It is believed that an uprising of BP secondary to a stimulus known or unknown trigger this event. During the initial uprising of BP the endothelium releases nitric oxide. When the arteries and arterioles detect this high BP, they respond with vasoconstriction and subsequently with hypertrophy to limit that the high blood pressure reaches cellular levels. The prolonged contraction of smooth muscle causes an endothelial dysfunction, a loss of nitric oxide release and an irreversible elevation of peripheral vascular resistance. Without the response of nitric oxide, there is a major endothelial damage. The endothelial dysfunction is triggered by inflammation induced by a distention mechanism that increases the expression of inflammatory markers such as cytokines, endothelial adhesion molecules and endothelin-1. These molecular events increase the endothelial permeability, inhibit fibrinolysis and as a result, they produce an activation of the coagulation cascade. This coagulation event, plus the adhesion and platelet aggregation cause the deposition of fibrinoid material, and also an increase in arterial inflammation and vasoconstriction. In addition of the whole event, there is an amplification of the renin-angiotensin system which contributes to vascular lesion and ischemia [₆₇].

Hypertensive emergency could be potentially threatening to life and is characterized by an elevated diastolic BP of 110 mm of Hg with end organ damage manifested by lightheadedness, confusion, altered mental status, encephalopathy, malaise, intracranial or subarachnoid hemorrhage, blurry vision, blindness, and retinal hemorrhages. Other findings are left ventricular insufficiency, pulmonary edema, angina, myocardial infarction, aortic dissection and an acute renal failure. It needs to be treated shortly.

Hypertensive urgency is characterized by a diastolic BP more than 110 mm of Hg, it does not have target organ damage and it is not threatening to life. It can be treated in hours or days with oral therapy [₈₉].

It is a drug that belongs to the dihydropyridines family or calcium channels blockers. It is a vasodilator that if it is quickly absorbed it may cause a very fast vasodilation that can produce an activation of the sympathetic system and release of catecholamines. Diltiazem and verapamile do not have these effects [₉]. Nifedipine inhibits the flow of transmembrane calcium ions to cardiac and smooth muscle from arteries and arterioles. Its half-life is 2 hours. It is indicated for vasospastic angina, chronic stable angina and HTN. The FDA cardio renal advisory committee does not approve the use of sublingual nifedipine in the treatment of a hypertensive crisis. Its side effects are: cephalea, fatigue, lightheadedness, nausea, paresthesias, somnolence, pruritus, rash, abdominal pain, dry mouth, dyspepsia, flatulence, arthralgias, tingling in lower legs, unspecific precordial pain, dyspnea, impotence and polyuria. All these side effects have an incidence of less than 3% [₁₁₁₂].

Its sublingual use has been debatable the last years. A reason of his sublingual administration is because the sublingual area is richly capillarized and after squeezing one nifedipine capsule it would be absorbed very quickly than if it is swallowed. There is no evidence to support this, though. There was a study that included 11 patients and they were asked to bite one 10-mg nifedipine capsule and kept all the contents in their mouths for a short period of 20 minutes without swallow. Blood samples were withdrawn and it was found that nifedipine plasma levels were low (10 nm/dl). Subsequently, the same group was asked to bite the capsule and immediately swallow it. This time, the absorption was much better and they found plasmatic levels of nifedipine more quickly (82 mg/dl). The authors concluded that the oral mucosa was a deficient barrier for the absorption of nifedipine [₁₃]. In other study, patients underwent general anesthesia with an inflated nasogastric tube. They received the content of one 10-mg nifedipine capsule in the sublingual mucosa. In the meanwhile the investigators were measuring the plasmatic levels of nifedipine, and found that this was low. When the investigators deflated the nasogastric tube, they registered high plasmatic levels of nifedipine. They concluded that the contents of one nifedipine capsule were mixed with saliva and flow down through the esophagus to be absorbed in the gastric mucosa [₁₄].

Watcher et al [₁₅] reported 3 cases of symptomatic hypotension in which patients developed tachycardia, lightheadedness, nausea, and chest pain after multiple nifedipine doses and none of the patients had past medical history of cardiac disease. O’ Malia et al [₁₆] reported 3 cases of patients without a past medical history of cardiac disease and developed marked hypotension after receiving one 10 mg-nifedipine capsule. 2 of these patients had an anterior myocardial infarction based on changes in the EKG and elevated cardiac enzymes. The authors advised that patients with a history of coronary artery disease and left ventricular hypertrophy should not be taking this drug. Peters et al [₁₇] published one case of one patient with hypotension and prolonged QT interval after nifedipine use. An hour later, the patient developed torsade de pointes and ventricular fibrillation. A metanalysis that included 19,000 patients in 28 studies found that nifedipine is direct and proportionally related to an increase in mortality with doses that are more of 60 mg daily [₁₈]. Nifedipine has been associated to cerebrovascular accidents as well, most likely secondary to a sudden lowering of high BP [₁₉].

The study was performed in the IMSS General Hospital “Lic. Benito Juárez” at Ciudad Juárez, Chihuahua, México. It was an observational, prospective study. We included 23 patients with no past medical history of cardiac disease that were going to receive one 10-mg nifedipine capsule sublingually prescribed by the emergency room doctor. All of the patients underwent a basal EKG and BP taken prior to receiving the sublingual dose, and after 30 minutes we perform another EKG and took BP again and we compared the changes.

Heart rate: 11 out of 23 patients had a mild increase in heart rate, whereas 3 patients had mild decrease in heart. 9 patients maintained the same heart rate in the basal EKG and in the one taken after.

PR segment and QT interval: There were not changes in these parameters.

ST segment: 5 patients had not changes in this parameter. In 13 patients we identified nonspecific changes of ST segment. 3 patients had nonspecific incomplete atrioventricular block. We identified one case of patient with a QS wave.

T wave: We detected one case of a female patient with peaked T-waves in leads V5 and V6.

Figure 1

Figure 1: EKGs from a female patient taken before and after one dose of sublingual nifedipine with inverted peaked T-waves in leads V5 and V6.

Figure 2

Changes in BP: The highest BP registered before the treatment of sublingual nifedipine was 210/140 mm of Hg and the lowest 140/110 mm of Hg. The BP taken 30 minutes after the use of sublingual nifedipine improved with an average of 24 mm of Hg for systolic BP and an average of 26 mm of Hg improvement in diastolic BP. At the end all of the patients, remained with high BP.