ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00347.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

This article considers the interactions between drugs and renal function, first, the adverse effects of nephrotoxic drugs and the changes in drug response associated with renal failure. It then discusses drugs intended to alter urinary sodium excretion (diuretics) and urinary pH as well as drugs which alter renal concentrating and diluting capacity. In each case emphasis is placed on the relationship between the drug effects and normal renal mechanisms. Reasons for the special vulnerability of the kidney to the toxic effects of drugs (e.g. antibiotics) are discussed and the practical problems of adjustment of drug dosage according to renal function are indicated. Finally, consideration is given to drugs, notably oral sorbents, which can partially substitute for renal function and might therefore eventually prove ideal for the management of advanced renal failure in small animals.

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00348.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

The pharmacokinetics of propranolol were investigated in dogs following intravenous, single oral, and multiple oral doses. Mean half‐life of the compound following single intravenous administration was 1.09 h, following single oral dose 1.58 h, and 2.14 h after chronic oral dosing. Half‐life values previously reported in dogs for the levo and dextro isomers were 0.77 and 1.08h, respectively. The bioavailability of oral propranolol was low (2–17% available) following a single oral dose, but increased substantially after chronic oral dosing, suggesting saturation of the disposition processes for propranolol with multiple dosing reg

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00349.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

As information on the comparative bioavailability of digoxin tablets in dogs is scarce, three brands of digoxin tablets, commercially available in Belgium, were compared in 6 healthy dogs in a cross‐over randomized design. Each dog received 1 mg digoxin on four occasions (once intravenously and 3 times orally). The mean areas under the curve relative to the intravenous value were 80, 71 and 65%. For the 3 oral preparations peak plasma concentrations were reached within 1 hour after dosing and often within 30 minutes. The mean peak concentrations were 11.0, 10.0 and 8.1 ng/ml. The times for 50% dissolution were 4.5, 7.5 and 25 minutes. Although differences between brands were only significant for the dissolution rate, the same ranking order was present for all parameters. It is therefore concluded that it may be advisable not to switch a digitalized dog from one brand to anothe

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00350.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

The disposition kinetics and systemic availability of phenylbutazone were studied in healthy dairy cows. The same dose (6mg/kg) of phenylbutazone was administered by the i.v., i.m. and oral routes. The elimination half time after intravenous administration ranged from 32.4 to 60.8h. The result suggested that the distribution of phenylbutazone in cows can be described by a two‐compartment open model. Total body clearance of the drug had a mean value of 0.0016 ml/kg‐h. The overall tissue to plasma level ratio (k12/k21‐β), after distribution equilibrium had been attained was 0.64. Phenylbutazone was shown, by an equilibrium dialysis method, to be highly bound to plasma proteins (93%) at serum levels of 100 μ/ml. The systemic availability of phenylbutazone was 69% and 89% when administered orally and intramuscularly respectively. Animals receiving half the dose of phenylbutazone (3 mg/kg) intravenously did not differ from cows receiving 6 mg/kg in elimination half‐life and other distribution and elimination kinetic parameters. Based on the experimental data obtained, a dosage regimen is proposed, consisting of a priming oral dose of 9 mg/kg and maintenance doses of 4.5 mg/kg of phenylbutazone orally administered at 48 h intervals. The relatively long half‐life in cattle, however, complicates the use of phenylbutazone because of the drug resi

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00351.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

In experiments on goats it was found that the binding of chlorpromazine (Cpz) to the proteins in plasma and milk ranged between 91–99 and 91–97 %, respectively, and was independent of the drug concentration in the samples. Thein vitrobinding of chlorpromazine in whole milk (96%) was significantly higher (P<0.01) than the protein binding in skim milk (91%) because the drug was concentrated in the butterfat. The concentration of Cpz was always higher in the milk than in the corresponding plasma samples. The renal clearance of Cpz in goats with normal urine pH was very small (0.16 ml min‐1) due to the high degree of plasma protein binding and of back diffusion. The mechanisms involved during the renal excretion of Cpz in goats included glomerular filtration, probably active tubular secretion and pH dependent back diff

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00352.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

The effect of the centrally acting α‐adrenoceptor agonist, clonidine, on plasma LH and FSH was studied in oestradiol‐primed and unprimed ewes and in oestrous ewes. In unprimed anoestrous ewes, clonidine stimulated LH and FSH release after a lag period of 18 h, and noradrenaline intracarotid injection or i.v. infusions immediately stimulated LH release. In oestradiol‐infused anoestrous ewes, clonidine produced either a delay or inhibition of the gonadotrophin surge and noradrenaline i.v. infusion advanced the LH surge. In oestrous ewes treated with clonidine, there was marked delay in the LH surge, but the magnitude of the LH and FSH surges were unaffected. Intravenous administration of α‐adrenoceptor blockers, phentolamine and phenoxybenzamine, blocked the oestradiol‐induced gondotrophin surge in anoestrous ewes. The effect of phenoxybenzamine on gonadotrophin surge was dose dependent in oestrous ewes. Small doses (4 mg/kg i.v.) of phenoxybenzamine delayed the synchronous LH and FSH surges. There was complete blockade of the LH surge and partial blockade of FSH surges in ewes given phenoxybenzamine (8 mg/kg i.v.) before the expected synchronous gonadotrophin surges. After this experiment, the initial rise of plasma progesterone concentrations did not occur until day 6 of oestrous cycle. Administration of phenoxybenzamine before the expected second FSH surge had no effect on the second FSH surge. Gonadotrophin release induced by gonadotrophin‐releasing hormone was attenuated by phenoxybenzamine, but not by clonidine. The results suggest that the LH surge is under α‐adrenergic control and the first FSH surge is under partial α‐adrenergic control, but the second FSH surge is not under α‐adrenergic control. The results also suggest oestradiol modulation of α‐a

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00353.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

The effects of 5‐hydroxytryptamine (5‐HT) on the longitudinal smooth muscle from the rumen and reticulum of the bovine forestomach were investigated. 5‐HT (0.25–490 μM) caused a contraction and a relaxation of the ruminal strips while it produced only an excitatory effect on the reticular strips. These effects were not affected by tetrodotoxin, hexamethonium, atropine or morphine, but were blocked by methysergide, LSD‐25 or phenoxybenzamine. 5‐HT potentiated the contraction evoked by stimulation of the intramural cholinergic nerves but did not show any effect on the relaxation produced by the non‐adrenergic inhibitory nerves' excitation. The 5‐HT‐induced potentiation was not affected by morphine, LSD‐25, methysergide and hexamethonium or high concentration of nicotine. Nicotine and dimethylphenylpiperazinium also caused a transient augmentation of the nerve‐mediated contraction, but these effects were abolished by the competitive ganglionic blockers. The evoked contraction was depressed in high‐Mg2+solution, but this depression was antagonized partly by 5‐HT. The affinity of the cholinomimetics to post‐synaptic muscarinic receptor was not affected by 5‐HT. It is concluded that contractions or relaxations of bovine forestomach strips induced by 5‐HT are mediated through activation of D‐receptors in the smooth muscle, and the 5‐HT‐induced potentiation of the evoked contraction may be elicited through presynaptic neural eff

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00354.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Intravenous injection of endotoxin fromEscherichia coli(0.01 μg and 0.1 μg per kg body weight), sodium nucleinate from yeast (5 mg and 10 mg per kg body weight) or Poly I: Poly C (15 μg and 30 μg per kg body weight) caused fever, changes in heart rate and stasis of the extrinsic ruminal contractions in conscious goats. It appears that ruminal stasis is associated with clinical and experimental fever. The febrile responses were abolished by the prior intravenous administration of flurbiprofen (2 mg per kg body weight), a potent non‐steroidal anti‐inflammatory and antipyretic agent. This agent, however, only had a partial antagonistic influence upon pyrogen‐induced ruminal stasis. The secondary changes in heart rate were not prevented by the drug. It seems unlikely that the inhibition of the extrinsic ruminal contractions by exogenous pyrogens is due simply to a release of prost

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00355.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Methylene blue is widely accepted as an antidote for nitrite toxicosis because of its ability to stimulate reduction of methemoglobin (ferrihemoglobin) to hemoglobin. It is usually used only in low dosage (4mg/kg) because of its purported enhancement of methemoglobin formation in high dosages. Methylene blue was evaluated as a nitrite toxicosis antidote using methemoglobin reduction and lethality protection as evaluation parameters. Tolonium chloride (toluidine blue) another structurally related dye was also evaluated using the same parameters. Both dyes were very effective antidotes. Methylene blue increased in effectiveness as the dose was increased up to 22 mg/kg. Tolonium chloride provided approximately equivalent protection at 8.8 mg/kg but may be more toxic than methylene blue. High concentrations of either dye did not result in appreciable production of methemoglobin. In cases of severe intoxication by methemoglobin formers such as nitrite, larger doses of methylene blue than generally recommended, may be of considerable therapeutic value.

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1979.tb00356.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY