DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

adverse effects listed for tolvaptan are GI effects, hyperglycemia,
and pyrexia. Less common are cerebrovascular accident, deep vein
thrombosis, disseminated intravascular coagulation, intracardiac
thrombus, ventricular fibrillation, urethral hemorrhage, vaginal hemorrhage,
pulmonary embolism, respiratory failure, diabetic ketoacidosis,
ischemic colitis, increaese in prothrombin time and
rhabdomyolysis.
Conivaptan. Conivaptan is metabolized by CYP3A4 and as a result
is associated with a variety of drug-drug interactions. It should not
be administered in patients receiving ketoconazole, itraconazole,
ritonavir, indinavir, clarithromycin, or other strong CYP3A4
inhibitors. Conivaptan increases levels of simvastatin, digoxin,
amlodipine, and midazolam. It is not known to interact with warfarin
or prolong the QT c
interval. Due to multiple drug-drug interactions
conivaptan is no longer being developed for chronic long-term
oral use. The most common adverse effect of conivaptan is an infusion
site reaction. The manufacturer recommends that the drug only
be infused into large veins and that infusion sites be changed daily.
Other adverse effects have included headache, hypertnesion,
hypotension, hypokalemia, and pyrexia.
Future Directions in Vasopressin Analogs
Nonpeptide vasopressin receptor antagonists and agonists
are being developed for a wide range of clinical
indications, including for V 1a
-selective antagonists: dysmenorrhea,
preterm labor, and Raynaud’s syndrome; for
V 1b
-selective antagonists: stress-related disorders, anxiety,
depression, ACTH-secreting tumors, and Cushing’s
syndrome; for V 2
-selective and V 1a
/V 2
-selective antagonists:
heart failure, SIADH, cirrhosis, hyponatremia,
brain edema, nephrotic syndrome, diabetic nephropathy,
and glaucoma; and for V 2
-selective agonists: central DI,
nocturnal enuresis, nocturnal polyuria, and urinary
incontinence (Wong and Verbalis, 2001).
Preliminary data support several of the indications
mentioned earlier for vasopressin receptor antagonists
and agonists. Relcovaptan (SR 49059) is a
V 1a
-selective antagonist that has efficacy in primary
dysmenorrhea (Brouard et al., 2000), and nelivaptan
(SSR 149415) is a V 1b
-selective antagonist that demonstrates
anxiolytic activity in animal models of stress
(Griebel et al., 2002). Aquaretics are drugs that
increase free-water clearance with minimal effects on
electrolyte excretion. The V 2
-selective antagonist lixivaptan
(VPA-985) is an effective aquaretic in patients
with hyponatremia of various etiologies (Wong et al.,
2003). In contrast, the V 2
-selective agonist OPC-51803
has strong antidiuretic effects in animals and is being
developed for central DI, nocturnal enuresis, and urinary
incontinence (Nakamura et al., 2003). It is likely
that more nonpeptide vasopressin receptor antagonists
and agonists will become available clinically in the
near future.
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CHAPTER 25
REGULATION OF RENAL FUNCTION AND VASCULAR VOLUME