Module 31

Question 1

1. Pheochromocytomas are uncommon tumors, usually not malignant, that produce large amounts of both norepinephrine and epinephrine. Even though they are not usually malignant, they can be fatal because they can cause extreme hypertension. What symptoms would you expect these patients would have, and how would you treat the patient until surgical removal of the tumor.

Answer 1

• When you are frightened such as during a difficult exam, there is an increase in the release of epinephrine. This can lead to anxiety, a feeling of impending doom, cold clammy hands, tachycardia, and increased blood pressure.
  
  • Pheochromocytomas result in much more pronounced symptoms. They really do have a sense of impending doom. It is interesting that fright causes the release of epinephrine, and conversely, epinephrine causes fright. The cold clammy hands is interesting because most sweat glands are innervated by the cholinergic neurons, but in the hands and under the arms, there are sweat glands that are innervated by adrenergic neurons.
  • The increased release of norepinephrine and epinephrine leads to an increase in blood pressure, although it can be episodic. Thcate catecholamines also lead to gluconeogenesis, and many patients with pheochromocytomas develop diabetes.
  • It is important to block alpha-adrenergic receptors and bring the blood pressure down before surgery, because the surgery usually leads to a marked increase in release of catecholamines, which can be fatal. Beta-blockers should not be used until alpha-receptors have been completely blocked because blocking ß-receptors alone can lead to a further increase in blood pressure; beta-receptors cause vasodilation.

Question 2

What are the mechanism and manifestations of anaphylaxis? What are the treatments for anaphylaxis, and how do the agents work?

Answer 2

• True anaphylaxis is mediated by factors released by degranulation of mast cells and basophils when stimulated by IgE antibodies.
  
  • These factors include histamine and leukotrienes.
    ○ They cause vasodilatation, leakage of fluid from the vasculature, and bronchoconstriction.
    ○ The vasodilation and fluid leakage leads to a decrease in blood pressure, i.e. shock. The leakage of fluid leads to edema, which in the upper airways causes obstruction of the airways. The bronchoconstriction causes lower airway obstruction. These effects can obviously lead to death
  • Epinephrine decreases these effects, i.e. decreases the drop in blood pressure, decreases edema, and decreases bronchoconstriction. It is the therapy of choice, although its duration of action is short, and patients should be watched for an extended period of time because anaphylaxis can recur.
  • Antihistamines are often used but have limited effects, both because they only block the effects of histamine, which is not the major factor leading to shock, and they only prevent binding of histamine to its receptors, they do not displace histamine that is already bound.
  • Corticosteroids are also often used, but their effects are very slow in onset, i.e. ~24 hours, and therefore are not useful for acute treatment of a life-threatening reaction.

Question 3

What is ritodrine used for? What is its mechanism of action? Which other adrenoreceptor agonists can, in principle, be used for this purpose as well? What serious side-effects are associated with its use, and what are the risk factors for these side-effects?

Answer 3

• Ritodrine is a ß2-adrenergic agonist marketed to stop premature labor, but other ß-agonists also work.
  
  • Ritodrine can cause serious pulmonary edema; however, the mechanism is not clear, and it is also not clear why pregnant women are at increased risk other than the fact that they are usually treated with IV fluids to decrease the risk of hypotension in case of acute blood loss.

Question 4

What effects do adrenergic agents have on immune response?

Answer 4

In general the effects are mostly immunosuppressive. The point of the question is that different systems, which we study separately, significantly influence one another. In this case there is an interaction between the nervous system and the immune system. I would not ask this on an exam, but it is something that I think you should to be aware of.