Amiodarone binding

Second, tissue protein binding of medication can affect drug disposition in the elderly patient. For example, amiodarone binds strongly to tissue proteins, which greatly increases its volume of distribution. In the elderly or chronically ill patient, tissue proteins may change or decline, which can also affect the serum levels of medications. 

At the cellular level, the major electrophysiological effect appears to be rate-dependent blockade of sodium channels [22]. The onset for this Class I effect (64 + 9% of the final depression of between the first and second beat of the train) was similar to that for Class IB agents [23]. The offset rate (recovery of from rate-dependent depression) for amiodarone was 1.48 s. This value falls between those seen for Class IB agents (200-500 ms) and lA agents (2.3-12.2 s) [23]. Amiodarone inhibited the binding of pH]ba-trochotoxinin A 20a-benzoate to the sodium channel, suggesting that it binds to inactivated sodium channels [24]. 

The antiarrythmic drug amiodarone inhibits reserpine binding in a concentration-dependent manner and has a sympatholytic, anti-adrenergic effect in the heart, inhibiting the uptake of norepinephrine (Haikerwal et al., 1999). Blockers of VMAT and L-type calcium channels have also been reported to exert reciprocal inhibitory actions (Mahata et al., 1996). 

AMIODARONE ANION EXCHANGE RESINS Colestyramine 1 amiodarone levels Colestyramine binds amiodarone, reducing its absorption and interrupting its enterohepatic circulation Avoid co-administration... 

A number of medications have been shown to alter thyroid function and thyroid function tests.Few drugs are associated with the development of clinically significant thyroid disease (amiodarone may be an exception), but difficulty in the interpretation of thyroid function tests results when patients are placed on medications that affect thyroid function testing. In general, drugs do not interfere chemically with the assays for thyroid hormones or TSH. The medications most likely to affect TSH concentrations are glucocorticoids and dopamine (reduced TSH concentrations) and amiodarone (increased TSH concentrations). The most commonly encountered variations in thyroid hormone measurements induced by medications are reduced peripheral conversion of T, to T3 or altered binding of T4 and T3 to carrier proteins. Some of the medications that affect thyroid function tests are shown in Table 52-2. 

Two hundred milligrams of amiodarone contains 75 mg of iodine. Patients treated with the common daily dose of 200 mg amiodarone, get a load of 7 mg free iodide/ day, which is 35-times the daily recommended iodine dose. Amiodarone is lipophilic and concentrates in adipose tissue, cardiac and skeletal muscle, and in the thyroid (Daniels, 2001). The amiodarone plasma half life is approximately 52 23 days (Hermann, 2004). Typical changes in thyroid function are an increase in serum T4 and reverse triiodothyronine (rT3), and a decrease in serum T3 concentrations related to the inhibition of 5 -deiodinase-activity, resulting in a decrease in the generation of T3 from T4 and a decrease in the clearance of rT3 (Martino et al, 2001) and an inhibition ofT3 receptor binding and action (Daniels, 2001). 

This interaction probably occurs because colestyramine binds with amiodarone in the gut, thereby reducing its absorption. It may also affect the enterohepatic recirculation of amiodarone. This is consistent with the way colestyramine interacts with other drugs. 

Uncertain. It seems possible that amiodarone inhibits the liver enzymes concerned with the metabolism of phenytoin, resulting in a rise in its serum levels. It seems unlikely that drug displaeement from protein binding sites had a part to play as free and bound levels of phenytoin remained constant. ... 

This chapter describes research by an interdisciplinary and international team focused on the preparation and evaluation of some dispersions of nanomatetials having potential application for injection into overdosed humans and to reverse cardiac toxicity by absorbing or binding the toxin. Specifically, the commonly overdosed therapeutics amiodarone, amitriptyline, and bupivacaine, and the illicit drug cocaine, are the deleterious chemicals under consideration for rapid reduction in concentration in blood. 

Nervous system Bilateral anterior optic neuropathy has been reported in an otherwise healthy 43-year-old man who took terbinafine 500 mg/day for onychomycosis [1" ]. Terbinafine was withdrawn and his visual acuity improved considerably within 1 month, but there was slight pallor of the left optic disc and the visual fields of both eyes were still concentrically constricted. One plausible explanation for this effect of terbinafine may be that it is amphiphilic, which may allow binding to polar lipids and accumulation within lysosomes. Drug-induced lysosomal impairment has been presumed to be the basis of the retinal changes observed with other amphiphilic drugs, such as amiodarone, perhexilene, and suramin. 

Amiodarone and its metabolites bind to lipofuscin in macrophages. They tend to concentrate in areas of highly sun-exposed skin. Moreover, ultraviolet light induces amiodarone and its metabolites to bind to blood vessels walls and perivascular tissue. This reaction triggers vasodilatation that increases the diffusion of these metabolites, which in turn causes chronic accumulation in the tissues [18]. 

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