A 26-year-old man named Johnathan Trott is brought by his friends to the emergency department of Brooklyn hospital because he has been exhibiting strange behavior for the past several days. Johnathan's friends are aware of the fact that he is a recreational user of methamphetamine. Normally, Johnathan is in a state of high after consuming methamphetamine, however, this time the outcome of drug abuse is very different. Johnathan has not eaten or slept in the last 48 hours. He threatened to shoot one of his friends because he believes this friend is plotting against him.
On admission to the hospital Johnathan is extremely agitated, appears to be underweight, and is unable to give a coherent history. He has to be restrained to prevent him from walking out of the emergency department and into traffic on the street. His blood pressure is 160/100 mm Hg, heart rate 100, temperature 39°C, and respirations 30/min. His arms show evidence of numerous intravenous injections. The remainder of his physical examination is unremarkable and his blood work does not show presence of HIV. After evaluation, Johnathan is given a sedative, fluids, a diuretic, and ammonium chloride parenterally.
1) It seems like Johnathan took a relatively high dose of methamphetamine this one time. Why do you think Johnathan felt the need to take a higher dose? Justify your answer by correlating it with receptor biology.
2) Given Johnathan's condition and the drug he is abusing; what are the major physiological conditions that the physician took into account before administering the therapy and why?
3) Why do you think the physician prescribed fluids, diuretics, and ammonium chloride?
4) Methamphetamine can bind the dopamine transporter (DAT), prevent neurotransmitter dopamine from binding DAT, and increase the amount of free dopamine levels in the synapse. Compare the structures of dopamine and methamphetamine and hypothesize the pharmacophore required for binding DAT. (Describe the groups that are required to bind DAT).