Histamine and Antihistamine Agents Flashcards Preview

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Flashcards in Histamine and Antihistamine Agents Deck (22):
1

Histamine structure

Imidazole heterocycle and ethylamine side chain

2

Biosynthesis of histamine

Catalysis of L-histidine (amino acid)

3

Histamine location

Found mainly in skin and mucosal cells of bronchi, intestines, etc.
Stored in mast cells and basophilic granulocytes

4

H1 receptor

Widespread throughout body (CNS, respiratory smooth muscles, GI tract, etc.)
Stimulates phospholipase C
Involved in CNS (sleeping/waking, food intake, emotions, memory, learning, etc.), immune response, and other physiologic processes (itching, vasodilation, hypotension, tachycardia, etc.)

5

H2 receptor

Stimulates cAMP
Mediates many of the same physiological responses as H1 receptor
Mediates gastric acid secretion (unique to this receptor)
Plays a role in allergy, autoimmunity, malignant disease, and graft rejection

6

H3 receptor

Mainly found in CNS
Lesser role in peripheral nerve tissues

7

H4 receptor

Immune response (can produce white blood cells, involved in allergic inflammatory response)
Transmits intracellular signals similar to H3 receptor

8

General allergic response

Histamine is released from mast cells and basophils in response to antigen
Early allergic response: H1 and H2 (headache, hypotension, tachycardia, flushing), H1 and H3 (cutaneous itch, nasal congestion)
Late allergic response: stimulation of cytokine production and lymphocyte movement and response

9

3 ways to terminate histamine action

Cellular uptake
Desensitization of cells
Metabolism (enzymatic inactivation; most common termination mechanism)

10

Antihistamine generations

1st generation: H1 receptor blocking
2nd generation: non-sedating, derivatives of 1st gen drugs, more specific

11

Antihistamine mechanism of action

Inverse agonists: stabilize inactive form of H1 receptors to shift equilibrium towards inactive state
Some block histamine release

12

1st generation antihistamine SAR

2 aryl groups
Connecting X atom (O, N, C)
Carbon chain (usually ethyl)
Terminal amine

13

Antihistamine usage

Treat allergies, colds, vertigo
Side effects: drowsiness/sedation (blockage of H1 receptors), cardiotoxic

14

1st generation antihistamine subtypes

Aminoalkyl ethers (ex- Benadryl)
Ethylenediamines
Piperazines
Propylamines (most active H1 antagonists)
Phenothiazines (also used as antipsychotics)
Dibenzocycloheptenes/heptanes

15

Differences between 1st and 2nd generation antihistamines

2nd gen: less sedation effects and less binding to non-target proteins that create side effects, larger N-tertiary amine substitutions, don't accumulate in CNS

16

Examples of 2nd generation antihistamines

Claritin, allegra, zyrtec

17

Mast cell stabilizers

Inhibit activation of mast cells and release of histamine
Can also inhibit chemotaxis (WBC movement)

18

Dual-acting antihistamines

Both H1 receptor action and mast cell stabilization

19

H2 antagonists

Treatment of acid-peptic disorders
Decrease secretion of acid in gastric mucosa by parietal cells

20

H2 antagonist SAR

Methylation of 5-position of imidazole ring: improved selectivity for H2 receptor
Increased length of side chain
Replacement of guanidino with methyl thiourea (Burimamide) or cyano-imino group (Cimetidine; improved potency and decreased toxicity)

21

Proton pump inhibitors

Lower gastric acid secretion independently of histamine action
Example: prilosec

22

H3 agonists

Possible therapeutic for learning and memory impairment, ADHD, obesity, epilepsy