enalapril and Pain

Besides the well-known role of the angiotensin system in blood pressure control, an interaction of angiotensin and pain perception has been suggested. This study sought to investigate whether an angiotensin converting enzyme inhibitor, which facilitates bradykinins, algesic peptides, and/or an AT1 receptor antagonist may modify hypertension-related hypoalgesia in humans. The study was approved by the ethical committee of our Department.. A total of 22 hypertensive patients were submitted to dental pulp stimulation to obtain the dental pain threshold and tolerance, and to 24 h blood pressure monitoring together with a control group of 55 normotensives. Then the hypertensives were randomized to enalapril or losartan treatment and were re-evaluated (dental pain perception and ambulatory monitoring) after 8 weeks of the first treatment and after an additional 8 weeks of the second treatment.. Untreated hypertensives showed a reduced perception to painful stimuli when compared with normotensives. A significant reduction of both pain threshold and tolerance was observed during the anti-hypertensive treatments (Friedman test: P = 0.007 and P = 0.006, respectively). Pain sensitivity was similar during the two treatments and it did not differ from pain sensitivity values of normotensive controls. ANCOVAs were computed to evaluate the relationship between anti-hypertensive agents and pain sensitivity, after controlling for blood pressure. A 24 h mean pressure served as covariate, removing any effect of blood pressure; a significant difference was observed entering both pain threshold and tolerance as dependent variables (F = 5.28, P = 0.0076; F = 8.16, P = 0.0007, respectively).. Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Dental Pulp; Electric Stimulation; Enalapril; Humans; Hypertension; Losartan; Male; Middle Aged; Pain; Pain Threshold; Receptor, Angiotensin, Type 1; Reference Values

Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.

Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Amlodipine; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Double-Blind Method; Drug Interactions; Dyspepsia; Enalapril; Female; Humans; Hypertension; Indomethacin; Male; Middle Aged; Nausea; Pain; Renin

We describe the case of a 77-year old mildly hypertensive woman with no underlying renal disease who was admitted to the Emergency Department (ED) in a comatose state with fever. The patient had been on low dose enalapril and a potassium rich diet. Five days before admission, rofecoxib, a new selective COX-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID), was added for leg pain. She was found to have severe hyperkalemia and died 90 min after her arrival. We cannot absolutely determine whether the COX-2 inhibitor was the dominant contributor to the development of hyperkalemia or the combination itself, with an intercurrent infection and some degree of dehydration. Physicians should be aware of this possible complication and only prescribe NSAIDs, including the new COX-2 drugs, to the elderly under close monitoring of kidney function and electrolyte tests.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cyclooxygenase Inhibitors; Diet; Drug Interactions; Drug Therapy, Combination; Enalapril; Fatal Outcome; Female; Humans; Hyperkalemia; Hypertension; Lactones; Musa; Pain; Sulfones

Effects of the angiotensin-converting enzyme (ACE) inhibitors, imidapril and enalapril, on kaolin-induced writhing reaction, which is believed to be caused by bradykinin (BK), were examined in mice. The number of writhes was increased significantly by 200 microg/kg of imidapril and by 100 and 200 microg/kg of enalapril. The intensity of writhing reaction was significantly suppressed by 1,000 nmol/kg of icatibant, a selective bradykinin B2 receptor antagonist, in the imidapril-, but not in the enalapril-treated groups. These results suggest that the potentiating effect of enalapril on kaolin-induced writhing reaction is greater than that of imidapril. This might depend on the difference of their inhibitory effects on BK degradation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin Receptor Antagonists; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Enalapril; Imidazoles; Imidazolidines; Kaolin; Male; Mice; Mice, Inbred ICR; Pain

To present a case of respiratory depression following the administration of nebulised morphine.. A 74-yr-old, 51-kg woman with a history of hypertension controlled with 5 mg.day-1 enalapril and 50 mg.day-1 atenolol was admitted for evaluation of low back pain, loss of appetite, and weight loss. Investigation revealed advanced metastatic disease with a probable primary in the right lung. The patient's pain was well controlled with 10 mg continuous release morphine p.o. three times daily, and 10 mg immediate release morphine p.o. for breakthrough pain as required. During the two weeks following the commencement of this treatment she occasionally complained of shortness of breath. Examination revealed a fully conscious patient with slight dyspnoea and mild wheezing which responded to oxygen 30% and nebulised bronchodilators. An oncological consultation recommended 4 mg nebulised morphine and 4 mg dexamethasone in saline as treatment for the bouts of breathlessness. Approximately 15 min after the first administration of nebulised morphine the patient became markedly bradypneic (respiratory rate: 4-5 bpm), hypotensive (BP 70/40 mmHg), and responded only partially to command. The pupils were pinpoint. The trachea was immediately intubated and the lungs ventilated with oxygen 40% for four hours. Following this occurrence of respiratory depression nebulised morphine was discontinued and no further events occurred.. Patients receiving inhaled morphine should be closely monitored and resuscitation equipment should be readily available.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Aged; Analgesics, Opioid; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antihypertensive Agents; Bone Neoplasms; Bronchodilator Agents; Dexamethasone; Dyspnea; Enalapril; Female; Glucocorticoids; Humans; Hypertension; Intubation, Intratracheal; Lung Neoplasms; Morphine; Nebulizers and Vaporizers; Oxygen Inhalation Therapy; Pain; Palliative Care; Respiration; Respiration, Artificial; Respiratory Insufficiency; Respiratory Sounds