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Histamine is metabolized by 2 pw
- oxidation- diamine oxidase
- methylation- s adenosyl l methione - becomes methlylinidazole acetic acid which is the mahor urinary metabolite of histamine in man
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pharmacology of histamine
- if i inject you or another subject it has ... an effect- effect of an exogenous substance
- unilateral headache- cerebral vasodilation
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pathological role of histamine
- causing HA in pt
- gastric secretion and pain- not necessarily a physiologic mediator, many factors affect acid secretion
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triple response- 3 comps h1 and h2
- direct dilation of terminal arterioles
- stimulation of a local axon reflex- flare of local afferent nerves with discahrge of vasodilating efferent nerves
- wheal- edema increased perm of venules seperating the endothelial cells
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H1 effect
- intense vasodilation of resistance vessels- hypotension
- contraction of bronchiolar smooth muscle
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h1 induced relaxtion of vascular smooth muscle requires
intact endothelial cell which release EDRF aka NO
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H2
- in the gastric mucousa- stimulation increase pepsin and acid output- promoting secretion
- also in atria- activates HR chronotropic
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why does an h2 blocker have more gastric than cardiac effect?
more histamine in stomach than blood- not blocking any effect in heart
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h1 pw
phospholoipase c- ca is key
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immunologics and histamine
have histamine release in allergic rxn- 1 immunologic specific- because of sensitized ab binds to
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antigen induces histamine release
- step 1 make ige becuase of sensitization
- step 2 IgE binds to mast cells
- step 3 pollen crosslink to tissue bound ige and mast cell activates to release histamine
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nonimmunologcial rxn
histamine releasing drugs- not an immunologic response- like neuromusclar drugs or codeine, contrast media,
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clinical problems of histamine
- urticaria, pigmentosa, systemic mastocytosis
- need to be treated like with antagonists
- anaphylaxis- epinephrine
- inflmmation
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antihistamines
h1 or h2 blocker
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h1 antagonists
- 1st gen- sedating
- 2nd- nonsedating
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1st geb h1 blocker
- diphenhydramine
- tripelenamine
- chlorphenirameine
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h1 therrapeutic use-
for rhinitis, urticaria, can sedate, topical anesthetic for sore throat, for menieres,
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SE of h1 gen 1 blockers
cns depressors, NV
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second gen h1 blockers
- not brain penetrating- minimal cns se
- lack anticholinergic and serotonin and much longer duraton of action
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h2 blockers
- cimetidine
- ranitidine
- famtidine
- nizatidine
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h2 therapy
- control of gi bleeding
- etc
- stress related erosice sysndrome
- trauma, burns, ARF, shock, sepsis, stroke- use h2 blocker to prevent this empirically
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cimitadine
- p450 blocker- only h2 to do this
- theophylline- inhibition of metabolism
- warforin- increased anticoag effect
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antirelease agents
- cromoglycate prototype and nedocromyl
- aniallergic drugs
- cromolyn prevents antigen induced mast cell degranulation in young with allergic asthma
- given prophylactically for asthma
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