Beta-blockers are used to treat high blood pressure , heart disease, migraine headaches, hyperthyroidism, generalized anxiety, and essential tremor. Beta receptors receive messages from signaling chemicals in your body and pass that message along. Beta-blocker medications prevent that message from being received. There are two kinds of beta receptors in your body: beta-1 and beta Your heart has more beta-1 receptors.
Your airway has more beta-2 receptors. There are other beta-blockers that target the beta-1 receptors in your heart. They cause the airways to narrow and become more sensitive. On average, they cause lung function to decline by Nearly everyone with asthma reacts to non-selective beta-blockers. Beta-blockers are often used after a heart attack to improve survival and quality of life. These medications target the beta-1 receptors in your heart.
ACE inhibitors are used to treat high blood pressure, heart disease, and kidney disease related to diabetes. The main side effect of taking an ACE inhibitor is cough. The study compared mg celecoxib two times a day with mg ibuprofen three times a day and mg naproxen two times a day.
The subjects suffered from osteoarthritis or rheumatoid arthritis and at the same time were at increased risk for CV events. Celecoxib was found to be non-inferior to ibuprofen and naproxen for the primary outcome of a composite of CV death, non-fatal myocardial infarction MI cor non-fatal stroke.
Clinical studies of newer coxibs also brought distressing results. In patients not on low dose ASA, cardiovascular events occurred more frequently in the selective COX-2 group, but the difference was not statistically significant 0.
The study group consisted of patients with osteoarthritis [ 19 ]. In another study enrolling patients after coronary artery bypass grafting CABG , a series of events affecting the cardiovascular system emerged, ultimately leading to rejection of parecoxib prodrug of valdecoxib by the food and drug administration FDA [ 20 ].
An increased number of cardiovascular events compared with placebo and with traditional NSAIDs was also reported in the case of etoricoxib [ 22 ]. On the other hand, in the recently published retrospective analysis by de Souza Brito, et al. The study included a robust number of patients. On the other hand, all NSAIDs were grouped together without specifying the actual medications used, which poses a significant limitation.
Therefore in recent years, the cardiovascular safety of NSAIDs has been addressed in many clinical trials and meta-analyses. Trelle, et al. These conditions were met by 31 studies, involving a total of , patients with over , patient-years of follow-up.
The primary outcome was acute myocardial infarction AMI. As secondary outcomes, stroke, CV death and death from any cause were studied. Results were statistically evaluated for three non-selective NSAIDs naproxen, ibuprofen, diclofenac and four coxibs rofecoxib, celecoxib, lumiracoxib, etoricoxib. Another meta-analysis of randomized trials found RR of major coronary events to be 1. The increased risk of thrombotic events mediated by non-selective NSAIDs and selective COX-2 inhibitors has been also shown by large-scale epidemiological studies.
The results of 23 controlled observational studies six cohort and 17 case-control were summarized by McGettigan and Henry in their meta-analysis [ 26 ]. The case-control studies included 86, patients with cardiovascular events and , controls. Patients were followed for more than , patient-years. The RR of AMI and death from coronary causes during analgesic therapy lasting less than 90 days: naproxen- 0.
The first theory trying to explain the risk of thrombotic events of selective COX-2 inhibitors was based on the assumption that COX-2 in the vessel wall was an important source of prostacyclin, whereas COX-1 was responsible for the production of thromboxane in platelets.
Selective COX-2 inhibition would in this situation decrease the production of PGI-2, which is a vasodilating and antithrombotic substance, without inhibiting the vasoconstricting and thrombogenic TXA The resulting imbalance between pro-thrombotic and antithrombotic factors could lead to thrombosis [ 28 ]. On the other hand, the greater risk of thrombotic events with highly selective COX-2 inhibitors when compared with non-selective NSAIDs apparently cannot be explained only by the concomitant inhibition of platelet function with the non-selective agents.
This happens only with aspirin, and in certain situations with high dose naproxen [ 29 ]. The overall strength of COX-2 inhibition appears to be the most important determinant of cardiovascular risk [ 29 ]. Results of numerous experiments show the important role of COX-2 in production of prostacyclin in the vascular bed [ 30 ]. The inhibition of PGI-2 production causes an increase in vascular tone, blood pressure elevation, thrombogenic state and likely atherosclerosis.
Cyclooxygenase-2 and PGI-2 also seem to play a key role in the resistance of the myocardium to ischemic-reperfusion injury observed after ischemic preconditioning or after administration of certain medications [ 31 - 32 ]. The potential importance of cardioprotective effects of COX-2 was also underscored in the position paper written by the working group for cardiovascular pharmacotherapy of the European Society of Cardiology [ 33 ].
Administration of statins before ischemia leads to reduction in the size of myocardial necrosis in animal models of ischemia-reperfusion injury. Selective COX-2 inhibition attenuates this statin-induced cardioprotection [ 32 - 34 ]. In their study, Birnbaum, et al.
In a study on healthy volunteers, it was demonstrated that administration of rosuvastatin before forearm ischemia results in a reduction of endothelial dysfunction induced by ischemia and reperfusion and that the beneficial effect of the statin disappears if celecoxib is co-administered [ 36 ]. Guidelines for the management of various forms of coronary artery disease recommend administration of statins to normocholesterolemic patients at high risk of coronary events [ 37 ].
The clinical benefit of statin therapy in this situation might at least partially be mediated by its pleiotropic effects. Patients with coronary artery disease are mostly elderly and often suffering from musculoskeletal conditions with the need to use NSAIDs. Further studies are therefore needed to clarify the potential interactions between statins and NSAIDs in this scenario.
Despite of the above described theories, the exact mechanisms responsible for the high variability of the thrombotic risk with various NSAIDs remain unknown. To further elucidate the reason behind the differences in the observed degree of CV risk between various NSAIDs, more focus should be placed on studies scrutinizing their exact pharmacokinetic and pharmacodynamic properties [ 38 ]. NSAIDs can cause sodium and water retention, as well as reduce formation of the vasodilator prostacyclin in the vessel wall.
According to a meta-analysis by Johson, et al. The blood pressure increasing effect is present also in the case of selective COX-2 inhibitors. According to a meta-analysis by Chan, et al. The same study highlighted the differences between various coxibs. Significant increases in blood pressure were found with rofecoxib and etoricoxib, while the effect of celecoxib on blood pressure appeared to be minimal.
The risk of NSAID-mediated BP increase in patients with pharmacologically controlled hypertension also depends on the antihypertensive drug used by the patient. The effect of beta-blockers and various renin-angiotensin-aldosterone system RAAS inhibitors seems to be influenced the most [ 40 , 42 ].
The most likely reason is that NSAIDs under normal circumstances inhibit the production of renin as a compensatory mechanism for the retention of water and sodium caused by them and also by direct COX-2 inhibition. If RAAS is inhibited chronically by the antihypertensive regimen used by the patient, the previously described compensatory mechanism can't help to avoid an increase in the blood pressure [ 43 ]. Most patients with severe rheumatoid arthritis and osteoarthritis are elderly and often have multiple co-morbidities, including hypertension treated with antihypertensive drugs.
Under these circumstances the safe and effective treatment of their symptoms is problematic [ 44 ]. In a pilot study by Varga, et al. Inhibition of prostanoid production in the kidney may reduce glomerular filtration and excretion of sodium and water. NSAIDs are therefore associated with risk of hypervolemia and worsening heart failure. The study by Heerdink, et al. The authors did not find a significant difference between individual NSAIDs, which suggests a class effect.
The highest risk of heart failure decompensation was present within the first days of treatment initiation and gradually decreased to the level of placebo after a month. NSAID users were found to have a relative risk of 2. Aspirin intolerance in asthmatic patients has been reported to be underdiagnosed [3]. The most important drugs involved in cross-intolerance are propionic acid derivatives, in most cases ibuprofen, and in sustained-release pyrazolones.
In cross-intolerance, the most frequently reported clinical entities are urticaria and angioedema; however, the airway can also be involved [1]. It has been suggested that the possibility of ibuprofen-induced bronchospasms should be considered before administering ibuprofen to children with asthma [5].
Moreover, this asthmatic reaction is dose-dependent and can occur with sub-therapeutic doses [6]. We, therefore, investigated the effect of short-term ibuprofen treatment on pulmonary function in asthmatic children.
Ninety 9- to year-old children 49 males were enrolled and divided into three groups of 30 children each. The Study group comprised of children with mild to moderate asthma as classified by the GINA guidelines and a self-reported history of aspirin-allergy. The Allergic control group had children with allergic rhinitis or atopic dermatitis, and the Healthy control group included healthy children attending our hospital for vaccination.
The children in the allergy and healthy control groups had no history of aspirin-allergy. The participants took ibuprofen 2. Children taking systemic steroids within one week of the initiation of the study were excluded. After the children had received the intervention for two days, a worsening of pulmonary function and asthma exacerbation was seen in a significant number of children in the study group Table I.
As ibuprofen has cross-intolerance with aspirin, the children with mild to moderate asthma in this study had an increased frequency of coughing with or without short of breath, and required double the dose of ICS or the use of short acting beta-agonists to ease the exacerbation of asthma symptoms.
Kanabar, et al. In addition, Kidon, et al. The most important drugs involved in cross-intolerance are propionic acid derivatives, in most cases ibuprofen, and in selective responders, pyrazolones.
In cross-intolerance, the most frequent clinical entities are urticaria and angioedema, and to a lesser extent airway involvement [1]. Overview Aspirin acetylsalicylic acid, or ASA and other non-steroidal anti-inflammatory drugs NSAIDs such as ibuprofen or naproxen Advil, Motrin, Aleve and others are used to treat both pain and fever and are widely used in both children and adults. There are certainly restrictions. It is also possible to have allergic or allergic-like hypersensitive reactions to these medications.
Symptoms An allergy or hypersensitivity to both ASA and NSAIDs may cause any of the following: hives , itching, swelling, shortness of breath, nasal congestion, wheezing, feeling faint or even passing out.
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