Penicillin class & Lincosamide

● Mechanism of action (Drug class)

Penicillin
Drug Class: Penicillin antibiotic
Use: Treatment of bacterial infections
MOA: Penicillin inhibits the synthesis of bacterial cell wall via binding of
the beta-lactam ring to the DD-transpeptidase. Thus, inhibiting cross
linking activity and eventually causing cessation of the bacterial cell wall
synthesis.

● History & nomenclature (Drug class)

Penicillin was discovered by Alexander Fleming in 1928. Fleming found a mould growing on a
petri dish of staphylococcus bacteria. He realized that the mould was preventing the bacteria
from growing and propagating. Fleming soon claimed that the Penicillum mould produced a
chemical that could kill the bacteria. Since then, Penicillin became the first antibiotic and the
most widely used antibiotic agent up to this day.

● Drug example - penicillin V.,

a. Resistance - Penicillin resistance is frequently related with nonsusceptibility to

other -lactam antibiotics, and vice versa. Penicillin resistance is conferred by
mutations in pbp2x, which may be significant for the cell in becoming resistant to
oral cephalosporins.

b. Therapeutic Application - Penicillin V potassium is being used to treat bacterial

illnesses such pneumonia as well as other respiratory disease, scarlet fever, and
infections of the ear, skin, gums, mouth, and throat.

c. Pharmacokinetic (if available) - Tubular secretion is the primary route of

elimination for penicillin V and its metabolites. Within 6–8 hours, around 20–65%
of an oral dosage is eliminated in urine as unmodified drug and metabolites; tiny
quantities are eliminated in feces and bile. In plasma, penicillin has a poor protein
binding capacity. Penicillin bioavailability varies by type: penicillin G has a poor
bioavailability of less than 30%, whilst penicillin V has a greater bioavailability of
60 to 70%. Penicillin is eliminated by the kidneys and has a short half-life.

d. Common Adverse Effects, Precautions and Toxicity - Thickness in the throat,

tongue, or lips. discomfort in the joints fever, sore throat, chills, or other
indications of infection returning severe diarrhea (bloody or watery feces) that
 may be accompanied by a fever and stomach discomfort (may occur up to 2
months or more after your treatment). A severe allergic response to penicillin V is
possible. Skin rash both with and without blisters is one of the symptoms. Fever,
feeling sick, or joint discomfort are flu-like symptoms.

Note: Differences of Penicillin V (Phenoxymethylpenicillin) and Penicillin G

(Benzylpenicillin)
● Benzylpenicillin = Natural, direct fermentation from Penicillium
crysogenum, treatment for bacterial infections.
● Phenoxymethylpenicillin = Derivative of Benzylpenicillin. A broad
spectrum beta-lactam antibiotic with bactericidal action against Gram-
positive bacteria and Gram-negative cocci. Its antimicrobial action is
similar to that of benzyl penicillin.

Structure:

Penicillin V (Phenoxymethylpenicillin)

Penicillin G (Benzylpenicillin)
Lincosamide

Drug Class: Lincosamide antibiotic Use: Lincosamides have an unusual antimicrobial

spectrum, being active against only Gram-positive and not Gram-negative aerobic bacteria.
They exhibit a significant antibiotic activity against some anaerobic bacteria. They are used
therapeutically, especially in cases where synergistic effects of a mixed anaerobic and aerobic
microflora are anticipated. Lincomycin and clindamycin are also useful alternatives to penicillin
and its derivatives in the treatment of upper respiratory tract infections in patients with allergy to
penicillin MOA: Their mechanism of action is via inhibition of protein synthesis in sensitive
micro-organisms.

History - The first lincosamide, lincomycin, was isolated in 1962 from Streptomyces
lincolnensis ssp. lincolnensis found in a soil sample from Lincoln, NE (MacLeod et al. 1964;
Bryskier 2005a). In 1967, lincomycin was licensed in the United States for the treatment of
infections caused by Grampositive bacteria. G R O U P 1 Nomenclature The nomenclature of
the penicillins, as with most antibiotics, is complex. The Chemical Abstracts system is defi nitive
and unambiguous but too complex for ordinary use (Fig. 33.12). For example, the chemical
name for benzylpenicillin sodium is monosodium (2S,5R,6R)-3,3- dimethyl-7-oxo)-6-(2-
phenylacetamido)-4thia-lazabicyclo[3.2.0]heptane-2-carboxylate.

Resistance - CLINDAMYCIN-RESISTANT GROUP B STREPTOCOCCUS, Group B

Streptococcus (GBS) is a type of bacteria that can cause severe illnesses—including
bloodstream infections, pneumonia, meningitis, and skin infections—in people of all ages. The
bacterias are inherently resistant to clindamycin because of poor permeability of the cellular
outer envelope to the drug.

Therapeutic Application - Clindamycin works well for grampositive coccal infections,

especially in patients allergic to βlactams, and also has generally better activity against
anaerobes. Clindamycin has excellent activity against Propionibacterium acnes when applied
topically (88). A very water-insoluble palmitate hydrochloride prodrug of clindamycin is also
available (lacks bitter taste).

Drug example - Clindamycin G R O U P 1 Pharmacokinetic - Clindamycin is absorbed well

orally and can be given parenterally. Clindamycin diffuses well into body fluids except
cerebrospinal fluid; it is concentrated in phagocytes. Most of the drug is metabolized;
metabolites are excreted in bile and urine. Common Adverse Effects, Precautions and Toxicity -
Clindamycin, may cause overgrowth of dangerous bacteria in the large intestine. This may
cause mild diarrhea or may cause a life-threatening condition called colitis (inflammation of the
large intestine). Clindamycin is more likely to cause this type of infection than many other
antibiotics, so it should only be used to treat serious infections that cannot be treated by other
antibiotics.adverse effects that occur with clindamycin toxicity are GI or allergic. There is no
antidote for clindamycin toxicity, and the adverse effects will resolve with dose adjustment or
discontinuation of the antibiotic G R O U P 1 it is associated with GI complaints (nausea,
vomiting, cramps, and drug-related diarrheas) (88). The most severe of these (black box
warning) is pseudomembranous colitis caused Clostridium diffi cile, an opportunistic anaerobe.
Its overgrowth results from suppression of the normal fl ora whose presence otherwise
preserves a healthier ecologic balance