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Biomedical subjects

P Pentel

Publications and source records attributed to P Pentel.

14 recordsLinked to original sources
PubMed1989

Suppression of human peripheral blood mononuclear cell function by methadone and morphine.

Recent studies have shown that in vitro exposure of peripheral blood mononuclear cells (PBMC) to morphine results in suppressed respiratory-burst activity of monocytes and impaired interferon-gamma (IFN-gamma) production by lymphocytes. To investigate the potential in vivo effect of an opiate on these cell functions, PBMC were obtained from patients maintained on methadone. These freshly isolated mononuclear cells had a significantly impaired capacity to generate superoxide anion (O2-) in response to phorbol myristate acetate (PMA), while production of IFN-gamma by concanavalin A-stimulated cells was intact. After cell culture for 48 h, the defective O2- generating capacity was sustained. Also, culturing PBMC from healthy controls in the presence of methadone or morphine at concentrations as low as 10(-12) M caused significant suppression of PMA-stimulated O2- release. Because reactive oxygen intermediates produced by PBMC may participate in host defense against opportunistic pathogens in AIDS, these results underscore the need for investigations of the biological consequences of opiate-mediated immunosuppression.

Adult↗
PubMed1988

Effects of infused norepinephrine and angiotensin-II on vasopressin levels in humans.

Angiotensin II (A-II) has been shown to stimulate plasma arginine vasopressin (AVP) secretion in experimental animals, although offsetting effects from a rise in arterial pressure may obscure the effect. A rise in plasma norepinephrine (NE) may have several effects on plasma AVP because of changes in arterial pressure and central adrenergic stimulation. As little data exist concerning these neurohumoral interrelationships in humans, the current investigation was performed to examine the role of acute changes in plasma NE and A-II in the control of arginine vasopressin (AVP). The question is of potential importance because of diffuse disturbances in neurohumoral control in diseases such as hypertension and congestive heart failure. We measured heart rate, arterial pressure, and plasma AVP during 2.5 and 5.0 micrograms/min infusions of NE, and during .05 and .10 micrograms/kg/min infusions of A-II. NE increased mean blood pressure from 81 +/- 11 mm Hg to 87 +/- 16 mm Hg at 2.5 micrograms/min and to 93 +/- 16 mm Hg at 5.0 micrograms/min (p less than .001). Heart rate was unchanged during the 2.5 micrograms/min infusion but declined from 58 +/- 9 beats/min to 54 +/- 9 beats/min during the 5.0 micrograms/min infusion (p = NS). Plasma AVP, 3.0 +/- 0.9 pg/mL, did not change. During A-II infusions, mean arterial pressure increased from 81 +/- 13 mm Hg to 92 +/- 17 mm Hg and 112 +/- 21 mm Hg at the two rates (p less than .001); heart rate declined from 61 +/- 6.8 beats/min to 59 +/- 9.1 beats/min and 56 +/- 11.3 beats/min (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning.

Tricyclic antidepressants (TCA) are drugs with Type IA antiarrhythmic properties that cause severe cardiac conduction blocks, hypotension, and ventricular dysrhythmias at toxic levels. Phenytoin has been proposed as a prophylaxis and treatment of these dysrhythmias, since it is thought to improve conduction in this setting. Anesthetized dogs were given a loading dose of phenytoin, followed by constant amitriptyline infusion until death. Variables known to affect TCA toxicity, such as arterial pH, were carefully controlled. There were no significant differences between the phenytoin and control group in any physiologic parameter, including toxicity, drug levels, or dose to death. However, duration and frequency of episodes of ventricular tachycardia were dramatically increased in the phenytoin group. It is concluded that prophylactic phenytoin in this animal model provides no benefits and may in fact increase the severity of ventricular tachycardia and hypotension. In addition, it is speculated that similar adverse effects of phenytoin might be seen in other Type IA antiarrhythmics if the extremely toxic levels seen in this study with TCA were reached.

Amitriptyline↗
PubMed1986

Hyperthermia associated with drug intoxication.

Hyperthermia (temperature of at least 40.5 degrees C for at least one hour) associated with drug intoxication was identified in 12 patients over a 5-yr period. Intoxication was due to anticholinergic drugs (tricyclic antidepressants, antipsychotics, antihistamines), CNS stimulants (phencyclidine, cocaine, 3,4-methylene dioxyamphetamine, mescaline, lysergic acid diethylamide), salicylates, or combinations of these. Hyperthermia was present in four patients on admission, but its onset was delayed up to 12 h in the remainder. Outcome of hyperthermic patients was poor: five died and four had severe permanent neurologic sequelae. Clinical signs common to patients who developed hyperthermia were increased muscular activity and absence of sweating. Five patients suffered seizures, and four did not respond to anticonvulsant medication until body temperature was lowered. Cooling did not appear to favorably affect the outcome after body temperature had remained above 40.5 degrees C for a prolonged period. Prevention of death or neurologic sequelae from drug-induced hyperthermia depends upon the recognition of risk factors and the prompt treatment of hyperthermia.

Adolescent↗
PubMed1985

Fatal acute selenium toxicity.

Selenium is used widely in industry and as a dietary supplement. Reports of acute selenium toxicity are infrequent, however, and the relationship of toxicity to selenium concentrations in blood and tissues has not been established. We describe a patient who died eight days after ingesting selenious acid in the form of gun blueing. The patient's clinical course demonstrated many of the features of inorganic selenium toxicity described in animals; hypotension as a result of both vasodilation and decreased cardiac output, adult respiratory distress syndrome, severe myopathy which contributed to respiratory failure, and a garlicky odor to the breath. Four days after ingestion the serum selenium concentration was twenty times normal and urinary excretion seventy times normal. Postmortem tissue selenium concentrations were up to 40 times normal.

Female↗
PubMed1984

Toxicity of over-the-counter stimulants.

Over-the-counter stimulants (phenylpropanolamine hydrochloride, ephedrine, pseudoephedrine, caffeine) are used widely as decongestants, anorectic agents, amphetamine substitutes, and "legal stimulants." Toxic effects may result from overdose, drug interactions, or diseases that increase sensitivity to sympathomimetic agents. The most important toxic effect of the alpha-adrenergic agonist phenylpropanolamine is hypertension, which may result in hypertensive encephalopathy or intracerebral hemorrhage. The therapeutic index of phenylpropanolamine is low, and severe hypertension may occur after ingestion of less than three times the therapeutic dose. Ephedrine and pseudoephedrine may also cause hypertension, as well as tachyarrhythmias due to beta-adrenergic stimulation. Toxic reactions from caffeine are characterized by agitation, seizures, tachyarrhythmias, and hypotension. Management of toxic reactions to over-the-counter stimulants includes control of hypertension with a rapidly acting vasodilator, beta-blockers for tachyarrhythmias, and control of seizures.

Caffeine↗
PubMed1984

Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats.

Alkalinization of the blood by administration of sodium bicarbonate or hyperventilation is widely recommended for treatment of cardiac toxicity due to tricyclic antidepressant overdose, yet its efficacy and mechanism of action are poorly defined. We studied the effects and possible mechanism of action of 1 M NaHCO3 on desipramine (DMI) toxicity in anesthetized, paralyzed rats. Administration of DMI (45 mg/kg i.p.) produced a mean increase in QRS duration of 142% and a mean decrease in mean arterial pressure of 46%. Treatments were administered i.v. 35 min after DMI and their effects were assessed 10 min later. NaHCO3 (1 M) at doses of 3 and 6 mEq/kg decreased mean QRS duration 15 +/- 5 and 24 +/- 6%, respectively (mean +/- S.D.) and was superior to no treatment (P less than .01). NaCl (1 M) was as effective as NaHCO3 in decreasing QRS duration, as was 1 M NaHCO3 supplemented with 48 mM KCl. Respiratory alkalosis and 10% mannitol did not decrease QRS duration. NaHCO3, NaCl and NaHCO3/KCl all produced comparable increases in mean arterial blood pressure. Respiratory alkalosis and mannitol did not increase mean arterial pressure, but did prevent the decline seen in control animals. Acidosis produced by ventilation with 10% CO2 exacerbated QRS prolongation due to DMI. In acidotic animals, NaHCO3 and NaCl were equally effective in reversing QRS prolongation and hypotension. Correction of respiratory acidosis by discontinuation of inhaled CO2 did not improve QRS duration or mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMedDate not supplied

Pharmacokinetic and pharmacodynamic considerations in drug therapy of cardiac emergencies.

In the drug therapy of cardiac emergencies, it is necessary to rapidly achieve therapeutic drug concentrations and adjust drug dose as the patient's clinical status changes. Cardiac dysfunction is often present and may alter drug pharmacokinetics. Circulatory failure causes sympathetically mediated vasoconstriction in most tissues, with relative sparing of the brain and heart due to autoregulation. Blood flow to vasoconstricted tissues is reduced, and the available cardiac output is redistributed so that the heart and brain receive a greater fraction. Drug distribution to tissues is therefore slowed, and the initial concentration of drug in blood is higher when circulatory failure is present than when it is absent. This higher blood concentration is reflected by higher concentrations of drug in the brain and heart, which are relatively well perfused. Initial doses of many drugs need to be reduced in patients with circulatory failure to prevent cardiac or central nervous system toxicity. Cardiac output is markedly diminished during cardiopulmonary resuscitation (CPR), but blood flow distribution is qualitatively similar to that of circulatory failure with spontaneous circulation. Pneumatic trousers increase lower extremity vascular resistance and may produce a similar redistribution of blood flow. Drug distribution during the use of CPR or pneumatic trousers should be similar to that of circulatory failure with spontaneous circulation, but few data are available to guide drug dosing during the use of these interventions. Animal data suggest that the central volume of distribution of some drugs during CPR may be as small as one-tenth of normal. Drug metabolism in circulatory failure may be impaired by reduced hepatic blood flow resulting in decreased clearance of highly extracted drugs, or by hepatocellular dysfunction resulting in decreased clearance of poorly extracted drugs. Drug excretion may be impaired by reduced renal blood flow resulting in decreased filtration or secretion and increased reabsorption. The maintenance dose of many drugs must therefore be reduced in the presence of circulatory failure. Intravenous drug administration is preferred in patients with circulatory failure. The central intravenous route is often convenient but must be used cautiously when administering potentially cardiotoxic drugs. Intratracheal administration appears to be a promising alternative for some drugs, such as adrenaline (epinephrine). Intracardiac injections are hazardous and offer no demonstrated advantage over other routes.(ABSTRACT TRUNCATED AT 400 WORDS)

Atropine↗