CBSE FINAL EXAM 2023/2024 GRADED A LATEST
VERSION
A 66-year-old woman comes to the physician because of severe lower back pain. She is otherwise
healthy with well-controlled hypertension and hyperlipidemia. She does not drink, but has smoked one
pack of cigarettes per day for the past 20 yea...
CBSE FINAL E XAM 2023/2024 GRADED A LATEST VERSION A 66 -year -old woman comes to the physician because of severe lower back pain. She is otherwise healthy with well -controlled hypertension and hyperlipidemia. She does not drink, but has smoked one pack of cigarettes per day for the past 20 years. An x -ray of the lumbar spine shows an anterior wedge compression fracture of L1. Results of dual -energy X -ray absorptiometry (DEXA) scan shows substantially decreased bone density in the region of L3 to S1. Laboratory studies show serum calcium of 9.2 mg/dL, serum phosphorus of 3.7 mg/dL, and serum parathyroid hormone of 42 pg/mL (normal range: 10 -60 pg/mL). Which of the following drugs is most likely to exacerbate this patient's condition? Cortisone The co rrect answer is C. Our patient presents with a vertebral fracture and decreased bone density, pointing towards osteoporosis as the underlying disease process (see figure). She has classic risk factors including post -menopausal age and a history of smoking. Glucocorticoids should be avoided in these patients, because they accelerate bone resorption while inhibiting formation; thus, their use is associated with early rapid bone loss. With chronic use, suppression of bone formation becomes the predominant skel etal effect. The decrease in bone formation is mediated by direct inhibition of osteoblast proliferation and differentiation. Glucocorticoids also decrease intestinal calcium absorption, in part by opposing the effects of vitamin D as well as decreasing th e expression of calcium channels in the duodenum. The glucocorticoids also increase renal calcium excretion by decreasing calcium reabsorption. Hydrochlorothiazide (choice D) is a thiazide diuretic used for the treatment of various edematous states and h ypertension. Although most diuretics (e.g., furosemide and torsemide) decrease calcium levels, hydrochlorothiazide increases blood calcium levels. The thiazides inhibit the Na+ -Cl- symport in the distal convoluted tubule, which reduces intracellular Na+ co ncentration and thereby enhances the voltage gradient driving passive Ca2+ influx across the apical membrane. This results in increased Ca2+ reabsorption and potentially hypercalcemia, which should not worsen this patient's condition. Risedronate (choice E) is a bisphosphonate used for both treatment and prevention of postmenopausal osteoporosis. It acts by inhibiting osteoclast activity, reducing bone resorption and turnover. Histone methylation mostly makes dna mute: (histone methylation usually cause s reversible transcriptional suppression) Heterochromatin is sterically inaccessible and is thus transcriptionally inactive Euchromatin is expressed DNA methylation changes the expression of a DNA segment without changing the sequence. It is involved in aging, carcinogenesis, Histone acetylation: removal of histones positive charge, resulting in relaxed DNA coiling and thus increased transcription Histone deacteylation: removal of acetyl groups, resulting in DNA coiling and decreased transcription Amino acids necessary for purine synthesis: Glycine Aspartate Glutamine Deamination reactions: Cytosine ——— > uracil Adenine ——— > hypoxanthine Guanine ——— —> xanthine 5 methylcytosine —— > thymine Leflunomide inhibits dihydrootate dehydrogenase 5-flourouracil and is prodrug CAPECITABINE forms 5 -F-dUMP which inhibits thymidylate synthase Prodrug: a biologically inactive compound which can be metabolized in the body to produce a drug. 6-mercaptopurine and it's prodrug azathioprine inhibits de novo purine synthesis Mycophenolate and ribavirin: inhibits ionosine monophosphate dehydrogenase Methotrexate and trimethoprim inhibits dihydrofolate reductase CPS1 acts in the urea cycle and works in the mitochondria CPS2 acts in the cytosol HGPRT is the "salvage enzyme" for the purines: it channels hypoxanthine and guanine back into DNA synthesis. Failure of this enzyme has two results: Cell breakdown products cannot be reused, and are therefore degraded. This gives rise to increased uric acid, a purine breakdown product . The HGPRT deficiency causes a build -up of uric acid in all body fluids. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production. This results in both high levels of uric acid in the blood and urine, associated with severe gout and kidney problems.
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