Pharmacology: Gastric Acid Secretion and Relief

Antacids and Laxatives

• Antacids do not affect the rate of gastric acid secretion.
• Therapeutic indications of antacids include symptomatic relief of upset stomach associated with hyperacidity and hyperacidic conditions like peptic ulcer and gastritis.
• Antacids are combined with other medications to increase their effectiveness, such as macrogol, which increases the volume of stool, and lactulose, which makes stool softer.

Laxatives

• Therapeutic indications of laxatives include short-term relief of constipation, prevention of straining in conditions like CHF, post-MI, postpartum, and post-op, and preparation for diagnostic examinations.
• Types of laxatives include:
  • Bulk-forming laxatives, such as methylcellulose, ispaghula, and sterculia, which absorb water to increase faecal mass and stimulate intestinal motility.
  • Stimulant laxatives, such as glycerol, bisacodyl, senna, and docusate sodium, which increase intestinal motility by stimulating colonic nerves.
  • Stool softeners, such as dioctyl sodium and docusate calcium, which decrease stool surface tension leading to increased water penetration.
  • Enemas or suppositories, such as phosphate-based enema, tap-water enema, and glycerin suppository, which distend the rectum to initiate the defaecation reflex and soften stool.

Side Effects of Laxatives

• Common side effects of laxatives include diarrhea, abdominal cramping, nausea, and fluid and electrolyte imbalance.

Pharmacology

• The neuroendocrine system, controlled by the pituitary and hypothalamus, coordinates body functions by transmitting messages between individual cells and tissues.
• The endocrine system releases hormones into the bloodstream, which have a longer response time than nerve impulses and require seconds to days to cause a response that may last for weeks or months.
• The hormones secreted by the hypothalamus and the pituitary are all peptides that act by binding to specific receptor sites on their target tissues.

Hypothalamic and Pituitary Hormones

• The hypothalamus synthesizes precursor proteins of vasopressin and oxytocin, which are stored in the posterior pituitary.
• Pituitary hormone preparations are used therapeutically for specific hormonal deficiencies, but most have limited therapeutic applications.
• Hormones of the anterior and posterior pituitary are administered either intramuscularly, subcutaneously, or intranasally, but not orally, because of their peptidyl nature.

Adrenocorticotropic Hormone (ACTH)

• Corticotropin-releasing hormone (CRH) is responsible for the release of ACTH.
• ACTH is released from the pituitary in pulses with an overriding diurnal rhythm, with the highest concentration occurring at approximately 6 AM and the lowest in the late evening.
• Stress stimulates ACTH secretion, whereas cortisol acting via negative feedback suppresses its release.
• The target organ of ACTH is the adrenal cortex, which leads to the synthesis and release of the adrenocorticosteroids and the adrenal androgens.
• Therapeutic uses of ACTH include diagnostic use for differentiating between primary adrenal insufficiency and secondary adrenal insufficiency.
• Adverse effects of ACTH are similar to those of glucocorticoids, including osteoporosis, hypertension, peripheral edema, hypokalemia, emotional disturbances, and increased risk of infection.

Growth Hormone (Somatotropin)

• Growth hormone is a large polypeptide released by the anterior pituitary in response to growth hormone-releasing hormone produced by the hypothalamus.
• Secretion of GH is inhibited by somatostatin.
• GH is released in a pulsatile manner, with the highest levels occurring during sleep.
• With increasing age, GH secretion decreases, being accompanied by a decrease in lean muscle mass.
• Somatotropin influences a wide variety of biochemical processes, including stimulation of protein synthetic processes, cell proliferation, and bone growth, boosting cartilage synthesis, stimulating lipolysis, and antagonizing insulin to elevate blood sugar level.
• Somatostatin is a growth hormone-inhibiting hormone that inhibits the release of GH, insulin, glucagon, and gastrin.