Penicillins

Penicillins

Penicillins remain one of the most important and useful antibac-terials, despite the availability of numerous others. The penicillins can be divided into four groups:

§    natural penicillins (penicillin G benzathine, penicillin G potassi-um, penicillin G procaine, penicillin G sodium, penicillin V potas-sium)

§    penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin)

§    aminopenicillins (amoxicillin, ampicillin)

§    extended-spectrum penicillins (carbenicillin, ticarcillin).

Pharmacokinetics

After oral administration, penicillins are absorbed mainly in the duodenum and the upper jejunum of the small intestine.

Absorb these factors

Absorption of oral penicillin varies and depends on such factors as the:

§    particular penicillin used

§    pH of the patient’s stomach and intestine

§    presence of food in the GI tract.

§    Most penicillins should be given on an empty stomach (1 hour before or 2 hours after a meal) to enhance absorption. Penicillins that can be given without regard to meals include amoxicillin, penicillin V, and amoxicillin/clavulanate potassium.

Distribution

Penicillins are distributed widely to most areas of the body, in-cluding the lungs, liver, kidneys, muscle, bone, and placenta. High concentrations also appear in urine, making penicillins useful in treating UTIs.

Metabolism and excretion

Penicillins are metabolized to a limited extent in the liver to inac-tive metabolites and are excreted 60% unchanged by the kidneys. Nafcillin and oxacillin are excreted in bile.

Pharmacodynamics

Penicillins are usually bactericidal in action. They bind reversibly to several enzymes outside the bacterial cytoplasmic membrane.

Playing with PBPs

These enzymes, known as penicillin-binding proteins (PBPs), are involved in cell-wall synthesis and cell division. Interference with these processes inhibits cell-wall synthesis, causing rapid de-struction of the cell.

Pharmacotherapeutics

No other class of antibacterial drugs provides as wide a spectrum of antimicrobial activity as the penicillins. As a class, they cover gram-positive, gram-negative, and anaerobic organisms, although specific penicillins are more effective against specific organisms.

Oral vs. I.M. route

Penicillin is given by I.M. injection when oral administration is in-convenient or a patient’s compliance is questionable. Because long-acting preparations of penicillin G (penicillin G benzathine and penicillin G procaine) are relatively insoluble, they must be administered by the I.M. route.

Drug interactions

Penicillins may interact with various drugs.

§    Probenecid increases the plasma concentration of penicillins

§    Penicillins reduce tubular secretion of methotrex-ate in the kidney, increasing the risk of methotrexate toxicity.

§    Tetracyclines and chloramphenicol reduce the bactericidal ac-tion of penicillins.

§    Neomycin decreases the absorption of penicillin V.

§    The effectiveness of hormonal contraceptives is reduced when they’re taken with penicillin V or ampicillin. Be sure to advise the patient to use a reliable, alternative method of contraception in addition to hormonal contraceptives during penicillin therapy.

§    Large doses of I.V. penicillins can increase the bleeding risk of anticoagulants by prolonging bleeding time. Nafcillin and di-cloxacillin have been implicated in warfarin resistance.

Acting against aminoglycosides

High dosages of penicillin G and extended-spectrum penicillins (carbenicillin and ticarcillin) inactivate aminoglycosides. More-over, penicillins shouldn’t be mixed in the same I.V. solutions with aminoglycosides. (See Adverse reactions to penicillins.)