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This patient demonstrates the dramatic diuresis that can be achieved in patients on chronic loop diuretic therapy after addition of a thiazide diuretic. The drop in systolic blood pressure and the weight loss are consistent with the rapid diuresis achieved in this patient, with hypovolemia follow-ing. This effect has now led to acute kidney injury in this patient with preexisting advanced kidney disease. This case demonstrates the need for very close monitoring of patients after addition of thiazide diuretics to chronic loop diuretic therapy (particularly if they have pre-existing chronic kid-ney disease). This is often best achieved in the inpatient setting.
Histamine, Serotonin,
Bertram G. Katzung, MD, PhD
A healthy 45-year-old physician attending a reunion in a vacation hotel developed dizziness, redness of the skin over the head and chest, and tachycardia while eating. A short time later, another physician at the table developed similar signs and symptoms with marked orthostatic hypotension. The menu included a green salad, sautéed fish with rice, and apple pie. What is the probable diagnosis? How would you treat these patients?
It has long been known that many tissues contain substances that, when released by various stimuli, cause physiologic effects such as reddening of the skin, pain or itching, and bronchospasm. Later, it was discovered that many of these substances are also present in nervous tissue and have multiple functions. Histamine and serotonin (5-hydroxytryptamine, 5-HT) are biologically active amines that function as neurotransmitters and are also found in non-neural tissues, have complex physiologic and pathologic effects through multiple receptor subtypes, and are often released locally. Together with endogenous peptides (see Chapter 17), prostaglandins and leukotrienes (see Chapter 18), and cytokines (see Chapter 55), they constitute the autacoid group of drugs.
Because of their broad and largely undesirable peripheral effects, neither histamine nor serotonin has any clinical application in the treatment of disease. However, compounds that selectively activate certain receptor subtypes or selectively antagonize the actions of these amines are of considerable clinical value. This chapter therefore emphasizes the basic pharmacology of the agonist amines and the clinical pharmacology of the more selective agonist and antagonist drugs. Obesity, a poorly understood condition, appears to involve many receptors, including some histamine and serotonin receptors. It is discussed in a special section following the discussion of serotonin and its antagonists. The ergot alkaloids, compounds with partial agonist activity at serotonin and several other receptors, are discussed at the end of the chapter.