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Atazanavir inhibits the polymorphic UGT1A1 enzyme, which mediates the conjugation of glucuronic acid with bilirubin. Decreased UGT1A1 activity results in the accu-mulation of unconjugated (indirect) bilirubin in blood and tissues. When levels are high enough, yellow discoloration of the eyes and skin, ie, jaundice, is the result. The plasma levels of indirect bilirubin concentrations are expected to increase to greater than 2.5 times the upper limit of nor-mal (grade 3 or higher elevations) in approximately 40% of patients taking once-daily atazanavir boosted with ritonavir and at least 5 times the upper limit of normal (grade 4 eleva-tion) in approximately 4.8% of patients. Carriers of the UGT1A1 decreased function alleles (*28/*28 or *28/*37) have reduced enzyme activity and have an increased risk of atazanavir discontinuation. Genotyping showed that the patient was homozygous for the UGT1A1*28 allele polymor-phism. This probably led to the high levels of bilirubin and the subsequent discontinuation of atazanavir secondary to the adverse drug reaction of jaundice.
Introduction to Autonomic Pharmacology
Bertram G. Katzung, MD, PhD
A 56-year-old woman is brought to the university eye center with a complaint of “loss of vision.” Because of visual impair-ment, she has lost her driver’s license and has fallen several times in her home. Examination reveals that her eyelids close involuntarily with a frequency and duration sufficient to pre-vent her from seeing her surroundings for more than brief moments at a time. When she holds her eyelids open with her fingers, she can see normally. She has no other muscle dysfunction. A diagnosis of blepharospasm is made. Using a fine needle, several injections of botulinum toxin type A are made in the orbicularis oculi muscle of each eyelid. After observation in the waiting area, she is sent home. Two days later, she reports by telephone that her vision has improved dramatically. How did botulinum toxin improve her vision? How long can her vision be expected to remain normal after this single treatment?