Histamines and Antihistamines Flashcards Preview

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Flashcards in Histamines and Antihistamines Deck (59)
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1

name the H2 blockers

cimetidine

ranitidine

famotidine

nizatidine

1

What is the name of the enzyme responsible for converting histidine to histamine?

L-histidine decarboxylase

2

Describe the structure of histamine and its important components.

ethylamine chain is important for drug behavior at H1 receptors

imidazole ring is important for action at H2 receptors

3

Discuss the metabolism of histamine.

oxidative deamination by N-methyltransferase and MAO (and other dehydrogenases)

finally turned into an acetic acid derivative

histaminase (diamine oxidase) is another pathway

4

diamine oxidase

found in high concentrations in the digestive tract

important for metabolizing ingested histamine

5

general sites of action of histamine

non-vascular smooth muscle

vascular smooth muscle (and sensory nerve endings in man)

gastric acid secretion

isolated heart peparations

possible neurotransmitter roles

6

effect of histamine on non-vascular sooth muscle

all are H1 effects

bronchoconstriction - smooth muscle very sensitive

intestinal smooth muscle contracts - high doses can cause diarrhea

7

effect of histamine on vascular smooth muscle

effects all mediated by H1

triple response of lewis due to skin trauma

8

triple response of Lewis

redness - direct dilatation

flare - indirect dilatation

wheal - edema

9

triple response of Lewis - redness

direct dilatation of blood vessels

reflected as a local red spot appearing within seconds after injection or injury

immediate effect mediated by H1 receptors

at higher doses, a sustained H2 component participates in redness

10

triple response of Lewis - flare

indirect dilatation reflected as an irregular reddish area that develops slowly and extends beyond the original redness by about 1 cm

occurs indirectly via an axon reflex whereby histamine or injury excites sensory nerve terminals from the skin

impulses then travel up sensory nerve into spinal cord and also diverge via an axon collateral, which releases substance P

substance P binds to mast cells and release histamine, causing the flare

11

triple response of Lewis - wheal

edema at injection site and the area of initial redness becomes raised due to increased permeability of small blood vessels, causing edema

12

effect of histamine on gastric acid secretion

in very low doses, histamine causes secretion of gastric juice from parietal and chief cells of the mucosa respectively (H2 mediated)

13

enterochromaffin-like (ECL) cells

paracrine cells that release histamine to induce parietal cells to release HCl

gastrin and ACh are other stimulants that cause these cells to release histamine

14

effect of histamine on isolated heart preparations

increases the rate and force of cardiac contraction (via H2 receptors) and slows conduction int he AV node (via H1 receptors, this is a minor effect)

may be important in producing arrhythmias during allergic reactions

15

the effect of histamine on neurons

most important clinical effects of the H1 antihistamines int he CNS are due to blockade of muscarinic receptors

16

What cells contain histamine?

mast cell and the basophilic leukocyte

17

What makes up the secretory granules of mas cells?

histamine

proteases

heparin

cytokines

18

alpha-tryptase

a neutral protease found in the mast cell granule

19

What cytokines are found in mast cell granules?

ECF-A - eosinophil chemotactic factor of anaphylaxis

TNFs - tumor necrosis factors

20

anaphylaxis

the physiological stimulus to secretion of mast cells

leads to type I immediate hypersensitivity

21

Describe the signaling pathway that causes mast cells to release their granules and their contents.

  1. IgE antibodies become fixed to mast cells
  2. exposure to antigen triggers binding to antibodies
  3. phophorylation of interaction leads to activation of phospholipase C
  4. causes IP3 synthesis and calcium liberation from storage sites in the ER
  5. CRAC channels open in response to increased calium
  6. increased cytoplasmic calcium concentrations promote exocitosis and dissociation of the component parts of the granules

22

urticaria pigmentosa

a disease characterized by huge numbers of mast cells in the skin

when touched, may set of an exaggerated triple response

calcium dependent process, also activating phospholipase A2

detection of alpha-tryptase and histamine metabolites as well as prostaglandin metabolites in the urine

anaphylactoid - not IgE mediated

23

mechanism of insect stings and bites

poison has a phospholipase A2 component as well as mast-cell degranulating peptides

G-protein induced histamine release

24

histamine release inhibitors

increases in cAMP inhibit release from human basophils and animal mast cells (epinephrine and theophylline through beta-receptors)

25

evokers of histamine release

atropine, curare, substance P, morphine, certain antibiotics, ACh, peptides, and other agents in high concentrations

26

signaling mechanism for H2 receptors

G-protein coupled receptor

increases cAMP and thus PKA phosphorylation

27

mechanism of H1 receptor antagonists

competitive inhibitors of histamine at the H1 receptor

potently inhibit the effects of histamine if histamine is present at these receptor sites

all are substituted ethylamine derivatives

28

first generation H1 receptor antagonists (What are some side-effects?)

classical

phenothiazines

piperazines

**CNS effects and thus sedating

**peripheral anti-muscarinic effects

29

chlorpheniramine

first generation, classical

contained in all OTC anti-allergy preparations (brompheniramine also popular)

useful to treat mild allergic reactions

also contained in cold tablets - relief due to anti-cholinergic effect of drying up secretions