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PubMed2004

Severe hyperphosphatemia and hypocalcemia following the rectal administration of a phosphate-containing Fleet pediatric enema.

BACKGROUND: Toxicity secondary to rectally administered hypertonic phosphate solution in patients with normal renal function is rarely reported in the literature. We report a case of electrolyte disturbance and seizure secondary to the rectal administration of 2 Fleet pediatric enemas. CASE REPORT: A 4-year-old white female with spinal muscular atrophy and chronic constipation was brought to the emergency department with complaints of lethargy and difficulty breathing following the administration of 2 Fleet pediatric enemas. In the emergency department, physical examination was significant for a depressed level of consciousness and shallow respirations. A basic metabolic profile was significant for a calcium of 3.3 mg/dL, phosphate of 23 mg/dL, and sodium of 153 mEq/L. Arterial blood gases revealed a pH of 7.24, Pco2 of 38 mm Hg, Po2 of 220 mm Hg. Electrocardiogram revealed a prolonged QT interval of 340 milliseconds with a corrected QT interval of 498 milliseconds. Sixteen hours postexposure, she experienced a generalized seizure unresponsive to multiple doses of lorazepam and responsive only to 100 mg of intravenous calcium chloride. Two days after presentation, the patient experienced complete resolution of symptoms. CONCLUSION: Osmotically acting hypertonic phosphate enemas can result in severe toxicity if retained. This is true even in patients without predisposing risk factors.

Acidosis↗
PubMed2003

Newer formulations of the triptans: advances in migraine management.

Migraine is a common, frequently incapacitating, headache disorder that imposes a substantial burden on both the individual patient and society. The last two decades have witnessed an explosion in our understanding of the pathophysiology of migraine, and in our development of an efficacious and diverse therapeutic armamentarium. There are several routes of drug administration available to patients with migraine. All the serotonin 5-HT(1B/1D) receptor agonists (triptans) are available as oral tablets (sumatriptan, rizatriptan, zolmitriptan, naratriptan, almotriptan, frovatriptan and eletriptan). Only sumatriptan is available as a subcutaneous injection. Some triptans are also available via newer routes of administration, including orally disintegrating tablets (rizatriptan and zolmitriptan), rectal suppositories (sumatriptan) and intranasal sprays (sumatriptan and zolmitriptan). Oral disintegrating tablets and other non-oral triptan routes (subcutaneous, intranasal, rectal) are a useful alternative to conventional oral tablets for patients who have difficulty swallowing pills or prefer not to do so, and for patients whose nausea and/or vomiting precludes swallowing tablets and/or makes the likelihood of complete absorption unpredictable. This is important because epidemiological studies in migraine reveal that the vast majority of patients (>90%) have experienced nausea during a migraine attack and more than 50% have nausea with the majority of attacks. Similarly, most (almost 70%) have vomited at some time during an attack and of these patients, almost one-third vomit in the majority of attacks. The newer formulations, rapidly dissolving tablets and intranasal sprays, afford patients the opportunity to use abortive therapy without the need for liquids, at anytime and anywhere, at the onset of a migraine attack. Furthermore, the intranasal sprays are absorbed rapidly and have a prompt onset of action allowing for significant pain free rates versus placebo as early as 15 minutes post administration. The ability to administer treatment early in a migraine attack and have a rapid onset of action is particularly important in acute migraine treatment in order to prevent the development of central sensitisation. While many patients and physicians choose conventional oral tablets because of familiarity and ease of administration, the newer formulations, oral disintegrating tablets and intranasal sprays, should be given consideration as first-line agents in selected patients.

Analgesics↗
PubMed1990

Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. I. Effects of ionic strength, adjuvant composition, and lipid structure on the nasal absorption of [D-Arg2]kyotorphin.

Bile salts and synthetic surfactants have been used to promote nasal absorption of peptide drugs. Although a marked increase in nasal absorption has been achieved, this may not be adequate and the possibility of adjuvant-induced membrane toxicity exists. The present study employs a rat in situ nasal perfusion technique and mixed micelles between sodium glycocholate (NaGC) and various lipids as potential nasal absorption enhancers of a stable model dipeptide, [D-Arg2]kyotorphin. NaGC alone enhanced the nasal absorption of the dipeptide in a concentration-dependent manner. When linoleic acid was added to form mixed micelles with NaGC, the absorption was further enhanced (P less than 0.01). The effect of mixed micelles was synergistic and much greater than with single adjuvants. Increasing ionic strength was found to increase the adjuvant activity of both NaGC and NaGC-lipid mixed micelles. Structure of the lipid component of the mixed micelles also affected the adjuvant potency. Oleic acid, a cis-unsaturated fatty acid, was more effective than elaidic acid, the trans-isomer, whereas cis-linoleic acid and trans-linolelaidic acid were equally effective (alpha = 0.05). Mixed micelles of mono-glycerides such as monoolein and monolinolein were also more effective than NaGC alone (alpha = 0.05). Micellar solubilization of these polar lipids by NaGC appears to be important for nasal absorption enhancement to occur. Reversal of the membrane permeability was also observed within approximately 20-40 min after removal of the adjuvants from the rat nasal cavity. These observations are similar to the effects of mixed micelles on the rectal mucosa and may involve the same mechanism.

Adjuvants, Pharmaceutic↗
PubMed1975

Superior mesenteric blood flow in man studied with a dye-dilution technique.

The superior mesenteric blood flow in the post-absorptive state was studied with a dye-dilution technique using indocyanine green in 37 patients with apparently normal small bowel function. All the patients except 2 had been, or were to be, treated because of malignant disease, mostly rectal carcinoma. The investigations were performed in connection with portography. The dye was injected into the superior mesenteric artery as a single injection during continuous sampling of blood from the superior mesenteric vein, catheterized through the reopened umbilical vein. The blood flow was calculated from the dye-dilution curves obtained with a modified Stewart-Hamilton formula. As recirculating dye appeared in the later part of the dye-dilution curves, the appearance of the recirculating dye was timed in 4 patients. The hepatic extraction of the amount of dye usually injected, 1.25 mg, was 60%. The superior mesenteric blood flow averaged 706 ml/min (397 ml/min/m-2 body surface) or 12% of the cardiac output. The appearance time, mean transit time, vascular resistance and vascular volume were also determined.

Adolescent↗
PubMed1997

[Photochemotherapy with indocyanine green in cutaneous metastases of rectal carcinoma].

HISTORY AND ADMISSION FINDINGS: Six weeks before admission of a 47-year-old man with known rectal carcinoma, small nodular metastases had occurred over the front of both his thighs. Examination showed many aggregatet cuti-color or livid nodes, diameter 0.5 cm. The patient's poor general condition excluded the usual palliative measures. TREATMENT AND COURSE: Photochemotherapy of the skin metastases with indocyanine green (ICG; absorption maximum 805 nm), a non-toxic dye approved for diagnostic purposes, was undertaken on a trial basis. The dye, being bound to plasma proteins, is retained in the intravacular space. Immediately after administration of the dye (2.5 mg/kg intravenously) the skin metastases were irradiated by diode laser (lambda = 805 nm, 100 J/cm2, 3 W/cm2, radiation diameter 2 cm). This necrosed the metastases and clinically as well as histologically resulted in their complete disappearance with scarring of the treated area. CONCLUSION: This case illustrates the effectiveness of photochemotherapy with ICG against solid skin tumours of increased microvascular density.

Humans↗
PubMed1992

The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit.

The transport barrier of the epithelial presents one of the major problems limiting the effective use of these tissues as alternate delivery routes for macromolecules such as peptides and proteins. In the present study, two membrane transport properties, namely, the permeability and permselectivity of the shunt pathway, were investigated and compared in various tissues including the nasal, tracheal, bronchial, buccal, rectal, vaginal, corneal, epidermal, duodenal, jejunal, ileal, and colonic epithelia. Membrane permeability was evaluated using a combined method based on electrical conductance and flux measurements of a hydrophilic fluorescent probe, 6-carboxy fluorescein (CF). Membrane permselectivity or the charge discriminating ability of the membrane was evaluated by KCl diffusion potential measurements. The results indicate that all epithelia under investigation possess a relatively high degree of permeation barrier and are highly selective for the absorption of positively charged solutes. Shunt path permeability was found to vary greatly among tissues from different epithelia, whereas membrane charge selectivity was relatively constant in these tissues. A good correlation was observed between membrane electrical conductance and steady-state flux of CF, indicating a paracellular transport of the compound. The rank order of the intrinsic membrane permeability was as follows: intestinal approximately nasal greater than or equal to bronchial greater than or equal to tracheal greater than vaginal greater than or equal to rectal greater than corneal greater than buccal greater than skin. Membrane permselectivity, expressed as the ratio of transport number (positive over negative), ranges from 1.78 for the buccal to 1.33 for the rectal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of enteral formula infusion rate, osmolality, and chemical composition upon clinical tolerance and carbohydrate absorption in normal subjects.

It is a common clinical practice to initiate enteral hyperalimentation using low flow rates or diluted formula. These adjustments are made in an effort to minimize patient intolerance. Using complex and elemental enteral formulas, we investigated whether various flow rates or osmolalities effected clinical intolerance or carbohydrate malabsorption in 20 healthy volunteers. Our infusion rates ranged between 50 and 150 kcal/hr and the osmolalities ranged between 325 and 690 mOsm/Kg of water. Even at the maximal flow rate and osmolality, our results show that both types of enteral formulas were well tolerated as assessed by the frequency of abdominal pain, bloating, passage of rectal gas and stooling. No carbohydrate malabsorption was detected as measured by breath hydrogen. In well nourished subjects, our findings do not support the common clinical practice of initiating alimentation with low flow rates or diluted formula.

Adult↗
PubMed1998

Constipation in advanced cancer patients.

Constipation is a frequent, distressing, and underestimated complication in patients with advanced cancer. It may develop from general disturbances that may or may not be cancer related, but the use of opioids is one of the main causes in this population. Opioids affect the intestine by reducing motility and secretions and by increasing fluid absorption and blood flow. Untreated constipation may lead to several complications. Effective management of constipation starts with a careful assessment of the patient, including the history of the frequency and difficulty of defaecation, symptoms caused by constipation, and physical and rectal examinations. When the diagnosis of constipation is unclear, an abdominal X-ray may be required. The treatment of constipation includes general interventions, such as the availability of comfort and privacy or the elimination of medical factors that may contribute to constipation, and therapeutic interventions including oral or rectal laxatives and the use of prokinetic drugs and naloxone. The purpose of this paper is to review the pathophysiology and causes of constipation and the effects of opioids on the gastrointestinal tract, and to propose an approach for its assessment and management. Randomized clinical trials between different laxatives and/or prokinetic agents in cancer patients are needed, and future studies should focus on the validation of different clinical assessment tools for constipation.

Constipation↗
PubMed1990

Effect of swimming to exhaustion, at low temperatures, on serum Zn, Cu, Mg and Ca in rats.

In order to study the response of plasma trace minerals during exercise in cold water at varying temperatures, three groups of ten male Wistar rats each were forced to swim until exhaustion in water at different constant temperatures (10, 20 and 32 degrees C), while another 3 groups were kept at rest in water at the same temperatures and another group at rest out of the water, at room temperature (21 degrees C). Rectal temperature (RT) was measured before and after the exercise. Samples of arterial blood were obtained under anaesthesia (pentobarbital) from the abdominal aorta after the exercise, and serum concentrations of Cu, Zn, Mg and Ca were determined by flame atomic absorption spectrophotometry (FAAS). The swimming time (ST) decreased in cold water, the values obtained at 10 and 20 degrees C being 3.3% and 8.5%, respectively, of those observed at 32 degrees C. The RT of the animals swimming at 32 degrees C was 32.5 +/- 1.8 degrees C (mean +/- SD) and fell to 25.0 +/- 2.0 and to 19.1 +/- 1.5 degrees C in those swimming, respectively, at 20 and 10 degrees C. The concentrations of Mg, Cu and Ca were significantly higher (+50%, +36% and +7%, respectively) in animals subjected to exercise with respect to the control groups in water, although there were no differences among the three groups. On the contrary, Zn rose progressively with the increase of WT (+32% at 10 degrees C, +60% at 20 degrees C and +76% at 32 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Biological actions of synthetic locust ion transport peptide (ITP).

Locust Ion Transport Peptide (ITP) a member of the arthropod neuropeptide family which includes hyperglycemic, vitellogenesis-inhibiting, and moult-inhibiting hormones (CHH, VIH, MIH, respectively) was synthesized as proposed by Meredith et al. (1996) with terminal amidation of amino acid residue 72 and with 3 disulphide bridges. This is the first member of this family to be synthesized. Biological activities of synthetic ITP (synITP) were very similar to those previously reported for ITP purified from Schistocerca corpora cardiaca (ScgITP) and partially sequenced by Audsley et al. (1992a, b). Dose-response curves for both synITP and ScgITP on ileal transport of Cl- (measured as increased short-circuit current, delta Isc), were similar with a EC50 of 1-2 nM. The Isc time course and maximum delta Isc across ileal epithelia at different dosages of synITP and ScgITP had similar patterns as did changes in transepithelial open-circuit potential (Vt) and resistance (Rt), reflecting changes in salt transport which drives fluid absorption. Disulphide bridges were shown to be required for biological activity of synITP, which caused the same 4-fold increase in ileal fluid transport rate (Jv) as previously reported for ScgITP. Both synITP and ScgITP caused only partial stimulation of rectal Isc and had no significant effect on rectal Jv. These results indicate that the structure of ITP predicted earlier from cDNA is correct.

Animals↗
PubMed1986

Pharmacokinetics of isoxicam following intravenous, intramuscular, oral and rectal administration in healthy volunteers.

1 The pharmacokinetic characteristics and bioavailability of isoxicam were investigated in healthy male volunteers following various routes of administration. Plasma concentrations were determined up to 96 or 120 h following each administration using a selective h.p.l.c. method. 2 Twelve subjects received an i.v. and an i.m. injection of 150 mg and an oral dose of 200 mg (two capsules) in a three-way crossover design. 3 The plasma concentration-time curves after intravenous administration followed two compartmental characteristics with a rapid initial distribution phase and a predominant terminal elimination phase. The area under the distribution phase contributed only 0.4% to the total AUC. Mean disposition parameters were: t1/2, lambda 1 = 3.3 min t1/2, lambda z = 28 h, Vc = 5.61, Vdarea = 12.71, CL = 5.1 ml min-1. 4 Following other routes of administration, the isoxicam plasma profile could be adequately described by a one compartment model. 5 After the i.m. dose, isoxicam was rapidly and completely absorbed: within 15 min 40% of the peak concentrations were attained. Maximum plasma concentrations of 11.7 micrograms ml-1 were reached after an average of 3 h. 6 After oral administration isoxicam was completely bioavailable. Mean peak concentrations of 12.3 micrograms ml-1 were obtained within 10 h. 7 The bioavailability of suppositories containing 200 mg of active substance was investigated in another 10 volunteers relative to capsules (2 X 100 mg). The formulations tested were bioequivalent with respect to the amount absorbed. 8 Comparison of AUCs (normalized for dose and body weight) resulting from all treatments, did not show significant differences among the various formulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2001

Pharmacokinetics and rectal bioavailability of hydrocortisone acetate after single and multiple administration in healthy subjects and patients.

The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after intravenous administration of hydrocortisone. Only a very small part of the rectal dose (100 mg) was absorbed; the mean absolute bioavailability was 3.1% in healthy volunteers and 4.5% in patients. There was substantial intersubject variability. Although maximum hydrocortisone levels after single or multiple doses were significantly higher (about 70%) in the patient group, the systemic bioavailability is very low so that the risk of systemic side effects after rectal administration of hydrocortisone acetate foam has to be considered very low.

Administration, Rectal↗
PubMed2006

Comparison of three anesthetic protocols for intraduodenal drug administration using endoscopy in rhesus monkeys (Macaca mulatta).

The purpose of this study was to evaluate 3 anesthetic protocols for intraduodenal drug administration by endoscopy in rhesus monkeys (Macaca mulatta). Anesthesia was induced using intramuscular ketamine and midazolam, isoflurane (inhalant gas), or intravenous propofol in male and female rhesus monkeys. A noninvasive dosing line was placed in the duodenum by use of endoscopy, and 50% dextrose (3 ml/kg) was administered. Blood pressure, heart rate, body temperature, and reflexes (corneal, palpebral, pharyngeal) and myorelaxation (mandibular reflex and reaction to limb manipulation) were evaluated every 5 min. To estimate intestinal absorption, glycemia was evaluated prior to dextrose administration and at 2, 5, 10, 15, 20, 30, 45, and 60 min after dosing. All 3 protocols resulted in successful induction of anesthesia. Recovery from isoflurane and propofol was significantly faster than from ketamine-midazolam. Duration of the recovery period after isoflurane was less variable than with propofol, but isoflurane produced greater hypothermia. Isoflurane and propofol resulted in predictable glucose absorption after intraduodenal dextrose administration, whereas ketamine-midazolam led to an inconsistent increase in glycemia.

Administration, Rectal↗
PubMed2003

Clinical use of the hyperthermia treatment planning system HyperPlan to predict effectiveness and toxicity.

PURPOSE: The main aim is to prove the clinical practicability of the hyperthermia treatment planning system HyperPlan on a beta-test level. Data and observations obtained from clinical hyperthermia are compared with the numeric methods FE (finite element) and FDTD (finite difference time domain), respectively. METHODS AND MATERIALS: The planning system HyperPlan is built on top of the modular, object-oriented platform for visualization and model generation AMIRA. This system already contains powerful algorithms for image processing, geometric modeling, and three-dimensional graphics display. A number of hyperthermia-specific modules are provided, enabling the creation of three-dimensional tetrahedral patient models suitable for treatment planning. Two numeric methods, FE and FDTD, are implemented in HyperPlan for solving Maxwell's equations. Both methods base their calculations on segmented (contour based) CT or MR image data. A tetrahedral grid is generated from the segmented tissue boundaries, consisting of approximately 80,000 tetrahedrons per patient. The FE method necessitates, primarily, this tetrahedral grid for the calculation of the E-field. The FDTD method, on the other hand, calculates the E-field on a cubical grid, but also requires a tetrahedral grid for correction at electrical interfaces. In both methods, temperature distributions are calculated on the tetrahedral grid by solving the bioheat transfer equation with the FE method. Segmentation, grid generation, E-field, and temperature calculation can be carried out in clinical practice at an acceptable time expenditure of about 1-2 days. RESULTS: All 30 patients we analyzed with cervical, rectal, and prostate carcinoma exhibit a good correlation between the model calculations and the attained clinical data regarding acute toxicity (hot spots), prediction of easy-to-heat or difficult-to-heat patients, and the dependency on various other individual parameters. We could show sufficient agreement between the calculations and measurements for power density (specific absorption rate) within the range of assessed precision. Tumor temperatures can only be estimated, because of the rather variable perfusion conditions. The results of the FE and FDTD methods are comparable, although slight differences exist resulting from the differences in the underlying models. There are also statistically provable differences among the tumor entities regarding the attained specific absorption rate, temperatures, and volume loads in normal tissue. However, gross fluctuations exist from patient to patient. CONCLUSION: The hyperthermia planning system HyperPlan could be validated for a number of the 30 patients. Further improvements in the implemented models, FE and FDTD, are required. Even at its present state of development, hyperthermia planning for regional hyperthermia delivers valuable information, not only for clinical practice, but also for further technologic improvements.

Algorithms↗
PubMed2004

Decreased expression of apical Na+ channels and basolateral Na+, K+-ATPase in ulcerative colitis.

Impaired absorption of sodium (Na+) and water is a major factor in the pathogenesis of diarrhoea in ulcerative colitis (UC). Electrogenic Na+ absorption, present mainly in human distal colon and rectum, is defective in UC, but the molecular basis for this is unclear. The effect of UC on the expression of apical Na+ channels (ENaC) and basolateral Na+, K+-ATPase, the critical determinants of electrogenic Na+ transport, was therefore investigated in this study. Sigmoid colonic and/or proximal rectal mucosal biopsies were obtained from patients with mild to moderate UC, and patients with functional abdominal pain (controls). ENaC subunit expression was studied by immunohistochemistry, western blot analysis, and in situ hybridization, and Na+, K+-ATPase isoform expression was studied by immunohistochemistry, western blotting, and northern blot analysis. UC was associated with substantial decreases in the expression of the ENaC beta- and gamma-subunit proteins and mRNAs, whereas the decrease in ENaC alpha-subunit protein detected by immunolocalization was less marked. The levels of expression of Na+, K+-ATPase alpha1- and beta1-isoform proteins were also lower in UC patients than in controls, although there were no differences in Na+, K+-ATPase alpha1- and beta1-isoform mRNA levels between the two groups. Taken together, these results show that UC results mainly in decreased expression of the apical ENaC beta- and gamma-subunits, as well as the basolateral Na+, K+-ATPase alpha1- and beta1-isoforms. In conclusion, these changes provide a basis for the low/negligible levels of electrogenic Na+ absorption seen in the distal colon and rectum of UC patients, which contribute to the pathogenesis of diarrhoea in this disease.

Colitis, Ulcerative↗
PubMed1992

Enhancement of bioavailability of dopamine via nasal route in beagle dogs.

Dopamine (DA), which is ineffective by oral administration due to first pass metabolism and is usually injected, was administered to dogs via rectal, dermal, buccal and nasal routes. The nasal route had the highest bioavailability and best avoided first pass metabolism. The effects of the addition of hydroxypropyl cellulose (HPC), sodium deoxycholate, POE (6) hydrogenated caster oil (HCO-60) and Azone on the nasal absorption increased bioavailability from 11.7% (control) to about 20%, 35%, 25% and 68%, respectively. Further, with a combination of 2% HPC and 5% Azone, bioavailability was increased to almost the same level as with i.v. administration. At the same time, plasma concentrations were maintained at a high level for more than 7 h. The increase in bioavailability is presumed to be caused by an enhancement in absorption and prolongation of the time DA is retained in the nasal cavity due to Azone and HPC, respectively.

Administration, Intranasal↗