Search Results

Cytochrome P450 families of enzymes. These pie graphs provide a conceptualization of the relative importance of the microsomal enzymes. The graph on the top reflects the relative quantities of enzymes that have been isolated, while the graph on the bottom reflects their relative importance for drug interactions. For example, while small in overall quantity, CYP2D6 enzymes have major significance for drug interactions.

Acetaminophen toxicity. The major portion of acetaminophen is metabolized to nontoxic metabolites excreted in urine. Only 5–15% is oxidized by cytochrome P450 (CYP 450) enzymes to a potentially toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). The normally small amounts of this metabolite are readily converted to harmless mercapturic acid conjugates by glutathione. When high doses of acetaminophen are consumed, glutathione can be depleted, allowing NAPQI to accumulate and produce hepatic necrosis. Also, normal biotransformation is diminished with compromised liver function, including that associated with malnutrition and alcohol abuse. Toxicity can be further accentuated by ethanol consumption, which induces CYP 450 activity, leading to greater portions of acetaminophen converted to NAPQI. Emergency management of acetaminophen overdose consists of administering high doses of acetylcysteine, which replenishes glutathione.

Epinephrine‐beta blocker interaction. In this illustration the following cardiovascular changes follow the administration of epinephrine in a dosage of 10 µg/min. (A) First, it is essential to understand the precise cardiovascular influences of epinephrine in a normal (control) patient. The cardiotonic effects of epinephrine are most familiar. It activates beta‐1 receptors on the sinoatrial node to increase heart rate (HR) and also activates beta‐1 receptors on myocardial cells increasing their force of contraction. This provides an increase in systolic blood pressure (SBP). In addition to its cardiotonic effects, epinephrine has the ability to activate both alpha and beta‐2 receptors on blood vessels producing constriction or dilation, respectively. Epinephrine is commonly viewed only as a vasoconstrictor by many clinicians because this is the effect it produces when injected subcutaneously or submucosally. This is because the tiny vessels found in these locations contain only alpha receptors and are constricted by epinephrine. In contrast, larger systemic arteries that determine vascular resistance and diastolic blood pressure contain both alpha and beta‐2 receptors, with the latter most prevalent. Following absorption, low doses of epinephrine found in local anesthetic formulations (eg, 20–100 µg) preferentially activate beta‐2 receptors which dilate the arteries, and diastolic blood pressure (DBP) actually declines. (B) In the presence of a nonselective beta blocker (eg, propranolol) the cardiovascular influences of epinephrine are strikingly different. This is primarily due to the blockade of beta‐2 receptors on systemic arteries. Epinephrine will now activate the remaining alpha receptors leading to vasoconstriction and an increase in diastolic blood pressure. To meet this increase in resistance, intrinsic mechanisms within myocardial cells respond with greater force and elevate systolic blood pressure as well. Together this will increase mean arterial pressure (MAP). The sudden elevation in MAP is sensed by baroreceptors within the carotid sinuses triggering a reflex slowing in heart rate, which is further accentuated by the fact that the beta‐1 receptors in the sinoatrial node are blocked.