to the small intestine delayed by gastric emptying. In some parts of the alveolar region the airways to blood pathlength is less than 0. This property facilitates very rapid transfer of gases, vapors and other small molecules.