Intracerebroventricular administration of drugs.

Intracerebroventricular drug administration is a method that bypasses the blood-brain barrier and other mechanisms that limit drug distribution into the brain, allowing high drug concentrations to enter the central compartment. Instillation of drugs directly into the ventricles of the brain must be done carefully and with full consideration of factors affecting the efficacy and safety of this route of administration. These factors include the osmolarity, pH, volume, and presence of preservatives and diluents of the drug solution being administered. Very few studies have formally investigated intraventricular therapies, and dosing recommendations may vary widely depending on the agent and the patient. Many antimicrobials have been given intraventricularly, although very few prospective studies have evaluated this strategy. There are wide variations among the reports regarding dosage regimens and the pharmacokinetics of the antimicrobials used. Guidance on appropriate formulations and their use is lacking. Clinicians should be aware of their patients' ongoing disease processes and neurologic status, as well as pertinent physiochemical properties of drugs when formulating them for intracerebroventricular administration; a high index of suspicion should be maintained when monitoring patients for adverse drug events after instillation.

Terlipressin: vasopressin analog and novel drug for septic shock.

OBJECTIVE: To review and assess available literature on chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical studies, adverse events, drug interactions, and dosing and administration of terlipressin in septic shock. DATA SOURCES: A literature search of MEDLINE (1966-September 2006), International Pharmaceutical Abstracts (1970-September 2006), and Cochrane database (third quarter 2006) was conducted, using key terms of terlipressin, lypressin, triglycyl-lysine vasopressin, hemodynamic support, septic shock, vasopressor, and V1 receptor agonist. Bibliographies of relevant articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Available English-language literature, including abstracts, animal studies, preclinical studies, clinical trials, and review articles, were examined. DATA SYNTHESIS: Because of potentially favorable pharmacokinetics versus vasopressin and limited availability of vasopressin in some countries, the effects of terlipressin, a vasopressin analog, have been studied recently for the treatment of septic shock. When administered as a 1-2 mg intravenous dose in patients with septic shock, terlipressin increases mean arterial pressure, urine output, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work index while decreasing heart rate, cardiac output, lactate, and oxygen delivery and consumption index. It is unclear whether lower doses of terlipressin would produce a similar vasopressor response with fewer cardiopulmonary effects and whether the effects of the drug on oxygen transport indices are detrimental. CONCLUSIONS: Terlipressin is a promising investigational medication for treatment of septic shock. Small trials have shown terlipressin to have favorable effects on hemodynamics in patients with septic shock refractory to conventional vasopressor treatment. It should be used with extreme caution in patients with underlying cardiac or pulmonary dysfunction. Further studies are needed to verify safety, efficacy, and dosing of terlipressin in patients with septic shock, and its use cannot be recommended in lieu of vasopressin at this time.