Classes of antimicrobial agents

MBSM 713: BIOCHEMISTRY OF ANTI MICROBIAL AGENTS

Lecture Two:

Survey of major antimicrobial drug groups

1.ANTIBACTERIAL AGENTS(Antibiotics)

Dr. G. Kattam Maiyoh

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GKM/KISIIU/MBSM713 /BIOC.AMIC.AGENS.LEC02

Classification: Mode of action

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/BIOC.AMIC.AGENS.LEC02

Inhibitors of Cell Wall Synthesis





Bacterial cell wall• There are three types

– Gram-positive (e.g. Staphylococci, Listeria

• Have many peptidoglycan layers

• stains with crystal violet• typically lack the outer

membrane found in gram-ve.

– Gram-negative (e.g. E.coli, Salmonella)

• Have few peptidoglycan layers• (stain safranin or fuchsin)

– Acid-fast Positive (Mycobacteria)• Cell wall contains waxy

substance (Mycollic acid)• Stains with acid fast (heating

required)

Antibiotics - Cell wall synthesis inhibitors

Beta-lactam antibiotics:

1928 - Alexander Fleming observes the antibacterial effects of Penicillin

1940 - Florey and Chain extract Penicillin



The beta lactams• The β-lactam group of antibiotics

includes an enormous diversity of natural and semi-synthetic compounds that inhibit several enzymes associated with the final step of peptidoglycan synthesis.

• All of this enormous family are derived from a β -lactam structure: a four-membered ring in which the β -lactam bond resembles a peptide bond.

• The multitude of chemical modifications based on this four-membered ring permits the astonishing array of antibacterial and pharmacological properties within this valuable family of antibiotics.



The Beta-Lactams

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R – variable side chain

Monobactam nucleus

Penicillinase (β Lactamase)

- Represents a great challenge to the action of the beta lactams

Figure 20.8

More when we discuss antibiotic resistance



• Penicillium notatum produces the only naturally occurring agent – penicillin G or benzylpenicillin

• Penicillium chrysogenum produces 6-aminopenicillanic acid, raw material for semi-synthetics penicillins



Targets for beta lactams1. The targets for β-lactam drugs are the penicillin binding

proteins (PBP's), so called because they bind radioactive penicillin and can be detected by autoradiography of gels on which bacterial proteins have been separated electrophoretically.

• The penicillin binding proteins have transpeptidase or carboxypeptidase activity and they act to regulate cell size and shape.

• They are also involved in septum formation and cell division. Bacteria have several individual penicillin binding proteins, each with a separate function.

• Conventionally these are numbered according to size, with PBP 1 as the largest protein.

• The PBP 1 of one bacterium will not necessarily have the same function as the PBP 1 of a different organism.



Target2. The β-lactam antibiotics also stimulate the activity of autolysins by inactivating an inhibitor => lysis

• Autolysins are enzymes that are responsible for the natural turnover of cell wall polymers to permit growth of the cells.

• Under normal conditions, these enzymes produce controlled weak points within the peptidoglycan structure to allow for expansion of the cell wall structure.

• This activity is stimulated by β-lactams, causing a breakdown of peptidoglycan and leading to osmotic fragility of the cell and ultimately to cell lysis.



Penicillins - classification– Narrow spectrum – penicillinase sensitive

– Narrow spectrum – penicillinase resistant

– Broad spectrum penicillins

– Extended-spectrum penicillins• Cephalosporines

• Carbapenems

• Monobactams

• Vancomycin, Bacitracin



Penicllins (pharmacokinetics)

• Attains therapeutic concentration in most tissues

• However has poor CSF penetration• Renal excretion (Excretion)• Side effects: hypersensitivity, nephritis,

neruotoxicity, platelet dysfunction



Narrow spectrum – penicillinase (= β-lactamase) sensitive• Benzylpenicillin

– Naturally occuring

– Poor oral availability (sensitive to stomach acid)

=> given by injection

– Active against gram-positive bacteria

• Phenoxymethylpenicillin

– Better oral availability (acid resistant)



Narrow spectrum – penicillinase (= β-lactamase) resistant• Methicillin

– Semisynthetic– Poor oral availability (only parenteral)– Active against gram-pos bacteria– Mostly used for Staphylococcus aureus

• Oxacillin– Good oral availability

• Cloxacillin• Dicloxacillin



Broad spectrum – penicillinase (β-lactamase) sensitive

(Also referred to as Aminopenicillins)

• Ampicillin– Semisynthetic

– Good oral availability

– Active against gram-pos and gram-neg bacteria

– Active against enterobacteria e.g. kleb. Shig. Salm

• Amoxicillin

– Excellent oral availability



Extended spectrum – penicillinase (β-lactamase) sensitive

(Also called Carboxypenicillins)

• Carbenicillin– Semisynthetic– Poor oral availability– Active against gram-pos and gram-neg bacteria– Active against Pseudomonas aeruginosa and

Klebsiella

• Ticarcillin• Mezlocillin• Pipercillin



Penicillins

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Cephalosporins• Share the same antibiotic mechanism as penicillins• Cross-allergies with penicillins are common• Some CSs antagonize Vitamin K => leads to bleeding• Some CSs block alcohol oxidation => disulfiram effect (allergic

reactions, seizures, extreme tiredness and dark urine)

Classified into generations: 1- 4 • Increasing activity against gram-negative bacteria and

anaerobes• Increasing resistance to destruction by beta-lactamases• Increasing ability to reach cerebrospinal fluid



Cephalosporins

• The first to be discoverded were called first generation while later, more extended spectrum cephalosporins were classified as second, third and 4th generation cephalosporins in this order.

• Each newer generation has significantly greater gram-negative antimicrobial properties than the preceding generation,

• Most cases with decreased activity against gram-positive organisms.

• Fourth generation cephalosporins, however, have true broad spectrum activity.





Cephalosporin structure

• Base molecule is 7-aminocephalosporanic acid produced by a Sardinian sewer mold

• R groups determine spectrum of activity and pharmacological properties

• Mechanism of action/resistance and class pharmacology is essentially the same as penicillins



First Generation Cephalosporins

• Cefazolin, cephalexin, cephadroxil

• Excellent against susceptible staph and strep

• Modest activity against G -ve• Cefazolin given parentally,

others orally• More than half of the drug is

bound to plasma proteins• Excreted by kidneys

unmetabolized• Good for staph and strep skin

and soft tissue infections



Second Generation Cephalosporins• Include;– Cefaclor,– cefuroxime, – cefprozil

• Modest activity against G+, increased activity against G-, works against anaerobes

• Cefaclor and cefprozil given orally• Absorption and excretion same as first

generation.• Good for treating respiratory tract infections,

intra-abdominal infections, pelvic inflammatory disease, diabetic foot ulcers



Third Generation Cephalosporins• Ceftaxime, ceftriaxzone,

cefoperazone, cefpodoxime• Broad spectrum killers• Drugs of choice for serious

infections• No effect against Listeria and beta-

lactamase producing pneumococci• Cefpodoxime given orally, others

parentally• Most excreted by kidney• Therapeutic uses – Bacterial meningitis– Lyme disease– Life-threatening G -ve sepsis

(infection)



Fourth Generation Cephalosporin

– e.g.Cefepime

–Have true broad spectrum activity ( and more beta-lactamases resistanc (effective against Gm+ and Gm-)

–Given parentally, excellent penetration into CSF

–Good for nosocomial infections



Toxicity/Contraindications of Cephalosporins

• Hypersensitivity reactions (uncommon) essentially same as for penicillins

• Cross-reaction between 2 classes



Inhibitors of Cell Wall Synthesis

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Carbapenems

• Beta-lactam ring is fused to a 5 member ring system

• Effect on microbes and pharmacology of carbapenems similar to penicillins


Selected Carbapenems• Imipenem– Broad spectrum including anaerobes

and Pseudomonas aeruginosa– Parentally administered– Must be combined with cilastatin to be

absorbed– Excreted by kidneys

• Meropenem, ertapenem, and doripenem are similar to imipenem but don’t need co-administration with cilastatin

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Toxicity/Contraindications of Carbapenems

• Nausea and vomiting (common)• Hypersensitivity reactions (uncommon)– Essentially the same as for penicillins– Cross-reactivity is possible



Aztrenam – a monobactam

• Monobactam - beta-lactam compounds wherein the beta-lactam ring is alone and not fused to another ring

• Works only on Gm -ve, including Pseudomonas aeruginosa

• Useful for treating G-ve infections that require a beta-lactam because it does not elicit hypersensitivity reactions


Beta-lactamase inhibitorsa. Clavulanic acid

– Irreversible inhibitor of β-lactamase– Good oral absorption– Combined with amoxicillin or ticarcillin

b. Sulbactam


Peptide AntibioticsPeptide antibiotics are drugs with

polypeptides structureSub-group of Peptide Antibiotics

Polymyxins e.g.»Polymyxin B»Colistin

Glycopeptides e.g.»Vancomycin»Teicoplanin»Avoparcin

BacitracinStreptogramins

Each drug group has its own mechanism of action4 groups and 4 mechanism



PolymyxinsPolymyxinsDrug members

Polymyxin BColistin (Polymyxin E)

Mechanism of actionDetergent-like actionDamage to cell membrane functionBind to Lipopolysaccharides (LPS) and

destroy outer membrane of Gram-negative bacteria

BactericidalConcentration-dependentNon-selective on bacterial membrane

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PolymyxinsPolymyxins• Pharmacokinetics–Not absorbed via GI tract– If injection, drug accumulated and

slowly excreted• Toxicities–Highly toxic if systemic injection–Nephrotoxic–Neurotoxic

• Clinical uses–Oral treatment–Local treatment



GlycopeptidesGlycopeptides• Group members–Vancomycin

• Antibacterial activity– Inhibition of cell wall synthesis–Active against Gram-positive bacteria

• Not absorbed orally, must administered IV

• High toxicity–Local irritation , ototoxicity,

nephrotoxicity• Clinical uses–Hardly used in animals–Used only resistant case i.e. to beta-

lactams



BacitracinBacitracin• Drug activity– Inhibit cell wall synthesis–Activity on Gram-positive bacteria–Bactericidal

• Nephrotoxic if systemic injection• Clinical uses – the same as polymyxin–Oral – as growth promoter–Local or topical drugs



Antibiotics that Inhibit Protein Synthesis



Protein synthesis inhibitors– Aminoglycosides

– Tetracyclins

- Spectinomycin

– Macrolides

– Chloramphenicol

– Clindamycin



Inhibition of Protein Synthesis by Antibiotics

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Review of Initiation of Protein Synthesis

30S1 32 GTP

1 2 3 GTP

Initiation Factors

mRNA

3

12 GTP

30S Initiation Complex

f-met-tRNA

Spectinomycin

Aminoglycosides

12

GDP + Pi 50S

70S Initiation Complex

AP



Review of Elongation of Protein Synthesis

GTP

AP

Tu GTP Tu GDP

Ts

TsTu

+

GDPTs

Pi

P ATetracycline

AP

Erythromycin

Fusidic Acid

Chloramphenicol

G GTPG GDP + Pi

G

GDP

AP

+GTP



Antimicrobials that Bind to the 30S Ribosomal Subunit



a) Aminoglycosides (bactericidal)streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, neomycin (topical)

• Mode of action - The aminoglycosides irreversibly bind to the 16S ribosomal RNA and freeze the 30S initiation complex (30S-mRNA-tRNA) so that no further initiation can occur.

• They also slow down protein synthesis that has already initiated and induce misreading of the mRNA. – By binding to the 16 S r-RNA the aminoglycosides increase

the affinity of the A site for t-RNA regardless of the anticodon specificity.

• May also destabilize bacterial membranes.



Microbe Library

American Society for Microbiology

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b) Aminoglycosides (bactericidal)streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, neomycin (topical)

• Spectrum of Activity –Effective against many gram-negative and some gram-positive bacteria;

• Not useful for anaerobic (oxygen required for uptake of antibiotic) or intracellular bacteria.

• Resistance - Common• Synergy - The aminoglycosides synergize with β -lactam

antibiotics. The β -lactams inhibit cell wall synthesis and thereby increase the permeability of the aminoglycosides.


c) Tetracyclines (bacteriostatic)tetracycline, minocycline and doxycycline

• Mode of action - The tetracyclines reversibly bind to the 30S ribosome and inhibit binding of aminoacyl-t-RNA to the acceptor site on the 70S ribosome.

• Spectrum of activity - Broad spectrum; Useful against intracellular bacteria

• Resistance - Common

• Adverse effects - Destruction of normal intestinal flora resulting in increased secondary infections; staining and impairment of the structure of bone and teeth.



d) Spectinomycin (bacteriostatic)

• Mode of action - Spectinomycin reversibly interferes with m-RNA interaction with the 30S ribosome. It is structurally similar to the aminoglycosides but does not cause misreading of mRNA.

• Spectrum of activity - Used in the treatment of penicillin-resistant Neisseria gonorrhoeae

• Resistance - Rare in Neisseria gonorrhoeae



Antimicrobials that Bind to the 50S Ribosomal Subunit



a) Chloramphenicol, Lincomycin, Clindamycin (bacteriostatic)

• Mode of action - These antimicrobials bind to the 50S ribosome and inhibit peptidyl transferase activity.

• Spectrum of activity - Chloramphenicol - Broad range;Lincomycin and clindamycin - Restricted range


• Adverse effects - Chloramphenicol is toxic (bone marrow suppression) but is used in the treatment of bacterial meningitis.



b) Macrolides (bacteriostatic)erythromycin, clarithromycin, azithromycin, spiramycin

• Mode of action - The macrolides inhibit translocation.

• Spectrum of activity - Gram-positive bacteria, Mycoplasma, Legionella




Macrolides : ClassificationMacrolides : Classification• Macrolides are drugs with lactone ring

structure• Sub-groups are based on no. of ring atom– 12-membered ring macrolides– 13-membered– 14-membered (many drugs)– 15-membered– 16-membered (many drugs)

• Special groups– Azalides – name for 15-membered– Triamilides – name for tulathromycin

(combination of 13- and 15-membered)– Ketolides – name for 14-membered with 3

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MacrolidesMacrolidesDrug examples13-membered

Tulathromycin (Triamilides)14-membered

ErythromycinClarithromycin, Roxithromycin,

Dirithromycin15-membered

Azithromycin (Azalides)Tulathromycin (Triamilides)

16-memberedSpiramycinTylosin



Macrolides – general Macrolides – general propertiesproperties

• Mechanism of action– Inhibit protein

synthesis– Bind to 50S

ribosomal unit– Bacteriostatic

• Spectrum of activity– Gram-positive– Some Gram-

negative– Anaerobes–Mycoplasma



Macrolides Macrolides Pharmacokinetics

Broad distribution in body tissues

High intracellular concentration



MacrolidesMacrolides

Additional properties of Macrolides

• Anti-inflammatory effect– Inhibitory effect on

neutrophils– inhibit

proinflammatory cytokines

– Useful for treatment of inflammatory pulmonary disease

• Prokinetic effect– Stimulate movement

of GI tract



ErythromycinErythromycin

• Erythromycin is a standard or basic drug of macrolides

• Other drug members are usually compared with erythromycin

• Important adverse effect - severe diarrhea– Especially in adult horse and ruminants

• Clinical uses– Second choice (alternative drug) in

humans– Small animals– Fowls– Some cases in ruminants



Tylosin andTylosin and SpiramycinSpiramycin• Tylosin and Spiramycin– Activities are similar

to erythromycin– Good activity on

Mycoplasma• Examples of Clinical

uses–Whooping couph– Pneumonia– VDs– Used in ruminants

and pigs



http://www.hiwtc.com/photo/products/20/08/63/86341.jpg

Advanced generation Advanced generation MacrolidesMacrolides

Example drugsRoxithromycinDirithromycinClarithromycinAzithromycin

General activity – the same as erythromycinBetter Pharmacokinetic properties

Acid stableFewer GI side effectHigher oral availabilityLonger serum half-livesHigher tissue concentrations



KetolidesKetolides• Ketolides are 14-

membered ring macrolides with 3 keto group

• Specific drugs– Telithromycin– Cethromycin (still

in clinical study)• Important

properties– Less resistance– Good activities on

bacteria resistant to erythromycin



Fusidic acid (bacteriostatic)

• Selectivity due to differences in prokaryotic and eukaryotic elongation factors

• Mode of action - Fusidic acid binds to elongation factor G (EF-G) and inhibits release of EF-G from the EF-G/GDP complex.

• Spectrum of activity - Gram-positive cocci


Antimicrobials that Interfere with Elongation Factors

Inhibitors of Nucleic Acid Synthesis

~Inhibitors of DNA synthesis~Inhibitors of RNA synthesis



Inhibitors of RNA SynthesisFor this class of antibiotics, selectivity is due to differences between prokaryotic and eukaryotic RNA polymerase i.e.

All RNA polymerases are multi-protein complexes, however, the number of proteins that are assembled to form the active enzyme is much larger in eukaryotes;

•The basic catalytic core is made up of 12 subunits.

•By comparison, bacterial RNAP has 5 subunits.



Rifampin, Rifamycin, Rifampicin, Rifabutin (bactericidal)

• Mode of action - These antimicrobials bind to DNA-dependent RNA polymerase and inhibit initiation of mRNA synthesis.

• Spectrum of activity - Broad spectrum but is used most commonly in the treatment of tuberculosis

• Resistance – Common– For example; – Resistance to rifampicin develops quickly during treatment, so

monotherapy should not be used to treat these infections — it should be used in combination with other antibiotics.

– Resistance to rifampicin arises from mutations that alter residues of the rifampicin binding site on RNA polymerase, resulting in decreased affinity for rifampicin.

• Combination therapy - Since resistance is common, rifampin is usually used in combination therapy.



Inhibitors of DNA SynthesisFor this class of antibiotics, selectivity due to differences between prokaryotic and eukaryotic DNA replication enzymes

Consider the following:

Eukaryotic replication is more complicated. •First, they have multiple ori per chromosome that allow for bidirectional synthesis of the linear chromosome. •They also use several DNA polymerases (I, II, III), and ligase (seals the nicks in the DNA strand), and RNA primer (gives a 3' end for the DNA polymerase to start synthesis).

•As for other differences in their synthesis of DNA is their speed, prokaryotes can replicate their chromosome at about 1,000 bp/sec, while eukaryotes can replicate their chromosomes at about 100 bp/sec. •They also differ in the number of ori, eukaryotes (as it was stated above) has multiple ori, while prokaryotes have only one.



The Quinolones

• Current drugs are fluoridated 4-quinolones

• Broad coverage (some broader than others)

• Targets DNA gyrase ( G-) and topoisomerase IV (G+)

• Resistance due to efflux and mutations in targets



Pharmacological attributes of Quinolones• Favorable pharmacological attributes– Orally administered, quickly absorbed,

even with a full stomach– Excellent bioavailability in a wide

range of tissues and body fluids (including inside cells)

• Mostly cleared by the kidneys– Exceptions are pefloxacin and

moxifloxacin which are metabolized by liver

• Ciprofloxacin, ofloxacin, and pefloxacin are excreted in breast milk

““Got Cipro?”Got Cipro?”



Therapeutic Uses of Quinolones

• Urinary tract infections

• Prostatitis• STD’s– Chlamydia– Chancroid - painful

sores on the genitalia– Not syphilis or

gonorrhea (due to increased resistance)




• GI and abdominal – Travelers diarrhea– Shigellosis– Typhoid fever

• Respiratory tract– New agents for strep. pneumonia




• Bone, joint, soft tissue– Ideal for chronic

osteomylitis - infection of the bone or bone marrow• Resistance developing in

S. aureus, P. aeruginosa, and S. marcesens

– Good against polymicrobial infections like diabetic foot ulcers




• Ciprofloxacin for anthrax and tuleremia (rabbit fever, deer fly fever, Ohara's fever)

• Combined with other drugs, useful for atypical Mycobacterium sp.

Pulmonary AnthraxPulmonary Anthrax



Toxicity/Contraindications of Quinolones• Nausea, vomiting, abdominal discomfort (common)• Diarrhea and antibiotic-associated colitis (uncommon to rare)• CNS side effects

– Mild headache and dizziness (common to rare)– Hallucinations, delirium, and seizures (rare)

• Arthropy in immature animals (common)– Quinolones not given to children unless benefits outweigh the risks

• Leukopenia, eosinophilia, heart arythmias (rare)

delirium - disorder involving incoherent speech, hallucinations, etc., caused by intoxication, fever, etc



Antimetabolite Antibiotics



Inhibitors of Folic Acid Synthesis

• Basis of Selectivity• Review of Folic

Acid Metabolism

p-aminobenzoic acid + Pteridine

Dihydropteroic acid

Dihydrofolic acid

Tetrahydrofolic acid

Pteridine synthetase

Dihydrofolate synthetase

Dihydrofolate reductase

ThymidinePurines

Methionine

Trimethoprim

Sulfonamides



Sulfonamides, Sulfones (bacteriostatic)

• Mode of action - These antimicrobials are analogues of para-aminobenzoic acid and competitively inhibit formation of dihydropteroic acid.

• Spectrum of activity - Broad range activity against gram-positive and gram-negative bacteria; used primarily in urinary tract and Nocardia infections.

• Resistance - Common• Combination therapy - The sulfonamides are used in

combination with trimethoprim; this combination blocks two distinct steps in folic acid metabolism and prevents the emergence of resistant strains.



Trimethoprim, Methotrexate, Pyrimethamine (bacteriostatic)

• Mode of action - These antimicrobials binds to dihydrofolate reductase and inhibit formation of tetrahydrofolic acid.

• Spectrum of activity - Broad range activity against gram-positive and gram-negative bacteria; used primarily in urinary tract and Nocardia infections.

• Resistance - Common• Combination therapy - These antimicrobials are used in

combination with the sulfonamides; this combination blocks two distinct steps in folic acid metabolism and prevents the emergence of resistant strains.



Sulfonamides

• Analogues of para-aminobenzoic acid

• Broad spectrum• Competitive inhibitors of

dihydropteroate synthase – needed for folic acid synthesis

Gerhard Domagk gets a Nobel Gerhard Domagk gets a Nobel for Medicine, 1939.for Medicine, 1939.



Sulfonamides• Mostly absorbed from GI tract• Binds variably to serum albumin • Wide tissue distribution, including

transplacentally• Variably inactivated in liver by

acetylation and then excreted in urine

• Some agents can precipitate in acid urine



1. Rapidly Absorbed and Eliminated Sulfonamides

• Sulfisoxazole, sulfamethoxazole, sulfadiazine

• Bind extensively to plasma proteins

• Highly concentrated in urine (cidal)

• Sulfamethoxazole combined with trimethoprim (Bactrim) is widely used to treat a variety of infections (esp. UTI)



2. Poorly Absorbed Sulfonamides

• E.g. Sulfasalazine• Poorly absorbed in GI tract• Used to treat ulcerative colitis

and irritable bowel syndrome• Gut flora metabolize drug into

2 compounds, 1 toxic- sulfapyridine, 1 therapeutic (5-aminosalicylate)

• Hence is a prodrug – effective after breakdown

Ulcerative Colitis



Sulfonamides for Topical Use

• E.g. 1.Sulfacetamide– Good penetration in eye

– Non-irritating

• 2. Silver sulfadiazine– Prevention and treatment of

burn wound infections

Bacterial corneal infectionBacterial corneal infection



Long Acting Sulfonamide

• Serum half-life is measured in days rather than minutes or hours

• E.g. Sulfadoxine

• Combined with pyirethamine to treat malaria

Plasmodium vivaxPlasmodium vivax



Therapeutic Uses of Sulfonamides

• Urinary tract infections• Nocardiosis -serious infection

caused by a fungus-like bacterium that begins in the lungs and can spread to the brain.

• Toxoplasmosis - caused by protozoan (avoid using in pregnant women)

Nocardia asteroidesNocardia asteroides



Toxicity/Contraindications of Sulfonamides - UT

• Crystallization in acid urine– Common to uncommon

depending on drug.

– Alkalize urine or increase hydration



Toxicity/Contraindications of Sulfonamides - blood

• Acute hemolytic anemia – Rare to extremely rare

– Associated with glucose-6-phosphate dehydrogenase activity in RBC

• Agranulocytosis - failure of the bone marrow to make enough white

blood cells (neutrophils). (extremely rare)

• Aplastic anemia - marrow doesn't make enough new blood cells.

(extremely rare)



Toxicity/Contraindications of Sulfonamides - immune

• Hypersensitivity reactions (common to uncommon)– Skin and mucous membrane

manifestations (rashes)– Serum sickness - type III hypersensitivity

reaction that results from the injection of heterologous or foreign protein or serum

– Focal or diffuse necrosis of the liver (rare)



Toxic Epidermal Necrolysis (TEN)



Toxicity/Contraindications of Sulfonamides - miscellaneous

• Nausea, anorexia, vomiting (common)

• Kernicterus; damage caused by excessive jaundice– Displacement of bilirubin from

plasma albumin to brain resulting in encephalopathy(disease of the brain)

– Never give sulfa drugs to a pregnant or lactating woman

• Potentiation of oral coagulants, sulfonylurea hypoglycemic drugs, and hydrantoin anticonvulsants

Bilirubin deposits in neonatal Bilirubin deposits in neonatal brainbrain



INJURY TO THE PLASMA MEMBRANE - Brief

• All cells are bound by a cell membrane. • And although the membranes of all cells are quite

similar, those of bacteria and fungi differ from eukaryotic cells.

• These slight differences allow for selective action of some antimicrobial agents.

• Certain antibiotics, like polymyxins, act as detergents to dissolve bacterial cell membranes by binding to phospholipids present in the membranes.



The End

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Classes of antimicrobial agents

Health & Medicine

Transcript of Classes of antimicrobial agents