Sulfhydryl drugs

Thiono and sulfhydryl drugs are also associated with a significant incidence of a lupus-like syndrome. Propylthiouracil is associated with a significant incidence of lupus [18] as well as liver toxicity [19, 20] and agranulocytosis [21], Penicillamine is associated with lupus, agranulocytosis [22] and a variety of autoimmune syndromes as discussed later. 

Csako G, Elin RJ. Spurious ketonuria due to captopril and other free sulfhydryl drugs. Diabetes Care 1996 19(6) 673. ... 

Takatsuka H, Takemoto Y, Yamada S, Mori A, Wada H, Fujimori Y, Okamoto T, Kanamaru A, Kakishita E. Similarity between eruptions induced by sulfhydryl drugs and acute cutaneous graft-versus-host disease after bone marrow transplantation. Hematology 2002 7(l) 55-7. 

Kitamura K, Aihara M, Osawa J, Naito S, Ikezawa Z. Sulfhydryl drug-induced eruption a clinical and histological study. J Dermatol 1990 17(1) 44-51. 

Accretion of a viscid mucus is the hallmark of the more chronic forms of obstructive pulmonary disease. The presence of the mucus exacerbates the pathology both by providing a mechanical block to the inspiration and expiration of air and by preventing topical drugs from reaching the distal bronchi. Although not universally accepted, therapy which will liquify the mucus so that It can be expectorated should have a place in the treatment of COPD. Sulfhydryl drugs such as N-acetylcysteine are available for this use. 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

Malik, N.A., Otiko, G. and Sadler, P.J. (1980) Control of intra- and extra-cellular sulfhydryl-disulfide balances with gold phosphine drugs Phosphorus-31 nuclear magnetic resonance studies of human blood. Journal of Inorganic Biochemistry, 12, 317-322. 

D. (1991). The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. Drug Alcohol Depend. 28, 291-294. 

In a somewhat similar scheme, Noguchi et al. (1992) prepared a carboxylate spacer arm by reacting 6-bromohexanoic acid with a dextran polymer. The carboxylate then was aminated with ethylene diamine to form an amine-terminal spacer (Figure 25.15). This dextran derivative finally was reacted with N-Succinimidyl 3-(2-pyridyldithio)propionate (SPDP) (Chapter 5, Section 1.1) to create the desired sulfhydryl-reactive polymer (Section 2.4, this chapter). The SPDP-activated polymer then could be used to prepare an immunoconjugate composed of an antibody against human colon cancer conjugated with the drug mitomycin-C. 

The number of drugs susceptible to S-methylation is still limited but greater than the number turned over by COMT. Thiopurine methyl transferase (TPMT) is an important enzyme responsible for detoxifying mercaptopurine—a drug used to treat leukemia— as well as azathioprine —a prodrug that is metabolized to mercaptopurine (Fig. 7.12). This enzyme is polymorphic and patients who are homozygous for the deficient enzyme experience severe toxicity when given usual doses of mercaptopurine (19). Similar aromatic and heterocyclic sulfhydryls can also be substrates for TPMT. The similar thiol... 

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