Category Penicillin

Drug

Mechanism of Action *Bactericidal *Interfere with the synthesis of the bacterial cell wall peptidoglycan *Transpeptidase is a bacterial enzyme which cross links the peptidoglycan chains to form rigid cell walls *Bind to and inactivate transpeptidase (penicillinbinding proteins) which result in loss of cell rigidity and cell death *Inhibits cross linking of peptidoglycans

Mechanism of Resistance 1. Penicillinase (βlactamase) breaks the betalactam ring ex. Staph. Aureus 2. Alteration of the penicillinbinding protein ex. Staph. Aureus; MRSA; Penicillin resistant pneumococci 3. Reduced permeability in Gram (-) cell membranes ex. Pseudomonas

Pharmacokinetics

Use

Narrow Spectrum Penicillin G (Penicillinase (parenteral) susceptible) -Streptococci -Pneumococci -Meningococci -Treponema Pallidum

*Acid labile, given i.m. or i.v. *Gram (+) *Repository Penicillin G (longacting): Procaine & *DOC: Syphillis (Treponema Benzathine Penicillin G Pallidum) *Penetrates the CSF to a significant extent only during inflammation *Eliminated via tubular secretion -Probenacid competitively inhibits the renal tubular secretion of Penicillin ; thus it increases the concentration and prolongs its activity *Streptococcal, meningococcal *Strains of pneumococci, Staph. Aureus & Neisseria gonorrheae are resistant Prophylaxis: Benzathine Penicillin Rheumatic fever Benzathine/Procaine Gonorrhea/Syphillis in sexual partner

Penicillin V (oral)

Category Drug Narrow Spectrum Methicillin (Penicillinase resistant) -Staphylococci (except MRSA)

Mechanism of Action

Mechanism of Resistance

Pharmacokinetics

Use *Staph. Aureus (except MRSA) -Penicillinase producing antistaphylococcal infections *Resistant to inactivation by betalactamase

Naficillin Oxacillin Broad Spectrum (Penicillinase susceptible) -Gram + cocci -Haemophillus influenza -Listeria Monocytogenes -H. Pylori Ampicillin

* MRSA & MRSE (Staph. Epidermidis) are resistant *Gram (+) *Gram (-): H. Influenza; Listeria Monocytogenes; H. Pylori; E. Coli; Proteus Mirabilis Amoxicillin : -endocarditis before major procedures -H. Pylori infections (peptic ulcers) Prophylaxis: Amoxicillin - bacterial endocarditis in patients with prosthetic heart valves, cyanotic heart disease or who are planning to undergo surgical procedures *Drug Combo

Amoxicillin

Extended Ticarcillin Spectrum or Antipseudomonal (Penicillinase susceptible) -Gram - rods -Psuedomonas Aeruginosa Piperacillin Azlocillin

*Gram (-) rods Pseudomonas Aeruginosa Enterobacter infections *Psuedomonas infection (which is common in patients with Cystic Fibrosis) *Drug Combo

Adverse Effects *Relatively safe *Hypersensitivity -5-7% incidence -severity varies from urticarial skin rashes to acute anaphylaxis *Cross-sensitivity between individual penicillins possible

Adverse Effects *Intersitial nephritis

*Maculopapular rash *Suprainfection: Diarrhea pseudomembranous enterocolitis (C. Difficile)

Category Cephalosporins

Drug

Mechanism of Action *Bactericidal *Interfere with the synthesis of the bacterial cell wall peptidoglycan *Transpeptidase is a bacterial enzyme which cross links the peptidoglycan chains to form rigid cell walls *Bind to and inactivate transpeptidase (penicillinbinding proteins) which result in loss of cell rigidity and cell death *Inhibits cross linking of peptidoglycans

Mechanism of Resistance 1. Penicillinase (β-lactamase) breaks the betalactam ring ex. Staph. Aureus 2. Alteration of the penicillinbinding protein ex. Staph. Aureus; MRSA; Penicillin resistant pneumococci 3. Reduced permeability in Gram (-) cell membranes ex. Pseudomonas

Pharmacokinetics

Use

Adverse Effects * Hypersensitivity reaction (rashes, fever) *Cross-hypersensitivity between cephalosporins completely possible *Cross-reaction between penicillins is less likely (510%) caution still needed *History of anaphylaxis to penicillin is a contraindication for cephalosporins *Suprainfection: Diarrhea pseudomembranous enterocolitis (C. Difficile) *If given with aminoglycosides - increases the chances of nephrotoxicity

Cephalexin (oral) Cefazolin (parenteral)

Gram + cocci PEcK Proteus E. Coli Klebsiella Surgical prophylaxis

1st Generation

Category

Drug Cefoxitin Cefotetan

Mechanism of Action Gram - bacteria HEN PEcKS H. Influenza E. Coli Neisserea Proteus Enterobacter Klebsiella Serratia

Mechanism of Resistance

Pharmacokinetics

Use Bacteriodes Fragillis

Adverse Effects Contains a methylthiotetrazole group (MTT group) - may cause Disulfiram like reactions with ethanol

Cefaclor Cefamandole

H. Influenza Contains a methylthiotetrazole group (MTT group) - may cause Disulfiram like reactions with ethanol Enters CSF, but the others do not

2nd Generation Cefuroxime

Cefoperazone

Gram - bacteria Good penetration into BBB (except Cefoperazone & Cefixime )

Pseudomonas

Contains a methylthiotetrazole group (MTT group) - may cause Disulfiram like reactions with ethanol

3rd Generation

Ceftazidime Ceftriaxone (parenteral)

*DOC: Gonorrhea Salmonella Typhi *Meningitis *DOC: Gonorrhea *Meningitis

Cefixime (oral) Cefotaxime

Cefipime (iv) Cefpirome 4th Generation

Resistant to inactivation by β lactamases Excellent penetration into Gram - bacteria Wider spectrum than 3rd generation (both Gram + & Gram -)

Category Monbactam

Drug Aztreonam

Mechanism of Action Mechanism of Resistance *Bactericidal *Interfere with the synthesis of the bacterial cell wall peptidoglycan *Transpeptidase is a bacterial enzyme which cross links the peptidoglycan chains to form rigid cell walls *Bind to and inactivate transpeptidase (penicillinbinding proteins) which result in loss of cell rigidity and cell death *Inhibits cross linking of peptidoglycans

Pharmacokinetics Structure has a single ring Resistant to β lactamases

Use Adverse Effects *ONLY against Gram - *NO cross rods hypersensitivity reaction between No effect on Gram + penicillins and bacteria and anerobes Aztreonam *Use in Gram infections especially in patients allergic to Penicillins or Cephalosporins

Category Carapenems

Drug Imipenem

Mechanism of Action Mechanism of Resistance *Bactericidal *Interfere with the synthesis of the bacterial cell wall peptidoglycan *Transpeptidase is a bacterial enzyme which cross links the peptidoglycan chains to form rigid cell walls *Bind to and inactivate transpeptidase (penicillin-binding proteins) which result in loss of cell rigidity and cell death *Inhibits cross linking of peptidoglycans

Pharmacokinetics

Use Broad spectrum: Gram + & Gram bacteria, anaerobes Bacteriodes Fragilis; Clostridia

Adverse Effects *GI distress *Skin rash *In high doses: Seizures

Notes Imipenem is rapidly inactivated by renal dehydropeptidase I *Imipenem is combined with Cilastatin to prevent hydrolysis by enzymes in the renal brush border *Cilastatin is an inhibitor of renal dehydropeptidase; thus it increases the plasma 1/2 life of Imipenem

Meropenem Ertapenem

Category

Drug Vancomycin

Mechanism of Action *Bactericidal *Glycoprotein *Acts by binding to D-Ala-D-Ala terminal of the nascent peptidoglycan pentapeptide side chain

Mechanism of Resistance 1. Occurs in strains of enterococci and staphylococci (VRE & VRSA)

Pharmacokinetics

Use *ONLY Gram + *MRSA, Enterococci, Clostridium Difficile

Adverse Effects *Red Man Syndrome because of release of histamine (flushing, redness of face, hypotension) - can be prevented with antihistamines

2. Resistance involves a decreased affinity of Vancomycin for the binding site; this is because of the *This leads to inhibition of replacement of the terminal transglycosilation and in turn D-Ala by D-Lactate prevents the peptidoglycan chain elongation

*MRSA infections given by slow IV infusion

*Nephrotoxicity *Anti-biotic associated *Ototoxicity Enterocolitis (C. Difficile) orally

Category Aminoglycosides

Drug

Mechanism of Action *Bactericidal *Binds to 30S ribosomal subunit and inhibits bacterial protein synthesis

~Not effectively absorbed by GI (always given 2. Impaired cell penetration parenterally - iv, im) 1. Interfere with the of aminoglycoside into the initiation complex of cell ~Limited tissue peptide formation by ~Streptococci and penetration blocking the association enterococci are resistant to of 50S subunit with mRNA aminoglycosides due to ~Most cleared by 30S decreased penetration kidney (monitor levels in patients with renal 2. Induce misreading of 3. The receptor protein on failure/elderly) mRNA, which causes the 30S ribosomal subunit incorporation of wrong may be deleted or altered ~Attain high amino acids into the as a result of a mutation concentrations in otic peptide, resulting in a perilymph and renal nonfunctional toxic cortical tissue protein 3. Cause breakup of polysomes into nonfunctional monosomes

Mechanism of Resistance 1. Production of transferase enzyme by the bacteria that inactivates the aminoglycoside

Pharmacokinetics ~Polar compounds

Use *ONLY Gram aerobic bacilli, but lack activity against anaerobes Synergistic activity with βlactam drugs ~Enterococcal infections (AG + Penicllin G/Ampicillin) ~P. Aeurginosa infections (AG + extended spectrum penicillin/ cephalosporins)

Adverse Effects *Ototoxicity ~Cochlear damage: results in deafness (irreversible) ~Vestibular damage: headache, nausea, vomiting, dizziness, nystagmus, vertigo, ataxia (reversible) ~Toxicity can be enhanced by loop diuretics *Nephrotoxicity ~Proteinuria, hypokalemia, acidosis ~Acute tubular necrosis, enhanced by Vancomycin, Cyclosporin, Amphotericin, Cisplatin *Neuromuscular Blockade (with high doses) ~May result in respiratory paralysis, reversible by administration of Calcium & Neostigmine

3. Cause breakup of polysomes into nonfunctional monosomes

Amphotericin, Cisplatin *Neuromuscular Blockade (with high doses) ~May result in respiratory paralysis, reversible by administration of Calcium & Neostigmine

Category

Drug Gentamicin Neomycin

Mechanism of Action

Mechanism of Resistance

Pharmacokinetics

Use Used topically burn wounds

Adverse Effects Most vestibulotoxic Most nephrotoxic

~Not significantly absorbed in the GI ~After oral administration, the intestinal flora is suppressed or modified and the drug is excreted in the feces ~This effect is used in hepatic coma to decrease the coliform flora ~This decreases the production of ammonia that causes the levels of free nitrogen to decrease in the bloodstream

In a patient with Most nephrotoxic a hepatic coma, decrease in the production and absorption of ammonia from the GI will be beneficial

Amikacin Tobramycin Streptomycin

Used topically burn wounds Used topically burn wounds

Most nephrotoxic

~Tuberculosis Most vestibulotoxic ~Tularemia ~Bubonic Plague

Kanamycin Netilmicinaa

Notes 1. ConcentrationDependent Killing = increasing concentrations kill an increasing proportion of bacteria at a more rapid rate 2. Post-antibiotic Effect = the antibacterial activity persists beyond the time during which measurable drug is present (1x daily dosing)

Notes

Category Tetracyclines

Drug

Mechanism of Action Mechanism of Resistance *Binds to the 30S subunit 1. Development of efflux pumps *Interferes with the attachment of aminoacyl 2. Decreased activity of the tRNA to the acceptor site uptake systems *This prevents addition of amino acids to the growing peptide

Pharmacokinetics ~Chelating property binds Ca2+, Mg2+, Fe2+ which decreases their absorption *Should not be given with milk products, antacids ~Binds to tissues like teeth, bones which are undergoing calcification ~Can cross placenta and concentrate in fetal bones & teeth ~Elimination by kidney for most - dose ↓in renal dysfunction

Use ~Broad spectrum antibiotics Gram +: Clostridia, Listeria, Coryneacterium, B. Anthracis Gram -: Y. Pestis, H. Pylori Spirochetes: T. Pallidum, Borrelia Atypical Bacteria: Rickettsia, Chlamydia, Mycoplasma - highly sensitive Protozoa: E. Histolytica, Plasmodium Falciparum

*Contraindicated in ~Pregnancy ~Children ~Renal insufficiency Category Drug Mechanism of Action Mechanism of Resistance Pharmacokinetics Use

Primary Uses: ~Chlamydial infections: Lymphogranuloma venerum Granuloma inguinake ~Atypical pnuemonia caused by Mycoplasma ~Cholera - caused by Vibrio Cholera ~Spirochetal infections: Lyme disease (Borrelia Burgdoferi) Relapsing fever (Borrelia Recurrentis) ~Ricketsial Infections: Rocky Mountain Spotted Fever, Typhus, Q Fever ~Brucellosis Chlortetracycline Oxytetracycline Demeclocycline

Syndrome of Inappropriate Secretion of ADH (SIADH) blocks the ADH actions onf the CD ~Eliminated through the liver - safe in renal dysfunction ~Prostatitis (reaches high levels in prostatic fluid) ~Choloroquine resistant Falciparum Malaria Meningococcal carrier states during an epidemic, but Rifampin is preferred

Doxycycline

Minocycline

~Best CSF penetration ~Concentrates in saliva & tears

Adverse Effects *Teeth: permanent brown discoloration & ill-formed teeth *Stunted bone growth *Photosensitvity on exposure to UV light *Superinfections: Diarrhea; Candida *Epigastric pain, abdominal distention, nausea, vomiting *Hepatic injury *Nephrotoxicity - except Doxycycline *Fanconi's Syndrome: a form of renal tubular acidosis is attributed to use of outdated tetracyclines

Adverse Effects

Secondary Uses: ~Alternative drug to penicillin in Syphillis ~H. Pylori associated peptic ulcers ~Acne ~Leptospirosis

Photosensitivity

Photosensitivity

Category

Drug Chloramphenicol

Mechanism of Action *Bacteriostatic *Binds to 50S ribosomal subunit *Inhibits transpeptidation and transfer of peptide chain from site P to acceptor site *Inhibits formation of peptide bond by inhibiting peptidyltransferase

Mechanism of Resistance Inactivation by acetyltransferase

Pharmacokinetics

Use Broad spectrum Gram - & Anaerobes Highly active: Salmonella H. Influenza N. Meningitis Anaerobic infections: Bacteriodes Fragilis Less active on Gram + cocci, Spirochetes & Rickettsia

Enteric Fever or Salmnellosis (alternative Ciprofloxacin, Ceftriaxone/Cefotaxime)

Adverse Effects Highly toxic Less used systemically Superinfections: Candidiasis Bone Marrow Suppression: dose dependent causing aplastic anemia *Gray Baby Syndrom: occurs in neonates - due to deficient hepatic glucuronsyltransferase lack of effective glucuronic acid conjugation degradation of Chloramphenicol ~Vomiting, abdominal distention, cyanosis, refusal to feed, CV collapse, death

Category Macrolides

Drug

Mechanism of Action *Binds reversibly to the 50S subunit *Protein synthesis is inhibited because of aminoacyl translocation reactions and the formation of initiation complexes are blocked *Inhibits peptidyltransferase *Inhibits translocation of peptidyl tRNA

Mechanism of Resistance Pharmacokinetics 1. In Gram + organisms resistance is due to: ~Efflux pump (throws drug out from within the cell wall) ~Production of methylase enzyme 2. In Enterobacteriaceae resistance is due to formation of drug metabolizing esterases 3. Acquired resistance: ~Specific mutations in the ribosome RNA of the 50S ribosomal subunit ~Acid labile enteric coated tablets ~Short plasma 1/2 life = 1.5 hrs

Use

Erythromycin

~Mycoplasma Pneumoniae ~C. Diptheriae ~Campylobacter Jejuni ~Chlamydia ~Legionella ~Bordetella Pertussis ~Strep. Pyogenes

*Atypical pneumonia *Whooping cough *Chancroid *Streptococci infections in patients who are allergic to Penicillins *Diptheria *Campylobacter enteritis *Legionnaire's pneumonia

Category

Drug Roxithromycin Clarithromycin

Mechanism of Action ~Chlamydia ~Mycobacterium Avium ~Toxoplasma Gondii ~H. Pylori

Mechanism of Resistance

Pharmacokinetics

Use *H. Pylori treatment in recurrent peptic ulcers *Upper & lower respiratory tract infections, skin infections *Atypical pneumonia *MAC infection in AIDS patients *Leprosy

Azithromycin

~DOC: Chlamydia ~M. Avium ~H. Influenza ~Neisseria

~Acid stable ~Long 1/2 life = 2-4 days ~High concentration inside macrophages & fibroblasts

*Legionnaire's pneumonia *Chlamydia infection of urogenital tract, pneumonia, trachoma *MAC infection in AIDS patients

Telithromycin

Category Lincosamides

Drug

Mechanism of Action *Binds reversibly to the 50S subunit *Protein synthesis is inhibited because of aminoacyl translocation reactions and the formation of initiation complexes are blocked *Inhibits peptidyltransferase *Inhibits translocation of peptidyl tRNA

Mechanism of Resistance

Pharmacokinetics

Use *Bacteriodes Fragilis *Pneumocystis Jiroveci *Toxoplasma Gondii

Clindamycin

*Anaerobic infections: Bacteriodes Fragilis *Prophylaxis of endocarditis in valvular disease patients who are allergic to Penicillins *Pneumocystis Jiroveci penumonia

Category

Drug Linezolid

Mechanism of Action Mechanism of Resistance Pharmacokinetics *Binds to 23S ribosomal *No cross resistance to other RNA of the 50S ribosomes protein synthesis inhibitors

Use 1. VRSA (Vancomycin Resistant Staph. Aureus) 2. VRSE (Vancomycin Resistant Enterococcus) 3. Multi-drug resistant Pneumococci

Category Streptogramins

Drug QuinupristinDalfopristine

Mechanism of Action *Binds to 50S ribosomes, they prevent the interaction of aminoacyltRNA with acceptor site and stimulates its dissociation from ternery complex *It also decreases the release of completed polypeptide by blocking its extrusion *It also inhibits tRNA synthetase activity

Mechanism of Resistance

Pharmacokinetics

Use 1. MRSA (Methicillin Resistant Staph. Aureus) 2. VRSA (Vancomycin Resistant Staph. Aureus) 3. VRSE (Vancomycin Resistant Enterococcus)

Last option for multiresistant strains

Adverse Effects

*Diarrhea (major cause for discontinuation) *GI distress: as it stimulates motillin receptors *Rashes, fever *Cholestatsis, jaundice with Erythromycin Estolate

Drug Interactions *It is a CYP450 enzyme inhibitor with Terfenadine/Astemizole/ Cisapride ~can cause prolongation of QT interval, ventricular arrythimia

Adverse Effects

Does not interact with hepatic CYP enzymes = NO drug interactions

Adverse Effects

1st known drug to cause pseudomembranous enterocolitis

Adverse Effects *Thrombocytopenia

Adverse Effects *Arthralgia-Myalgia syndrome *Fever *It is a CYP450 enzyme inhibitor

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