Histamine and Antihistamine

Question 1

Major Effects of Histamine

Answer 1

1. Mediates hypersensitivity “allergic” reactions, acute inflammatory responses, and asthma attacks
2. Stimulates gastric acid secretion
3. Inhibitory CNS neurotransmitter

Question 2

Histamine Receptor Subtypes

Answer 2

H1, H2, H3, H4

Question 3

H1

Answer 3

SM: GI, Vasc, uterus, bronchi, CNS

SM contraction (except vasc.)
↑ nausea, ↓ sleep

Question 4

H2

Answer 4

Parietal cells, heart, Mast Cells, CNS

Acid release in stomach
↑ heart rate, allergy

Question 5

H3

Answer 5

CNS

Inhibitory auto R

Question 6

H4

Answer 6

Mast cells, lymphocytes, CNS

Inflammation, pruritis

Question 7

Hypersensitivity/Inflammatory Response

Answer 7

1. ↑ heart rate and cardiac contractile force
2. ↑ blood flow
3. Bronchoconstriction (bronchospasm /coughing)
4. Stimulation of cutaneous nerve endings = itching / pain
5. Loss of fluid from cardiovascular system /associated tissue swelling - “runny nose”

Question 8

Cytolytic Histamine Release

Answer 8

1. Involves membrane rupture
2. Promoted by high concentrations of
   -phenothiazines
   -H1 receptor antagonists
   -opioid analgesics
   (not involving IS)

Question 9

Non-Cytolytic Histamine Release

Answer 9

1. ATP and calcium-dependent
2. Occurs through exocytosis of granules
3. Triggered by binding of IgE-allergin
   - complement factors C3a and C5a,
   - opioids
   - non-depolarizing muscle relaxants
4. Concentration-independent

(G-protein mechanism = vesicle fusion with membrane)

Question 10

Anaphylaxis/Anaphylactic Shock

Answer 10

1. Induced by binding of IgE-allergin to Fc receptor on
   basophil/mast cell
2. Symptoms: hypotension, vasodilation, irregular heartbeat, urticaria (hives), angioedema (movement of fluid from circulatory system to tissues), bronchoconstriction/bronchospasm
3. Non-cytolytic release of histamine = independent of drug dose

Question 11

Anaphylaxis/Anaphylactic Shock Treatment

Answer 11

Epinephrine is used to treat hypotension, irregular
heartbeat, and bronchoconstriction associated with
anaphylactic shock
(stimulate B2 R - relaxation// propanolol worsens - B blocker)

Question 12

Anaphylactoid

Answer 12

reaction has symptoms of anaphylaxis but is induced by factors other than IgE (e.g. drugs);

Cytolytic release = drug dose-dependent

Question 13

Antihistamine Drugs

Answer 13

1. Histamine release inhibitors
2. H1 receptor antagonists
3. H2 receptor antagonists

Question 14

What do Histamine Release Inhibitors do

Answer 14

Used primarily for the treatment of asthma

Mechanism: Inhibits Non-Cytolytic release of histamine from mast cells Exact mechanism unknown but appears to involve the phosphorylation of a moesin-like protein.
Phosphorylation causes this protein to cluster
around histamine-filled secretory granules

Question 15

Histamine Release Inhibitors

Answer 15

Examples: CROMOLYN SODIUM, nedocromil

Side effects: bronchial irritation, revolting taste,headache

Question 16

What do H1 Antagonists do

Answer 16

Uses: Treatment of allergies, insomnia, and taken to avoid motion sickness

Mechanism: competitive inhibition of the binding of histamine to H1 receptors
Inhibit histamine release from mast cells

Question 17

H1 Antagonists

Answer 17

DIPHENHYDRAMINE + LORATADINE

Side effects of diphenhydramine: Antimuscarinic effects (result of binding to ACh receptors) including desiccation of mucous membranes; drowsiness (CNS effect) can be an undesired effect when taken for allergy

Question 18

What do H2 Antagonists do

Answer 18

Uses: peptic ulcer and acid reflux disease

Mechanism: Competitive inhibitor of H2 receptors, decreases H+ ion secretion from gastric parietal cells

Question 19

H2 Antagonists

Answer 19

CIMETIDINE, ranitidine

Side effects: May interfere with metabolism of numerous other drugs

not recommended for long-term use = decrease H+ secretion chronically - problems with digestion / broken down by P450 enzymes (drug interactions)

Question 20

Non-Histamine Blocking Ulcer Treatment:

Answer 20

Proton Pump Inhibitors
• Uses: Peptic ulcer and acid reflux disease
• Mechanism: Irreversible inhibition of parietal cell H+K+ ATPase

Question 21

Proton Pump Inhibitor

Answer 21

OMEPRAZOLE
• Side effects: diarrhea and headache (rare/severe)
• Recent report indicates proton pump inhibitors
may reverse cisplatin and 5FU drug resistance

Question 22

what are 2 types of WBC that contain histamine

Answer 22

basophils (circulating form) and neutrophils

Question 23

histamine synthesis and metabolism

Answer 23

product of metabolism of amino acid L-histidine by histidine decarboxylase => histamine

Question 24

histamine can be degraded by enzymes but is not a potential drug target why / alternative

Answer 24

enzyme inhibitor

target: histidine decarboxylase = synthesis of histamine

Question 25

2 types of histamine release

Answer 25

cytolytic and non-cytolytic

Question 26

secretion of H+ into stomach

Answer 26

H/K ATPase - K IN from lumen/ H OUT to stomach
activated by ACh M3, Histamine H2, Gastrin G

Histamine antagonist = block H2 pathway

Question 27

how do gastrin and ACh act to promote acid secretion

Answer 27

directly by acting on mast cells

Question 28

why does loratadine not have side effects of diphenhydramine

Answer 28

the selectivity of different H1 receptors peripherally as opposed to effects of CNS
specifically targets receptors peripherally = release of fluids from sinuses - runny nose
(without drowsiness/nausea)