Chapter 7: Adrenergic, Dopaminergic, and Serotonergic Pharmacology
Despite its ability to stimulate receptors in the sympathetic nervous system, norepinephrine has relatively little capacity to increase bronchial airflow because the receptors in bronchial smooth muscle are largely of the
Answer is a. An important factor in the response of any cell or organ to sympathomimetic amines is the density and proportion of α- and β adrenergic receptors (see Table 5-1). For example, NE has relatively little capacity to increase bronchial airflow, since the receptors in bronchial smooth muscle are largely of the β2 subtype.
A 38-year-old man is taking tranylcypromine, an MAO inhibitor, for depression. After a celebratory dinner, he develops a severe headache and chest pain. At hospital his blood pressure is 190/135 mm Hg. His hypertensive crisis is likely due to the ingestion of
Answer is c. MAO is an enzyme involved in the inactivation of catcholamines (see Figure 7-1). Patients who have received MAO inhibitors may experience severe hypertensive crises if they ingest cheese, beer, or red wine. These and related foods, which are produced by fermentation, contain a large quantity of tyramine, and to a lesser degree, other phenylethylamines. When GI and hepatic MAOs are inhibited, the large quantity of tyramine that is ingested is absorbed rapidly and reaches the systemic circulation in high concentration. A massive and precipitous release of NE can result with consequent hypertension that can be severe enough to cause myocardial infarction or a stroke (see Figures 7-1 and 7-2).
Figure 7-1. Steps in the metabolic disposition of catecholamines. Norepinephrine and epinephrine are first oxidatively deaminated to a short-lived intermediate (DOPGAL) by monoamine oxidase (MAO). DOPGAL then undergoes further metabolism to more stable alcohol or acid deaminated metabolites. Aldehyde dehydrogenase (AD) metabolizes DOPGAL to 3,4-dihydroxymandelic acid (DOMA) while aldehyde reductase (AR) metabolizes DOPGAL to 3,4-dihydroxyphenyl glycol (DOPEG). Under normal circumstances DOMA is a minor metabolite with DOPEG being the major metabolite produced from norepinephrine and epinephrine. Once DOPEG leaves the major sites of its formation (sympathetic nerves; adrenal medulla), it is converted to 3-methoxy, 4-hydroxyphenylglycol (MOPEG) by catechol-0-methyl transferase (COMT). MOPEG is then converted to the unstable aldehyde ...