Histamines and Antihistamines Flashcards
Where is histamine stored?
Intracellularly in granules complexed with anions
Where do you have more turnover of histamine?
Enterchromaffin-like cells and neurons (than in mast cells and basophils)
What are the roles for endogenous histamine? (5)
(1) Mediator of immediate inflammatory and allergic response
(2) Stimulation of gastric acid secretion (enterchrommafin-type cells)
(3) Neurotransmitter
(4) Modulator of local vascular perfusion
(5) Chemotaxis (white blood cells)- causes the responses**
What results in allergies?
Excess release from mast cells and basophils
T/F Anaphylaxis is an autocoid.
FALSE; histamine is released everywhere in your body in that situation
What are the 2 types of histamine?
(1) That involved in routine physiological homeostasis
- gastric acid secretion
- neurotransmission
(2) That involved in immediate inflammatory and allergic responses
- mast cells and basophils
What is crucial in determining the responses of inflammatory and allergic actions of histamine?
Location of mast cells and basophils; they tend to be distributed in areas prone to physical and chemical injury
In almost all cases, how is histamine released? What are the mast cells and basophils triggered by?
By a stimulus-secretion coupling process involving calcium and exocytosis; IgE antigen binding, complement cascade, physical injury, chemical injury
What is another way histamine can be released? (2)
Can be provoked by a high concentration of basic (positively charged) drugs after rapid IV administration
- Vancomycin
- Morphine
- Tubocurarine
T/F Most actions of histamine release relate to smooth muscle and vascular permeability.
TRUE
What are the major actions of histamine? (2)
(1) Systolic and Diastolic hypotension- H1 (major) and H2 (minor) mediated; arteriolar and precapillary sphincter smooth muscle relaxation
(2) Edema- H1 mediated increase in postcapillary permeability
What are 4 other actions of histamine?
(1) Increase secretion of gastric acid (H2)
(2) Cramps (H1)
(3) Bronchoconstriction (H1)
(4) Itching and burning sensation (H1 in skin)
What antagonists are generally referred to as “antihistamines”?
H1 receptor antagonists
What are the H1 first generation antagonists?
(1) Diphenhydramine
(2) Chorpheniramine
What do H1 first generation antagonists do?
- Treatment of hay fever, urticaria, vasomotor rhinitis, not generally useful in asthma
- Also act on muscarinic receptors, serotonin antagonists, and local anesthetics
What “other” therapeutic uses for H1 first generation antagonists have developed?
Sedation, motion sickness (nausea and vomiting)
What are the toxicities of H1 1st generation antagonists?
(1) Sedation- hyperexcitability in children and elderly
(2) Typical antimuscarinic actions (dry mouth, cycloplegia, urinary retention)
(3) Orthostatic hypotension
(4) Local anesthesia
What are the 2nd generation H1 antagonists?
(1) Fexofenidine
(2) Loratidine
(3) Cetrizine
Why were the 2nd generation H1 antagonists made? How was this possible?
To lessen the sedatino caused by older antihistamines
- more hydrophilic (do not cross blood-brain barrier)
- more specific
What are the H2 antagonists?
(1) Cimetidine
(2) Ranitidine
(3) Famotidine
Where do you see H2 antagonists?
- Covered in large measure in GI drugs (peptic ulcer disease, GERD, gastritis)
Which has more inhibition of acid secretion: H2 receptor antagonists or pump inhibitors?
Pump inhibitors
What are the toxicities of H2 antagonists?
Cimetidine
- inhibits P450 synthesis;
- can cause slurred speech, delerium, confusion, esp. in elderly patients
- antiandrogenic effects (RARELY)
What is Anaphylactic Shock?
- Acute systemic and severe Type 1 Hypersensitivity allergic reaction
- An allergic response triggers a quick release of large quantities of immunological mediators (histamines, prostaglandins, leukotrienes)from mast cells
- Histamine induces vasodilation of arterioles and constriction of bronchioles in the lungs, also referred to as bronchospasm
- Systemic vasodilation causes a sudden drop in blood pressure and edema of bronchial mucosa (difficulty breathing)
What is the treatment of choice for anaphylactic shock?
Epinephrine
What does epinephrine do?
physiological antagonism of the major, life-threatening aspects of anaphylaxis
Why don’t antihistamine work in the treatment of anaphylaxis?
because they still would not antagonize the actions of other inflammatory autocoids released along with histamine (will not deal with the inflammation in the local area)
