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PubMed1994

Pain forum. Part 2. Neuropathic pain.

Neuropathic pain is often a reason for an unfavourable response to morphine or other opioids in treating cancer pain. This type of pain is difficult to manage and may co-exist with nociceptive cancer pain. There is still a potential for opioid responsiveness, although the doses needed will be higher, and adjuvant drug therapies are best employed concurrently with opioid drugs. Adjuvant drugs used are the antidepressants, anticonvulsants, including benzodiazepines, corticosteroids and neurolepts. Less commonly, agents such as baclofen and clonidine, and sympatholytic drugs such as prazosin can be employed for sympathetically maintained neuropathic pain (discussed in Part 3). The type of agent selected will depend on the natural history of the disease process, as well as a description of the pain--the lancinating pains tending to respond better to anticonvulsants. Non invasive neurostimulatory approaches such as transcutaneous electrical nerve stimulation (TENS) may be useful in management, and a few patients may require an invasive procedure such as dorsal column stimulation.

Adrenal Cortex Hormones↗
PubMed1993

[Ventricular arrhythmia and sudden cardiac death: the significance of left ventricular hypertrophy as risk factor].

Left ventricular hypertrophy is a frequent and early manifestation of cardiac structural adaptation in patients with essential hypertension. Prospective studies have clearly demonstrated that left ventricular hypertrophy represents a risk factor for cardiovascular morbidity and mortality, including sudden cardiac death. The increased risk is independent of the impact of high blood pressure and other risk factors on the cardiovascular system. Various clinical studies noted increased prevalence and severity of premature ventricular beats in hypertensive patients with left ventricular hypertrophy. Hypertrophy of myocardial cells, dilation of the left ventricle, increased stress of subendocardial myocardium and impaired coronary reserve are discussed as a possible pathogenetic link between myocardial hypertrophy and ventricular arrhythmias. Therapeutically, the primary goal for ventricular arrhythmias in hypertensive patients with left ventricular hypertrophy is regression of left ventricular mass. For this purpose, centrally sympatholytic agents, angiotensin converting enzyme inhibitors, betablockers and calcium antagonists have been found to be effective. Recently we observed that a reduction of left ventricular hypertrophy was associated with a decreased prevalence and severity of ventricular arrhythmias. Nevertheless, prospective studies are required to demonstrate whether reduction of severe ventricular arrhythmias helps to prevent sudden cardiac death due to left ventricular hypertrophy in hypertension.

Antihypertensive Agents↗
PubMed1994

[Cerebral neuroprotection and ketamine].

Ketamine is said to increase intracranial pressure (ICP), cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) and hence to be unsuitable for neuroanaesthesia. This may require reconsideration in the light of the neuroprotective properties mediated by the interaction of ketamine with the N-methyl-D-aspartate receptor (NMDA). Meta-analysis of published experimental rodent studies yields contradictory conclusions. Ketamine does not provide neuroprotection against hypoxic hypoxaemia or focal cerebral ischaemia. During complete forebrain ischaemia of 10 min duration, ketamine offers some degree of protection only if administered before (i.e. prophylactically) and after (i.e. therapeutically) a transient ischaemic episode. In experimental head injury, ketamine may be protective if administered therapeutically within 2 h after the trauma. In the case of incomplete forebrain ischaemia, ketamine provides neuroprotection if administered both before and during ischaemia. Clinical or primate studies are not available; extrapolation of results derived from rodent studies requires caution and has limitations. With respect to the pharmacodynamic action providing neuroprotection, NMDA-receptor antagonism may be just one of several mechanisms; others include scavenging of free radicals, a central sympatholytic effect and augmentation of dopamine metabolism in the caudate. The suitability of ketamine for neuroanaesthesia, which must also take account of its effects on ICP, CBF and CMRO2, is--for the time being--questionable.

Animals↗
PubMedDate not supplied

Comments on this issue of Alaska Medicine--from then (1960) until now (1993).

The drugs used in frostbite injury care are: Plasma volume expanders (low molecular weight dextran); vasodilating agents (tolazoline hydrochloride); hypotensive agents (guanethidine monosulfate, reserpine); hemorrheologic agents (oxpentifylline); calcium blocking agents (nifedipine); sympatholytic agents (phenoxybenzamine hydrochloride); anticoagulating agents (heparin); thrombolytic enzymes (streptokinase, tissue plasminogen activator--TPA); an industrial solvent (dimethyl sulfoxide--DMSO); anti-inflammatory agents such as nonsteroidal drugs, and acetylsalicylic acid, Ibuprofen. As yet, no clear treatment policy has been determined for preventing injury secondary to the formation of oxygen free radicals, damaging neutrophils or reperfusion injury. The role of oxygen free radical scavengers and factors causing reperfusion injury is unclear at this date. Since that first reported series of 51 patients in 1960-61, 1,282 patients have been seen. Of that number, 1,026 had a diagnosis of frostbite; 151 were diagnosed as hypothermia; and 105 diagnosed as immersion injury.

Alaska↗
PubMed1993

[Physiological function of the gastrointestinal tract and pathophysiological changes in neonatal diarrhea of calves].

Firstly, the basic principles of absorption and secretion in the intestine of healthy animals are described. The etiology and the pathophysiologic mechanisms of neonatal diarrhea in the calf due to E. coli and rota-/coronavirus are discussed. Enterotoxins of E. coli stimulate primarily the secretion of chloride (and thereby water) in the small intestine without damaging the intestinal mucosa. The sodium-dependent transport systems for the absorption of glucose and amino acids remain intact. In contrast, infections with rota- or coronavirus lead primarily to a disturbance of absorption processes in the intestine due to villous atrophy. Crypt cells are indirectly affected by inflammation mediators. Intestinal motility is inhibited during most diarrheic episodes; the application of para-sympatholytics in therefore not favourable.

Animals↗
PubMed1977

[Treatment results with isoglaucon eye drops in sympatheticotone patients with early appearing primary glaucoma (author's transl)].

The sympatholytic substance Clonidin (Isoglaucon) that lowers the intraocular pressure as well as the general blood pressure was tested on a small but homogenous group of patients. This group consisted of 11 middle aged male patients with wide angle glaucoma, elevated blood pressure and sympathicotonia. The intraocular pressure was well controlled in 9 of these, and sufficiently lowered in the remaining two. At the same time the general blood pressure was consistently lowered to some extent and the sympathicotonia improved.

Adult↗
PubMed1993

Nonpharmacological interventions as an adjunct to the pharmacological treatment of hypertension: a statement by WHL. The World Hypertension League.

Nonpharmacological approaches lower medication requirements in patients with hypertension. A decreased salt intake to a sodium value of about 80 mmol/day lowers BP in the presence of diuretics, beta-blockers, converting enzyme antagonists and sympatholytics but apparently not in patients treated solely with calcium antagonists. A reduced medication requirement is seen in about half of the patients suggesting that the phenomenon of 'salt-sensitivity' still applies. Weight loss is an effective adjunctive therapy and simultaneously improves other cardiovascular risk factors. A high alcohol consumption is a confounding factor in the drug treatment of hypertension. Reducing the alcohol intake of hypertensive heavy drinkers significantly lowers their BPs and drug requirements. Aerobic exercise is an effective nonpharmacological treatment which simultaneously fosters weight loss and improves risk factors. Potassium supplementation does not decrease medication requirements in drug-treated patients who are ingesting a low salt diet but may do so in those eating large amounts of salt. Nonpharmacological approaches should be included in the management of all hypertensive patients irrespective of their drug therapy. These should include weight reduction through decreased food and alcohol consumption as well as regular, programmed exercise. Patients should be instructed in a low calorie diet rich in fresh rather than processed products and high in fruits and vegetables. Such a diet will contain relatively little salt, reduced fat, and ample amounts of potassium and calcium. However, physicians should not lose sight of the fact that cigarette smoking remains the most important risk factor to be addressed in their hypertensive patients.

Alcohol Drinking↗
PubMed1977

Effects of autonomic drugs on the cardiovascular system: dogs with achalasia (under halothane anesthesia).

The parasympathetic and sympathetic components of the autonomic systems as they relate to cardiovascular function were studied on dogs with achalasia of the esophagus. This was accomplished by administering the parasympathomimetic drugs methacholine (0.2 mg/kg, subcutaneously), 2 doexy-D-glucose (100 mg/kg, intravenously (IV), the parasympatholytic drug atropine (0.2 mg/kg, IV), the sympathomimetic agent epinephrine (2.5 microng/kg, IV), and the beta adrenergic blocker propranolol (0.5 mg/kg, IV); and then measuring cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, PaCO2, PaO2, pH, and base deficit. Cardiovascular responses to the administration of the parasympathomimetic drugs, methacholine and 2 deoxy-D-glucose, or the parasympatholytic drug, atropine, were similar to those observed in normal dogs. Cardiovascular responses to the administration of the sympathomimetic drug epinephrine and the sympatholytic drug propranolol or beta blocker were also consistent with those observed in normal dogs. It can be interpreted from this pharmacologic evidence that parasympathetic and sympathetic innervations to the cardiovascular system are present in dogs with achalasia of the esophagus. Fewer cardiovascular variables were significantly altered in dogs with achalasia than in normal dogs. Since this was true for both the sympathetic and the parasympathetic values, it is interpreted as reflecting their general health rather than a specific lesion.

Anesthesia, Inhalation↗
PubMed1977

[Approaches in medical treatment in glaucoma (author's transl)].

The developments concern methods of application and therapeutic agents. Regarding drug aplication Ocusert has to be mentioned: inserted in the cul de sac of the eye once a week it releases a low concentration of a substance continuously and with a constant rate. For acetazolamid (Diamox) it has been shown, that in long term treatment much lower concentrations than usual are effective. Efforts regarding new local agents reducing intraocular pressure are stimulating as well as inhibiting the sympathetic tone. The practically most important discovery so far is Clonidine, whose pressure lowering mechanism is not quite clarified yet and which, due to other problems, demands a very critical indication. Beta-receptor-blocking agents, such as Propranolol could become somewhat important, as well as for some special indications the chemical sympathectomy by 6-Hydroxydopamine. The sympatholytic agent Guanethidine proves to be very valuable in special cases. Besides the pressure reducing treatment medicamentally achieved increase of the blood supply to the optic nerve becomes more important. It becomes more and more evident that the elevation of the stroke volume--thus heart output--by cardiac therapy is important what demands collaboration with colleagues of other disciplines.

Acetazolamide↗
PubMed1995

[Total intravenous anesthesia (TIVA) in geriatric surgery. S-(+)-ketamine versus alfentanil].

In this prospective, randomized study, two regimens of total intravenous anaesthesia (TIVA), with propofol and S(+)-ketamine (S-ketamine) and with propofol and alfentanil, were compared with reference to endocrine stress response, circulatory effects and recovery. METHODS. The investigation was conducted in two groups of 20 ASA I-III patients over 60 years of age who were scheduled for endoprothetic orthopaedic surgery. After oral premedication with midazolam, patients received a TIVA with body-weight-adjusted doses of propofol, and S-ketamine or alfentanil as the analgesic component. For CPPV (PEEP 5 mbar), air and oxygen (FiO2 33%) were used. For muscle relaxation, patients of both groups received vecuronium in body-weight-adjusted doses. Blood samples were taken through a central venous line at seven time points before induction of anaesthesia and on the first morning after the operation also for analysis of epinephrine, norepinephrine (by HPLC/ECD), and ADH, ACTH and cortisol (by RIA). In addition, SAP, HR, arterial oxygen saturation, recovery from anaesthesia and side effects were observed. RESULTS. The two groups had comparable group mean values for age (S-ketamine group 71 years, alfentanil-group 70 years), other biometric data, and duration of anaesthesia and operation (Table 1). Plasma levels of epinephrine, norepinephrine (Table 2, Fig. 1), ADH (Table 2, Fig. 2) ACTH and cortisol (Table 2, Fig. 3) were higher in the S-ketamine-group (P < 0.05) owing to the intraoperative course of these endocrine parameters. Before induction, and on the first morning after the operation, levels were comparable between the groups. 5 min after the induction of anaesthesia, SAP and HR (Table 3) were significantly lower in the alfentanilgroup (P = 0.001). Recovery from anaesthesia (orientation with respect to person and location) was faster in the alfentanilgroup (16 vs 39 min, P = 0.001). An arterial oxygen saturation below 90% was observed in 7 patients in the S-ketamine- and 13 patients in the alfentanilgroup (P = 0.03). Four patients with S-ketamine reported dreams, and 1 dream was judged negative. Postoperative emesis was found in 6 patients in the S-ketaminegroup and 12 patients in the alfentanilgroup (P = 0.03). All patients said they would agree to undergo the same anaesthetic technique again. CONCLUSIONS. Considerable differences were found in the endocrine stress response of the two groups. With respect to endocrine response and circulation, TIVA with propofol and S-ketamine had sympathomimetic properties with positive circulatory effects and led to moderate endocrine stimulation. This should be kept in mind in patients with hypotension, hypothyrosis, or adrenocortical insufficiency; because "eustress" might be beneficial in this group of patients. On the other hand, TIVA with propofol and alfentanil showed sympatholytic properties, with negative circulatory effects and a remarkable reduction of endocrine stress response. This might be beneficial in patients with hypertension and states of endocrine hyperfunction. Both regimens were accompanied by such typical side effects as dreams, delayed recovery, reduced ventilation, and emesis, which should also be considered.

Aged↗
PubMed1996

Effects of quinazoline (3H, 1H)-4-one-2-thiones with axial and central chirality on the contractile response of smooth muscle.

Quinazolines are versatile nitrogen heterocyclic compounds displaying a broad spectrum of biological and pharmacological activities. The influence of some new synthesized quinazolines with axial and central chirality was studied on the isometric muscle tension of rat ileum, rat uterus, and porcine coronary artery. While structural changes of the compounds showed only little influence on peristaltic movement of the ileum, quinazoline derivatives induced a relaxation in the uterus and in the coronary artery depending on the kind and position of the substituent. The introduction of axial chirality into the molecule of modification of the side chain caused an increase in the pharmacological action. These effects could not be inhibited by sympatholytics. So far the mechanisms and receptors causing the spasmolysis are unknown.

Animals↗
PubMed1997

Perioperative sympatholysis. Beneficial effects of the alpha 2-adrenoceptor agonist mivazerol on hemodynamic stability and myocardial ischemia. McSPI--Europe Research Group.

BACKGROUND: Mivazerol hydrochloride is a new alpha 2-adrenoceptor agonist. In vitro and animal studies have demonstrated both sympatholytic and antiischemic properties. To evaluate the safety and efficacy of mivazerol in patients during perioperative stress, this multicenter phase II clinical trial studied hemodynamic stability and myocardial ischemia in patients with coronary artery disease undergoing noncardiac surgery. METHODS: Three hundred patients, from twenty-three European medical institutions, participated in this placebo-controlled, double-blind, randomized, parallel-group trial. Ninety-eight were given high-dose mivazerol (1.5 micrograms.kg-1.h-1); 99, low-dose mivazerol (0.75 microgram.kg-1.h-1); and 103, placebo, continuously intraoperatively and for 72 h postoperatively. Blood pressure and heart rate were monitored for 96 h. Myocardial ischemia was assessed by Holter electrocardiography for at least 8 h before induction of anesthesia until 96 h after surgery. Twelve-lead electrocardiograms and creatine kinase myocardial band isoenzyme levels were obtained before and serially after surgery. Adverse cardiac events were assessed for the intraoperative, early postoperative (0-24 h), and late postoperative (24-72 h) periods. RESULTS: The incidence of tachycardia was significantly lower with high-dose mivazerol (vs. placebo) during the intraoperative (30% vs. 51%; P = 0.002), early postoperative (29% vs. 50%; P = 0.002), and late postoperative periods (46% vs. 70%; P = 0.001). Also, the percentage of patients treated for tachycardia was significantly lower with the high dose (vs. placebo) during the early (10% vs. 20%; P = 0.043) and late (6% vs. 15%; P = 0.024) postoperative periods. The incidence of hypertension was significantly lower with both high and low doses (vs. placebo) during the intraoperative period (46% and 43%, respectively, vs. 63%; P = 0.010); treatment was similar at both high and low doses (33% and 34%, respectively, vs. 46%; P = 0.066). The incidence of bradycardia was significantly higher at both dose levels than with placebo during and after drug administration (intraoperatively-3%, 7%, and 9%; early postoperative-0%, 5%, and 6%; late postoperative-0%, 4%, and 6%; after drug-0%, 6%, and 6%; placebo, low-dose, high-dose, respectively), but the need for treatment did not differ for the groups. The incidence of, and treatment for, hypotension were similar for the three groups. Intraoperative myocardial ischemia was significantly lower with high-dose mivazerol than with placebo (20% vs. 34%, respectively, P = 0.026). When intraoperative data were subdivided into emergence vs. nonemergence periods (post boc analysis), the incidence of myocardial ischemia was significantly lower with high-dose mivazerol than with placebo during emergence (11% vs. 30%; P = 0.001). Regarding blood pressure, heart rate, and ischemia, no rebound response occurred in the 12 h after discontinuation of mivazerol. The high-dose, low-dose, and placebo groups did not differ in the incidence of adverse cardiac outcomes (3%, 2%, and 8%, respectively) or the diagnosis of myocardial infarction (2%, 1%, and 6%, respectively). CONCLUSIONS: Continuous, 72-h perioperative administration of mivazerol to high-risk patients appears to be relatively safe, producing no significant hypotension or adverse events but some evidence of bradycardia not associated with adverse clinical events. Mivazerol decreased the incidence of, and treatment for, tachycardia, hypertension, and myocardial ischemia, particularly during high stress periods. Therefore, these salutary effects of mivazerol indicate further study in large-scale trials that assess mivazerol's effects on adverse cardiac outcomes, including death and myocardial infarction.

Adrenergic alpha-Agonists↗
PubMed1997

Drug therapy for hypertension.

By matching the profile of an antihypertensive drug to the clinical and demographic characteristics of the patient (e.g., risk factors, coexisting diseases, goals of therapy beyond lowering blood pressure), the physician can maximize the efficacy of the regimen and minimize the adverse effects the patient may experience. Optimal therapy requires a knowledge of the pharmacologic properties of the six broad classes of antihypertensive drugs: diuretics, sympatholytics (including central and peripheral adrenergic receptor blockers), direct vasodilators, angiotensin-converting enzyme inhibitors, calcium channel blockers and angiotensin II receptor antagonists.

Antihypertensive Agents↗
PubMed1997

Nitric oxide inhibition causes an exaggerated pressor response in Yucatan miniature swine.

The involvement to nitric oxide (NO) in cardiovascular and renal function was evaluated in 12 anesthetized Yucatan miniature swine. The effect of NO blockade on blood pressure was measured in six additional conscious swine. In the anesthetized swine, mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), and urinary excretion of water, sodium, and potassium were measured after systemic inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME), and were compared with values for a control period. After NO synthesis blockade, MAP increased by 63 +/- 5 mm Hg, a far greater increase than those observed in rats, dogs, domestic swine, or humans. The changes in GFR, urine flow rate (UFR), and sodium excretion (UNaV) were time-dependent. The GFR decreased to 50 +/- 6% of control values immediately after L-NAME administration, but returned to control values within 1 h. Significant increases in UFR and UNaV were observed only during the third experimental period, 40 to 60 min after drug infusion. In the conscious swine, L-NAME administration increased MAP by 24 +/- 4 mm Hg. Administration of the sympatholytic hexamethonium bromide fully reversed the increase of MAP in anesthetized and conscious swine. These findings indicate that NO has an important role in the maintenance of cardiovascular and renal function in Yucatan miniature swine. The exaggerated pressor response to NO blockade in miniature swine appears to involve the sympathetic nervous system.

Animals↗
PubMed1997

[Digoxin in chronic heart failure and sinus rhythm: is the end of the controversy in sight?].

It has for years been a matter of debate whether digoxin may/should be used in chronic heart failure with sinus rhythm. Interest in digoxin was renewed when it was found that the substance had a vagotonic as well as a sympatholytic effect in heart failure patients. A recent clinical trial led to the conclusion that although digoxin had no effect on the mortality among heart failure patients, it did lead to a reduction of the number of hospital admissions, particularly because of heart failure (indicating reduced morbidity and deceleration of the progression of the disease). Many heart failure patients continue to have symptoms in spite of treatment with diuretics and ACE inhibitors. As only few alternatives are available, many physicians in the near future will go on using digoxin in these patients- and as the recent study shows, rightly so.

Aged↗
PubMed1997

[Adrenergic receptor and alpha 2 agonist--2: Function analysis of adrenoceptor subtype by knockout mice and knockdown rats].

Alpha 2 adrenergic agonists will soon be used in the anesthetic management for their sedative/hypnotic, anesthetic-sparing, analgesic and sympatholytic properties. But the clinically available alpha 2 agonists have unwanted side-effects such as acute hypertension and bradycardia following a bolus injection because these agonists do not discriminate between the 3 alpha 2 adrenoceptor subtypes. Molecular biological methods can identify mediating receptor subtype for each response. Knockout mice study reveals that the alpha 2 B adrenoceptor subtype mediates the hypertensive response to alpha 2 agonists. Knockdown study using the antisense technology demonstrates that the alpha 2 A adrenoceptor subtype mediates the hypnotic and analgesic effects of alpha 2 agonists. The next generation of alpha 2 agonists should be alpha 2 A selective to maximize anesthetic and analgesic effects while minimizing hypertensive response.

Adrenergic alpha-Agonists↗
PubMed1997

[Adrenergic receptor and alpha 2 agonist--4: Applied and clinical pharmacology of alpha 2 agonist].

Alpha 2 adrenergic agonists currently are used in the anesthetic management of the surgical patient for their sedative/hypnotic, anesthetic-sparing, analgesic, and sympatholytic properties. Experimental and clinical studies have progressed to the point where anesthesiologists are now focusing on the use of these agents for their analgesic and anesthetic effects. This interest has coincided with the development and clinical introduction of dexmedetomidine. Clinical studies using existing alpha 2 agonists have revealed a tremendous potential for these agents that will be fully realized when more selective and specific compounds become available.

Adjuvants, Anesthesia↗