Cisplatin actions

Amifostine (Elhyol) [Antineoplastic/Thiophosphate Cytoprotective] Uses Xerostomia prophylaxis during RT (head, neck, ovarian, NSCLQ -I- renal tox w/ rqjeated cisplatin Action Prodrug, dqjhosphorylated by alkaline phosphatase to active thiol metabohte Dose 910 mg/mVd 15-min IV inf 30 min prior to chemo Caution [C, +/—] CV Dz Disp Inj SE Transient X BP (>60%), NA, flushing w/ hot or cold chills, dizziness, X Ca % somnolence, sneezing Notes Does not -1- effectiveness of cyclophosphamide + cisplatin chemo Interactions T Effects W/ antih5 pertensives EMS Monitor BP for hypotension OD Severe hypotension treat w/IV fluids... 

Other subgroups of alkylating agents are the nitrosoureas (examples carmustine, BCNU lomustine, CCNXJ) and the triazenes (example dacarbazine, DTIC). Platinum derivatives (cisplatin, carboplatin, oxaliplatin) have an action that is analogous to that of alkylating agents (formation of crosslinks) and therefore are appended to this class, as well. 

The mechanism of action of this unrelated group of drag is not entirely clear. Examples of miscellaneous antineoplastics include cisplatin (Platinol) and hydroxyurea (Hydrea). 

While carboplatin has the same mechanism of action as cisplatin, it has a much less toxic side-effect profile than cisplatin. The pharmacokinetics of carboplatin are best described by a two-compartment model, with an a half-life of 90 minutes and a terminal half-life of 180 minutes. Carboplatin is eliminated almost entirely by the kidney by glomerular filtration and tubular secretion. Many chemotherapy regimens dose carboplatin based on an area under the curve (AUC), which is referred to... 

Eastman, A. The Mechanism of Action of Cisplatin From Adducts to Apoptosis. In Cisplatin Chemistry and Biochemistry of a Leading Anticancer Drug Lippert, B., Ed. Wiley-VCH Weinheim, 1999, pp, 111-134. 

Several biological assays pointed to an unusual mechanism of action for 7, which is clearly different from cisplatin, as expected from its remarkable cytotoxic activity. For example, different levels of p53 and caspase activity were observed. Unusual... 

Modes of Action of Anti-tumor Drug Cisplatin... 

Although the specific mechanisms of action of cisplatin and its derivatives against different tumors are beginning to unfold [48— 52], it is, for example, still under dispute in which form the drug reaches the cellular DNA and binds to its targets, i.e. as Pt[NH3]2[H20][Cl]+ or as Pt[NH3]2[H20] + [53-55],... 

There are a few reports on possible sites of action of 5-HT3 antagonists. Low doses of zacopride administered directly into the fourth ventricle (i.c.v.) antagonized cisplatin (i.v.[-induced emesis in the cat [108]. A similar antagonism was demonstrated when routes of drug administration were interchanged. Similarly, GR 38032F, GR 65630 and MDL 72222, administered i.c.v. onto the area postrema at very low doses, antagonized cisplatin-induced... 

Fig. 1. Some of the factors involved in the mechanism of action and resistance of cisplatin.

---