Hypotension case 3

Hypotension case 3

A 20-year-old college student presents to the campus health service complaining of a purulent penile discharge. When his culture reveals
gonococcal infection, he returns to the clinic for treatment, and is given an intramuscular injection of ceftriaxone. While checking out, he tells the
receptionist that he feels ilI. He complains of feeling weak, dizzy, and short of breath, as well as a "funny" sensation around his mouth. On
physical examination, he is sweaty and pale. His lips appear swollen. His blood pressure cannot be auscultated; via palpation, his systolic
pressure is estimated at 74 mm Hg. His pulse is 116/min, and respirations are 30/min.

Q 1
This is an example of which of the following types of hypersensitivity reactions?
/ A. Type l
/ B. Type ll
/ C. Type lll
/ D. Type IV


Q 2
Which of the following immunoglobulins initiates this patient's disease process?
/ A. IgA
/ B. IgD
/ C. IgE
/ D. IgG
/ E. IgM


Q 3
As resuscitation efforts begin, 0.5 mg of epinephrine is administered subcutaneously. Which adrenergic receptors, in which tissues, are
responsible for the beneficial effect of epinephrine in this patient?
/ A. AIpha-1 receptors in vascular smooth muscle, alpha-2 receptors in the heart, and beta-1 receptors in bronchial smooth muscle
/ B. AIpha-1 receptors in vascular smooth muscle, alpha-2 receptors at presynaptic nerve terminals, beta-1 receptors in bronchial smooth
muscle
/ C. AIpha-1 receptors in vascular smooth muscle, beta-1 receptors in the heart, and beta-2 receptors in bronchial smooth muscle
/ D. AIpha-2 receptors in vascular smooth muscle and beta-2 receptors in vascular smooth muscle
/ E. Beta-1 receptors in the heart alone


Q 4
The patient is also given a dose of hydrocortisone. Which of the following is the most likely molecular mechanism by which steroids have their
effect?
/ A. Adenosine receptor blockade
/ B. Direct mast cell stabilization
/ C. Histamine receptor blockade
/ D. Inhibition of cyclooxygenase
/ E. Inhibition of phospholipase A2
/ F. Leukotriene receptor blockade


Q 5
At discharge from the hospital several days later, the patient is warned that he is allergic to cephalosporins. Which other drug should he be
warned not to take in the future?
/ A. Aztreonam
/ B. Gentamicin
/ C. Indomethacin
/ D. Penicillin
/ E. Trimethoprim-sulfamethoxazole

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Hypotension case 3 answers

A1
The correct answer is A. IgE antibody is produced in response to an initial challenge by an antigen, and binds to Fc receptors on mast cells and basophils. Reexposure to the antigen causes degranulation of mast cells and release of vasoactive amines (e.g., histamine and adenosine), chemotactic cytokines, and enzymes (e.g., proteases and kinins). Mast cells go on to synthesize and release arachidonic acid metabolites (leukotrienes, prostaglandin D2) and platelet-activating factor. These multiple mediators, in turn, initiate a rapid inflammatory response, resulting in recruitment of neutrophils and eosinophils, and production of increased vascular permeability, tissue edema, and epithelial cell injury. The clinical manifestations of anaphylaxis are urticaria, tissue swelling and angioedema, laryngeal edema, bronchoconstriction, and hypotension, as well as abdominal cramping and diarrhea. Other Type I type hypersensitivity reactions are more localized, as in some forms of bronchial asthma, allergic rhinitis, and allergic gastroenteritis.
Type II hypersensitivity reactions (choice B) include antibody-dependent cytotoxic responses, in which antibody (IgG or IgM) binds to antigen on a cell surface, resulting in either the activation of complement, or cell-mediated cytotoxicity via nonspecific neutrophils, monocytes, eosinophils, and NK cells that bind to the Fc fragment of IgG. Examples of Type II reactions are transfusion reactions, autoimmune hemolytic anemias, erythroblastosis fetalis, and Goodpasture syndrome. Type II hypersensitivity also includes noncytotoxic antibody-mediated dysregulation such as the anticholinergic receptor antibodies of myasthenia gravis and the anti-TSH receptor antibodies of Graves disease.
Type III hypersensitivity reactions (choice C) are immune-complex mediated reactions in which antibody-antigen complexes are formed, thereby activating complement. The antigen may be endogenous or exogenous. Examples are serum sickness, systemic lupus erythematosus, and some acute glomerulonephritides.
Type IV hypersensitivity (choice D) also called delayed-type hypersensitivity, is entirely cell-mediated and requires the presentation of antigen on a cell surface, resulting in CD4 cell activation followed by CD8 cell-mediated direct cytotoxicity. The most common example of this is the cutaneous tuberculin reaction: this is also involved in contact dermatitis and in rejection of solid organ transplants


A2
The correct answer is C. Antigen binds to IgE on the surface of mast cells and basophils, initiating anaphylaxis.
IgA (choice A) is secreted primarily by mucosal plasma cells and is the principal immunoglobulin present in secretions. It is a major component of immunologic defense against viruses. Approximately 1 in 800 people is IgA-deficient.
IgD (choice B) acts as an antigen-binding receptor on B cells, although very small quantities also circulate.
IgG (choice D) represents approximately 75% of circulating antibody and is the predominant antibody made after rechallenge of a host with antigen, as well as a major component of antibacterial immunity, initiating neutrophil and monocyte responses as well as activating complement.
IgM (choice E) is the antigen-binding receptor on the B cell. IgM also circulates as a pentamer. Since no class-switching is required to form it, IgM constitutes the primary antibody response on initial host antigen challenge. IgM activates complement efficiently, and is an important mediator of rheumatoid arthritis and of immune complex diseases.


A3
The correct answer is C. Epinephrine is a nonselective adrenergic agonist and a valuable resuscitative drug because of its effects at multiple adrenergic receptor subtypes. In the treatment of anaphylaxis, epinephrine increases myocardial contractility, accelerates heart rate, causes constriction of vascular smooth muscle, and causes relaxation of bronchial smooth muscle. The principal pharmacologic effects of epinephrine that are beneficial in anaphylaxis are mediated via: alpha-1 receptors in vascular smooth muscle, resulting in vasoconstriction, beta-1 receptors in the heart, resulting in increased contractility, and beta-2 receptors in bronchial smooth muscle, resulting in relaxation and relief of bronchoconstriction. (One simple mnemonic for the respective locations of beta-1 and beta-2 receptors is "one heart, two lungs.") Beta-2 receptors are also found, however, in vascular smooth muscle (especially in skeletal muscle beds), where, just as in bronchial smooth muscle, they promote relaxation. (Epinephrine dilates skeletal muscle vascular beds to maximize oxygen delivery for the "fight-or-flight" response.) The resulting vasodilation in skeletal muscle vascular beds would, by itself, tend to decrease blood pressure, which might tend to worsen the effects of anaphylactic shock, but this effect is mitigated by the intense alpha-1 receptor stimulation, causing vasoconstriction in multiple beds. The principal action of alpha-2 receptors is at the presynaptic nerve terminal, where receptor stimulation reduces the release of norepinephrine from the nerve terminal. Epinephrine does stimulate these receptors, but it does not really contribute to the beneficial actions of epinephrine in resuscitation.
Alpha-2 receptors are not located in the heart (except at presynaptic nerve terminals), alpha-2 receptors do not have a significant beneficial effect in resuscitation, and beta-1 receptors are not located in bronchial smooth muscle, but are located in the heart (compare with choice A).
Beta-1 receptors are located in the heart, not in bronchial smooth muscle. The adrenergic receptor that produces bronchial smooth muscle relaxation is beta-2 (compare with choice B).
Alpha-2 receptors are located primarily at presynaptic nerve terminals, and because the beta-2 receptors in vascular smooth muscle cause vasodilation, this not a helpful effect of epinephrine in this case (compare with choice D).
In the patient with anaphylaxis, epinephrine is resuscitative also by raising blood pressure via alpha-1 receptors in vascular smooth muscle and relieving bronchoconstriction via beta-2 receptors in bronchial smooth muscle (compare with choice E).


A4
The correct answer is E. Steroids inhibit phospholipase A2, which cleaves cell membrane phospholipids into arachidonic acid. Inhibition of this enzyme, in turn, prevents the formation of thromboxane, as well as all the prostaglandins and leukotrienes.
Adenosine receptor blockade(choice A) is one of the mechanisms of action of the methylxanthines, including caffeine, theophylline, aminophylline, and theobromine. Adenosine is a potent bronchoconstrictor. Theophylline and aminophylline are used in the treatment of asthma.
Prevention of mast cell degranulation (choice B) is thought to be the mechanism of action of cromolyn sodium, an inhaled drug used in asthma.
Histamine receptor blockade (choice C) is a central part of the therapy for anaphylaxis, and is accomplished by using both H1 receptor blockers such as diphenhydramine as well as H2 receptor blockers like cimetidine.
Inhibition of cyclooxygenase (choice D) is the principal mechanism of action of the nonsteroidal anti-inflammatory agents, which generally inhibit both the COX1 (constitutive) and COX2 (inducible) isoforms of this enzyme, preventing the conversion of arachidonic acid into prostaglandin and thromboxane precursors. Newer NSAIDs are relatively selective for COX2, and therefore do not inhibit prostaglandin formation in normal tissue to the same degree that they do in inflamed tissues.
Leukotriene receptor blockade (choice F) is the mechanism of action of a new class of asthma drugs such as montelukast and zafirlukast.


A5
The correct answer is D. Penicillins and cephalosporins share a common beta-lactam ring, which is the most likely antigen responsible for triggering the anaphylaxis cascade in this patient.
Aztreonam (choice A) is a monobactam antibiotic which, although closely related to the penicillins and cephalosporins, does not appear to have antigenic cross-reactivity.
Gentamicin (choice B) is an aminoglycoside antibiotic and is not chemically related to cephalosporins. Aminoglycosides are frequently prescribed in conjunction with beta-lactam antibiotics because of their synergy against gram-positive bacteria.
Indomethacin (choice C) is a nonsteroidal anti-inflammatory agent, not an antibiotic or related to the cephalosporins. NSAIDs and aspirin can, however, trigger severe bronchospasm and upper airway obstruction, as well as angioedema in susceptible individuals, most frequently asthmatic patients, probably as the result of an imbalance in prostaglandin and leukotriene production. This is not an IgE-mediated reaction and this patient should not be at significantly increased risk.
The combination of trimethoprim, (a diaminopyrimidine) and sulfamethoxazole (a sulfonamide) (choice E) provides two antimicrobials with different targets in the bacterial folic acid synthesis pathway, to create a synergistic and widely prescribed combination. There is no chemical relation to or cross-reactivity with cephalosporins or penicillins.