Pharmacopeia

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Field	BENZYL PENICILLIN Anti-infectives · Anti-infectives · Level 1	METRONIDAZOLE Anti-infectives · Anti-infectives · Level 3	CLINDAMYCIN Anti-infectives · Anti-infectives · Level 3
Mechanism of action	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	Converted to active form or nitroso free radical by obligate anaerobes. Inhibits DNA synthesis. Causes DNA degradation	Inhibitor of bacterial 50S ribosomal subunit Prevents protein synthesis
Absorption	Orally not absorbed (need penicillin V)	50% PO BA 75% Rectal BA	IV or PO
Distribution	CSF and bone penetration if inflammation present	Widely distributed to all tissues	Wide distribution including bone but not CSF
Protein binding	60% PB	10% PB	90% PB
Volume of distribution	Vd <1L/kg	Vd 0.75 L/kg	—
Metabolism	Inactive metabolite penicollic acid	Hepatic Oxidation and glucuronidation	Hepatic metabolism
Excretion	90% excreted in urine by tubular secretion 25% unchanged	Renal excretion 60% unchanged	Biliary. Long post antibiotic effect leads to clostridium overgrowth
Half-life	—	T1/2 = 6-10hrs Renal dose adjustment not required	—
Adverse Effects Toxicity	GIT– abdominal pain, N/V/D, pseudomembranous colitis, hepatitis HAEM- agranulocytosis CNS- confusion, seizure, encephalopathy HYPERSENSITIVITY- rash, anaphylaxis	GIT– abdominal pain, N/V/D, jaundice, pancreatitis HAEM- leukopenia CVS– T wave flattening, QT prolongation CNS– ataxia, seizures, insomnia, paraesthesia HYPERSENSITIVITY– rash OTHER– metallic taste	- Pseudomembranous colitis due to c.diff - Contact dermatitis - Metallic taste - Anaphylaxis
Antimicrobial Spectrum	Narrow-Spectrum Natural Penicillin Highly bactericidal, only gram positives/anaerobes, susceptible to betalactamases Targets GPC: Streptococci, Meningococcus Listeria (GPB) GNC: Neisseria, Clostridia Treponemma (Spiral) Synergistic effects with aminoglycosides	Active against anaerobes (including clostridium, N.Gonorrhoea, N.Menigitidis, Bacterioides and Fusobacterium) and protozoa (trichomonas, Giardia)	Aerobic G+ cocci including MRSA (except enterococci) Anaerobic G- bacilli Most aerobic G- bacilli are resistant including pseudomonas (except Capnocytophagia canimorus)
Class Group	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: NITROIMIDAZOLE	ANTIBIOTIC: LINCOSAMIDE
Indications Uses	—	—	• Clindamycin is used to treat serious anaerobic and gram positive infection (not enterococcus) and also has MRSA and Plasmodium falciparum cover (but not p. vivax or gram negative aerobes) • Can be used (along with primaquine) to treat PCP • Can be used to treat toxin mediated septic syndromes including necrotizing fasciitis and toxic shock syndrome • MOA: inhibits bacterial synthesis by disrupting the function of 50S ribosomal subunit. Can be bacteriostatic or bacteriocidal depending on concentration and microbe being treated
Introduction	Narrow spectrum naturally occurring penicillin	Nitroimidazole	Lincosamide
Legacy Cicm Level	Level 1	Level 3	Level 3
Resistance Mechanism	Resistance MRSA Many Staph -Betalactamase prod Gram Negatives	reduced rate of uptake, by efflux or by reducing the rate of metronidazole reductive activation increased DNA repair efficiency	—