What allergies should a patient with hypertension be aware of when taking medications such as Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs), calcium channel blockers, and diuretics?

Key Drug Allergies and Hypersensitivity Reactions in Hypertension Treatment

Patients with hypertension taking ACE inhibitors, ARBs, calcium channel blockers, or diuretics need to be aware of several critical allergic and hypersensitivity reactions, with ACE inhibitor-induced angioedema being the most serious and potentially life-threatening concern.

ACE Inhibitor Allergies and Reactions

Angioedema (Most Critical)

• Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx can occur at any time during ACE inhibitor treatment and requires immediate discontinuation of the medication 1
• Laryngeal angioedema may be fatal and requires emergency treatment with subcutaneous epinephrine (1:1000,0.3-0.5 mL) and airway management 1
• Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of angioedema while receiving an ACE inhibitor 1
• If angioedema occurs with an ACE inhibitor, ARBs are the preferred alternative, though there is a 2-17% risk of cross-reactivity, particularly in patients who experienced angioedema (not simple rash) with ACE inhibitors 2

Intestinal Angioedema

• Patients may present with abdominal pain (with or without nausea/vomiting), often without prior facial angioedema 1
• This should be included in the differential diagnosis of any patient on ACE inhibitors presenting with abdominal pain 1

Anaphylactoid Reactions

• Life-threatening anaphylactoid reactions can occur during desensitization treatment with hymenoptera (bee/wasp) venom while taking ACE inhibitors 1
• These reactions are avoided when ACE inhibitors are temporarily withheld but reappear upon rechallenge 1
• For patients requiring venom immunotherapy who cannot substitute their ACE inhibitor with an equally effective alternative, the life-saving benefit of venom immunotherapy may warrant continuing the ACE inhibitor with careful monitoring 3

Dialysis Membrane Reactions

• Anaphylactoid reactions occur in patients dialyzed with high-flux membranes (particularly polyacrylonitrile/AN69 membranes) while taking ACE inhibitors or ARBs 1, 4
• Patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption are also at risk 1
• Never use ACE inhibitors or ARBs with AN69 dialysis membranes due to risk of life-threatening anaphylactoid reactions 4

ACE Inhibitor-Induced Rash

• For patients who develop a rash (not angioedema) from ACE inhibitors like lisinopril, ARBs (candesartan, losartan, or valsartan) are the preferred first-line alternative 2
• Alternative options include calcium channel blockers (particularly dihydropyridine CCBs) or thiazide-like diuretics 2
• Beta-blockers should be considered primarily in patients with specific comorbidities such as coronary artery disease or heart failure 2

ARB Considerations

• ARBs have a different mechanism of action than ACE inhibitors and are generally well-tolerated alternatives 2
• The small cross-reactivity risk (2-17%) applies mainly to angioedema, not simple rash 2
• ARBs can also cause anaphylactoid reactions with AN69 dialysis membranes, similar to ACE inhibitors 4

Calcium Channel Blocker Allergies

• Calcium channel blockers are generally well-tolerated with minimal allergic reactions 3, 5
• They can be safely combined with either ACE inhibitors or ARBs (but never both together) 6
• No specific drug allergies or cross-reactivities are commonly reported with CCBs in the guidelines reviewed

Diuretic Allergies

Sulfonamide Cross-Reactivity

• Thiazide and thiazide-like diuretics contain a sulfonamide moiety, which theoretically could cause reactions in patients with sulfa drug allergies
• However, the clinical significance of cross-reactivity between sulfonamide antibiotics and non-antibiotic sulfonamides (like thiazide diuretics) is controversial and likely overestimated in clinical practice

Critical Combination to Avoid

Never combine ACE inhibitors with ARBs, as this significantly increases the risk of hyperkalemia and acute kidney injury without providing additional clinical benefits 3, 6

Monitoring Requirements

• When initiating ARB therapy after an ACE inhibitor reaction, assess blood pressure, renal function, and electrolytes within 1-2 weeks 2
• Monitor serum creatinine, estimated GFR, and potassium levels at least annually for all patients on ACE inhibitors, ARBs, or diuretics 3
• Pay particular attention to patients with diabetes, renal impairment, or low systolic blood pressure (<80 mm Hg) 2