Doses - AZATHIOPRINE, AZATHIOPRINE SODIUM
Dogs: 
As an immunosuppressive: a) For adjunctive therapy for immune-mediated hemolytic anemia (probably should bereserved for dogs w/fulminant intravascular hemolysis, autoagglutination or those thatrequire repeated transfusion or have persistant reticulocytopenia): Initially at 2mg/kg/day PO. Reduce to 1 mg/kg/day after the first 7-10 days. (Bucheler and Cotter 1995)
b) For adjunctive therapy of immune-mediated glomerulopathy: 2 mg/kg PO once dailyinitially. When remission is achieved, give at same dose every other day. Prednisoloneand azathioprine should be given on alternate days at this time. (Polzin and Osborne 1985)
c) For adjunctive therapy in myasthenia gravis in non-responsive patients: 2 mg/kg POonce a day to every other day; may decrease dose if response is seen. (LeCouteur 1988)
d) For adjunctive therapy of chronic atrophic gastritis: 0.5 mg/kg PO once a day to everyother day (with corticosteroids). (Hall and Twedt 1988)
e) For adjunctive therapy in chronic active hepatitis: If no improvement seen with corticosteroids, add azathioprine at 2 - 2.5 mg/kg PO once daily; recheck in 10-14 days. Ifimproved, continue for additional 2-3 months; if no improvement, reconsider diagnosis.(Cornelius and Bjorling 1988)
f) For adjunctive therapy in immune-mediated hemolytic anemia:2 mg/kg PO once daily (in combination with corticosteroids ± cyclophosphamide; seereference or individual monographs). (Maggio-Price 1988)
g) For adjunctive therapy in immune-mediated thrombocytopenia: If corticosteroids ineffective, may add azathioprine at 2 mg/kg PO; taper to 0.5 - 1.0 mg/kg PO every otherday. Alternatively, may use vincristine or cyclophosphamide. (Young 1988)
h) For adjunctive therapy in autoimmune skin diseases: 2.2 mg/kg PO once a day to everyother day. May require 2-3 weeks before benefits are seen; may allow reduction orwithdrawal of prednisone. (Giger and Werner 1988)
i) For adjunctive therapy of SLE or other multisystemic immune-mediated diseases: 2.2mg/kg PO once a day to every other day;. used alone or in combination with otherimmunosuppressants. Once remission is achieved, may reduce dose to 1 - 2 mg/kgevery other day. (Giger and Werner 1988)
j) For immune-mediated chronic inflammatory bowel disease: 50 mg/m2 once daily for 2weeks, then every other day. Used rarely, but is helpful in a few cases. (Richter 1989)
i) For rheumatoid arthritis: In conjunction with a glucocorticoid (predniso(lo)ne); giveazathioprine 2 mg/kg PO once daily for 14-21 days; then give every other day (usuallyalternating with corticosteroids) until 1 month after remission of synovial inflammation.(Tangner and Hulse 1988)
For adjunctive treatment of ocular fibrous histiocytomas:
a) 2 mg/kg PO daily for 2 weeks, reevaluate, and reduce to 1 mg/kg every other day for 2weeks, then 1 mg/kg once weekly for 1 month. (Riis 1986)
Cats: Note: Several authors do not recommend azathioprine for use in cats because of the potential for development of fatal toxicity and the difficulty in accurately dosing.
As an immunosuppressive:
a) For immune-mediated dermatologic diseases: Cats are prone to develop bone marrowtoxicity from azathioprine and the drug is generally recommended not to be used in thatspecies. However, if the drug is to be used, the dose is 1.1 mg/kg PO every other day.(Rosenkrantz 1989)
Monitoring Parameters -
Client Information - Clients must be briefed on the possibilities of severe toxicity developingfrom this drug, including drug-related neoplasms or mortality. Clients should contact veterinarianshould the animal exhibit symptoms of abnormal bleeding, bruising, anorexia, vomiting or infection.
Although, no special precautions are necessary with handling intact tablets, it is recommended to wash hands after administering the drug.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None
Human-Approved Products:
Azathioprine Tablets 50 mg; Imuran® (Glaxo Wellcome) (Rx)Azathioprine Sodium Injection 100 mg per vial in 20 ml vials; Imuran® (Glaxo Wellcome) ;(Rx); generic, (Rx)BAL in Oil ¯ see Dimercaprol
BARBITURATE PHARMACOLOGY
Also see the monographs for Phenobarbital, Pentobarbital, Thiamylal, & Thiopental
While barbiturates are generally considered to be CNS depressants, they can invoke all levels of
CNS mood alteration from paradoxical excitement to deep coma and death. While the exactmechanisms for the CNS effects caused by barbiturates are unknown, they have been shown toinhibit the release of acetylcholine, norepinephrine, and glutamate. The barbiturates also have effectson GABA and pentobarbital has been shown to be GABA-mimetic. At high anesthetic doses, barbiturates have been demonstrated to inhibit the uptake of calcium at nerve endings.
The degree of depression produced is dependent on the dosage, route of administration, pharmacokinetics of the drug, and species treated. Additional y, effects may be altered by the age orphysical condition of the patient, or the concurrent use of other drugs. The barbiturates depress thesensory cortex, lessen motor activity, and produce sedation at low dosages. Some barbiturates suchas phenobarbital are useful as anticonvulsants because they tend to have sufficient motor activitydepression, without causing excessive sedation. In humans, it has been shown that barbituratesreduce the rapid-eye movement (REM) stage of sleep. Barbiturates have no true intrinsic analgesicactivity.
In most species, barbiturates cause a dose-dependent respiratory depression, but in some speciesthey can cause slight respiratory stimulation. At sedative/hypnotic doses respiratory depression issimilar to that during normal physiologic sleep. As doses increase, the medullary respiratory centeris progressively depressed with resultant decreases in rate, depth, and volume. Respiratory arrestmay occur at 4 times lower the dose that will cause cardiac arrest. These drugs must be used verycautiously in cats as they are particularly sensitive to the respiratory depressant effects ofbarbiturates.
Besides the cardiac arresting effects of the barbiturates at euthanatizing dosages, the barbiturateshave other cardiovascular effects. In the dog, pentobarbital has been demonstrated to causetachycardia, decreased myocardial contractility and stroke volume, and decreased mean arterialpressure and total peripheral resistance.
The barbiturates cause reduced tone and motility of the intestinal musculature, probably secondaryto its central depressant action. The thiobarbiturates (thiamylal, thiopental) may, after initialdepression, cause an increase in both tone and motility of the intestinal musculature. However, theseeffects do not appear to have much clinical significance. Administration of barbiturates reduces thesensitivity of the motor end-plate to acetylcholine, thereby slightly relaxing skeletal muscle. Becausethe musculature is not completely relaxed, other skeletal muscle relaxants may be necessary forsurgical procedures.
There is no direct effect on the kidney by the barbiturates, but severe renal impairment may occursecondary to hypotensive effects in overdose situations. Liver function is not directly affected whenused acutely, but hepatic microsomal enzyme induction is well documented with extendedbarbiturate (especially phenobarbital) administration. Although barbiturates reduce oxygen consumption of all tissues, no change in metabolic rate is measurable when given at sedative dosages.
Basal metabolic rates may be reduced with resultant decreases in body temperature whenbarbiturates are given at anesthetic doses.