anaphylaxis Flashcards
What are the roles and functions of histamine?
- mediator of allergic reactions and inflammatory processes
- affects gastric secretion
- neurotransmitter
- neuromodulator
- found in plants, animals, insects
how is histamine stored?
- tissue histamine is bound into vesicles in mast cells or basophils (inactive in bound form)
- mast cells found in nose, mouth, feet, internal body surfaces, blood vessels
- non-mast cell histamine found in the brain as an endogenous neurotransmitter
- stored and released from enterochromaffin-like cells of the fundus of the stomach (activate acid production from parietal cells)
describe histamine release
major pathophysiologic mechanism of mast cell and basophil histamine release is immunologic
- cells have IgE antibody attached to membrane; when antigen is exposed to cell, degranulation of cell occurs causing release of histamine and other mediators
- initial exposure antibodies form, 2nd exposure histamine release
- negative feedback from H2 receptors found in skin and basophils (NOT IN LUNGS) limits reaction in skin and blood
- bronchoconstriction not limited
how do amine drugs affect histamine?
amine drugs (morphine, tubocurarine) compete with histamine for sites within cells and displaces it *effects are the same but not r/t mast cells releasing
describe H1 receptors
similar to muscarinic receptors
- located postsynaptic in the brain
- located in endothelium, smooth muscle cells, nerve endings (brain)
- effects: bronchoconstriction, slowed conduction through AV node, coronary artery vasoconstriction
describe H2 receptors
similar to 5-HT1 receptors
- located postsynaptic in the brain (where neurotransmitter histamine acts in brain to cause PONV)
- located in the gastric mucosa, cardiac muscle cells, and some immune cells
- effects: CNS stimulation, increased myocardial contractility and HR, bronchodilation, increased secretion of H+ ions by gastric parietal cells
describe H3 receptors
similar to H4 receptors
- located in the heart presynaptic postganglionic sympathetic nervous system: decreases NE release
- decreases synthesis and release of histamine
- H2 blockers also have some block on H3, so more histamine is produced and released; if on chronic H2 blocker, something causing histamine release can have exaggerated effects
describe H4 receptors
similar to H3 receptors
-located in the blood cells in the bone marrow and blood (eosinophils, neutrophils)
what are CV effects of histamine at both H1 and H2 receptors?
- decrease in SBP and DBP d/t vasodilation of arterioles and precapillary sphincters (cause skin wheels)
- increase HR d/t direct stimulation, reflex, and release of NE, E from adrenal medulla
- vasodilation d/t release of nitric oxide (flushing)
- coronary vasoconstriction (H1) opposed by vasodilation (H2)
- edema from separation of endothelial cells in the microcirculation allowing leakage of fluid and small proteins into tissue (hives)
what are direct effects of histamine on the myocardium?
- increased contractility
- increased rate
- result of H2 receptor stimulation
how does histamine effect H1 and H2 receptors differently r/t CV effects?
- H1 receptors are stimulated at lower concentration to cause rapid onset but transient vasodilation (doesn’t last long)
- H2 receptors have a slower onset, but more sustained vasodilation
what are pulmonary effects of histamine?
- bronchoconstriction at H1 receptors (outweighs dilation)
- bronchodilation at H2 receptors
- asthma patients have 100 - 1000x greater sensitivity
what are GI effects of histamine?
- excessive secretion of gastric fluid with a low pH
* caused by plasma histamine levels so low that no hemodynamic effect is evident
what are CNS effects of histamine?
CNS stimulation at H2 receptors
what are the effects of drugs on histamine?
histamine receptor blockers do not inhibit the release of histamine
what are specific effects of H1 blockers?
- prevent activation of H1 receptors by histamine (competitive antagonist)
- may activate muscarinic cholinergic, 5-HT3, alpha-adrenergic receptors
drugs: diphenhydramine (Benadryl), dimenhydrinate (Dramamine), meclizine (Bonine), promethazine (Phenergan)
what are the specific effects of H2 blockers?
- prevent increase in intracellular cAMP which would activate the proton pump of the gastric parietal cell to secrete hydrogen ions
drugs: cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac)
what drug prevents the release of histamine?
Epinephrine
*drug of choice for anaphylaxis treatment
what are the effects of Epi?
- acts on different receptos
- opposite effect on smooth muscles
- prevents release of histamine (Cromolyn and beta 2 agonists) by decreasing the degranulation of mast cells that occurs with immunologic triggering
what is anaphylaxis?
severe immediate hypersensitive reaction mediated by IgE antibodies formed in response to a foreign antigen
what is anaphylactic shock?
the cardiovascular collapse that results from anaphylaxis
what are anaphylactoid reactions?
non IgE mediated reaction that clinically resembles anaphylaxis
what are the mast cell mediators involved in anaphylaxis?
- histamine 1: contracts bronchial smooth muscle, vasodilation
- histamine 2: vasodilation, mucous secretion, increased HR and contractility
- kinins: increases vascular permeability, vasodilation; contracts smooth muscle including bronchoconstriction
- heparin: intravascular coagulation
- leukotrienes: inflammatory injury, constriction of smaller airways, coronary vasospasm, increase vascular permeability, myocardial depression
- platelet-activating factor: increase vascular permeability; contract smooth muscle; wheal
- prostaglandins: coronary vasospasm
- serotonin
what are physiologic manifestations of anaphylaxis?
- bronchospasm
- tachycardia, hypotension
- edema, urticarial
- excessive respiratory/ GI secretions
- inflammation
- abdominal pain, nausea, vomiting, diarrhea
what are signs of anaphylaxis?
- cutaneous: urticarial, angioedema, erythema, periorbital and facial edema
- respiratory: coughing, sneezing, hoarseness, intraoral edema, laryngeal edema, stridor, cyanosis, tachypnea, WHEEZING, decreased pulmonary compliance, pulmonary edema, acute respiratory distress
- CV: diaphoresis, hypotension, tachycardia, arrhythmias, decreased SVR, cardiac arrest, pulmonary hypertension
- other: vomiting, diarrhea, acute intravascular coagulation
- *under anesthesia, only sign may be CV collapse (LATE SIGN)
what are risk factors for anaphylaxis?
- receiving IV drugs
- history of allergies or atopy
- history of asthma
- women 2.5x r/t cosmetics and cleaning chemicals with quaternary ammonium structures
- history of previous anesthetic
what are some drugs associated with anaphylaxis?
- muscle relaxants (succs, roc)
- morphine, Demerol, codeine
- induction agents: pentothal, ketamine, benzo, propofol
- local anesthetics: esters > amide, preservatives
- antibiotics
- blood products
- protamine
- LATEX, vascular graft material, methylmethacrylate bone cement
how do you treat anaphylaxis?
-remove offending agent
-aggressive airway management (100% FiO2, epi aerosol, intubation)
-circulatory management (40% loss to interstitial space)
IV fluids (volume expansion; 25-50 ml/kg or 2-4 L); epi, vasopressin
-discontinue anesthetic agents (vasodilates)
-adjunctive drugs
what dose of epinephrine is used with anaphylaxis?
- 10-100 mcg for moderate hypotension
- 1-3 mg for circulatory collapse/pulseless
- infusion: 4-10 mcg/min
- start epi with small doses (too much r/t death)
what are adjunct drugs for anaphylaxis treatment?
- antihistamines (H1-benadryl 1mg/kg max 50 mg; H2 Pepcid 20 mg)
- glucocorticoids (hydrocortisone 5 mg/kg or 50-150 mg)
- aminophylline (load 5-6 mg/kg; infusion 0.4-0.9 mg/kg/hr) for bronchoconstriction
- epi infusion (0.02-0.05 mcg/kg/min)
- dopamine infusion (5-20 mcg/kg/min) hemodynamic support
- norepinephrine infusion (0.05 mcg/kg/min) needed vasoconstriction
- NaBicarb 0.5-1 mEq/kg initially, then titrate to ABGs (acidosis from poor perfusion)
how can anaphylaxis be prevented?
- avoid risky patterns of practice
- careful history taking
- intradermal skin testing
- RAST test
- leukocyte histamine release test
- pharmacologic prophylaxis (Benadryl, decadron, ranitidine 1-2 mg/kg)
