Histamines and Antihistamines

Question 1

Where is histamine stored?

Answer 1

Intracellularly in granules complexed with anions

Question 2

Where do you have more turnover of histamine?

Answer 2

Enterchromaffin-like cells and neurons (than in mast cells and basophils)

Question 3

What are the roles for endogenous histamine? (5)

Answer 3

(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**

Question 4

What results in allergies?

Answer 4

Excess release from mast cells and basophils

Question 5

T/F Anaphylaxis is an autocoid.

Answer 5

FALSE; histamine is released everywhere in your body in that situation

Question 6

What are the 2 types of histamine?

Answer 6

(1) That involved in routine physiological homeostasis
- gastric acid secretion
- neurotransmission
(2) That involved in immediate inflammatory and allergic responses
- mast cells and basophils

Question 7

What is crucial in determining the responses of inflammatory and allergic actions of histamine?

Answer 7

Location of mast cells and basophils; they tend to be distributed in areas prone to physical and chemical injury

Question 8

In almost all cases, how is histamine released? What are the mast cells and basophils triggered by?

Answer 8

By a stimulus-secretion coupling process involving calcium and exocytosis; IgE antigen binding, complement cascade, physical injury, chemical injury

Question 9

What is another way histamine can be released? (2)

Answer 9

Can be provoked by a high concentration of basic (positively charged) drugs after rapid IV administration

• Vancomycin
• Morphine
• Tubocurarine

Question 10

T/F Most actions of histamine release relate to smooth muscle and vascular permeability.

Answer 10

TRUE

Question 11

What are the major actions of histamine? (2)

Answer 11

(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

Question 12

What are 4 other actions of histamine?

Answer 12

(1) Increase secretion of gastric acid (H2)
(2) Cramps (H1)
(3) Bronchoconstriction (H1)
(4) Itching and burning sensation (H1 in skin)

Question 13

What antagonists are generally referred to as “antihistamines”?

Answer 13

H1 receptor antagonists

Question 14

What are the H1 first generation antagonists?

Answer 14

(1) Diphenhydramine

(2) Chorpheniramine

Question 15

What do H1 first generation antagonists do?

Answer 15

• Treatment of hay fever, urticaria, vasomotor rhinitis, not generally useful in asthma
• Also act on muscarinic receptors, serotonin antagonists, and local anesthetics

Question 16

What “other” therapeutic uses for H1 first generation antagonists have developed?

Answer 16

Sedation, motion sickness (nausea and vomiting)

Question 17

What are the toxicities of H1 1st generation antagonists?

Answer 17

(1) Sedation- hyperexcitability in children and elderly
(2) Typical antimuscarinic actions (dry mouth, cycloplegia, urinary retention)
(3) Orthostatic hypotension
(4) Local anesthesia

Question 18

What are the 2nd generation H1 antagonists?

Answer 18

(1) Fexofenidine
(2) Loratidine
(3) Cetrizine

Question 19

Why were the 2nd generation H1 antagonists made? How was this possible?

Answer 19

To lessen the sedatino caused by older antihistamines

• more hydrophilic (do not cross blood-brain barrier)
• more specific

Question 20

What are the H2 antagonists?

Answer 20

(1) Cimetidine
(2) Ranitidine
(3) Famotidine

Question 21

Where do you see H2 antagonists?

Answer 21

• Covered in large measure in GI drugs (peptic ulcer disease, GERD, gastritis)

Question 22

Which has more inhibition of acid secretion: H2 receptor antagonists or pump inhibitors?

Answer 22

Pump inhibitors

Question 23

What are the toxicities of H2 antagonists?

Answer 23

Cimetidine

• inhibits P450 synthesis;
• can cause slurred speech, delerium, confusion, esp. in elderly patients
• antiandrogenic effects (RARELY)

Question 24

What is Anaphylactic Shock?

Answer 24

• 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)

Question 25

What is the treatment of choice for anaphylactic shock?

Answer 25

Epinephrine

Question 26

What does epinephrine do?

Answer 26

physiological antagonism of the major, life-threatening aspects of anaphylaxis

Question 27

Why don’t antihistamine work in the treatment of anaphylaxis?

Answer 27

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)