Systemic inhibitors therapy

Clearly, inhibition of enzymatic degradation is fundamental to the medical management of corneal ulceration. The ocular surface is openly accessible to topical proteinase inhibitor therapy, administered by direct instillation or via a sub-palpebral lavage system. Inhibitor therapy is of most value in acute frank ulceration where it is used in conjunction with antimicrobial agents, but it may also be useful in promoting healing of refractory ulcers and chronic superficial erosions. Antiproteinases may be used prophylactically along with antibiotics in superficial injury where ulceration threatens. 

These patients may also exhibit symptoms of excessive stimulation of muscarinic receptors (abdominal cramps, diarrhea, increased salivation, excessive bronchial secretions, miosis, bradycardia). Small doses of edrophonium (1-2 mg intravenously) will produce no relief or even worsen weakness if the patient is receiving excessive cholinesterase inhibitor therapy. On the other hand, if the patient improves with edrophonium, an increase in cholinesterase inhibitor dosage may be indicated. Clinical situations in which severe myasthenia (myasthenic crisis) must be distinguished from excessive drug therapy (cholinergic crisis) usually occur in very ill myasthenic patients and must be managed in hospital with adequate emergency support systems (eg, mechanical ventilators) available. 

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

The authors cited evidence that the kallikrein/kinin system is involved in cold urticaria, that ACE inhibitors increase wheal-and-flare reactions to cutaneously applied bradykinin, and that ACE inhibitor therapy is associated with raised plasma kinin concentrations. They therefore recommended avoidance of ACE inhibitors in patients with cold urticaria. 

In addition to topical antimycotic therapy, systemic NSAIDs and topical atropine sulfate are used to the control pain and ameliorate the effects of anterior segment injury associated with the iridocyclitis that inevitably accompanies ker-atomycosis. Topical proteinase inhibitor therapy is of significant clinical benefit in controlling stromal breakdown and, since potentially pathogenic bacteria contaminate most mycotic lesions, concurrent broad-spectrum, topical antibacterial agents should be used. 

Functional renal insufficiency is manifested as increases in serum creatinine and blood urea nitrogen. As cardiac output and renal blood flow decline, renal perfusion is maintained by the vasoconstrictor effect of angiotensin II on the efferent arteriole. Patients most dependent on this system for maintenance of renal perfusion (and therefore most likely to develop functional renal insufficiency with ACE inhibitors) are those with severe heart failure, hypotension, hyponatremia, volume depletion, and concomitant use of NSAIDs. - Sodium depletion (usually secondary to diuretic therapy) is the most important factor in the development of functional renal insufficiency with ACE inhibitor therapy. Renal insufficiency therefore can be minimized in many cases by reduction in diuretic dosage or liberalization of sodium intake. In some patients, the serum creatinine concentration will return to baseline levels without a reduction in ACE inhibitor dose. Since renal dysfunction with ACE inhibitors is secondary to alterations in renal hemodynamics, it is almost always reversible on discontinuation of the drug. ... 

Use of NLO likely improves response and reduces systemic adverse effects and should be performed by all patients administering cholinesterase inhibitors. These agents should be used with caution in patients with asthma, retinal detachments, narrow angles, bradycardia, hypotension, heart failure, Down s syndrome, epilepsy, parkinsonism, peptic ulcer, and ocular inflammation, as well as in those receiving cholinesterase inhibitor therapy for myasthenia gravis or exposure to carbamate or organophosphate insecticides and pesticides. ... 

The thrombin time measures the conversion of flbrinogen to flbrin and is affected by quantitative and qualitative abnormalities of flbrinogen and the presence of thrombin inhibitors or flbrinogen degradation products. The thrombin time measures the time required for the formation and the appearance of the fibrin clot after thrombin is added to plasma. It may be used to monitor the effect of systemic fibrinolytic therapy and can be modified for monitoring heparin therapy. 

Aliskiren has also been shown to be associated with fewer cases of severe lower limb edema when combined with amlodipine compared with amlodipine alone [9 ]. It seems prudent that patients who develop calcium channel blocker-induced peripheral edema should receive a renin-angiotensin system inhibitor as part of rational combination therapy, rather than withdrawing the former, unless patients are already at their target blood pressure and combination treatment may lead to overtreatment [Iff]. 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Summarizing the fibrinolytic therapy, it should be emphasized that efficient treatment needs urgent application of plasminogen activator (within a few hours) to prevent the formation of crosslinks in the fibrin structure (Fig. 2) and to find the localization of thrombus to emerge plasmin on the surface of fibrin to prevent rapid inactivation of the enzyme by the inhibitor system of fibrinolysis (Fig. 3). 

Currently, there is no approved antiviral therapy specifically targeting hepatitis C virus (HCV). The development of an HCV replicon system and our improved understanding of the structure and function of HCV proteins have led to the development of several classes of specific HCV inhibitors. NS3-4A protease inhibitors and NS5B polymerase inhibitors are furthest in development as discussed in Chaps. 2-4 (De and Migliaccio 2005 Manns et al. 2007 Pawlotsky et al. 2007). 

It was hoped that the more complete blockade of angiotensin II s AT effects would confer greater long-term efficacy with ARBs compared to ACE inhibitors. However, prospective, randomized trials suggest that the clinical efficacy of ARBs is similar to that of ACE inhibitors for reduction of hospitalizations for HF, sudden cardiac death, and all cause mortality.23-25 Despite poorer suppression of AT2, comparable efficacy of ACE inhibitors may be due to the additional effects on the kallikrein-kinin system. Although ARBs produce hemodynamic and neurohormonal effects similar to those of ACE inhibitors, they are considered second-line therapy due to the overwhelming clinical trial experience with ACE inhibitors. 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

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