Penicillins intramuscular injection

The well-known adverse reaction formerly often observed after intramuscular injection of clemizol penicilUn in the treatment of syphilis with anaphylaxis-like symptoms plus CNS involvement in the absence of immimological sensitization to penicillin was called the Hoigne syndrome or embolic-toxic reaction, and might be explained by intravasal appUcation of LA with subsequent toxic effects [8]. 

The absorption and excretion of carbenicillin in man has been reported [396]. The antibiotic is not absorbed intact from the gut intramuscular injection (which is painful) often provides adequate serum levels (approximately 20 Mg/ntl) but infections with Pseudomonas strains having minimum inhibitory concentrations up to, or higher than, 100 Mg/ml require intravenous thbrapy to achieve such levels. No evidence of active metabolite formation has been obtained. Marked reductions in the half-life (and serum levels) of carbenicillin follow extracorporeal dialysis or peritoneal dialysis, the former producing the most striking effect [397]. These results were, of course, obtained in patients with severe renal failure. Patients with normal renal function rapidly eliminate the drug but, as with all penicillins, renal tubular secretion can be retarded by concurrent administration of probenecid. 

Intramuscular injections have been shown to produce elevations in serum enzyme activities presumably due to either inflammatory areas in the muscle or actual breakdown of cells and release of enzyme. In one study, preinjection values of creatine phosphokinase were in the normal range of 24-100 units. Multiple intramuscular injections of penicillin, diuretics, and narcotics every 6 hours caused the creatine phosphokinase values to rise to levels between 160 to 240 units, or up to 2.5 times the upper limit of normal. When the injections were stopped, the creatine phosphokinase values returned to normal within 48 hours (B7). Similar observations of aspartate aminotransferase activities were made in patients receiving intramuscular injections of penicillin every 4 hours. Activities rose to values as high as 200 units. Other workers have reported injection related serum creatine phosphokinase elevations following intramuscular administration of chlorpromazine and suxamethonium (HIO, M11,T6). 

Some penicillins cannot be given orally as their beta-lactam ring is hydrolyzed and inactivated in the stomach by gastric acid. In general intramuscular injections are painful and therefore not advised. The pharmacokinetic behavior of penicillins is further characterized by short elimination half-lives. Renal elimination is prominent. 

The activity of penicillin G was originally defined in units. Crystalline sodium penicillin G contains approximately 1600 units per mg (1 unit = 0.6 meg 1 million units of penicillin = 0.6 g). Semisynthetic penicillins are prescribed by weight rather than units. The minimum inhibitory concentration (MIC) of any penicillin (or other antimicrobial) is usually given in mcg/mL. Most penicillins are dispensed as the sodium or potassium salt of the free acid. Potassium penicillin G contains about 1.7 mEq of K+ per million units of penicillin (2.8 mEq/g). Nafcillin contains Na +, 2.8 mEq/g. Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for years at 4°C. Solutions lose their activity rapidly (eg, 24 hours at 20°C) and must be prepared fresh for administration. 

Benzathine and procaine penicillins are formulated to delay absorption, resulting in prolonged blood and tissue concentrations. A single intramuscular injection of 1.2 million units of benzathine penicillin maintains serum levels above 0.02 mcg/mL for 10 days, sufficient to treat B-hemolytic streptococcal infection. After 3 weeks, levels still exceed 0.003 mcg/mL, which is enough to prevent B-hemolytic streptococcal infection. A 600,000 unit dose of procaine penicillin yields peak concentrations of 1-2 mcg/mL and clinically useful concentrations for 12-24 hours after a single intramuscular injection. 

Benzathine penicillin and procaine penicillin G for intramuscular injection yield low but prolonged drug levels. A single intramuscular injection of benzathine penicillin, 1.2 million units, is effective treatment for 3-hemolytic streptococcal pharyngitis given intramuscularly once every 3-4 weeks, it prevents reinfection. Benzathine penicillin G, 2.4 million units intramuscularly once a week for 1-3 weeks, is effective in the treatment of syphilis. Procaine penicillin G, formerly a work horse for treating uncomplicated pneumococcal pneumonia or gonorrhea, is rarely used now because many strains are penicillin-resistant. 

Although it is not a major elimination route following intravenous or intramuscular injection of penicillin G to dairy cattle, milk constitutes a very important route of elimination following intramammary injection since most of the dose enters milk (58, 59). The persistence of residues in milk does depend on the formulation and route of administration, but, in a wide variety of trials, residues were not found to persist beyond 5 days after the end of treatment (59, 60). Transfer of penicillin G from treated to untreated quarters has also been observed... 

When procaine penicillin G was intramuscularly injected in pigs at the approved (15,000 lU/kg bw) label dose once daily for 3 days, residues were not found in liver after 1 day of withdrawal, in muscle and fat after 2 days of withdrawal, in plasma after 4 days of withdrawal, in skin after 5 days of withdrawal, or in kidney and the injection sites after 8 days of withdrawal (63). When these pigs were given an extralabel dose at the 66,000 lU/kg bw level, residues were not found in liver after 2 days of withdrawal, in fat after 3 days of withdrawal, or in muscle, skin, plasma, or injection sites after 7 days of withdrawal. 

Dicloxacillin is absorbed well from the gastrointestinal tract but the presence of food in the stomach reduces resorption. Although cloxacillin differs chemically from oxacillin only in the presence of a chlorine atom, their absorption profile after oral administration is not similar. Cloxacillin is more rapidly and effectively absorbed than oxacillin. However, absorption of all isoxazolyl penicillins is better when given by intramuscular injection. These agents can be also administered by intravenous, intrauterine, intra-articular, intrapleural, and intramammary injections. 

The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle (52). Chloramphenicol, tylosin, penicillins, dihydrostreptomycin, and oxytetracycline have been shown to produce local irritation at the site of injection, leading to residue persistence this may be exacerbated by the solvent used. However, residues do not persist with proper injection of drugs and use of formulations that do not cause severe irritation (52), as has been demonstrated with one oxytetracycline product that produced little irritation (53-55). 

Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for long periods (eg, for years at 4 °C). Solutions lose their activity rapidly (eg, 24 hours at 20 °C) and must be prepared fresh for administration. 

Several natural penicillins can be produced, depending on the chemical composition of the fermentation medium used to culture penicillium. Penicillin G (benzylpenicillin) has the greatest antimicrobial activity of these natural penicillins and is the only natural penicillin used clinically. However, penicillin G is not stable it is extremely acid-labile. Only about one-third of an oral dose is absorbed under the most ideal conditions. Therefore, it is generally not given orally but is administered by intramuscular injection. Several newer derivatives of penicillin G have been developed that do have good to excellent oral absorption (e.g., cloxacillin, ampicillin, and amoxicillin). 

Penicillins can canse local effects such as pain, induration, and tenderness at the site of an intramuscular injection. Administration of penicillin intravenously can also canse bnrning or phlebitis. Hematologic toxicity prodnced by penicillins is rare, but various types of dysctasias such as leukopenia, granulocytopenia, abnormal platelet aggregation, and anemia have been reported. 

The frequency of such reactions is about 1-3 reactions per 1000 intramuscular injections of penicillin G procaine, the usual dose being about 0.6-1.2 million units (175,213,225-227). Eight of 920 patients with venereal diseases had a definite toxic-like reaction with a dose of 4.8 million units of penicillin G procaine, corresponding to about one in 120 patients (228). In a series of 7700 intramuscular injections with only 400 000 units of penicillin G procaine, there was not one episode (221). 

Intramuscular injection of high doses of depot formulations of penicillins can lead to painful sweUing, especially... 

Repeated intramuscular injections into the thighs of newborns and infants can cause severe and widespread muscular contractures of the quadriceps femoris (SEDA-8, 560). In some cases, penicillin was implicated. 

Gerbeaux J, Couvreur J, Lajouanine P, Canet J, BonvaUet. Sur deux cas d ischemie etendue transitoire apres injection intramusculaire de benzathine-penicilline chez I enfant. [On 2 cases of transitory extensive ischemia after intramuscular injection of benzathine penicillin in children.] Presse Med 1966 74(7) 299-302. 

Cephalothin i.s absorbed poorly from the gastrointestinal tract and must be administered parcntcrally for. systemic infections. It is relatively nontoxic and acid stable. It is excreted rapidly through tlie kidneys about 60% i.s lo.si within 6 hours of administration. Pain at the. site of intramuscular injection and thrombophlebitis following intravenous injection have been reported. Hypersensitivity reactions have been observed, and there is some evidence of cross-.scn.siti v-ity in patients noted previously to be penicillin sensitive. 

Many penicillins, including penicillin V, are metabolized in the human body to other active compounds. Rolinson and Batchelor 140 administered the drugs orally or by intramuscular injection and evaluated both blood and urine samples by paper chromatography. Active metabolites were detected by bioautographic plates. Vanderhaeghe, Parmentier and Evrard 141 identified the major metabolite of penicillin V as p-hydroxyphenoxy-methyl penicillin. It represented about 10% of the microbiological activity in the urine. A small amount of o-hydroxyphenoxymethyl penicillin was also observed while in the urine of some patients another metabolite was detected. They speculated this might be the dihydroxy derivative. 

Parenteral Administration of Penicillin G After intramuscular injection, peak concentrations in plasma are reached within 15-30 minutes. This value declines rapidly (tj of 30 minutes). Repository preparations of penicilhn G increase the duration of its effect. Such compounds include penicillin G procaine (wycillin, others) and penicillin G benzathine (bicillin l-a, permapen), which produce relatively low but persistent levels of penicilhn in the blood. 

The oral administration of 200,000 units of penicillin G or penicillin V every 12 hours markedly decreases the incidence of recurrences of rheumatic fever in susceptible individuals. Intramuscular injection of 1.2 million units of penicillin G benzathine once monthly also yields excellent results. Because acute rheumatic fever has been observed in the fifth decade, some advocate that prophylaxis should be continued for life. 

A 14-year-old boy is developing signs of anaphylaxis after an injection of penicillin in the doctor s office. If an intramuscular injection of epinephrine is administered, which of the following is LEAST likely ... 

Watts PS, McLeod D, The estimation of penicillin in blood serum and milk of bo vines after intramuscular injection, J. Comp Pathol. Therap. 1946 56 170-176. 

Following sample isolations on day 28 of the experiment, the macaques are each given an intramuscular injection of penicillin G (20,000 U/kg). Two additional doses of penicillin G are given during the following week. Following antibiotic treatment, throat swabs are taken of the animals and used to confirm that they are culture-negative for GAS and hence have cleared the infection. 

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