What are the effects of histamine release?
Produces a variety of physiologic and pathologic responses in different tissues. Acts as a mediator for inflammation for inflammation in allergic disease. Cause an increased capillary permeability, hypotension, tachycardia, flushing, and HA.
What are the different histamine receptors?
H1, H2, H3.
What effect does histamine have on the CV system?
Causes dilation of arterioles and capillaries leading to flushing, ↓ in PVR, ↓ in systemic BP, ↑capillary permeability. Positive chronotropic effects and cardiac dysrhythmias.
What effect does histamine have on airways?
Histamine activates H1 receptors to constrict bronchial smooth muscle.
What patients are more likely to develop increase in airway resistance in response to histamine?
Patients with obstructive airway disease, such as asthma and bronchitis.
What effect does histamine have on the GI system?
Histamine stimulates the release of copious secretions of gastric fluid containing high concentrations of hydrogen ions. Vagal activity results in higher rate of hydrogen ion secretion.
What are the clinical uses of histamine?
Assesses the ability of gastric parietal cells to secret hydrogen ions and to determine parietal cell mass. Diagnosis of certain neurological conditions, pernicious anemia, atrophic gastritis, gastric carcinoma, Zollinger-Ellison syndrome.
What are some clinical uses of H1 antagonists?
Prevent and relieve the symptoms of allergic rhinoconjunctivitis. Dependent on agent and dose may provide protection against bronchospasm induced by stimuli such as exercise, cold air. Refractory urticaria.
What are the major S.E. of first generation H1 antagonists?
CNS effects (somnolence, diminished alertness, slowed reaction time, and impairment of cognitive function). Anticholinergics effects (dry mouth, blurred vision, urinary retention, impotence). Tachycardia, prolongation of Q-T interval, heart block, dysrhythmias.
What are the symptoms of OD associated with H1 antagonists?
Coma, seizures, dyskinesias, hallucinations.
What are the major S.E. of 2nd generation H1 antagonists?
Unlikely to produce CNS effects unless recommended are exceeded. Prolongation of Q-T interval.
How do 1st generation and 2nd generation H1 antagonists differ?
1st generation tend to produce sedation and may block muscarinic cholinergic, 5-hydroxytrytptomine (serotonin), or alpha adrenergic receptors. At high doses act as competitive antagonists. 2nd generation are more selective therefor have less CNS effects. Act as non-competitive antagonists.
What agents are used as H2 antagonists?
Cimetidine, ranitidine, famotidine, nizatidine.
What are the clinical uses of H2 antagonists?
Duodenal ulcers associated with hypersecretion of gastric hydrogen ions. Preoperatively used to ↑ the pH of gastric fluid. ↓ risk of acid pneumonitis. Given to patients with history of allergic reactions prior to procedures (dyes).
What are the clinical uses of H2 antagonists combined with H1?
Prevent effects of histamine releasing drugs such as morphine, atracurium, mivacurium, or protamine.
What is the MOA of H2 antagonists?
Competitively and selectively inhibit the binding of histamine to the H2 receptors.
What are the most serious adverse reactions with H2 antagonists?
Severe S.E. with all 4 H2 agents are low but increases in the presence of multiple medical illnesses and advanced age. Reversible increases in hepatic transaminases, esp. with high doses.
What are the most common S.E. associated with H2 antagonists?
Diarrhea, HA, fatigue, muscle pain.
What are the rare S.E. associated with H2 antagonists?
Mental confusion, dizziness, somnolence, gynecomastia, thrombocytopenia, drug fever, arrhythmias.
What S.E. are associated with cimetidine and ranitidine?
What S.E. occur with rapid administration of H2 antagonists?
Bradycardia and hypotension.
What is the principal mechanism of drug interactions associated with cimetidine?
Impairment of hepatic microsomal (cytochrome P-450) enzymes.
What are the most common drug interactions associated with the use of cimetidine?
Inhibits metabolism of propranolol, and diazepam. Increases toxicity of lidocaine, modestly decreases defluronation of methoxyflurane, and inhibits oxidative metabolism of halothane.
What are the most common drug interactions associated with the use cimetidine and ranitidine?
Can impair renal tubular secretion of procainamide and theophylline.
Which agents can decrease the absorption of H2 antagonists?
Magnesium and aluminum containing antacids.
How do the H2 antagonists differ in potency and duration?
Potencies vary from 20-50 fold. Cimetidine is least potent, famotidine is most potent. DOA range from 6 hrs with cimetidine to 10 hrs with ranitidine, famotidine, nizatidine.
How are H2 antagonists eliminated?
Renal clearance is 2-3 times greater than glomerular filtration reflecting extensive renal tubular secretion.
What are proton pump inhibitors?
Drugs that provide prolonged inhibition of gastric acid secretion regardless of stimulus.
What are the clinical uses of these agents?
Inhibits daytime and nocturnal acid secretion and meal stimulated acid secretion to a greater degree than H2. Heal duodenal and possibly gastric ulcers faster than H2. Superior to H2 for tx of reflux esophagitis, best tx for Zolliner-Ellison syndrome.
What agents are proton pump inhibitors?
Esomeprazole, lansoprazole, omeprazole, pantoprazole.
What is cromolyn?
An antihistamine that has poor oral absorption therefore given via inhalation.
What is the use of cromolyn?
Prophylactic tx of asthma.
What is the MOA of cromolyn?
Inhibits antigen-induced release of histamine and other autocoids, including leukotrienes, from pulmonary mast cells, as well as from mast cells at other sites.