Pathophysiology of drug-induced nephropathy Level of the nephron Action Drugs Preglomerular Afferent arteriolar Cyclosporine (afferent arteriole) constriction Glomerulus Decreased GFR NSAIDs (prostaglandins) Gold, NSAIDs Glomerulonephritis Penicillamine
, cisplatin Proximal tubules Acute tubular necrosis Aminoglycosides, radiocontrast dyes Distal tubules Renal tubular ACE inhibitors, acidosis type 4 cyclosporine Tubules and ducts Crystalluria Acyclovir, sulphonamide Interstitium Interstitial nephritis Penicillin, allopurinol Renal papilla Papillary necrosis NSAIDs, analgesics Table 2.
has been used in mercury poisoning (one report), in addition to its indication as a chelating agent for copper in the treatment of Wilson's disease.
and L-hydroxyproline [the latter three from Sigma Chemical Co, England] were used.
Numerous treatments, including prednisone, azathioprine, penicillamine
, CsA, methotrexate, MMF, thalidomide, clofazimine, anti-CD20 monoclonal antibody, ECP, phototherapy with bath PUVA, UVA1 or UVB, etretinate or various combinations, have been tried with varying success in sclerodermatous GVHD (2), (3), (5), (15-22).
It is often an associated condition with hypersensitivity pneumonia and as the result of medications such as penicillamine
N-acetyl cysteine and penicillamine
induce apoptosis via the ER stress response-signaling pathway.
Drugs like antihistamines, steroids, penicillamine
, dimethyl sulfoxide and inhibitors of collagen synthesis have also been tried but with complicating side effects.
Level two is antimalarials and gold therapy, and the third level penicillamine
, methotrexate and sufasalazine.
vitamin B6 is deactivated by drugs like penicillamine
, isoniazid, hydralazine).
The only other disease-modifying antirheumatic drugs that have been evaluated for the treatment of ankylosing spondylitis in randomized, placebo-controlled trials are penicillamine
(19) and auranofin, (18) and neither were effective.
Whether lead elevates homocysteine through enzyme inhibition, as earlier suggested, or conversely, whether homocysteine elevates lead because of intravascular binding [homocysteine has a structure similar to dimercaptosuccinic acid (DMSA) and penicillamine
, compounds that are known to bind lead], it is evident that the association exists at very low blood lead levels, and if the former mechanism is operative, supports a biologic effect of lead at low levels.
But the 68 year-old Teesside granddad admits he's one of the lucky ones - because his medication, Penicillamine
, has fought off most of the symptoms.