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Biopharmaceutics & Drug Disposition 1980The pharmacokinetics and relative systemic availability or oral propranolol were studied in three healthy volunteers following administration of 10, 40, and 80 mg of...
The pharmacokinetics and relative systemic availability or oral propranolol were studied in three healthy volunteers following administration of 10, 40, and 80 mg of propranolol hydrochloride. Plasma concentrations of propranolol were determined using a sensitive and specific fluorometric high pressure liquid chromatographic technique. In the dosage range studied, the amount of propranolol reaching the systemic circulation increased with dose, while half-lives remained unchanged. The apparent 'threshold dose' for propranolol was much smaller than previously reported, and its contribution to the observed dose-dependent availability is doubtful. Apparent intrinsic clearance values were shown to decrease with increase in dose, with a true maximal intrinsic clearance of 5.4 l kg-1 h-1. These data suggest the saturation of a low capacity enzyme system in the liver and are consistent with theoretical characteristics of a drug that is extensively metabolized during its first pass through the liver.
Topics: Administration, Oral; Adult; Biological Availability; Biotransformation; Female; Humans; Liver; Male; Metabolic Clearance Rate; Propranolol
PubMed: 7448344
DOI: 10.1002/bdd.2510010403 -
Medicina Intensiva Mar 2015The use of propranolol has been proposed to reduce the hypermetabolic response of patients with burn injuries. (Review)
Review
BACKGROUND
The use of propranolol has been proposed to reduce the hypermetabolic response of patients with burn injuries.
OBJECTIVES
To review the studies published up to December 2013 on the effects of propranolol in burn patients.
METHODS
A PubMed search was conducted using the terms "burns", "thermal injury", "beta-blocker" and "propranolol", with the filters "human" and "English" and "Spanish". A total of 42 citations were retrieved, 15 of which were randomized clinical trials. The main results are summarized.
MAIN RESULTS
Propranolol at doses adjusted to decrease the heart rate by 20% of the baseline value (4–6 mg/kg/day p.o.) reduces supraphysiological thermogenesis, cardiac work, resting energy expenditure and peripheral lipolysis. It likewise increases the efficiency of muscular protein synthesis and reduces central mass accretion. Most studies have been conducted in pediatric burn patients.
CONCLUSIONS
Propranolol reduces the hypermetabolic response in pediatric burn patients. More studies on its effects in adult burn patients are needed.
Topics: Adrenergic beta-Antagonists; Adult; Burns; Child; Humans; Propranolol
PubMed: 25305241
DOI: 10.1016/j.medin.2014.08.002 -
The Journal of Nervous and Mental... Mar 1998
Topics: Aged; Aged, 80 and over; Brain; Female; Hallucinations; Humans; Hypertension; Music; Neurocognitive Disorders; Propranolol
PubMed: 9521357
DOI: 10.1097/00005053-199803000-00010 -
Southern Medical Journal Feb 1980Three patients with no history of asthma or allergy developed bronchospasm while taking propranolol for hypertension. The bronchospasm was severe in all three and in one...
Three patients with no history of asthma or allergy developed bronchospasm while taking propranolol for hypertension. The bronchospasm was severe in all three and in one patient resulted in respiratory arrest. Since the bronchospasm was relieved with discontinuation of propranolol and supportive bronchodilator therapy, the bronchospasm was believed to be caused by propranolol. Furthermore, each patient was subsequently treated with other antihypertensive medications which, like propranolol, contain the stabilizer additive tartrazine. Bronchospasm did not recur, making it unlikely that tartrazine hypersensitivity caused this problem. Regardless of a negative history of asthma, therefore, life-threatening bronchospasm must be considered a possible complication of propranolol therapy.
Topics: Bronchial Spasm; Female; Humans; Hypertension; Male; Middle Aged; Propranolol
PubMed: 7355327
DOI: 10.1097/00007611-198002000-00030 -
Pharmacotherapy 1997We conducted an open-label study to determine the impact of cytochrome P-4502D6 (CYP2D6) on propranolol pharmacokinetics and response in 12 healthy men with CYP2D6... (Clinical Trial)
Clinical Trial
We conducted an open-label study to determine the impact of cytochrome P-4502D6 (CYP2D6) on propranolol pharmacokinetics and response in 12 healthy men with CYP2D6 extensive metabolizer (EM) phenotype and 3 healthy men with CYP2D6 poor metabolizer (PM) phenotype. Subjects received R,S-propranolol hydrochloride 80 mg every 8 hours for 16 doses. After the sixteenth dose, blood and urine samples were collected for 24 hours, and serum propranolol and urine metabolite concentrations were determined by chiral high-performance liquid chromatography. Heart rate response to treadmill exercise was measured serially over 24 hours. Apparent oral clearance of propranolol and partial metabolic clearance values of propranolol to 4-hydroxypropranolol (HOP), propranolol glucuronide, and naphloxylactic acid (NLA) were estimated. Apparent oral clearance and elimination half-life of propranolol were not different between EMs and PMs. Partial metabolic clearance of propranolol to HOP was significantly higher and to NLA was significantly lower in EMs than in PMs. No differences in percentage reductions in exercise heart rate were observed between EMs and PMs. The CYP2D6 PM phenotype has no effect on propranolol blood concentrations and does not alter response to propranolol. Our data also suggest that CYP2D6 mediates approximately 65% and 70% of S- and R-propranolol's 4-hydroxylation, respectively.
Topics: Adrenergic beta-Antagonists; Adult; Biotransformation; Cytochrome P-450 CYP2D6; Half-Life; Heart Rate; Humans; Hydroxylation; Male; Phenotype; Propranolol
PubMed: 9399616
DOI: No ID Found -
The American Journal of Pathology Jul 1977Acute renal failure caused in the rabbit by clamping one renal pedicle for 1 hour and removing the opposite kidney produced a histologic picture very similar to that...
Acute renal failure caused in the rabbit by clamping one renal pedicle for 1 hour and removing the opposite kidney produced a histologic picture very similar to that observed in "hypotensive" acute renal failure in man. Intravenous infusion of propranolol, a drug which prevents renin release, at 1 mg/kg for 70 minutes beginning at time of pedicle clamping resulted in significantly lower serum creatinine in this model (2.8 +/- 0.2 mg% at 48 hours with propranolol versus 5.2 +/- 0.8 mg% without). Renin stimulation by dehydration or feeding a low-salt diet enhanced the difference between treated and untreated groups (2.6 +/- 0.4 mg% with propranolol versus 6.2 +/- 1.8 mg% without, after dehydration; 3.5 +/- 1.0 mg% with propranolol versus 7.6 +/- 1.4 mg% without, after low-salt diet).Suppression of renin production by saline feeding eliminated propranolol's beneficial effect (5.6 +/- 0.9 mg% with propranolol versus 4.0 +/- 0.6 mg% without). In rabbits with a normal food and water intake, renal denervation using phenol also eliminated propranolol's effect (creatinine 8.6 +/- 1.4 mg% with propranolol versus 8.6 +/- 1.8 mg% without). In rabbits with intact kidneys, flow probe recording of renal blood flow showed a significantly higher blood flow immediately after unclamping in the propranolol-treated animals, and renal angiograms showed less vasoconstriction in this group after unclamping. In this model of acute renal failure, renal vasoconstriction plays an important role following the initial ischemic insult. Propranolol lessens the severity of this vasoconstriction and the resulting acute renal failure. Its probable action is interference with neurogenically stimulated renin release.
Topics: Acute Kidney Injury; Angiotensin II; Animals; Diet, Sodium-Restricted; Disease Models, Animal; Drinking; Female; Hypotension; Ischemia; Kidney; Propranolol; Rabbits; Radiography; Regional Blood Flow; Renal Artery; Renin; Vasomotor System
PubMed: 879269
DOI: No ID Found -
JAMA Feb 1982
Clinical Trial
Topics: Clinical Trials as Topic; Humans; Migraine Disorders; Placebos; Propranolol
PubMed: 7035707
DOI: 10.1001/jama.247.7.957 -
JAMA Oct 1968
Topics: Aged; Angina Pectoris; Arrhythmias, Cardiac; Heart; Heart Rate; Humans; Male; Propranolol
PubMed: 5695608
DOI: No ID Found -
Pharmacology, Biochemistry, and Behavior Dec 2014Taste recognition is a robust procedure to study learning and memory processes, as well as the different stages involved in them, i.e. encoding, storage and recall....
Taste recognition is a robust procedure to study learning and memory processes, as well as the different stages involved in them, i.e. encoding, storage and recall. Considerable evidence indicates that adrenal hormones and the noradrenergic system play an important role in aversive and appetitive memory formation in rats and humans. The present experiments were designed to characterize the effects of immediate post training corticosterone (Experiment 1) and propranolol administration (Experiment 2 and 3) on taste recognition memory. Administration of a high dose of corticosterone (5mg/kg, sc) impairs consolidation of taste memory, but the low and moderate doses (1 and 3mg/kg, sc) didn't affect it. On the other hand, immediate post-training administration of propranolol (1 and 2mg/kg, ip) impaired taste recognition memory. These effects were time-dependent since no effects were seen when drug administration was delayed 3h after training. These findings support the importance of stress hormones and noradrenergic system on the modulation of taste memory consolidation.
Topics: Animals; Corticosterone; Male; Memory; Propranolol; Random Allocation; Rats; Rats, Wistar; Recognition, Psychology; Taste
PubMed: 25268313
DOI: 10.1016/j.pbb.2014.09.013 -
Naunyn-Schmiedeberg's Archives of... Oct 1979The disposition of dl-propranolol was studied in spontaneously hypertensive rats (SHR), both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection of...
The disposition of dl-propranolol was studied in spontaneously hypertensive rats (SHR), both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection of 1 mg/kg. 1. Upon s.c. injection propranolol appeared rapidly in plasma. A maximum concentration of 374 +/- 33 ng/ml (N = 10) was reached 5 min after injection. After a distribution phase with a half-life of t 1/2 alpha = 17 min propranolol was eliminated with a t 1/2 beta = 59 min. 2. Both propranolol and its metabolites were taken up rapidly into all tissues studied. Highest concentrations (10.4 +/- 1.5 micrograms/g, N = 5) were found in lungs 30 min after injection. 3. Neither propranolol nor its metabolites accumulated in any of the tissues examined. 4. Upon i.c.v. injection of propranolol, a maximal concentration of 573 +/- 47 ng/ml (N = 3) was reached in plasma already 2 min after injection. In this case t 1/2 alpha was 13 min and t 1/2 beta was 80 min. 5. Dialysis experiments indicated that propranolol is bound to plasma proteins for 92% in the concentration range of 20--100 ng/ml. With increasing concentrations binding diminishes progressively. At the highest concentration tested (345 ng/ml) only 76% was bound. It is concluded that s.c. and i.c.v. injection of an identical dose of propranolol gives a similar plasma concentration-time profile. Moreover, it is suggested that the pharmacokinetic behaviour of propranolol in SHR does not explain the delayed antihypertensive effect of this drug.
Topics: Animals; Biotransformation; Hypertension; Injections, Intraventricular; Injections, Subcutaneous; Male; Propranolol; Protein Binding; Rats; Time Factors; Tissue Distribution
PubMed: 522894
DOI: 10.1007/BF00498752