Management of low back and neck pain by analgesics and adjuvant drugs: an update.

Although recent advances in drug therapy for low back and neck pain may seem slight, some consolidation of knowledge has taken place. Opiates, NSAIDs, and acetaminophen remain the drugs of choice. New NSAIDs, especially ketorolac, have some advantages. Injections of steroids and other agents into the lumbar area do not offer any distinct advantages. The use of adjunctive drugs such as muscle relaxants and antidepressants has not materially changed in the last few years.

Thrombolysis for pulmonary embolism.

More than 10 years ago, thrombolytic therapy with urokinase and streptokinase for pulmonary embolism was found to have considerable advantages over standard heparin therapy. After the introduction of alteplase, a recombinant tissue plasminogen activator, further studies confirmed this benefit. However, thrombolytic therapy for pulmonary embolism has not gained universal acceptance, even though it now has U.S. Food and Drug Administration approval. Clear advantages of thrombolytic therapy over conventional heparin therapy are improved pulmonary capillary blood volume, accelerated clot lysis and accelerated pulmonary perfusion. Earlier reversal of right-sided heart failure, a lower incidence of recurrent pulmonary embolism, a reduced risk of chronic pulmonary hypertension and reduced mortality have been claimed as advantages, but these have not been adequately proved. A recent survey suggests that about half of all patients with pulmonary embolism are potential candidates for thrombolytic therapy. In a subset of patients with hemodynamic compromise, thrombolysis has definite advantages over heparin therapy.

Adenosine for paroxysmal supraventricular tachycardia.

Adenosine is the most recent drug approved for the treatment of paroxysmal supraventricular tachycardia. Its advantage is that it is just as effective as verapamil and is far less toxic. The lack of toxicity is due to the extremely short half-life (one to seven seconds). The mechanism of action of adenosine is different from that of other antiarrhythmic agents. For the specific purpose of ameliorating paroxysmal supraventricular tachycardia, adenosine appears to be an ideal antiarrhythmic drug.

Coronary artery thrombolysis: comparison of approved agents.

Three agents approved for the lysis of thrombi in coronary arteries--alteplase, anistreplase and streptokinase--have undergone critical clinical experimental trials in Europe and the United States. Global comparison of their efficacy shows that alteplase is slightly more effective (71 percent) in restoring patency than anistreplase (60 percent) and streptokinase (58 percent). Streptokinase and anistreplase are allergenic, and repeat administration is not feasible in the short-term, a distinct advantage for alteplase. More accurate dosing of thrombolytic agents and skillful use of aspirin and heparin improve the efficacy of thrombolytic therapy but can also increase the risk of bleeding. A recanalization rate of 90 percent or more could be achieved if the thrombolytic agent is administered within the first hour after thrombosis. Administration this soon after the development of thrombosis may be possible if the agent is given outside the hospital by practicing physicians or, perhaps, paramedics.

Management of low back pain by analgesics and adjuvant drugs.

Ninety percent of all low back pain can be managed successfully by the skillful and appropriate use of the major analgesic drugs, NSAIDs, and the opioids. Adjunctive drugs, such as skeletal muscle relaxants and antidepressants, have their uses, but must be considered as temporary aids to the major analgesics. There is intensive research to develop new and more useful analgesic drugs. Ketorolac tromethamine, an NSAID recently approved by the Food and Drug Administration, is suitable for intramuscular administration for the short-term management of postsurgical and other acute pain.

Ketorolac: an injectable NSAID.

Ketorolac tromethamine is the first injectable nonsteroidal anti-inflammatory drug approved for the management of acute pain. In analgesic potency and ability to relieve postoperative pain, it is comparable to morphine. The advantages of ketorolac over opiates are the absence of respiratory depression and lack of drug abuse potential. Ketorolac has a longer duration of action than morphine, but it has less effect on the central nervous system. Ketorolac should not be used for obstetric analgesia.

Tartrazine sensitivity.

Tartrazine (FD & C Yellow No. 5) is an approved azo dye present in many drugs and food products. During the 1970s, many cases of tartrazine sensitivity were reported. This led to new regulations that required the listing of azo dyes on package inserts of drugs and on packages of food products. Tartrazine sensitivity is most frequently manifested by urticaria and asthma. Although azo dyes have been implicated in accentuating hyperkinetic syndromes, tartrazine is not considered an offender. Vasculitis, purpura and contact dermatitis infrequently occur as manifestations of tartrazine sensitivity. Cross-sensitivity in aspirin-sensitive and NSAID-sensitive patients may also occur. The mechanism of sensitivity is obscure and has been called pseudoallergic. Management consists mainly of avoidance of drugs and food products that contain tartrazine.

Magnesium replacement therapy.

Magnesium is involved as a cofactor in many vital enzymatic reactions. It is also important in the maintenance of membrane electric potential. Diagnosis of magnesium disturbances must often be based on clinical judgment. Hypomagnesemia is frequently associated with hypokalemia and hypocalcemia; hypermagnesemia most often occurs in patients with acute or chronic renal failure. Hypomagnesemia presents as neuromuscular, central nervous system and cardiac abnormalities. Inadequate dietary intake of magnesium occurs in alcoholism, catabolic states and gastrointestinal diseases. Intravenous administration of magnesium can cause neuromuscular paralysis and cardiac arrhythmias.

Metoclopramide: a dopamine receptor antagonist.

A dopamine receptor antagonist, metoclopramide has unique properties of increasing lower esophageal sphincter pressure and increasing the rate of gastric emptying. These gastrointestinal motility actions are useful in the treatment of diabetic gastroparesis and severe gastroesophageal reflux and in postoperative situations involving visceral atony. Metoclopramide is a useful adjunctive drug for intestinal intubation and radiologic examination. It has also been used intravenously to control the nausea and vomiting of intensive cancer chemotherapy, such as with cisplatin. Metoclopramide is a powerful antiemetic because of its combined actions on the chemoreceptor trigger zone and intestinal motility. This agent is generally not intended for long-term use. The oral preparations are recommended for four to 12 weeks of therapy. Use of parenteral metoclopramide should be limited to one or two days. The most common adverse reactions are restlessness, drowsiness, fatigue and lassitude. Extrapyramidal symptoms occur rarely and only with high dosage or prolonged use.

Nimodipine in subarachnoid hemorrhage.

Nimodipine has recently been approved for the treatment of cerebral ischemia caused by subarachnoid hemorrhage. Chemically, nimodipine is in the same group of calcium channel blockers as nifedipine and nicardipine. It has greater lipid solubility and, thus, greater selectivity for cerebral blood vessels. Nimodipine has been shown in most studies to reduce the morbidity and mortality from cerebral ischemia following subarachnoid hemorrhage. However, recent clinical studies have cast some doubt on this benefit. At recommended doses, the drug is well tolerated and toxicity is low. However, other approaches to the treatment of cerebral ischemia from vasospasm should not be omitted when using nimodipine.

Misoprostol: a prostaglandin for peptic ulcer.

Misoprostol, an E1 prostaglandin analog, protects gastric mucosa against the ulcerogenic effects of a wide variety of noxious agents, including aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). This synthetic prostaglandin was recently approved by the Food and Drug Administration for use in patients at high risk of gastric ulceration because of chronic NSAID therapy for osteoarthritis, rheumatoid arthritis and related conditions. Side effects of misoprostol are minimal, but the drug is relatively expensive. Protection against gastrointestinal bleeding has not been established.