Smooth Muscle Histamine Flashcards
what are autacoids
biological factors which act like local hormones, have a brief duration and act near the site of synthesis
histamine is a(n) _____________________
autacoid
paracrine autacoid
effects are mostly localized but large amounts can be produced and moved into circulation
endocrine autacoid effect
may have systemic effect by being transported via circulation
endogenous peptides that cause vasoconstriction
- angiotensin 2. vasopressin 3. endothelins 4. neuropeptide Y 5. urotensin
endogenous peptides that cause vasodilation
- bradykinins/kinins 2. natriuretic peptides 3. vasoactive intestinal peptides 4. substance P 5. neurotensin 6. calcitonin gene related peptide 7. adrenomedullin
Fx/Activity of histamine
- allergic and inflammatory rxns 2. anaphylaxis 3. gastric acid secretion (H2) 4. neurotransmitter 5. neuromodulator 6. immune fx via chemotaxis of WBC
histamine is sequestered/bound in granules on _______________ & _____________ cells
basophils; mast
mast cell histamine is located in what tissues
- nose, mouth, feet 2. internal body surfaces 3. blood vessels at pressure points and bifurcations
non-mast cell histamine is found in which tissues
- brain 2. enterochromaffin-like (ECL) cells
fx of non-mast cell histamine in the brain
- neuroendocrine control 2. CV regulation 3. thermal and body weight regulation 4. sleep and arousal
fx of non-mast cell histamine in the ECL cells of the fundus of the stomach
activates the acid producing parietal cells of the mucosa
release of histamine is mediated by _______________ via negative feedback in skin mast cells and basophils
H3
what types of histamine releasing cell is not mediated by H3 negative feedback
lung mast cells
_______________ release causes local vasodilation and release of inflammatory mediators (ex. CRP) and Antibodies
histamine
_______________ has a chemotactic attraction for inflammatory cells - neutrophils, eosinophils, basophils, monocytes, and lymphocytes
histamine
__________________ inhibits the release of lysosome contents and several T&B lymphocytes
histamine
rexposure of antigen causes degranulation –> release of histamine and other mediators, this is a ____________________ allergic reaction common with hay fever and urticaria
type I
what defines chemical release of histamine
- non-injury related release of histamine 2. release is triggered by an amine or a drug (morphine)
all histamine receptors are what type of receptor?
G-protein coupled (metabotropic)
H1 is similar to what other receptor
muscarinic R
H2 is similar to what other receptor
5-HT R
H3 & H4 receptors are _______% similar to eachother
40
T/F: all histamine receptors have constitutive activity
TRUE
T/F: drugs that act on histamine R’s could be an agonist at 1 receptor and an antagonist or reverse antagonist at another
TRUE
H1 & H2 receptors are _________-synaptic
post
H3 receptors are ____________-synaptic
pre
H1 receptors are found in what tissues
- smooth muscle 2. endothelium 3. brain
H2 receptors are found in what tissues
- gastric mucosa 2. cardiac muscle 3. mast cells 4. brain
H3 receptors are found where
- brain 2. myenteric plexus 3. neurons 4. heteroreceptors 5. presynaptic autoreceptors
H4 receptors are found where
- eosinophils 2. neutrophils 3. CD4 cells
Actions of H1 receptors (@ molecular level)
increase phophoinositol hydrolysis –> increased IP3 and ICF Ca2+
Actions of H2 R (@ molecular level)
- increase ICF cAMP 2. activates the IP3-DAG cascade (inc ICF Ca and protein kinase C)
actions of H3 receptors
decrease histamine release
actions of H4
chemotaxic effects on eosinophils and mast cells
histamine receptors are stimulants of sensory nerve endings, especially those that cause ____________ &______________
pain; itching
which histamine receptor is responsible for the urticarial response, reactions to insects and stings, and signal inspiration and expiration is respiratory neurons
H1
which histamine receptor(s) are responsible for appetite and satiety
H1 and H3
which histamine receptor regulates the Neurotransmitter release inthe brain and peripheral tissues (Ach, amine/peptide release)?
H3
low dose histamine will cause _______ - mediated __________________ effects in the CV system
H1; vasodilatory
higher dose histamine will cause _____________ - mediated, ____________________
H2; cAMP vasodialtion
edema is the result of ______________ effects on microcirculation
H1
CV effects of histamine release
- decrease in SBP and DBP 2. reflex tachycardia 3. arterial vasodilation –> warmth, flushing, and HA
histamine release causes an increase in HR via the _____________ receptor, in response to the decrease in BP
H2
which histamine is responsible for bronchoconstriction
H1
T/F: H1 mediated bronchoconstriction is not normally an issue in small doses
TRUE
H1 stimulation –> bronchoconstriction should be avoided in patients with what dz’s?
asthma & cystic fibrosis
effects of H1 stimulation on the GI
- contraction of intestinal smM 2. large doses of Histamine –> diarrhea
histamine release –> H2 agonism on _______________ cells –> increase in gastric acid secretion –> increase in ____________,________, & ___________
parietal; AC (autacoid); cAMP, ICF Ca
what is the “triple response” of histamine
- red spot (redness 2/2 VD of microcirc) 2. wheal/edema (inflammation 2/2 capillary/venular endothelium separation) 3. flare (itching 2/2 depolarization of sensory nerve ending)
dose related effects of histamine release
- flushing 2. hotn 3. tachycardia 4. wheals 5. bronchoconstriction 6. GI upset
what is an example of a physiologic anti-histamine
epinephrine
how doe physiologic anti-histamines, like epinephrine work?
have the opposite effect of histamine on smM but act on different receptors
what are some examples of histamine release inhibitors
- cromolyn 2. nedocromil 3. B2 agonists
what is an example of a H1 histamine receptor antagonists
diphenhydramine
what are examples of H2 receptor antagonist drugs
- famotidine 2. ranitidine 3. cimetidine
T/F: H3 and H4 receptor antagonist drugs are not available for clinical use
TRUE
MOA of histamine release inhibitors
- reduce mast cell degranulation resulting from IgE -Ag complex
biggest difference between 1st generation and 2nd generation H1 antagonist drugs?
2nd generation are non sedating, 1st generation = strong sedating effects
meds that are 1st generation H1 antagonists
- diphenhydramine 2. hydroxyzine (atarax) 3. meclizine 4. chlorpheniramine 5. promethazine
meds that are 2nd generation H1 antagonists
- foxofendadine (allegra) 2. loratidine (claritan) 3. cetirizine (Zyrtec)
H1 antagonist meds are absorbed rapidly with peak in __________ hrs and DOA of _____________h
1-2; 4-6
2nd generation H1 antagonists meds have a duration of action of _____________ hours
12-24
why do 2nd generation H1 antagonist meds have longer DOA compared to 1st generation
decreased lipid solubility with 2nd gen
H1 (2nd generation) antagonists are metabolized by the ___________________ liver enzyme
CYP3A4
MOA of H1 antagonists
reversible competitive binding to H1 , negligable effects on H2, little to no effect on H3
what are effects of H1 antagonists that are specfic to 1st generation meds
- sedation 2. anticholinergic effects 3. local anesthetics
effects of H1 antagonists (1st and 2nd gen)
- anti nausea/emesis 2. anti-parkinsonism 3. andreonrectpro blocking
toxicity of H1 antagonists
- excitation and convulsions in children 2. postural hotn 3. allergic response
clincial use of H1 antagonists
- prevention of allergic rxns 2. prevention of motion sickness (1st gen)
T/F: H1 antagonist medications are an effective way to treat pregnancy induced morning sickness
false; H1 antagonists are teratogenic!
what drug category is the first line in the prevention and treatment of allergic rxn’s, especially if given prior to exposure
H1 antagonists
in the tx of allergic rhinitis (hay fever), H1 antagonists are a 2nd line tx after ______________________
corticosteroids
purpose of using of H1 antagonists for atopic dermatitis
used more for sedation than anti-itch effect, it decreases awarness of itching (due to being so tired)
H1 antagonists have no effect on the tx of ________________ & ______________
asthma; angioedeam
if clinical effectiveness of one group of H1 antagonists decreases over time, how can you combat this?
change drug groups to restore effectiveness
