Cocaethylene Synthesis and Pathophysiology: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:Face_pic.gif|450 px|right|Billy Mays' autopsy reports detected the presence of cocaine metabolites and ethanol.]] | |||
===='''Case Study'''==== | ===='''Case Study'''==== | ||
A 24-year-old Caucasian male patient presents with a stabbing pain behind the eyes, sharp and piercing chest pain, inability to stand or elevate the arms, and loss of vision in the right eye. Patient has a history of hypertension and doctors have noted the presence of Marfan’s traits. Marfan’s syndrome is a disease caused by a mutated fibrillin protein which is involved in the integrity of the extracellular matrix for formation of elastic fibers which are abundant in the blood vessel walls and various other tissues in the body. Patient also has a history of drug and alcohol abuse since the third grade. Abuse of cocaine began in high school and the patient reports to co-administration of alcohol and cocaine on at least fifteen separate occasions with ten of those incidents occurring in the last two years. | A 24-year-old Caucasian male patient presents with a stabbing pain behind the eyes, sharp and piercing chest pain, inability to stand or elevate the arms, and loss of vision in the right eye. Patient has a history of hypertension and doctors have noted the presence of Marfan’s traits. Marfan’s syndrome is a disease caused by a mutated fibrillin protein which is involved in the integrity of the extracellular matrix for formation of elastic fibers which are abundant in the blood vessel walls and various other tissues in the body. Patient also has a history of drug and alcohol abuse since the third grade. Abuse of cocaine began in high school and the patient reports to co-administration of alcohol and cocaine on at least fifteen separate occasions with ten of those incidents occurring in the last two years. | ||
<br /><br /> | |||
===='''Background'''==== | ===='''Background'''==== | ||
Cocaine is a prevalent drug in America with over 15% of the general population (above age 12) admitting usage at least once in their lifetime. Approximately 30% of all drug-related emergency department visits in 2006 were related to cocaine and it has been reported that anywhere from 30-60% of people who abuse cocaine also consume alcohol concomitantly. In fact, a 1989 study put forth by the Drug Abuse Warning Network (DAWN) showed that 75% of all cocaine related deaths in America occurred in patients that were also under the influence of additional drugs, the majority of which were ethanol. | Cocaine is a prevalent drug in America with over 15% of the general population (above age 12) admitting usage at least once in their lifetime. Approximately 30% of all drug-related emergency department visits in 2006 were related to cocaine and it has been reported that anywhere from 30-60% of people who abuse cocaine also consume alcohol concomitantly. In fact, a 1989 study put forth by the Drug Abuse Warning Network (DAWN) showed that 75% of all cocaine related deaths in America occurred in patients that were also under the influence of additional drugs, the majority of which were ethanol. | ||
The significant occurrence of fatalities in patients that ingest alcohol and cocaine concurrently is supported by a growing body of evidence that shows increases in sudden death by as much as 25-fold as well as experiments on lab animals that show a lower lethal dosage to kill 50% of subjects (LD50) when this combination is administered.<br /><br /> | The significant occurrence of fatalities in patients that ingest alcohol and cocaine concurrently is supported by a growing body of evidence that shows increases in sudden death by as much as 25-fold as well as experiments on lab animals that show a lower lethal dosage to kill 50% of subjects (LD50) when this combination is administered. | ||
<br /><br /> | |||
===='''Pathophysiology of Alcohol'''==== | ===='''Pathophysiology of Alcohol'''==== | ||
Alcohol alone promotes a drop in blood pressure by at least two mechanisms: | Alcohol alone promotes a drop in blood pressure by at least two mechanisms: | ||
| Line 36: | Line 38: | ||
<br /> | <br /> | ||
===='''Human Carboxylesterase 1'''==== | ===='''Human Carboxylesterase 1'''==== | ||
{{STRUCTURE_1mx5 | PDB=1mx5 | SCENE= }} | |||
hCE1 is a promiscuous drug metabolizing enzyme which is encoded by the CES1 gene and is expressed in the liver, small intestine, kidney, lung, testes, heart, monocytes, macrophages, and blood. hCE1 promiscuity allows for processing of such compounds as lovastatin, lidocaine, heroin, a number of military grade chemical gases, and cocaine. In the human body, hCE1 converts cocaine into benzyolecgonine and methanol by hydrolyzing the methyl ester linkage. In the presence of alcohol, however, hCE1 catalyzes a transesterification of the methyl and ethyl ester linkages to form cocaethylene. | |||
In 2003, a crystal structure of hCE1 was developed using X-ray diffraction techniques to obtain a resolution of 2.80 Angrstoms. The structure was shown in complex with homatropine, a cocaine analogue, and it comprised of two trimers for a total of six identical subunits. Each subunit is 548 amino acids long and each is equipped with two catalytic binding sites to process cocaine. Each trimer subunit associates with a chloride ion, and the overall protein is aptly named a glycoprotein due to ligand interactions forming with n-acetyl-d-glucosamine, 2-(acetylamino)-2-deoxy-a-d-glucopyranose, and o-sialic acid | |||