Creatinine receptor

Figure 11. (a) Stabilization of one tautomer of the receptor by complexation with creatinine, (b) Increase of the UV absorption of a creatinine receptor upon extraction of creatinine from an aqueous solution into a 1 mM CH2CI2 solution of the receptor (reprinted from Tetrahedron 1993, 49, 596. Copyright 1993, with permission from Elsevier Science Ltd.). 

Subat, M., Borovik, A. S., Konig, B. Synthetic creatinine receptor imprinting of a Lewis acidic zinc(II) cyclene binding site to shape its molecular recognition selectivity, J. Am. Chem. Soc. 126 (2004), 3185 — 3190. 

ACE, angiotensin-converting enzyme aPTT, activated partial thromboplastin time ARB, angiotensin receptor blocker BP, blood pressure CBC, complete blood count ECC, electrocardiogram HR, heart rate INR, International Normalized Ratio RR, respiratory rate SCr, serum creatinine, TTP, thrombotic thrombocytopenic purpura. 

Pramipexole (Mirapex ) Activate postsynaptic D2 DA receptors Start with 0.125 mg three times daily increase about weekly by 0.375-0.75 mg/day to a MD of 0.5-1.5 mg three times daily dosage reduction needed in patients with creatinine clearance less than 60 mL/minute... 

Amantadine (Symmetrel ) NMDA-receptor antagonist that blocks glutamate transmission, promotes DA release, and blocks Ach Start with 1 00 mg daily at breakfast after 1 week, add 1 00 mg daily in the early afternoon decrease dose as creatinine clearance decreases less than... 

ATC, lymphocyte immune globulin, antithymoglobulin equine AZA, azathioprine BUN, blood urea nitrogen CSA, cyclosporine Cl, gastrointestinal IL-2RA, interleukin 2 receptor antagonist MMF, mycophenalate mofetil OKT-3, muronomonab-CD3 PRED, prednisone SCr, serum creatinine SRL, sirolimus TAC, tacrolimus WBC, white blood cell. 

ACE-I, angiotensin-converting enzyme inhibitors ARB, angiotensin-receptor blockers AZA, azathioprine CMV, cytomegalovirus CPK, creatinine phos-phokinase CSA, cyclosporine HMG-CoA, 3-hydroxy 3-methylglutaryl coenzyme A reductase K+, potassium LFTs, liver function tests Rl, renal insufficiency SCr, serum creatinine SRL, sirolimus TAC, tacrolimus TMP-SMX, trimethoprim-sulfamethoxazole. 

ACE inhibitors and angiotensin-receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. Due to their ability to cause an initial bump in serum creatinine, these agents should be used cautiously when employed in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus (Table 52-8). In general, antihypertensive therapy should focus on agents with proven benefit in reducing the progression of cardiovascular disease and should be chosen on a patient-specific basis.55 See Chapter 2 for further recommendations for treating HTN. 

Diabetic patients are 3 4 times more susceptible to atherosclerosis and vascular insufficiency. The situation is similar for those suffering from renal insufficiency, independent of diabetes. Makita et al.5sl found that there was a direct correlation CP < 0.005) between serum AGE-peptide levels and renal function, as assessed by creatinine clearance. This led Bucala et a/.145 to consider that the modification of the plasma proteins, such as LDL, may arise due to the reaction with reactive, circulating AGE-peptides rather than glucose. AGE-LDL did form readily in vitro when native LDL was incubated with either synthesised AGE-peptides or AGE-peptides isolated directly from the plasma of patients. Such AGE-LDL exhibited markedly impaired clearance kinetics when injected into transgenic mice, expressing human LDL receptor. Their data indicate that AGE modification could contribute to elevated LDL levels in patients with diabetes or renal insufficiency. This hypothesis was further supported by the administration of AG to diabetic patients, when circulating levels of LDL decreased by almost 30%. Levels of Hb-AGE decreased too. 

Clinical PK/PD Calcitonin has a well-established mechanism of action published literature supports that salmon calcitonin, mediated through calcitonin receptors located on osteoclasts, inhibits bone resorption, thereby increasing bone mineral density. Since serum beta-CTx (C-telopeptides of type 1 collagen, corrected for creatinine) is a recognized marker of bone resorption, the effect of administered salmon calcitonin on serum beta-CTx is considered to be an adequate surrogate for pharmacodynamic comparisons. 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS CICLOSPORIN t risk of hyperkalaemia and renal failure Cidosporin causes a dose-dependent T in serum creatinine, urea and potassium, especially in renal dysfunction Monitor renal function and serum potassium weekly until stable, then at least every 3-6 months... 

Figure 4 Reversible binding of creatinine (6) to the designed receptor 5, forming a more deeply colored complex (5-6)...

The available data on a possible interaction between histamine H2 receptor antagonists and ciclosporin are inconclusive. Whereas neither cimetidine nor ranitidine significantly altered ciclosporin pharmacokinetics, there was an increase in serum creatinine concentration in patients taking both ciclosporin and cimetidine, but not ranitidine. The clinical significance of this interaction is probably limited, and it has been attributed to competition of cimetidine with creatinine for tubular secretion (251). 

A 69-year-old man with hypertension and heart failure took losartan 25 mg/day, increasing to 50 mg/day after 2 weeks. He also took spironolactone 50 mg/day, furo-semide 40 mg/day, digoxin 0.25 mg/day, acenocou-marol, and allopurinol. Two weeks later he developed acute renal insufficiency with a plasma creatinine concentration of 725 pmol/l (previously 115 pmol/l). Within 24 hours after losartan withdrawal (it was not stated whether spironolactone was also stopped) and hemodialysis, he recovered renal function (plasma creatinine 124 mg/1). He was later found to have bilateral renal artery stenosis, which is a contraindication to angiotensin II receptor antagonists. 

Interactions of cimetidine and other H -receptor antagonists with the renal secretion of several drugs have been repeatedly described, and comprehensively listed [146]. Thus, cimetidine inhibits renal secretion of procainamide in humans and prolongs its elimination half-life [147,148]. Similar inhibitory effects have been shown on creatinine, ranitidine and many other cationic compounds [149]. 

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