Get the latest news, exclusives, sport, celebrities, showbiz, politics, business and lifestyle from The VeryTime,Stay informed and read the latest news today from The VeryTime, the definitive source.

Dilemmas in Drug Therapy

28
Dilemmas in Drug Therapy Clinical decision-making is often complicated when dilemmas in therapy occur. This month's column will focus on two therapeutic dilemmas. The first dilemma is whether it is safe to use an angiotensin receptor blocker (ARB) in a patient who has a history of angioedema secondary to angiotensin-converting enzyme (ACE) inhibitors; the second involves how to manage a patient with congestive heart failure (CHF) receiving



-adrenergic blocking agents who subsequently requires hospitalization and management with positive inotropic drugs.
A 62-year-old African American woman presented to the emergency department with a 2-day history of worsening dyspnea on exertion, orthopnea, and increasing lower extremity edema. Her past medical history was significant for coronary artery disease (status post-three-vessel coronary artery bypass graft surgery in 1998), hypercholesterolemia, hypertension, and obesity. Her most recent medication history included furosemide 20 mg daily, digoxin 0.125 mg daily, ramipril 5 mg daily (started 2 years ago), amlodipine 5 mg daily, simvastatin 20 mg at bedtime, and aspirin 325 mg daily. She stopped her medications 1 week previous to presentation, secondary to swelling in her face and lips. She denied any known drug allergies as well as any history of allergies to foods. Her facial symptoms resolved over the subsequent 24 hours; however, her other symptoms are now progressing.

Question: Is This Reaction Compatible With ACE Inhibitor-Induced Angioedema and If So, Is It Safe to Use an ARB?

Current guidelines for the management of CHF all recommend the use of an ACE inhibitor based on evidence that has established their efficacy in improving symptoms, decreasing progression of heart failure, decreasing the need for hospitalization, and lowering mortality. Subsequently their use has increased significantly in the last 10 years. Most patients tolerate them, although they have been associated with a number of troublesome side effects including cough, and rarely, angioedema.

Angioedema secondary to medications usually presents as noninflammatory, nonpitting edema of the skin and subcutaneous tissue commonly involving the face, mouth, throat, and nose. The mucous membranes of the lips and tongue may also be involved, and less frequently, the gastrointestinal tract, extremities, trunk, and genitalia. Bronchospasm is rarely involved; however, airway obstruction secondary to swelling may occur and if it does, angioedema can become life threatening. Most cases of angioedema respond promptly to discontinuation of further exposure to the suspected offending agent, administration of diphenhydramine, and occasionally, glucocorticoids, and it resolves without sequelae. Rarely, intubation may be required if airway obstruction occurs.

ACE inhibitor-induced angioedema has been estimated to occur in 0.1%-1.2% of patients receiving them. There appears to be no predictive relationship to gender, age, dose, or specific product. African Americans have been reported to experience a higher incidence of ACE inhibitor angioedema and it has been estimated to occur in up to 5.5% of this group. Patients with a history of hereditary angioedema are thought to be at higher risk and it has been suggested that an allergy to seafood may be associated with an increased likelihood to develop angioedema. The onset of angioedema secondary to ACE inhibitor use may occur as early as a few hours or be delayed as long as 5 years. Patients who have experienced ACE inhibitor angioedema usually develop it upon rechallenge.

The mechanism for the development of ACE inhibitor-induced angioedema has not been clearly described. Accumulation of bradykinin has been the primary suspect as it also has been for development of the cough with ACE inhibitors. It does not seem to be an immune-mediated reaction. Other potential explanations include a histamine-mediated mechanism and finally, a deficiency of complement-1-esterase inactivator secondary to the ACE inhibition.

It was initially thought that ARBs were not associated with angioedema since they do not result in the accumulation of bradykinin. While it is true that ARBs are associated with a lower incidence of angioedema, it is now known that it can occur. Most of the cases have been described with the use of losartan. There are reports of angioedema associated with candesartan, valsartan, irbesartan, and telmisartan. It has occurred as early as 30 minutes to as late as 3 years following administration. Symptoms have included facial and uvula swelling, difficulty swallowing, and slurred speech. In one review of 19 cases of angioedema secondary to ARBs (18 losartan, 1 valsartan), six of the 19 cases occurred in patients with a history of angioedema from previous exposure to ACE inhibitors. The safety of ARB administration to patients who have developed angioedema has thus been questioned.

This patient's symptoms are suggestive of ACE inhibitor-induced angioedema; she is African American and this group does have an increased incidence of developing it. The time course for its presentation is so broad that this does not help, nor does the fact that there is a lack of association with age, selection of specific agent, or gender. Most cases like hers do resolve without any sequelae or complications. Since up to 30% of patients with ARB-induced angioedema previously experienced angioedema with ACE inhibitors, the risk for cross-reaction in this patient is significant, although the chance of a life-threatening reaction is small. Because ACE inhibitors and ARBs are so effective in modulating the neurohormonal profile in patients with CHF, some do feel that the risk is warranted. In our case, alternative therapies do exist. A combination of hydralazine and nitrates would be the preferred vasodilator regimen. Spironolactone and




-adrenergic blocking agents should also be considered as additional approaches to the management of her symptoms, in an effort to interrupt the maladaptive changes occurring in the renin-angiotensinaldosterone system. ARBs should be used with extreme caution in this patient and only if there is inadequate response to the addition of the alternative therapy. Their use would require very close monitoring and communication with the patient and her caregivers.


Source...
Subscribe to our newsletter
Sign up here to get the latest news, updates and special offers delivered directly to your inbox.
You can unsubscribe at any time

Leave A Reply

Your email address will not be published.