Chapter 15 Marini Pharmacotherapy

337

CHAPTER 15 • Pharmacotherapy

SQ injection a challenge. Therefore, close moni- toring of medications being given via SQ admin- istration is recommended or its use should be avoided. Intra-arterial Injections Intra-arterial injections are used to provide localized effects of a drug to a particular organ. Advantages of this type of administration include providing the highest concentrations of drug locally with maximum effect, minimizing systemic toxicity, and avoiding first-pass metabolism of the liver and the lung. The main disadvantage is that this type of administration requires great care and skill and therefore must be done by experts. There are several examples of intra-arterial drug administration. Cerebral vasospasm is commonly seen following aneurysmal subarachnoid hemorrhage but may also follow other intracranial hemorrhages (e.g., intraventricular or arteriovenous malformation hemorrhages). Intra-arterial injection of several drugs (e.g., nimodipine, papaverine, nicardipine, milri- none, verapamil) may be helpful in treating cerebral vasospasm by dilating the spastic artery. Although this type of therapy has been shown to help improve vasospasm, it is relatively short-lived and will require repeated therapy when vasospasm returns. Other examples of successful intra-arterial administration include chemotherapeutic agents for retinoblastoma, hepatocellular carcinoma, and CNS tumors, as well as thrombolytic therapy in peripheral artery disease, ischemic stroke, and very rarely, in massive pulmonary embolism occurring in high-risk patients. Intrathecal Therapy Intrathecal drug delivery involves direct injection of the drug into the cerebral spinal fluid (CSF) within the intrathecal space of the spinal column. This allows for circumvention of the blood–brain barrier and therefore allows delivery of smaller drug doses with reduced systemic side effects. Intrathecal drug delivery is used in chronic spasticity from conditions such as multiple sclero- sis and cerebral palsy (e.g., intrathecal baclofen), management of cancer, chronic nonmalignant or neuropathic pain (e.g., intrathecal morphine), che- motherapy treatment for lymphomatous meningitis

(e.g., methotrexate, cytarabine), and antibiotic treat- ment adjuvant to systemic antibiotic therapy in bac- terial meningitis/ventriculitis and other infections of the central nervous system (e.g., gentamicin, vancomycin). Intrathecal formulations are sterile isotonic drug solutions. The volume of intrathecal injections ranges from 0.5 to 5 mL. Achieving drug solubil- ity in such a small volume can be a challenge for lipophilic agents. It is imperative that intrathecal formulations are free from microorganisms because CSF protein and glucose can be an ideal environ- ment for bacterial growth; therefore, these formu- lations must be prepared using aseptic techniques. Also, intrathecal formulations must be preservative- free, because studies have shown that preservatives such as parabens and benzyl alcohol can cause inflammation of the arachnoid membrane and risk nerve damage. Intraperitoneal Therapy Themembranes of theperitoneal cavity canexchange drugs and metabolites as during peritoneal dialysis in end-stage renal disease patients. Transport of drugs across the peritoneum is affected by dosing variables (e.g., dose, volume, temperature, duration, composition of carrier solution), drug properties (e.g., molecular weight, ionic charge, lipid/water solubility), and characteristics of the peritoneum (e.g., surface area, charge, permeability). Intraperitoneal (IP) antibiotics are commonly used to treat episodes of bacterial peritonitis in peri- toneal dialysis patients. Using the IP route avoids the systemic IV route and targets the involved tissue directly. Commonly, cefazolin or vancomycin is used for empiric gram-positive bacterial coverage, and ceftazidime or gentamicin is used for gram-negative bacterial coverage. There are many published antibi- otic treatment regimens for treatment of peritoneal dialysis–associated peritonitis, and the International Society for Peritoneal Dialysis (ISPD) periodically updates the guideline as new information becomes available. Note that chemical peritonitis has been reported with high doses of vancomycin, and only short courses of aminoglycosides are recommended to avoid loss of residual renal function. Some agents intended for transfer into the general bloodstream can be given via the IP route. These include insulin, heparin, erythropoietin, nutrition, and gene therapy.