Parenteral doses

Methoxy-N,N-dimethyltryptamine (O-methylbufotenine 59) is hallucinogenic in man at a parenteral dose of approximately 6 mg (204). Numerous animal studies have shown that 5-OMeDMT is behaviorally quite active (16,65-67,71,178,184). This compound also produced limb-flick behavior in cats (119) and the serotonin syndrome in rats (209). Glennon et al. (85) demonstrated that 5-OMeDMT serves as a discriminative stimulus in rats and have employed rats trained to discriminate 5-OMeDMT from saline to investigate the structure-activity relationships of various substituted N,N-dialkyltryptamine derivatives. The results of these studies have recently been reviewed (84). 

Caution The T-2 mycotoxins are the only potential biological warfare agents that can harm and be absorbed through intact skin. Aerosol doses of T-2 toxins may be ten times more potent than parenteral doses. 

Parenteral dose forms include aqueous, aqueous organic, and oily solutions, emulsions, suspensions, and solid forms for implantation. These parenterals need to be sterile and pyrogen-free they are, if possible, buffered close to normal physiological pH and preferably are isotonic with the body fluids. 

Distribution - Following a 1 mg parenteral dose, nalmefene was rapidly distributed. A 1 mg dose blocked more than 80% of brain opioid receptors within 5 minutes after administration. The apparent volumes of distribution centrally and at steady state are 3.9 and 8.6 L/kg, respectively. Over a concentration range of 0.1 to 2 mcg/mL, 45% is bound to plasma proteins. 

Adults-The usual parenteral dose is 25 to 50 mg administered subcutaneously or IM, or 5 to 25 mg administered slowly IV repeated every 5 to 10 minutes, if necessary. 

When converting from Avinza or Kadian to parenteral opioids, it is best to calculate an equivalent parenteral dose and then initiate treatment at half of this calculated value. As an example, an estimated total 24-hour parenteral morphine requirement of a patient receiving Avinza or Kadian is one-third of the dose of Avinza or Kadian. This estimated dose should then be divided in half, and this last calculated dose is the total daily dose. This value should be further divided by 6 if the desire is to dose with parenteral morphine every 4 hours. 

Parenteral dose equivalent to 10 mg morphine. h"ime to onset and peak effect shorter. 

FLUPHENAZINE HYDROCHLORIDE Individualize dosage. The oral dose is approximately 2 to 3 times the parenteral dose. Institute treatment with a low initial dosage increase as necessary. Therapeutic effect is often achieved with doses... 

For an approximation of the total daily dose required, use the parenteral dose administered in the preceding 24 hours carefully monitor the patient for the first several days. Give the first oral dose within 12 to 24 hours following the last parenteral dose. 

Dialysis Approximately half the normal mg/kg dose can be given after hemodialysis in peritoneal dialysis, a parenteral dose of 7.5 mg/kg is given, and then amikacin is instilled in peritoneal dialysate at a concentration desired in serum. 

In dental, oral, or upper respiratory tract procedures (alternate regimen) 1 to 2 g (50 mg/kg for children) ampicillin plus 1.5 mg/kg (2 mg/kg for children) gentamicin not to exceed 80 mg, both IM or IV % hour prior to procedure, followed by 1.5 g (25 mg/kg for children) amoxicillin 6 hours after initial dose or repeat parenteral dose 8 hours after initial dose. 

MefaboZ/sm/Excref/on-Approximately 35% of the drug is metabolized 50% of a parenteral dose is excreted unchanged in the urine in the first 12 hours. About 65% of the drug is recoverable in 72 hours. 

Antimuscarinic drugs block contraction of the iris sphincter and ciliary muscles of the eye produced by ACh. This results in dilation of the pupil (mydriasis) and paralysis of accommodation (cycloplegia), responses that cause photophobia and inability to focus on nearby objects. Ocular effects are produced only after higher parenteral doses. Atropine and scopolamine produce responses lasting several days when applied directly to the eyes. 

Give parenteral dose with patient recumbent to prevent postural hypotension... 

Most opioid analgesics are well absorbed when given by subcutaneous, intramuscular, and oral routes. However, because of the first-pass effect, the oral dose of the opioid (eg, morphine) may need to be much higher than the parenteral dose to elicit a therapeutic effect. Considerable interpatient variability exists in first-pass opioid metabolism, making prediction of an effective oral dose difficult. Certain analgesics such as codeine and oxycodone are effective orally because they have... 

Penicillin concentrations in most tissues are equal to those in serum. Penicillin is also excreted into sputum and milk to levels 3-15% of those in the serum. Penetration into the eye, the prostate, and the central nervous system is poor. However, with active inflammation of the meninges, as in bacterial meningitis, penicillin concentrations of 1-5 mcg/mL can be achieved with a daily parenteral dose of 18-24 million units. These concentrations are sufficient to kill susceptible strains of pneumococci and meningococci. 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by C difficile. Parenteral doses must be administered intravenously. A 1-hour intravenous infusion of 1 g produces blood levels of 15-30 mcg/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal... 

Besides local toxicity, discussed above, there are numerous other modes of potential adverse interactions involving excipients (19,20). Many of these pose little threat provided the amounts of excipients are constrained to certain levels. Excessive amounts, however, can cause problems, particularly for patients who are intolerant of even modest levels. Commonly used phosphate buffers may cause calcium loss with formation of insoluble calcium phosphates when such buffers are administered in over-ambitious amounts (21). Calcium phosphate precipitation has been noted particularly in nutritional parenteral admixtures for neonates because of the high nutrient requirements. Similarly, renal toxicity has been associated with depletion of zinc and other trace metals caused by large parenteral doses of ethylenediaminete-traacetic acid (EDTA) (22). Excessive absorption of glycine solutions, when used as irrigants during transurethral resections, can cause hyponatremia, hypertension, and confusion (23). The use of preservatives has been associated with cardiac effects in a few patients (24). Premature neonates were found to be at risk for receiving toxic amounts of benzoic acid or benzyl alcohol in bacteriostatic solutions used to flush intravenous catheters (25). 

Results of pharmacokinetic studies of streptomycin are in most cases also applicable to dihydrostreptomycin and vice versa. In animals, the absorption of both streptomycin and dihydrostreptomycin is poor via the oral route but rapid after intramuscular administration. In cattle, peak serum levels were obtained 1 h after intramuscular injection of either streptomycin or dihydrostreptomycin (18), whereas serum concentrations produced in sheep and horses paralleled those obtained in cattle (19). As a result, most of an oral dose is recovered in the feces whereas most of a parenteral dose is recovered in the urine. However, if kidney function is severely impaired, little of an intramuscularly administered dose is excreted in the urine. 

The residue depletion profiles of closantel in cattle and swine are almost similar. Highest concentrations of closantel are seen in kidney, whereas the depletion of closantel from all edible tissues is very slow over the first 28 days of withdrawal. Within animal species, the parenteral and the oral routes of adminis-fration yield comparable residue concentrations provided that the oral dose is twice the parenteral dose. A dose linearity is also observed for residue concentrations in tissues doubling the dose for a particular route of administration doubles the residue level. 

Azaperone is a widely used sedative drug in pigs. Available pharmacokinetic studies are insufficient to determine the extent of absorption of azaperone from the gastrointestinal tract. However, by comparison with the excretion profile following parenteral dosing, absorption after oral dosing is probably high. Distribution within the body of rats was extensive, and excretion was primarily in the feces (81%), with lesser amounts in urine (16%) (104). 

Dosages and routes of administration Diamorphine is given by the oral as well as by parenteral (i.m., s.c) or intrathecal routes. Diamorphine is about twice as potent as morphine. The parenteral doses are 5-10 mg every 4 h, oral doses are up to two-fold higher. 

Dosages and routes of administration Meptazinol is used in parenteral doses of 50-100 mg, given every 2-4 hrs by intramuscular or slow intravenous injection. For shortterm treatment of moderate pain, the compound can be given by oral administration in doses of 200 mg every 3-6 h. 

Dosages and routes of administration Tilidine is most commonly used in oral formulations containing about 10% naloxone to avoid parenteral misuse (Worz and Worz, 1995). Tilidine without naloxone is given rectally and by various parenteral routes including intravenous, intramuscular and subcutaneous routes. Parenteral doses of up to 400 mg/day can be administered the oral and rectal single doses are 50 and 75 mg, respectively (Martin etal., 1999). 

Other examples of emulsions for reduction in adverse effects after parenteral dosing will be mentioned in subsequent sections. 

Glazko, A. J., W. A. Dill, A. W Kinkel, J. R. Goulet, W. J. Holloway, and R. A. Buchanan. 1977. Absorption and excretion of parenteral doses of chloramphenicol sodium succinate (CMS) in comparison with peroral doses of chloramphenicol (CM Iin. Pharmacol. Thei21 104. 

Ketorolac Toradol Can be administered orally or by intramuscular injection parenteral doses provide postoperative analgesia equivalent to opioids. 

Since vitamin K deficiency varies among patients, not all will require supplementation. When it is needed, the recommended oral dose is 1-2 mg/day. Toxicity from dietary vitamin K has not been described in adults, but a parenteral dose may cause hemolytic anemia in infants therefore, caution should be taken when administered to such patients. 

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