Lisinopril

Cardiovascular

The use of lisinopril in congestive heart failure has been reviewed [ ], including a section on tolerability and details of the ATLAS (Assessment with Treatment with Lisinopril and Survival) trial. The tolerance of high doses of lisinopril (32.5–35 mg od) in heart failure, one of the issues addressed by this trial, was not significantly different from that of low doses (2.5–5 mg od). Since high doses were more effective than low doses, the authors recommended that more aggressive use of ACE inhibitors is warranted [ ]. However, this conclusion is valid only in the conditions of the trial, with careful and slow dose escalation. With such a strategy, most patients with heart failure can be titrated successfully to high maintenance doses.

Shock after myocardial infarction has been attributed to an ACE inhibitor [ ].

• A 42-year-old woman suffered an acute anterior myocardial infarction, initially associated with pulmonary edema. After hemodynamic stabilization she was given lisinopril 10 mg orally. Two hours later she developed circulatory failure in conjunction with acute renal insufficiency. Right heart catheterization showed markedly reduced systemic vascular resistance but a normal cardiac index. After the usual causes of cardiogenic shock had been ruled out, repeated fluid challenges and intravenous noradrenaline failed to improve her hemodynamic status. She was therefore given angiotensin II intravenously (5–7.5 micrograms/minute), which immediately and markedly raised the systematic vascular resistance and resulted in subsequent regression of shock. She was discharged after an otherwise uneventful course.

Endocrine

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been attributed to lisinopril [ ].

• A 76-year-old woman taking lisinopril 20 mg/day and metoprolol for hypertension developed headaches, nausea, and a tingling sensation in her arms. Her serum sodium was 109 mmol/l, with a serum osmolality of 225 mosm/kg, urine osmolality of 414 mosm/kg, and urine sodium of 122 mmol/l. She had taken diclofenac 75 mg/day for arthritic pain for 6 years and naproxen for about 1 month. Propoxyphene napsylate and paracetamol had then been substituted and zolpidem had been started. A diagnosis of SIADH was postulated and thyroid and adrenal causes were excluded. Lisinopril was withdrawn and fluid was restricted to 100 ml/day. The serum sodium gradually corrected to 143 mmol/l.

The authors referred to three other similar cases, in two of which the diagnosis may have been confused by the concomitant use of diuretics in patients with heart failure. However, the present and one other case had occurred without co-existing risk factors for hyponatremia. They discussed a synergistic effect of zolpidem and/or diclofenac, and suggested a potential mechanism involving non-inhibition of brain ACE, which leaves brain angiotensin II receptors exposed to high circulating concentrations of angiotensin which would strongly stimulate thirst and the release of antidiuretic hormone.

Pancreas

Acute pancreatitis has been reported with several of the ACE inhibitors; recurrent pancreatitis attributed to lisinopril has been reported [ ]. The case demonstrated that the condition can recur while patients continue to take. The evidence relating to ACE inhibitor therapy and pancreatitis has also been reviewed [ ].

• A 67-year-old man without other risk factors developed acute pancreatitis only 3 hours after taking lisinopril. The originality of this case resides in the fact that the patient had experienced a similar but less severe reaction to the medication 3 months before. Thus, this case probably represents the first time a patient was rechallenged with lisinopril and had a more severe adverse reaction [ ].

• A 42-year-old woman, who was taking lisinopril, nicardipine, metoprolol, simvastatin, omeprazole, an estrogen, and sublingual glyceryl trinitrate, presented with epigastric pain and vomiting [ ]. Pancreatitis was diagnosed on the grounds of raised activities of lipase (200 IU/l) and amylase (117 IU/l) and diffuse homogeneous enlargement of the head and body of the pancreas on CT scan. The pancreatic enzyme activities normalized 5 days after lisinopril and simvastatin withdrawal. Two months later she was taking estrogen and simvastatin, but not lisinopril. Her amylase and lipase were normal.

The temporal relation in the second case suggests that lisinopril was causative. The authors raised the possibility that the concomitant use of an estrogen and simvastatin, as well as a history of familial hypertriglyceridemia, may have predisposed her to pancreatitis.

A further case has been reported in a patient taking lisinopril and hydrochlorothiazide [ ]. There was associated radiological evidence of biliary tract pathology, and the authors concluded that in this case the drug may have aggravated the acute illness.

Pancreatitis has been reported in a patient taking lisinopril and atorvastatin [ ]. The relative contributions of each drug were not explored.

Two other cases of lisinopril-induced pancreatitis have been reported [ , ]. The second case involved fatal necrotizing pancreatitis in a patient taking a combination of hydrochlorothiazide and lisinopril. Although it was likely that this was a drug-induced event, the authors did not try to implicate one drug over the other, as both have been reported to cause pancreatitis.

Skin

Dermatological adverse reactions are relatively uncommon with ACE inhibitors but erythematous rashes, urticaria, alopecia, and lichenoid eruptions have all been reported. A pityriasis rosea-like eruption has been reported [ ].

• A 72-year-old Caucasian man developed flat, round, or oval scaly patches, bright red to violet in color, on the trunk, abdomen, and proximal limbs. The scaly surface showed a typical marginal collarette. He reported severe itching, unresponsive to antihistamine treatment. The eruption had begun suddenly 1 month before, had been exanthematous from the start, and evolved in successive crops with no tendency to spontaneous remission. There were no general or prodromic symptoms. He had started to take lisinopril about 2 weeks before the onset of the eruption, was taking no other medications, and had never suffered adverse drug reactions. Lisinopril was withdrawn and the lesions ameliorated rapidly and healed in about a week, without specific treatment.

Pemphigus foliaceus has been reported with captopril, ramipril, enalapril, and fosinopril, as well as a wide variety of other drugs, and lisinopril has also been implicated.

• A 66-year-old man developed pemphigus foliaceus while taking lisinopril for hypertension and ischemic heart disease [ ]. Response to dechallenge was rapid, with resolution of blister formation within 48 hours. There was no recurrence during 3 weeks without ACE inhibitor treatment.

Although there was co-existent rheumatoid arthritis, which can be associated with pemphigus foliaceus, the authors concluded that the time relation in the case suggested that lisinopril was the more important factor.

Bullous pemphigoid has been attributed to lisinopril in a 75-year-old man with hypertension [ ]. The diagnosis of drug-induced pemphigoid was supported by the temporal nature of the reaction, which occurred 2 months after the start of treatment (similar to other cases of bullous pemphigoid, which tends to occur at 1–3 months), and the fact that treatment with corticosteroids was ineffective while the patient was taking lisinopril but remission was achieved quickly after withdrawal.

Worsening of pre-existing cold urticaria has been associated with lisinopril [ ].

• A 43-year-old Caucasian man had a history of mild cold urticaria during the preceding 10 years. Shortly after starting to take lisinopril 20 mg/day and hydrochlorothiazide 25 mg/day for hypertension his condition worsened considerably and he had several bouts of severe cold urticaria. On one occasion, after swimming in water at 24 °C, he developed severe urticaria and angioedema, and required emergency hospital admission. Standard ice-cube and cold-water immersion tests were strongly positive within 1 minute. Tests for a variety of causative factors were negative, and a diagnosis of acquired cold urticaria was made. Lisinopril was withdrawn, he was given valsartan 80 mg/day, and the dose of hydrochlorothiazide was reduced to 12.5 mg/day. During the next 24 weeks he had only mild symptoms of cold urticaria. Repeat ice-cube and cold-water immersion tests were negative at 1 and 3 minutes, but positive at 5 minutes.

The authors cited evidence that the kallikrein/kinin system is involved in cold urticaria, that ACE inhibitors increase wheal-and-flare reactions to cutaneously applied bradykinin, and that ACE inhibitor therapy is associated with raised plasma kinin concentrations. They therefore recommended avoidance of ACE inhibitors in patients with cold urticaria.

Erythema multiforme has been attributed to lisinopril [ ].

• A 68-year-old man who had taken lisinopril 10 mg/day for several years stopped taking it temporarily because of a cough. It was then restarted in a dosage of 5 mg/day and a few days later he developed several bean-sized non-pruritic erythematous plaques with scales over the whole body, particularly on the chest. The appearance was of seborrheic dermatitis, but histology showed the features of erythema multiforme. The eruptions cleared completely a few days after lisinopril withdrawal. Two months later, a rechallenge test was positive.

Erythroderma presumed to be secondary to lisinopril has been reported in an 85-year-old man with no previous history of skin disease [ ].