Systemic side effects

Loperamide is similar ia action and use to diphenoxylate however, it does not need to be formulated with atropiae and is available by prescription and OTC. It is reported to have fewer central nervous system side effects than diphenoxylate. 

There are hundreds of topical steroid preparations that are available for the treatment of skin diseases. In addition to their aforementioned antiinflammatory effects, topical steroids also exert their effects by vasoconstriction of the capillaries in the superficial dermis and by reduction of cellular mitosis and cell proliferation especially in the basal cell layer of the skin. In addition to the aforementioned systemic side effects, topical steroids can have adverse local effects. Chronic treatment with topical corticosteroids may increase the risk of bacterial and fungal infections. A combination steroid and antibacterial agent can be used to combat this problem. Additional local side effects that can be caused by extended use of topical steroids are epidermal atrophy, acne, glaucoma and cataracts (thus the weakest concentrations should be used in and around the eyes), pigmentation problems, hypertrichosis, allergic contact dermatitis, perioral dermatitis, and granuloma gluteale infantum (251). 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

The uptake of TRA into cervical tissue was determined by measuring tissue radioactivity following insertion of the collagen sponge cervical cap containing tritium-labeled TRA. The TRA concentrations peaked at 4 hr and then diminished rapidly by 24 hr. Since measurements of blood samples revealed that no systemic absorption had occurred, high local concentrations over an extended period of time may be possible without systemic side effects. 

There is still debate whether oral antihistamines control ocular allergy as well as topical antihistamines. Topical antihistamines are recommended before oral agent in step therapy because of the increased risk of systemic side effects with oral drugs. Additionally, topical antihistamines provide faster relief of ocular symptoms. Consider oral antihistamines... 

Loteprednol 1 drop in affected eye(s) four times daily Elevated intraocular pressure, cataracts, decreased wound healing, secondary ocular infections, systemic side effects possible... 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

Sustained- and controlled-release devices for drug delivery in the vaginal and uterine areas are most often for the delivery of contraceptive steroid hormones. The advantages in administration by this route—prolonged release, minimal systemic side effects, and an increase in bioavailability—allow for less total drug than with an oral dose. First-pass metabolism that inactivates many steroid hormones can be avoided [183,184],... 

Inspection of the retina during an ophthalmoscopic examination is greatly facilitated by mydriasis, or the dilation of the pupil. Parasympathetic stimulation of the circular muscle layer in the iris causes contraction and a decrease in the diameter of the pupil. Administration of a muscarinic receptor antagonist such as atropine or scopolamine prevents this smooth muscle contraction. As a result, sympathetic stimulation of the radial muscle layer is unopposed, causing an increase in the diameter of the pupil. These agents are given in the form of eye drops that act locally and limit the possibility of systemic side effects. 

Nonabsorbable antibiotics are appealing because they have fewer systemic side effects and may be safer for children and pregnant women as well as in patients with renal and hepatic dysfunction. One such antibiotic, aztreonam, showed little effect on anaerobic flora in human volunteers, producing most of its effect on the aerobic flora [49, 50], A trial showed efficacy of aztreonam for traveler s diarrhea, where most pathogens are aerobes [51]. While there are no data on rates of AAD for nonabsorbable antibiotics and C. difficile, these would likely be decreased. Given the preservation of the anaerobic flora, another poorly absorbed antibiotic, bicozamycin, has efficacy in traveler s diarrhea with its major effect being on fecal aerobes [52],... 

Local administration of NO to the lungs has been shown to reverse pulmonary hypertension in animal models [103], importantly with no systemic side effects. This is likely to be as a result of surplus NO being removed as nitrosyl-hemoglobin [104]. Such advantages of gaseous NO were first reported in 1991 [105, 106]. In 1999 and 2001 NO gas was approved as a drug in the USA and European Union, for treating hypoxemic respiratory failure in infants [107]. 

The use of polymeric nanoparticles in the eye has gained considerable interests in recent years. Ocular disposition, safety, efficacy, and pharmacokinetic profiles of various nanoparticles offer a wide range of application for the delivery of many drugs used to treat common ocular disorders. Polymeric nanoparticles have been utilized to enhance the performance of ibuprofen and cyclosporine, while reducing systemic side effect of carteolol compared with... 

Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann ME. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 2004 172(3) 1777-1785. 

This postulated phenomenon can have the beneficial effect of reducing the likelihood of systemic side-effects by effectively buffering the rate at which the drag enters the systemic circulation and hence reducing peak-to-trough variations in concentration. Conversely, high affinity for Hver Hssue may increase exposure to the enzymes of clearance and may therefore attenuate the first-pass extraction of drugs. 

To improve the tolerability of nervous system side effects, bedtime dosing is recommended during the first 2 to 4 weeks of therapy and in patients who continue to experience these symptoms. 

Pharmacology Dipivefrin is a prodrug of epinephrine. Dipivefrin, converted to epinephrine in the eye by enzymatic hydrolysis, appears to act by decreasing aqueous production and enhancing outflow facility. It has the same therapeutic effects as epinephrine with fewer local and systemic side effects. 

A range of legal drugs is sold by the pharmaceutical industry to treat illnesses of the nervous system. Advances in our understanding of the structure and function of the nervous system has accelerated the development of chemicals for treating diseases such as Parkinson s syndrome, Alzheimer s disease, and mild depression. The treatment of mild depression with drugs like Prozac is a billion dollar industry. On the other hand, some drugs may produce undesirable nervous system side effects that can limit their utility in disease treatment. The anticancer... 

Beside the cardiac indications /3-blockers can be used in the therapy of glaucoma. Systemic but also the local application of these compounds can reduce intraocular pressure. The mechanism of this action is a reduced production of aqueous humor by the ciliary body. Although applied locally, jS-blockers might be absorbed in sufficient amounts to induce systemic side effects in susceptible individuals. 

Increasing the concentration increases the penetration, but not to the same degree. Solubility of the corticosteroid in the vehicle is an other determinant of absorption and efficacy. So different formulations of the same corticosteroid can end up in a different efficacy classification. Efficacy can be further augmented by using the corticosteroid under occlusion. Occlusion with plastic enhances penetration and also absorption. However, with increased absorption also the risk of systemic side-effects increases. Systemic absorption will suppress the pituitary-adrenal axis and may cause Cushing s syndrome and a plethora of other adverse events (see Chapter 24, Section Il.b). Even small amounts absorbed may already cause growth retardation in children. 

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