GI tract

Theory and Equipment. Many diseases of the human body can be identified by visual appearance. Tumors in the upper gastrointestinal (GI) tract, for example, possess a characteristic salmon pink color (3). The presence of such a color can be an indication of disease. Endoscopy is the medical imaging tool used to detect such colors in the inside of hoUow internal organs such as the rectum, urethra, urinary bladder, stomach, colon, etc. An endoscope is the instmment used to perform endoscopy. Endoscopic imaging involves the production of a tme color picture of the inside of the human body using lenses and either hoUow pipes, a fiber optic bundle, or a smaU CCD camera. AU three use a large field-of-view, sometimes referred to as a fish eye, lens to aUow a 180° field of view. 

SRIF acts as an excitatory neuromodulator in the CNS inhibiting the release of TRH, corticotropin-releasing hormone (CRH), growth hormone releasing factor (GHRH), and NE. It produces general arousal and hypotension. It inhibits the release of a number of peptides and modulators in the GI tract. 

The best dmg candidates for incorporation into prolonged action systems are uniformly absorbed throughout the gastrointestinal (GI) tract, have medium (2—8 h) biological half-Hves, and are prescribed for chronic maintenance use. Dmgs in large doses are difficult to formulate into such products... 

UTI, GUT, skin infections, upper and lower RTI, and GI tract infection... 

Extravasation of barium sulfate iato the peritoneal cavity through a perforated GI tract can produce serious adverse reactions. When a perforation is suspected, the use of a water-soluble iodinated contrast medium is iadicated. In this case, oral or rectal administration of sodium or meglumine-sodium salts of diatrizoic acid (6) and oral use ofiohexol (11) are the preferred procedures. 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

Mexifitene is well absorbed from the GI tract and less than 10% undergoes first-pass hepatic metabolism. In plasma, 60—70% of the dmg is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.5—2.0 lg/mL. The plasma half-life of mexifitene is 10—12 h in patients having normal renal and hepatic function. Toxic effects are noted at plasma concentrations of 1.5—3.0 lg/mL, although side effects have been noted at therapeutic concentrations. The metabolite, /V-methy1mexi1itene, has some antiarrhythmic activity. About 85% of the dmg is metabolized to inactive metabolites. The kidneys excrete about 10% of the dmg unchanged, the rest as metabolites. Excretion can also occur in the bile and in breast milk (1,2). 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

Encainide is almost completely absorbed from the GI tract. Eood may delay absorption without altering its bioavailabiUty. The dmg is rapidly metabolized in 90% of the patients to two principal metaboUtes, 0-demethylencainide (ODE) and 3-methoxy-O-demethylencainide (MODE), while the other 10% metabolize encainide slowly with Htde or no ODE or MODE formed. Encainide, ODE, and MODE are extensively protein bound 75—80% for encainide and ODE and 92% for MODE. Peak plasma concentrations are achieved in 30—90 min. Therapeutic plasma concentrations are very low the concentrations of ODE and MODE are approximately five times those of encainide. The findings with the metaboUtes are significant because ODE is 2—10 times and MODE, 1—4 times more effective than encainide as antiarrhythmics. The half-Hves for encainide in fast and slow metabolizers is 1—2 h and 6—12 h, respectively. The elimination half-life for ODE is 3—4 h and for MODE 6—12 h in fast metabolizers. Excretion occurs through the Hver and kidneys (1,2). 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

Acebutolol is well absorbed from the GI tract. It undergoes extensive hepatic first-pass metabohsm. BioavailabiUty of the parent compound is about 40%. The principal metaboflte, A/-acetylacebutolol, has antiarrhythmic activity and appears to be more cardioselective. Binding to plasma proteins is only 26%. Peak plasma concentrations of acebutolol are achieved in 2.5 h, 3.5 h for A/-acetylacebutolol. The elimination half-Hves of acebutolol and its metabohte are 3—4 and 8—13 h, respectively. The compounds are excreted by the kidneys (30—40%) and by the Hver into the bile (50—60%). About 40% of the amount excreted in the urine is unchanged acebutolol, the rest as metabofltes (32). 

Because digitoxin is a nonpolar, lipophilic glycoside, absorption from the GI tract is complete. About 90% of the dmg in plasma is tightly bound to protein. It is metabolized in the Hver to many metaboHtes, including digoxin which is the only pharmacologically active metaboHte. The dmg is excreted via the bile into feces. The elimination half-life of digitoxin is seven to nine days (87). 

Because bretylium is poody absorbed from the GI tract (- 10%), it is adrninistered iv or im. Very litde dmg is protein bound in plasma. Bretylium is taken up by an active transport mechanism into and concentrated in postganglionic nerve terminals of adrenergicahy innervated organs. Peak plasma concentrations after im injections occur in about 30 min. Therapeutic plasma concentrations are 0.5—1.0 p.g/mL. Bretylium is not metabolized and >90% of the dose is excreted by the kidneys as unchanged dmg. The plasma half-life is 4—17 h (1,2). 

Erythrityl is readily absorbed from the GI tract. It undergoes extensive first-pass metaboHsm ia the Hver by glutathione organic nitrate reductase. Time to onset of effect is 5—10 min by subHngual adrninistration and 20—30 min when swallowed. The duration of effects for the two routes ate up to 3 and 6 h, respectively. Adverse effects are similar to those described for nitroglycerin (99). 

After po doses, atenolol is rapidly but incompletely absorbed ( 50%) from the GI tract, and 50% is excreted unchanged in the feces. Six to 16% of the plasma concentration is bound to protein. Atenolol undergoes Httie first-pass metaboHsm. Peak plasma concentrations occur in 2—4 h after po doses. The elimination half-hfe of atenolol is 6—7 h. Excretion of absorbed dmg is mainly by the kidneys and elimination can be impaired in patients having renal failure. The adverse effects of atenolol are similar to those seen for propranolol therapy (98,99,108). 

Betaxolol hydrochloride is a lipophilic, cardioselective -adrenoceptor blocker having no ISA and Httie membrane-stabilizing activity. The dmg is as equieffective and equipotent as atenolol. It is well absorbed from the GI tract, but does not undergo extensive first-pass metaboHsm in the Hver. Its elimination half-Hfe is 15—20 h. It is metabolized in the Hver ( 84%) to two principal inactive metaboHtes and one minor active metaboHte. About 16% of the dmg is excreted unchanged urine. Excretion of the dmg is unchanged in patients having renal or Hver impairment (43). 

Bevantolol hydrochloride is a moderately lipophilic, long-acting, cardioselective -adrenoceptor blocker. It has no ISA but has membrane-stabilizing activity. The dmg is in use in Europe for the treatment of hypertension and angina. It is rapidly absorbed from the GI tract. Peak plasma levels occur in 1—2 h. It is metabolized extensively in the Hver to a metaboHte that has some ISA. It is excreted by the Hver and the kidneys and excretion is delayed in patients having kidney failure. 

Because colestipol and cholestyramine are not absorbed, but simply pass through the body by the GI tract, few severe side effects occur. Patients often complain of distaste and constipation, however. More severe side effects such as GI bleeding ate relatively uncommon (151). 

Oral. The oral route for dmg dehvery includes the gastrointestinal (GI) tract and the oral cavity including the buccal mucosa. The buccal mucosa is considered separately because of differences in the approach to dmg dehvery via this route. 

Dmgs, such as opiates, may undergo metabolism both in the intestinal wall and in the fiver (first-pass metabolism). The metabolism may be extensive and considerably reduce the amount of dmg reaching the systemic circulation. Alternatively, the metabolite may be metabofically active and contribute significantly to the action of the parent dmg. Some compounds undergo enterohepatic circulation in which they are secreted into the GI tract in the bile and are subsequently reabsorbed. Enterohepatic circulation prolongs the half-life of a dmg. 

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