however, since it is just as easy to use larger doses of penicillin as to administer a second drug for the purpose of preventing its excretion. Probenecid, on the other hand, has an important clinical application as a uricosuric drug. A number of repository preparations of penicillin are available for the purpose of producing sustained blood levels. Procaine penicillin g and benzathine penicillin g are two such preparations. With the latter preparation, demonstra ble penicillin blood levels can be maintained for as long as 20 days. It is important to keep in mind, however, that demonstrable blood levels are often defined as 0. 03 unit/ml or more. This low concentration of the antibiotic may not suffice in many infections, although it may be beneficial in prev ention of streptococcal infections and prophylaxis of rheumatic fever. [ru: maetik] (prevention) Distribution of penicillin in the body is far from uniform First, the antibiotic is partially bound to plasma proteins. Under normal circumstances it penetrates poorly into the cerebrospinal fluid, aqueous humor, and joint fluids On the other hand, inflammation at these various sites greatly increases the permeability to penicillin. [seribrau'spa inal [pa: mia biliti
however , since it is just as easy to use larger doses of penicillin as to administer a second drug for the purpose of preventing its excretion. Probenecid, on the other hand, has an important clinical application as a uricosuric drug. A number of repository preparations of penicillin are available for the purpose of producing sustained blood levels. Procaine penicillin G and benzathine penicillin G are two such preparations. With the latter preparation, demonstrable penicillin blood levels can be maintained for as long as 20 days. It is important to keep in mind, however, that demonstrable blood levels are often defined as 0.03 unit/ml or more. This low concentration of the antibiotic may not suffice in many infections, although it may be beneficial in prevention of streptococcal infections and prophylaxis of rheumatic fever. [ ]（prevention） Distribution of penicillin in the body is far from uniform. First, the antibiotic is partially bound to plasma proteins. Under normal circumstances it penetrates poorly into the cerebrospinal fluid, aqueous humor, and joint fluids. On the other hand, inflammation at these various sites greatly increases the permeability to penicillin. [ ] [ ]
The cumulative urinary excretion of sodium penicillin G following its oral and intramuscular administration is shown in Fig. 53-2. As much as 80%o of the intramuscularly administered dose may be recovered in the urine in less than 4 hours. Only about 20% is usually recovered following the oral administration of the antibiotic. with oral administration, this difference results from lack of absorption of much of the administered dose. Tkaeta ian], Na+ The inherent toxicity of penicillin as determined in animal experiments is extremely low. In several animal species the acute toxicity of penicillin is so low that death from overdosage has been attributed to the cation rather than to penicillin itself. Unfortunately, however, a significant percentage of the human population shows hypersensitivity reactions to penicillin. These reactions are of many different types, ranging from immediate anaphylactic reactions to late manifestations of the serum sickness type. It is believed that several hundred severe anaphylactic reactions have occurred following penicillin injections, many terminating fatally. ypersensitivity reactions are seen most often following
The cumulative urinary excretion of sodium penicillin G following its oral and intramuscular administration is shown in Fig. 53-2. As much as 80% of the intramuscularly administered dose may be recovered in the urine in less than 4 hours. Only about 20% is usually recovered following the oral administration of the antibiotic. With oral administration, this difference results from lack of absorption of much of the administered dose. [ ],Na+ The inherent toxicity of penicillin as determined in animal experiments is extremely low. In several animal species the acute toxicity of penicillin is so low that death from overdosage has been attributed to the cation rather than to penicillin itself. Unfortunately, however, a significant percentage of the human population shows hypersensitivity reactions to penicillin. These reactions are of many different types, ranging from immediate anaphylactic reactions to late manifestations of the serum sickness type. It is believed that several hundred severe anaphylactic reactions have occurred following penicillin injections, many terminating fatally. Hypersensitivity reactions are seen most often following
topical use of penicillin and most rarely after oral administration The incidence of such reactions has been estimated to vary from 1% to 8% in the general population. Skin tests for the determination of penicillin allergy are unreliable and dangerous when penicillin g itself is injected n small quantities intracutaneously. On the other hand preparations are available, at least for experimental purposes, in which penicilloylpolylysine(PPL) is suitable for testing allergy to the major determinant. Also, a mixture of penicillin, penicillate, and other products is suitable for testing allergy to the minor determinants. Despite these refinements in diagnosing penicillin allergy, tests are mot completely reliable. As a consequence, the history of previous reactions is very important, and even in the presence of a negative intradermal test, it is best to be prepared for the possibility of anaphylactic reaction whenever the antibiotic is injected In addition to hypersensitivity reactions, penicillin is capable of producing other adverse effects. Neural tissue may be susceptible to penicillin, particularly when vulsive phenomena have been noted following such procedures. There is seldom any reason for injecting penicillin
topical use of penicillin and most rarely after oral administration. The incidence of such reactions has been estimated to vary from 1% to 8% in the general population. Skin tests for the determination of penicillin allergy are unreliable and dangerous when penicillin G itself is injected in small quantities intracutaneously. On the other hand, preparations are available, at least for experimental purposes, in which penicilloylpolylysine (PPL) is suitable for testing allergy to the major determinant. Also, a mixture of penicillin, penicilloate, and other products is suitable for testing allergy to the minor determinants. Despite these refinements in diagnosing penicillin allergy, tests are mot completely reliable. As a consequence, the history of previous reactions is very important, and even in the presence of a negative intradermal test, it is best to be prepared for the possibility of anaphylactic reaction whenever the antibiotic is injected. In addition to hypersensitivity reactions, penicillin is capable of producing other adverse effects. Neural tissue may be susceptible to penicillin, particularly when vulsive phenomena have been noted following such procedures. There is seldom any reason for injecting penicillin
intrathecally. Ampicillin(Penbritin, Omnipen, Polycillin)differs from penicillin g mainly in having a greater effect on many gram-negative microorganisms. Also the drug is more acid resistant and is absorbed better following oral administration. Ampicillin is effective in the treatment of urinary tract infections caused by Escherichia coli and Proteus mirabilis (susceptible strains ) The antibiotic is also effective in the treatment of respiratory infections and meningitis caused by susceptible Hemophilus strains. Ampicillin may cause skin rash in 10% of patients especially if the patient has infectious mononucleosis. Some rashes produced by ampicillin may not be allergic Ampicillin is available in capsules, 250 and 500 mg. The sodium salt is available for intramuscular and intravenous administration Amoxicillin trihydrate (Amoxil, Larotiddiffers from ampicillin only in producing somewhat higher serum
intrathecally. Ampicillin (Penbritin, Omnipen, Polycillin) differs from penicillin G mainly in having a greater effect on many gram-negative microorganisms. Also the drug is more acid resistant and is absorbed better following oral administration. Ampicillin is effective in the treatment of urinary tract infections caused by Escherichia coli and Proteus mirabilis（susceptible strains）. The antibiotic is also effective in the treatment of respiratory infections and meningitis caused by susceptible Hemophilus strains. Ampicillin may cause skin rash in 10% of patients, especially if the patient has infectious mononucleosis. Some rashes produced by ampicillin may not be allergic. Ampicillin is available in capsules, 250 and 500 mg. The sodium salt is available for intramuscular and intravenous administration. Amoxicillin trihydrate (Amoxil, Larotid)differs from ampicillin only in producing somewhat higher serum
concentrations and it may be better a bsorbed in children Carbenicillin disodium (Geopen) differs from ampicillin in its greater activity against Pseudomonas aeruginosa and Bacteroides fragilis. Also it may be active against strains of Hemophilus and Proteus that are resistant to ampicillin. A special feature of carbenicillin is its high sodium content. Since 1 g of the antibiotic contains 6 m eq of sodium, large doses may cause sodium overload in renal and cardiac patients. Carbenicillin disodium (Geopen) should not be given orally, since it is not absorbed. Carbenicillin indanyl sodium (Geocillin) is available in tablets for oral administration but is not commonly used Ticarcillin disodium Ticar) closely related carbenicillin and is available for intramuscular and intravenous use. It may have somewhat greater potency against the difficult gram-negative bacilli than carbenicillin The penicillinase-resistant penicillins are very useful in the treatment of infections caused by organisms that are resistant to penicillin G, such as hospital-acquired staphylococcal infections. If the organism turns out to be susceptible to penicillin G, it is best to switch because of its
concentrations, and it may be better absorbed in children. Carbenicillin disodium (Geopen) differs from ampicillin in its greater activity against Pseudomonas aeruginosa and Bacteroides fragilis. Also it may be active against strains of Hemophilus and Proteus that are resistant to ampicillin . A special feature of carbenicillin is its high sodium content. Since 1 g of the antibiotic contains 6 mEq of sodium, large doses may cause sodium overload in renal and cardiac patients. Carbenicillin disodium (Geopen) should not be given orally, since it is not absorbed. Carbenicillin indanyl sodium (Geocillin) is available in tablets for oral administration but is not commonly used. Ticarcillin disodium (Ticar) is closely related to carbenicillin and is available for intramuscular and intravenous use. It may have somewhat greater potency against the difficult gram-negative bacilli than carbenicillin. The penicillinase-resistant penicillins are very useful in the treatment of infections caused by organisms that are resistant to penicillin G, such as hospital-acquired staphylococcal infections. If the organism turns out to be susceptible to penicillin G, it is best to switch because of its