LINCOSAMIDES

• These are group of monoglycoside antibiotics containing an amino acid like side chain.
• They have limited use in veterinary and human therapeutics because of their adverse effects.
• Clindamycin, lincomycin and pirlimycin are important lincosamides.
• Lincomycin was first lincosamides to be isolated from Streptomyces lincolnensis in a soil sample.

Mechanism of action:

Lincosamides bind exclusively to 50S ribosomal subunit

They cause premature dissociation of peptidyl t-RNA from ribosome

Suppression of protein synthesis

Antimicrobial spectrum:

• They are broad-spectrum antibiotics
• They are more active against gram +ve organism with anaerobes showing more susceptibility than aerobes
• Gram -ve bacteria are resistant to lincosamides.

Bacterial resistance:

• Bacterial resistance to lincosamides appear gradually and slowly
• Mutation induced alteration in 50S ribosomal subunit is mostly involved in conferring resistance against lincosamides
• Lincosamides shows cross-resistance with macrolides.

Pharmacokinetics:

• They are absorbed to a variable extent (60-90%) after oral administration
• Absorption from IM injection site is good and rapid.
• After absorption they are widely distributed in body fluids and tissues with appreciable concentration in bones and soft tissues.
• Parent drug and its active and inactive metabolites are excreted in bile and urine.

Side effects/Adverse effects:

• I disturbances like diarrhoea, vomiting and anorexia are common
• Pseudomembranous colitis in ruminants, horses, rodents and human which could be fatal
• It can also induce ketosis in cattle
• At high concentration, they may inhibit neuromuscular transmission and cause paralysis of skeletal muscles.

Contraindications and precautions:

• In animals with fermenting gastrointestinal tract like ruminants and horses
• In hypersensitivity to lincosamides
• In animals having diarrhoea
• It should be used cautiously in liver disease due to impaired biotransformation
• It should be avoided in lactating animals due to accumulation in milk.

Drug interactions:

• It should not be used with general anesthetics and skeletal muscle relaxants as lincosamides increase neuromuscular blocking effect.
• Concurrent use of chloramphenicol or macrolide reduce the efficacy of lincosamides.

Indications:

• Occasionally used in veterinary practice for treatment of infections caused by susceptible organism.

Lincomycin:

• It is naturally occurring lincosamides antibiotic.
• It is prototype drug of this class and was first isolated from streptomyces lincolnensis in 1962.

Antibacterial spectrum:

• Mainly effective against gram +ve bacteria, anaerobes and mycoplasma.
• Primarily bacteriostatic but may act as bactericidal at high doses.

Pharmacokinetics:

• It is absorbed from GI tract to extent of about 60% after oral administration
• Peak plasma concentration occurs at 2-4 hours after oral administration
• Absorption from IM injection site is rapid with peak plasma levels occurring at 1-2 hours
• It is widely distributed in body tissues and fluids except in CNS
• They easily crosses placenta and also accumulates in milk
• It is partly metabolized in liver and excreted as unchanged in bile and urine
• Elimination half-lives in small animals is about 3-4 hours.

Side effects/Adverse effects:

• Colitis
• Diarrhoea
• Swine may develop GI disturbances
• Feed contaminated with lincomycin in cattle may result in drop in milk production, diarrhoea and inappetence
• Hypotension and cardiopulmonary arrest have been reported in animals following rapid IV administration.

Contraindications and precautions:

• They are not recommended orally in ruminants, horses, rodents and rabbits.

Indications:

• In control of swine dysentery
• In treatment of infection caused by Staphylococci, streptococci, Erysipelothrix & Mycoplasma, particularly of bone, respiratory tract and skin
• As growth promoter in poultry

Dose:

Dogs & cats: 20mg/kg, PO, 2 times daily

Cattle: 10mg/kg, IM, 2 times daily

Sheep: 5mg/kg, IM, once daily for 3-5 days

Pigs: 10mg/kg, IM, once daily

Birds: 100-200 mg/L, in drinking water, PO

Clindamycin:

• It is semi-synthetic derivative of lincomycin
• Chemical substitution of chlorine atom for hydroxyl group allows clindamycin to be more potent, better absorbed and less toxic than lincomycin
• They have same antibacterial spectrum as of lincomycin. It is bactericidal for more strains of bacteria.

Pharmacokinetics:

• They are rapidly absorbed after oral administration to about 90%
• Peak plasma concentration following oral administration is about 45-60 minutes and after IM administration is about 1-2 hours
• Accumulates in neutrophils and macrophages
• It shows a high degree of protein binding. About 90% drugs are plasma protein bound
• Metabolized in liver to both active and inactive metabolites.
• Metabolites and unchanged drug are excreted in bile and urine
• Elimination half-lives in dogs is about 3-5 hrs after oral administration and 10-12 hours after SC administration.

Side effects/Adverse effects:

• Colitis
• Diarrhoea
• Swine may develop GI disturbances
• Feed contaminated with clindamycin in cattle may result in drop in milk production, diarrhoea and inappetence
• Hypotension and cardiopulmonary arrest have been reported in animals following rapid IV administration

Contraindications:

• In patients with hypersensitivity to clindamycin

Indications:

• In treatment of anaerobic infections caused by susceptible anaerobic bacteria
• In patients hypersensitive to penicillin
• In treatment of periodontal disease, osteomyelitis, dermatitis, and deep tissue infection
• Also used in treatment of bone and joint infections
• In Toxoplasmosis

Dose:

Dogs & cats: 5-10 mg/kg, PO, 2 times daily

                       10 mg/kg, IM, 2 times daily