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Antimicrobial Drugs (the stuff Dr. Figueroa didn’t tell you about in MIP)

Antimicrobial Drugs (the stuff Dr. Figueroa didn’t tell you about in MIP). Jeffery A. Hobden, Ph.D. Wonder Drugs. Decreased morbidity and mortality in US after WWII from infectious diseases Made practical some areas of medicine Cancer chemotherapy Gut surgery

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Antimicrobial Drugs (the stuff Dr. Figueroa didn’t tell you about in MIP)

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  1. Antimicrobial Drugs(the stuff Dr. Figueroa didn’t tell you about in MIP) Jeffery A. Hobden, Ph.D.

  2. Wonder Drugs • Decreased morbidity and mortality in US after WWII from infectious diseases • Made practical some areas of medicine • Cancer chemotherapy • Gut surgery • Increased productivity in agriculture

  3. Antibiotics - Exploited • In 2007, two antibiotics were in the top 20 drugs prescribed in the US • Amoxicillin – 34,801,000 • Azithromycin – 23,782,000 • In 2000, 24 million pounds of antibiotics were used in agriculture (chickens, pigs, cattle, etc) vs. 3 million pounds used to treat sick humans • Unrestricted access

  4. Top 20 Prescribed Drugs

  5. Tainted Seafood • Chinese seafood tested between 10/06 and 05/07 were repeatedly positive for • Nitrofuran • Malachite green • Fluoroquinolones • Shipments banned from entering US • Buy only local seafood! Alabama officials hold a press conference – “Drugs in your seafood are bad, M’Kay?

  6. The Consequences “That which does not kill us makes us stronger.” - Friedrich Nietzsche

  7. Can’t we just get more? • Screening natural or synthetic compounds for antibacterial activity • Preclinical studies (animals) • Safety (what is safe for animals may not be true for humans) • Efficacy (pharmacological parameters are different in animals)

  8. Wait – there’s more… • Clinical studies (humans) • Phase 1 – short term studies in small number of healthy humans or patients with target disease, to determine metabolism and basic pharmacologic and toxicological properties of antibiotic • Phase 2 – first controlled clinical studies to assess the effectiveness of the antibiotic and to determine short-term side effects and risks. • Phase 3 – expanded controlled and uncontrolled clinical studies to gather data regarding benefit – risk relationship. • Phase 4 – marketing!

  9. Is it any wonder? • Antibiotics are big business for pharm • Freebies • Advertising • Sponsorships • Not as profitable as drugs for erectile dysfunction, cholesterol control, anxiety attacks, etc.

  10. After MIP, what else is there to know about antibiotics? • What’s the origin of that antibiotic? • What’s special about it’s chemistry? • What happens to it after its in my body? • Will it kill or maim me if I take it?

  11. Classification of Antibioticsby Mechanism of Action • Inhibition of cell wall synthesis • Beta-lactam drugs • Penicillins • Cephalosporins • Carbapenems • The others • Cycloserine • Vancomycin • bacitracin

  12. Classification of Antibioticsby Mechanism of Action • Disruption of cell membranes • Polymyxin • Polyenes (anti-fungal agents)

  13. Classification of Antibioticsby Mechanism of Action • Inhibition of protein synthesis • Reversible inhibition (bacteristatic) • Chloramphenicol • The tetracyclines • The macrolides (erythromycin) • Clindamycin • Streptogramins • Linezolid • Irreversible – the bactericidal aminoglycosides

  14. Susceptibility and Resistance • In vitro values are guides, not rules • In vivo, bug is resistant if cidal concentrations are toxic to the host • Achievable serum concentrations are what determine susceptibility or resistance to drug • Low pH, high protein concentrations, anoxia • Pharmacological parameters of drugs (serum versus other bodily fluids)

  15. Bacterial Mechanisms of Resistance • Prevent antibiotic from reaching its target • Destroy or inactivate antibiotic before it reaches target • Alter target

  16. Choosing the right antibiotic – is it really needed? • Nature of the illness – is it a bacterial infection or something else? • Presumptive diagnosis (based on history and clinical symptoms) says yes! • Empiric therapy – broad spectrum drug • Specific therapy – narrow spectrum

  17. Choosing the right antibiotic – pharmacokinetic considerations. • Location of infection • Some antibiotics may or may not reach therapeutic concentrations in certain bodily fluids (ex. CSF and urine) • Degree to which antibiotic binds serum proteins • Excessive binding will affect passive diffusion of antibiotic from serum to tissue

  18. Choosing the right antibiotic – host factors. • Status of host immune system (cidal vs. static) • Local environment of infected site (pus, foreign bodies, etc) • Age (organ function in newborns and elderly) • Inherited metabolic disorder • Pregnancy (fetal or neonatal development)

  19. Choosing the right antibiotic – host factors. • drug allergies • Rashes • Anaphylaxis • Co-morbid conditions are aggravated by some antibiotics • Seizures • Blood disorders SJS Syndrome

  20. First up…. • The sulfonamides • The quinolones • The beta-lactams • Penicillins • Cephalosporins • Carbapenems Looking a-head….

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