Emergency Therapeutics Part 1:DRUG ALLERGIES AND SIMILAR PROBLEMS Flashcards
Describe how to take a complete and accurate patient history of prior allergic reactions, and prior non-allergic ADR’s
Ask about current Rx drugs
Ask about current OTC drugs
Ask about current topical drugs (e.g. eye drops)
Ask about prior ADRs (e.g. nausea)
Ask about prior drug allergies (e.g. rash)
Ask specifically about the agent/class you are about to give (e.g. penicillins and other names)
(Discuss patient who developed leukocytoclastic vasculitis one day after beginning Augmentin)
Describe the differential diagnosis for an apparent anaphylactic reaction
anaphylaxis: angioedema (difficult intubation) + hives, urticaria
==> d/t IgE and mast cells
Tx: Diphenhydramine + Epinephrine + steroids + fluid resuscitation
anaphylactoid: isolated angioedema = massive swelling of lips, soft tissues, tongue
==> d/t another cause (bradykinin)
Tx: Epinephrine; Icatibant (synthetic bradykinin B2-receptor antagonist)
A 60-yo man underwent open reduction and fixation of a nasty ankle fracture. Two weeks after surgery and casting, he developed a documented extensive right leg DVT complicated by a PE (with slight hypotension). He was admitted to a local hospital, and was treated with streptokinase iv for 24 hours, then heparin iv plus oral warfarin. He did well for 8 days, and finally his PT and INR became therapeutic (INR 2.8, finally!). He was scheduled for discharge the next morning.
On day nine, he woke up in the hospital hoping to go home. However, he noted new onset of low-grade fever, malaise, myalgias, and arthralgias. He felt like “he had the flu.” On exam, he was slightly febrile, slightly tender over his liver, and he had a strange petecchial rash (see photo) over the distal dorsal and lateral aspects of his hands and feet. His INR was therapeutic (2.8), but he had new mild elevations of his ALT and AST. Fearing an allergy to heparin or warfarin (his only current drugs), his doctors at the community hospital discontinued both meds, and referred him to DHMC for further management, with likely insertion of an IVC filter to prevent future PE’s. Plts nml. -Dx -Pathophysiology -List of treatment options -Best treatment for THIS pt -What parameters? ongoing contract/alliance with patient
Assessment: Particular location on the petechiae on the lateral aspects (rather than usual thrombocytopenia that is on the ankles)
-Dx:
-Pathophysiology:
-List of treatment options
-Best treatment for THIS pt
-What parameters?
ongoing contract/alliance with patient
Adverse reactions
SJS
anaphylactic rxn
Distinctive features of drug allergies
No correlation with pharmacologic properties of the drug (not what the drug is supposed to do)
Not linearly dose-related
Often (but not always) associated with other “classical” signs and symptoms of allergy (fever, rash, hives, eosinophilia)
Period of induction common after first exposure
Occurs more rapidly, triggered by a smaller dose??, upon subsequent re-exposure (anamnestic response)
Disappears upon cessation of drug therapy (but may need help, sometimes steroids, and sufficient time)
Desensitization is sometimes possible in urgent cases
Common presentations of drug allergies:
Hives Angioedema Anaphylaxis Serum sickness Immune cytopenias (HIT) Skin eruptions (many types, by far the most common!!) Fever Hepatitis Nephritis (GN, IN) Pulmonary infiltrates Vasculitis (often leukocytoclastic)
A 60-yo man underwent open reduction and fixation of a nasty ankle fracture. Two weeks after surgery and casting, he developed a documented extensive right leg DVT complicated by a PE (with slight hypotension). He was admitted to a local hospital, and was treated with streptokinase iv for 24 hours, then heparin iv plus oral warfarin. He did well for 8 days, and finally his PT and INR became therapeutic (INR 2.8, finally!). He was scheduled for discharge the next morning.
On day nine, he woke up in the hospital hoping to go home. However, he noted new onset of low-grade fever, malaise, myalgias, and arthralgias. He felt like “he had the flu.” On exam, he was slightly febrile, slightly tender over his liver, and he had a strange petecchial rash (see photo) over the distal dorsal and lateral aspects of his hands and feet. His INR was therapeutic (2.8), but he had new mild elevations of his ALT and AST. Fearing an allergy to heparin or warfarin (his only current drugs), his doctors at the community hospital discontinued both meds, and referred him to DHMC for further management, with likely insertion of an IVC filter to prevent future PE’s. Plts nml. -Dx -Pathophysiology -List of treatment options -Best treatment for THIS pt -What parameters? ongoing contract/alliance with patient
Assessment: Particular location on the petechiae on the lateral aspects (rather than usual thrombocytopenia that is on the ankles)
- Dx: Serum sickness d/t streptokinase (due to the foreign protein)
- Pathophysiology: takes 8 days for immune system to react to foreign-protein induced serum sickness
-List of treatment options
==> stop drug and wait it out (2 weeks) –> your IgG is more numerous than foreign protein IgG
==> IgG - but this is another person’s IgG – can induce ANOTHER serum sickness
- Best treatment for THIS pt: wait
- What parameters? x2weeks total (1 wk more than what the streptokinase was already stopped)
- ongoing contract/alliance with patient
Risk factors for drug allergies: pt factors
History of atopy Pattern of drug metabolism Age Presence of kidney disease Presence of liver disease
==> why some have an immunologic response (whereas others do not)
Types of drug allergy
Type I Reaction (Acute, IgE, Anaphylactic)
Type II Reaction (Cytotoxic, hemolytic)
Type III Reaction (Serum Sickness)
Type IV Reaction (Delayed Hypersensitivity)
"Pseudoallergy" = Direct histamine release (e.g. morphine, contrast agents) Prostaglandin inhibition (e.g. aspirin)
Presentation of Type I drug allergy
- examples
- treatment
Most severe and acute form of drug allergy (+/- prior history)
==> urticaria (red-expanding border, with clear center)/hives/itching, angioedema, laryngospasm, laryngeal edema, bronchospasm, hypotension, vasodilatation, loss of ECV, shock, and even death!!!
=pathophys: release of histamine
Examples: PEN, streptokinase, local anesthetics
Usually comes on seconds-hours after exposure (sensitization from eating meat from livestock that are given antibiotic)
Presentation of Type I drug allergy
- treatment
Prompt/immediate intervention is CRUCIAL
(1) Stop the drug/infusion!!!
(2) Diphenhydramine/Benadryl™ 50 mg IV/PO ==> block H1 receptor
- (Cimetidine/Tagamet™ 300 mg IV) ==> block H2 receptor
(3) Epinephrine 0.3-0.5 mg SC (as 1:1000 solution) or IM, especially if patient is hypotensive (improved absorption»_space; subcu); IV route rarely needed (unless BP is bottoming out)
(4) Methylprednisolone/Solumedrol™ 50-125 mg IV == will help after 6h (to treat possible 2nd wave b/c IgE still binding mast cells)
(5) Normal saline/0.9% saline
Presentation of Type I drug allergy
- treatment
Prompt/immediate intervention is CRUCIAL
(1) Stop the drug/infusion!!!
(2) Diphenhydramine/Benadryl™ 50 mg IV/PO [1mL vial of 50mg/mL]==> block H1 receptor
- (Cimetidine/Tagamet™ 300 mg IV) ==> block H2 receptor
(3) Epinephrine 0.3-0.5 mg SC (as 1:1000 solution) or IM, especially if patient is hypotensive (improved absorption»_space; subcu); IV route rarely needed (unless BP is bottoming out)
- 1mg/mL
(4) Methylprednisolone/Solumedrol™ 50-125 mg IV == will help after 6h (to treat possible 2nd wave b/c IgE still binding mast cells)
(5) Normal saline/0.9% saline = for hypotension to replace 3rd spacing.
differentiate the different dosages of epinephrine
1 ml Ampule of epinephrine
==> Used for SC and IM injections of small volumes
-Also same concentration used in Epi Pens
-1:1,000 (1 g in 1000 ml water)
-1 mg per ml concentration
-Usual dose 0.3-0.5 mg = 0.3-0.5 ml (very easy)
10-ml syringe of epinephrine ==> Used for IV injection in code blue -Used to be used for intra-cardiac epinephrine -1:10,000 ratio -1 g in 10,000 ml water -1 mg per 10 ml concentration -Usual dose 1 mg = full syringe
Presentation of Type II cytotoxic drug allergy
- examples
Cells are killed and lysed!
Mediated by antibody and often complement
Drug can induce antibody to itself, or to a metabolite, or to a hapten, or to a cell surface antigen
==> SJS (skin sloughing off - sheets b/c the immune cells are attacking the epiderma/dermal layer)
Example: Penicillin-induced hemolysis–what will be the results of a Coombs Test?
While patient is taking the drug
One day after stopping the drug
Example: Methyldopa-induced hemolysis
Example: Heparin-induced thrombocytopenia HIT
Example: we think that Stevens-Johnson Syndrome is caused in this way
Specific metabolic pathway in subset of patients receiving sulfonamides
Why is serum sickness called serum sickness?
What is the most famous example delivering a drug that causes serum sickness?
Using horse serum to innoculate humans against tetanus
horse IgG –> gave kids serum sickness ==>
deposition of complexes (vasculitis, myalgias, petechiae)
Presentation of Type II cytotoxic drug allergy
- examples
Cell-mediated immunity develops after exposure to antigen
Sensitized lymphocytes are key
Skin tests are often used to measure reactivity (e.g. mumps, PPD, etc)
Poison ivy is a common clinical example
Ethylenediamine is one drug (excipient) example, and red rashes may be other examples
Allegy to nickel jewelry is another good example
Define: anaphylactoid rxn
-examples
Not IgE, but looks like anaphylaxis
Most commonly, drug causes mast cells to directly release histamine, leukotrienes, kinins, etc, but NOT mediated by IgE antibodies
Ex. Morphine very common (so often treated with an antihistamine that can potentiate analgesia, such as hydroxyzine/Vistaril™ or diphenhydramine/Benadryl™)
IV/IA contrast agents very common cause
Different mechanism: aspirin-induced bronchospasm in “allergic” patient with pre-existing asthma and nasal polyps
what is the chances of a life-threatening reaction to penicillin?
1:40,000
what is the chances of a life-threatening reaction to penicillin 10 years after someone had had a life-threatening rxn to it
30%
NOT WORTH THE CHANCE - unless can’t give something else - then give cephalosporin
A 35-yo woman had a long history of struggling with migraine headaches. She had moderately successful past responses to the triptan class of anti-migraine medicines. Acetaminophen had been minimally helpful. There was a desire to avoid opioid drugs.
Past use of Aleve™ had produced a rather serious anaphylactoid (or anaphyactic) reaction, with acute wheezing and upper airway symptoms.
Her headache physician heard of a new anti-migraine product called Treximet™, which contained a triptan, and was supposed to be even more effective than sumatriptan, and he prescribed it for the patient.
Comments?
Treximet = sumatriptan + naproxen
she is pseudoallergic to naproxen
when is skin-tesintg useful
for grasses and weeds
==> but not good for most drugs (besides Penicillin)
- Requires scratch or intradermal administration of tiny doses of parent drug, and penicilloyl polylysine (hapten-protein conjugate), and a metabolite not commercially available
Negative skin test does NOT rule out any allergic reaction, but does effectively rule out a severe or fatal Type I reaction
How to do sensitization (e.g. Penicillin G)
in patients where a drug like Pen G is clearly the drug of choice, then the benefits MAY outweigh the risks (in a few select patients)
==> Progressive doubling of the dose every 15-20 min, starting with scratch, then intradermal, then eventually IV, working up to 1-2 million units - Must continue without pause q2h
==> over 12h, depleting the mast cells
==> need to have epinephrine right nearby
A 65 yo African-American man was in residential alcohol detox 30-day program in Vermont
On HCTZ for chronic HTN; on day 5, BP was a bit higher, and second drug (oral lisinopril) was added to his daily regimen
On day 8, at 7:30 PM, he complained of tongue swelling and difficulty speaking clearly; VS, O2 sat, chest exam, mouth exam were normal (nurse)
By 8:00 PM, his tongue began to look a bit swollen; he was given diphenhydramine po (doctor and nurse)
By 9 PM, he said he also was having trouble breathing; VS, chest exam remained normal; he received second dose of oral diphenhydramine (doctor and nurse)
By 11:00 PM, he said his tongue felt more swollen, and his words were harder to understand; his chest remained clear, RR normal, O2 sat normal (nurse)
At 11:05 PM, he was sent by ambulance to the closest ER (nurse and doctor)
In ER at 11:10 PM, VS were normal; RR and O2 sat were normal; chest was clear; tongue was very swollen and asymmetric; anterior neck was swollen, and he had a thick neck to begin with; Benadryl™ and SoluMedrol™ were both given IV in the ER (Epinephrine was not given)
At 11:25, his speech seemed to deteriorate further; very hard to hear him, or understand his words; chest remained clear; O2 sat and RR remained normal
Your diagnosis? Your management plans?
-clearly moving air, but lips & neck & tongue were CLEARLY swollen
Dx: ANGIOEDEMA = AA male on ace-inhibitor (1-3%)
Patho: Bradykinin – causing vasodilatation & increased vascular permeability
==> which it why it doesn’t respond to diphenhydramine (b/c not IgE) - which is why the rest of his exam was “benign)
Tx: EPINEPHRINE stat.
