Anaphylactic Shock, Cheese Reaction, Digoxin+Quinidine.pptx

Anaphylactic Shock
Anaphylactic shock is a severe, life-threatening allergic reaction caused by an extreme immune response to allergens like drugs, food, or insect stings. It leads to vasodilation, hypotension, bronchospasm, and airway edema, requiring immediate treatment with epinephrine, antihistamines, and corticosteroids to prevent fatal outcomes.

Cheese Reaction
The cheese reaction occurs due to tyramine-rich food (e.g., aged cheese, wine) consumption in patients taking monoamine oxidase inhibitors (MAOIs). Tyramine causes excessive norepinephrine release, leading to hypertensive crisis, headache, sweating, and palpitations. Management includes avoiding tyramine-rich foods and administering antihypertensive agents if needed.

Digoxin + Quinidine Interaction
Quinidine inhibits P-glycoprotein, reducing digoxin clearance and increasing its serum levels, leading to digoxin toxicity. Symptoms include nausea, vomiting, arrhythmias, and visual disturbances. Monitoring digoxin levels and dose adjustment are crucial to prevent toxicity.

1. Anaphylactic Shock, Cheese Reaction & Drug Interaction between Digoxin and Quinidine Dr. Anto Rajiv, Junior Resident, Department of Pharmacology and Therapeutics, KGMU , Lucknow

2. Introduction Definition: Anaphylactic shock is a severe, potentially life-threatening hypersensitivity reaction that occurs rapidly within seconds or minutes of exposure of allergen and requires immediate medical attention. It can be allergic or non-allergic Importance: Understanding the causes, symptoms, and treatment of anaphylactic shock is crucial for effective emergency response.

3. Pathophysiology Allergen (re)exposure IgE binds to mast cells and basophils Release of histamine and other mediators Widespread vasodilation, increased vascular permeability, and smooth muscle contraction etc.

4. Mediators Histamine Function: Vasodilation: Causes a decrease in systemic vascular resistance, leading to hypotension. Increased Vascular Permeability: Leads to fluid leakage into tissues, causing edema and further contributing to hypotension. Bronchoconstriction: Narrows the airways, leading to wheezing and difficulty breathing. Stimulation of Nerve Endings: Causes itching and pain.

5. Leukotrienes (e.g., LTC4, LTD4, LTE4) Function: Bronchoconstriction: Strongly constricts the airways, more potent and prolonged than histamine. Increased Vascular Permeability: Contributes to edema and swelling. Chemotaxis: Attracts other inflammatory cells to the site of reaction.

6. Prostaglandins (e.g., PGD2) Function: Bronchoconstriction: Contributes to airway narrowing. Vasodilation: Assists in lowering blood pressure. Increased Vascular Permeability: Promotes fluid leakage and edema .

7. Cytokines (e.g., TNF-α, IL-4, IL-5, IL-6) Function: Inflammation: Promote and sustain the inflammatory response. Cell Recruitment: Attracts and activates other immune cells, amplifying the allergic reaction. Tissue Damage: Contributes to prolonged tissue inflammation and damage.

8. Platelet-Activating Factor (PAF) Function: Bronchoconstriction: Causes narrowing of the airways. Vasodilation and Increased Permeability: Lowers blood pressure and promotes edema. Platelet Aggregation: Contributes to clot formation and further release of mediators from platelets.

9. Tryptase Function: Mast Cell Marker: Elevated levels can indicate mast cell activation. Tissue Damage: Breaks down proteins in the extracellular matrix, contributing to tissue damage and inflammation.

10. Serotonin (5-HT) Function: Vasoconstriction and Vasodilation: Effects on blood vessels can vary, contributing to changes in blood pressure. Smooth Muscle Contraction: Affects gastrointestinal motility and can cause cramps.

11. Bradykinin Function: Vasodilation: Contributes to hypotension. Increased Vascular Permeability: Promotes fluid leakage and edema . Pain: Activates pain receptors.

12. Symptoms

13. Immediate Management Emergency Response: Call for emergency medical help immediately. Lay the patient flat, elevate legs, and keep them warm. First-Line Treatment: Epinephrine: Administer intramuscularly (auto-injector if available). Airway Management: Ensure open airway, provide oxygen if needed. Secondary Treatment: Antihistamines: To reduce symptoms (e.g., diphenhydramine). Corticosteroids: To reduce inflammation (e.g., prednisone). Fluids: Intravenous fluids to maintain blood pressure.

14. Long-term Management Avoidance of Triggers: Identifying and avoiding known allergens. Medications: Prescribe and educate on the use of epinephrine auto-injectors. Allergy Testing: Referral to an allergist for testing and desensitization therapies. Patient Education: Training on recognizing early symptoms and how to use an auto-injector.

15. Resuscitation Council of UK Guidelines Put the patient in reclining position, administer oxygen at high flow rate and perform cardiopulmonary resuscitation if required. Inject adrenaline 0.5 mg (0.5 ml of 1 in 1000 solution for adult, 0.3 ml for child 6-12 years and 0.15 ml for child upto 6 years) i.m. R epeat every 5–10 min in case patient does not improve or improvement is transient. This is the only life saving measure. Adrenaline should not be injected i.v. (can itself be fatal) unless shock is immediately life threatening. If adrenaline is to be injected i.v. , it should be diluted to 1:10,000 or 1:100,000 and infused slowly with constant monitoring.

16. Administer a H1 antihistaminic (pheniramine 20–40 mg or chlorpheniramine 10–20 mg) i.m. /slow i.v. Intravenous glucocorticoid (hydrocortisone sod. succinate 200 mg) should be added in severe/recurrent cases. It acts slowly, but is specially valuable for prolonged reactions and in asthmatics. It may be followed by oral prednisolone for 3 days. Adrenaline followed by a short course of Glucocorticoids is indicated for bronchospasm Attending drug hypersensitivity. Glucocorticoids are the only drug effective in type II, type III and type IV reactions.

17. Case study Patient Background Name: Alex Smith Age: 12 years Medical History: No significant past medical history

18. Presentation Chief Complaint: Severe allergic reaction following a bee sting History of Present Illness: Alex was playing in the yard when he was stung by a bee on his right forearm. Initially, he experienced localized pain and swelling. Fifteen minutes later, he developed shortness of breath, wheezing, and felt weak and dizzy. His parents brought him to the emergency department immediately.

19. Examination Vital Signs: Temperature: 37.1°C Pulse: 120 bpm Respiratory Rate: 39 breaths/min Blood Pressure: 69/45 mmHg

20. Physical Examination: General: Mild respiratory distress, drowsy, pale Skin: Generalized urticaria, no conjunctival edema Cardiovascular: Tachycardic without murmurs Respiratory: Mild wheezing, fair aeration, minimal retractions Gastrointestinal: Soft, non-tender Site of Bee Sting: Unremarkable, no foreign body

21. Management Epinephrine: 0.01 mg/kg of 1:1000 solution given subcutaneously/intramuscularly Albuterol : Updraft administered for wheezing IV Access: IV fluids initiated with normal saline bolus Medications: Diphenhydramine: 25 mg IV Cimetidine: 300 mg IV Methylprednisolone: 125 mg IV

22. Outcome Response to Treatment: Symptoms improved significantly post-epinephrine and albuterol. Blood pressure normalized, urticaria resolved, lungs cleared. Observation: Monitored for 3 hours in the emergency department. No recurrence of symptoms

23. Prevention Education: Educate patients, families, and caregivers about anaphylaxis and its triggers. Emergency Action Plan: Develop an action plan for managing anaphylactic emergencies. Medical Identification: Advise patients to wear medical alert bracelets.

24. Cheese Reaction A hypertensive crisis caused by the interaction between dietary tyramine and monoamine oxidase inhibitors (MAOIs). Importance: Recognizing and managing cheese reactions are crucial for preventing life-threatening hypertensive episodes in patients on MAOIs

25. Pathophysiology Tyramine is a byproduct of Tyrosine metabolism by MAO in the liver. Typically it will have low bioavailability due to extensive first-pass effect in the liver.  If the patient is taking a  MOA inhibitor,  tyramine accumulates in the bloodstream It has  indirect sympathomimetic action causing the release of stored catecholamines. It can lead to a sudden and dangerous elevation in blood pressure, resulting in a hypertensive crisis . This is known as the “Cheese Reaction”!!!

26. Causes Dietary Sources of Tyramine: Aged cheese (e.g., cheddar, blue cheese) Fermented foods (e.g., sauerkraut, soy sauce) Cured meats (e.g., salami, pepperoni) Alcoholic beverages (e.g., red wine, beer) Other sources (e.g., overripe fruits, certain beans)

27. Uses of MAOIs Refractory Obsessive-Compulsive Disorder (OCD) Post-Traumatic Stress Disorder (PTSD) Narcolepsy Smoking Cessation Specific Phob ias Major Depressive Disorder (MDD) Refractory Depression Panic Disorder Social Anxiety Disorder Parkinson's Disease Chronic Migraine Bulimia Nervosa

28. Symptoms Early Symptoms: Headache (often severe or throbbing) Nausea and vomiting Severe Symptoms: Chest pain or tightness Shortness of breath Anxiety or panic attacks Hypertension (sudden and severe increase in blood pressure) Palpitations or tachycardia Sweating and flushing

29. Clinical features Hypertension developed within 20 min - 1 hr Hallmark Presentation: Hypertension + Severe headache (occipital or temporal) Typically resolving within 4-6 hours However it can be fatal

30. Immediate Management Emergency Response: Stop consuming the suspected food immediately. Seek emergency medical help if severe symptoms occur. First-Line Treatment: Antihypertensive Medications: Administer medications like phentolamine, nifedipine, or nitroprusside to lower blood pressure. Monitoring: Continuous monitoring of blood pressure, heart rate, and oxygen saturation. Supportive Care: Provide oxygen if needed. Maintain an open airway and ensure adequate ventilation.

31. First-Line Treatment: Phentolamine ( N on-selective α 1 + α 2 adrenergic blocker) Dose: 5 mg IV bolus, may repeat every 10-15 minutes as needed. Alternative Treatment: Nitroprusside Dose: Start at 0.3 mcg/kg/min IV infusion, titrate to effect. Additional Medications: Benzodiazepines: For agitation and to lower blood pressure (e.g., Lorazepam 1-2 mg IV). Beta-Blockers: Only if there are tachyarrhythmias and no signs of heart failure (e.g., Labetalol 20 mg IV over 2 minutes, repeat or increase dose as needed).

32. Long-term Management Dietary Restrictions: Strictly avoid tyramine-rich foods and beverages. Provide a comprehensive list of restricted items to the patient. Medication Review: Regularly review all medications with a healthcare provider to avoid potential interactions. Patient Education: Educate patients on the importance of dietary compliance. Inform patients about the signs and symptoms of hypertensive crisis and the need for immediate medical attention.

33. Case Study Patient Background Name: John Doe Age: 45 years Medical History: Major Depressive Disorder, Hypertension Current Medications: Phenelzine (MAOI) 15 mg three times daily, Lisinopril 20 mg daily

34. Presentation Chief Complaint: Severe headache and palpitations History of Present Illness: John Doe presents to the emergency department with a sudden onset of severe throbbing headache, palpitations, and sweating that started 30 minutes ago. He reports consuming a large amount of aged cheese at a dinner party an hour prior to symptom onset. He denies any chest pain, shortness of breath, or visual disturbances.

35. Examination Vital Signs: Blood Pressure: 200/110 mmHg Heart Rate: 110 bpm Respiratory Rate: 18 breaths/min Temperature: 37.0°C Oxygen Saturation: 98% on room air

36. Physical Examination: General: Patient appears anxious and diaphoretic. Cardiovascular: Tachycardia without murmurs, strong peripheral pulses. Respiratory: Clear to auscultation bilaterally. Neurological: Alert and oriented, no focal deficits. Gastrointestinal: Soft, non-tender, normal bowel sounds. Dermatological: No rashes or lesions.

37. Diagnosis: Hypertensive crisis due to tyramine interaction with MAOI (cheese reaction). Immediate Management Discontinue MAOI: Phenelzine is held immediately. Initial Stabilization: Patient is placed in a semi-reclined position. Supplemental oxygen is provided via nasal cannula at 2 L/min.

38. Pharmacological Intervention: Phentolamine: 5 mg IV bolus administered, repeated once after 15 minutes due to insufficient blood pressure reduction. Labetalol: 20 mg IV over 2 minutes administered as an adjunct to phentolamine. Lorazepam: 1 mg IV for anxiety and to assist with blood pressure control. Monitoring: Continuous cardiac and blood pressure monitoring initiated. Neurological status monitored regularly for any changes.

39. Outcome Response to Treatment: Blood pressure gradually decreased to 150/90 mmHg over the course of an hour. Headache and palpitations resolved. Patient remained hemodynamically stable and symptom-free. Observation: Monitored in the emergency department for an additional 6 hours. No recurrence of symptoms, stable vital signs.

40. Drug Interaction: Digoxin + Quinidine Digoxin Overview Mechanism of Action: Increases the force of myocardial contractions by inhibiting the sodium-potassium ATPase pump. Used primarily for heart failure and atrial fibrillation. Pharmacokinetics: Oral bioavailability: 60-80% Half-life: 36-48 hours Primarily excreted unchanged by the kidneys.

41. Quinidine Overview: Mechanism of Action: Class I antiarrhythmic that blocks sodium channels, reducing the maximal rate of depolarization in the heart. Used for various cardiac arrhythmias. Pharmacokinetics: Oral bioavailability: 70-80% Half-life: 6-8 hours Metabolized in the liver, primarily by CYP3A4.

42. Mechanism of Interaction Increased Digoxin Levels: Quinidine inhibits P-glycoprotein, a transporter protein that helps in the excretion of digoxin from the kidneys and intestines. This inhibition leads to increased absorption and decreased excretion of digoxin, resulting in higher serum levels.

43. Symptoms of Digoxin Toxicity Cardiac: Bradycardia Arrhythmias Heart block Neurological: Confusion Dizziness Visual disturbances (yellow or blurred vision) Gastrointestinal: Nausea Vomiting Diarrhea

44. Management Strategies Monitoring: Regularly monitor serum digoxin levels when starting or stopping quinidine. Watch for signs and symptoms of digoxin toxicity. Dosage Adjustment: Reduce the dose of digoxin when starting quinidine. Consider discontinuing quinidine if digoxin toxicity occurs.

45. Preventive Measures Patient Education: Inform patients about the signs of digoxin toxicity. Advise patients to report any new symptoms immediately. Clinical Guidelines: Follow clinical guidelines for drug interactions and monitoring protocols. Use alternative medications if possible to avoid interactions.

46. Alternative Medications For Arrhythmias: Consider other antiarrhythmics with less potential for interaction with digoxin, such as amiodarone or beta-blockers (with caution). For Heart Failure: Evaluate the use of other medications like ACE inhibitors, ARBs, or beta-blockers that do not interact with digoxin.

47. Summary Anaphylactic Shock: Anaphylactic shock is a severe, systemic allergic reaction characterized by rapid onset and potentially life-threatening symptoms. It occurs when the immune system overreacts to an allergen, triggering the release of histamine and other inflammatory mediators. Symptoms include difficulty breathing, swelling, low blood pressure, and can progress rapidly without intervention. Treatment involves immediate administration of epinephrine (adrenaline) to reverse symptoms and stabilize the patient.

48. Cheese Reaction: A cheese reaction typically refers to adverse reactions that can occur after consuming cheese or dairy products in patients taking MAOIs. These reactions can range from mild intolerance symptoms, such as nausea, to more severe Hypertensive crisis. Treatment may include Antihypertensives, Antihistamines or avoidance of dairy products.

49. Drug Interaction between Digoxin and Quinidine: Digoxin and quinidine interact pharmacokinetically and pharmacodynamically, potentially leading to adverse effects. Quinidine can inhibit the metabolism of digoxin, increasing its blood levels and toxicity risk. Concurrent use requires close monitoring of digoxin levels and cardiac function to prevent digoxin toxicity, which can manifest as nausea, vomiting, visual disturbances, or cardiac arrhythmias. Adjustments in dosage or alternative therapies may be necessary under medical supervision.

50. References Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391-397. Tripathi KD, Essentials of Medical Pharmacology. 8 th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Finberg JP, Rabey JM. Inhibitors of MAO-A and MAO-B in psychiatry and neurology. Front Pharmacol . 2016;7:340. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth . 2005;95(4):434-441. Shulman KI, Herrmann N, Walker SE. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs. 2013;27(10):789-797. World Allergy Organization. WAO Anaphylaxis Guidelines: 2020 Update