A 38-year-old woman presents to the office with complaints of weight
loss, fatigue, and insomnia of 3-month duration. She reports that she has
been feeling gradually more tired and staying up late at night because
she canât sleep. She does not feel that she is doing as well in her occupation
as a secretary and states that she has trouble remembering things.
She does not go outdoors as much as she used to and cannot recall the
last time she went out with friends or enjoyed a social gathering. She
feels tired most of the week and states she feels that she wants to go to
sleep and frequently does not want to get out of bed. She denies any
recent medication, illicit drug, or alcohol use. She feels intense guilt
regarding past failed relationships because she perceives them as faults.
She states she has never thought of suicide, but has begun to feel increasingly
worthless.
Her vital signs and general physical examination are normal, although
she becomes tearful while talking. Her mental status examination is significant
for depressed mood, psychomotor retardation, and difficulty attending
to questions. Laboratory studies reveal a normal metabolic panel, normal
complete blood count, and normal thyroid functions.
⤠What is the most likely diagnosis?
⤠What is your next step?
⤠What are important considerations and potential complications of
management?
Sample Solution
his drug accumulates in the highly acidic environment of the parietal-cell canalicular lumen and it is activated. The active form, tetracyclic cationic sulfonamide, reacts with thiol groups of cysteines 813 and 822 of transmembranal H+ / K+ ATPase[183, 186]. This conversion must take place beside the gastric parietal cells, so pantoprazole must be absorped intact by GIT [184]. The pantoprazole is an acid labile drug, which undergoes degradation in the stomach [191-194]. Therefore, the drug should be targeted to the intestine; to bypass the stomach. The gastro resistant drug delivery system is designed for the acid labile drugs due to the necessity to pass intact through the stomach for reaching the duodenum for absorption. The dosage form is prepared to bypass the stomach by formulating a solution for intravenous administration (lyophilized powder for reconstitution) or as gastricâresistant tablets (oral delayedârelease dosage form) [195]. In the case of oral administration, the enteric coating prevents the drug from degradation in the gastric juice (at pH 1â2, for a few minutes [195-197]. Therefore the enteric coating, on the acid labile drug, is essential, thus they are less affected by pH. Thus the concept of gastro resistant drugs was generated. The wavelength of maximum absorbance for pantoprazole sodium sesquihydrate (λmax) was found to be 283.5 nm in 0.1N Hcl (pH 1.2) and 288.5 nm in phosphate buffer (pH 6.8). Calibration curves for pantoprazole sodium sesquihydrate in each of 0.1N Hcl (pH 1.2) and phosphate buffer (pH 6.8) were assessed from absorbance values, at λmax of a series of pantoprazole sodium sesquihydrate solutions containing different concentration of pantoprazole as shown in figure (1) and figure (2). The proposed nanoprecipitation (solvent displacement or interfacial precipitation) [143-148] method enabled the formulation of polymeric nanoparticles by using organic phase with different concentrations of Eudragit S100 (ES100) and HPMC phthalate HP55 with using Tween 80 and Poloxamer 407 as surfactant with different concentrations and different ratio of organic phase: aqueous phase. Although, all formulae produce nanoparticles, formulation factors significantly affect the size of prepared polymeric nanoparticles. 3.1. Effect of polymer concentration and polymer type on particle size of plain PNPs : Particle size of Eudragit S100 and HPMC Phthalate HP55 nanoparticles was directly proportional to polymer concentration (Eudragit S100 and HPMC Phthalate HP55 concentration respectively) as the particles size increased with increasing polymer concentration [211, 212] and this may be due to increasing the concentration of dissolved polymer resulted in increasing organic phase viscosity and reducing the efficiency of stirring which caused formation of the bigger emulsion droplets [213] >
his drug accumulates in the highly acidic environment of the parietal-cell canalicular lumen and it is activated. The active form, tetracyclic cationic sulfonamide, reacts with thiol groups of cysteines 813 and 822 of transmembranal H+ / K+ ATPase[183, 186]. This conversion must take place beside the gastric parietal cells, so pantoprazole must be absorped intact by GIT [184]. The pantoprazole is an acid labile drug, which undergoes degradation in the stomach [191-194]. Therefore, the drug should be targeted to the intestine; to bypass the stomach. The gastro resistant drug delivery system is designed for the acid labile drugs due to the necessity to pass intact through the stomach for reaching the duodenum for absorption. The dosage form is prepared to bypass the stomach by formulating a solution for intravenous administration (lyophilized powder for reconstitution) or as gastricâresistant tablets (oral delayedârelease dosage form) [195]. In the case of oral administration, the enteric coating prevents the drug from degradation in the gastric juice (at pH 1â2, for a few minutes [195-197]. Therefore the enteric coating, on the acid labile drug, is essential, thus they are less affected by pH. Thus the concept of gastro resistant drugs was generated. The wavelength of maximum absorbance for pantoprazole sodium sesquihydrate (λmax) was found to be 283.5 nm in 0.1N Hcl (pH 1.2) and 288.5 nm in phosphate buffer (pH 6.8). Calibration curves for pantoprazole sodium sesquihydrate in each of 0.1N Hcl (pH 1.2) and phosphate buffer (pH 6.8) were assessed from absorbance values, at λmax of a series of pantoprazole sodium sesquihydrate solutions containing different concentration of pantoprazole as shown in figure (1) and figure (2). The proposed nanoprecipitation (solvent displacement or interfacial precipitation) [143-148] method enabled the formulation of polymeric nanoparticles by using organic phase with different concentrations of Eudragit S100 (ES100) and HPMC phthalate HP55 with using Tween 80 and Poloxamer 407 as surfactant with different concentrations and different ratio of organic phase: aqueous phase. Although, all formulae produce nanoparticles, formulation factors significantly affect the size of prepared polymeric nanoparticles. 3.1. Effect of polymer concentration and polymer type on particle size of plain PNPs : Particle size of Eudragit S100 and HPMC Phthalate HP55 nanoparticles was directly proportional to polymer concentration (Eudragit S100 and HPMC Phthalate HP55 concentration respectively) as the particles size increased with increasing polymer concentration [211, 212] and this may be due to increasing the concentration of dissolved polymer resulted in increasing organic phase viscosity and reducing the efficiency of stirring which caused formation of the bigger emulsion droplets [213] >
