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53 Cards in this Set

  • Front
  • Back
What does antibiotic mean?
Chemical substance produced by microorganisms that suppress other microorganisms.
Life destroys life
What does antimicrobial mean?
Anti-infective.
includes synthetic derivatives with activity against bacteria and other microorganisms.
They do not affect mammalian cells.
What are the pathogenic effects of bacteria?
Compete with host for essential nutrients.
Release toxins.
Inititate inflammatory and immune responses.
Establish colonies: dormant but opportunistic
What are factors that determine susceptibility of microorganisms to antimicrobials?
1. Must achieve level of antimicrobial activity that tips to the favor of the host.
2. Concentration of blood must be below toxic level to humans.
3. Micro needs to susceptible to antimicorbial.
4. If drug concentartion exceeds that which is safe, microorganism is consisdered resistant.
How does one become an acquired bacterial resistanct?
1. Previously sensitive, now can withstand.
2. Acquisition by a usually stable genetic change. It has spontaneous mutation, tranformation, and transduction and transfer of resistant genes by conjugation.
3. Plasma encoded resistance.
4. Antimicrobial durg prescence is a selective force for resistant cells.
5. Cross resistance.
6. Resistance to penicillin.
What is the mechanism for drugs against the resisted bacteria?
Beta-lactamases such as Penicillinases and Cephalosporinases.
there is an alteration of bacterial cell permeability to the drug.
There is an efflux pump that actively transports the drug out of the bacteria and kills it.
How do antimicrobial durg become resistant?
Drugs eliminate sensitive cells but a few resistant cells become the dominant strain so R factor transfer increases.
Also indescriminate use to treat viral infections, insufficient dose, shot gun prophylaxis, substitute for sterile procedures.
Also an increased number of infections have arised.
What type of disease does Penicillin resistance give?
Community acquired pneumonia (CAP)
MRSA and VRSA length of stay
2-3 months in a dry environment.
What are adverse effects of antimicrobial drug?
Toxic effects
Allergic reactions such as sensitizing exposure (antibody production) and reactive exposure (antigen-antibody).
Superinfections (affects the flora)
Factors to consider in selection of antimicrobials
Identify microorganism
Host characteristics because some cross placental barrier, age, hepatic function, and renal function.
Have low ebb during cancer chemotherapy or with diabetes or AIDS.
Mechanism of Penicillin G (benzylpenicillin)
Beta-lactam ring required for activity.
Binds to penicillin binding proteins; This inhibits cross-linking of peptidoglycan in the final step of the cell wall synthesis.
What if the Penicillin G (benzylpenicillin) does not have the protective layer?
Have high intracellular osmotic pressure leading to a lysis of the bacterial cell.
Bactericidal action.
What are bacterial reistance mechanims of Penicillin G (benzylpenicillin)
Syntheisize beta-lactamse (penicillinase) by resitant strains.
Alterations in target peniciliin binding proteins (MRSA).
Reduced penetration or enhanced efflux from bacterial cell membrane.
Interations with Penicillin G (benzylpenicillin)
Food will cause less potency.
Reluctant penetration of the BBB.
Rapid kidney excretion of active drug.
Adverse effects of Penicillin G (benzylpenicillin)
Allergic reactions.
Direct toxicity is rare.
Therapeutic uses of Penicillin G (benzylpenicillin)
Non-penicillinase producing penumoncoccal, staphylococcal, and gonococcal infections.
Strep, meningogoccal, and Treponema infections.
Mechanism of Beta-lactamase inhibitors: Clavulanic acid
Inhibits many beta-lactamases.
Protects penicillins from inactivation.
Indications of Beta-lactamase inhibitors: Clavulanic acid
Tretats resistant organisms.
Monobactams and carbapenems are a broad specturm that are used for polymicrobial infections.
Mechanism os action of Cephalosporins: cephalexin (Keflex, po); cefazolin (Ancef, Kefzol iv)
Beta-lactam ring required for activity.
Binds to penicllin binding proteins by inhibiting cross linking of peptidoglycan in the final steps of cells wall synthesis.
Spectrum of Cephalosporins: cephalexin (Keflex, po); cefazolin (Ancef, Kefzol iv)
Good against some gram negative bacteria.
Have a wider spectrum than Penicllin G and are susceptible to inaction by penicillinase
Resistance to Cephalosporins: cephalexin (Keflex, po); cefazolin (Ancef, Kefzol iv)
Bacterial production of beta-lactamase (cephalosporinase)
Newer version have a greater stability to beta-lactamase
Adverse effects of Cephalosporins: cephalexin (Keflex, po); cefazolin (Ancef, Kefzol iv)
Potential cross-allerginicity with penicillins
Therapeutic effects of Cephalosporins: cephalexin (Keflex, po); cefazolin (Ancef, Kefzol iv)
Durgs of choice for very few infectfions.
Surgical prophylaxis.
3rd and 4th gneration of cephalosporins
Broadest spectrum and most stable of beta-lactamses. Designed to treat resistant, gram negative, and nosocomial infections.
Adverse effects of 3rd and 4th generation cepahlosporins
Allergic reactions. Hypoprothrombinemia which depletes vitamin K.
Superinfections.
Mechanism of Vancomycin (Vancocin)
Binds to D-alanine and prevents its incorporation into bacterial cell walls.
Is Vancomycin (Vancocin) given IV or SC?
IV only. Because it is not a beta-lactam.
Indications of Vancomycin (Vancocin)
Penicillin alternative for resistant infections or patients allergic to penicillins.
Adverse effects of Vancomycin (Vancocin)
Ototoxicity, nephrotoxicity, and redman syndrome.
Mechanism of Tetracyclines: Tetracycline (Achromycin)
Binds to 30S ribisomal unit. It inhibits the protein sysnthesis by blocking tRNA binding.
Bacterial mechaism of Tetracyclines: Tetracycline (Achromycin)
Increased efflux by active transport from bacterial cell (plasmid encoded: R factors).
Pharmacokinetics considerations
Antacids (Mg or Al), milk (Ca), and other divalent cations interfere with GI absorption.
Major excretion is done by the kidney.
Adverse effects of Tetracyclines: Tetracycline (Achromycin)
Superinfections: Staph, Candida albicans.
GI irritation
Photosensitivity
Hepatotoxicity
Localizes in rapidly-metabolizing (liver) and calcium-containing (bones and teeth) structures
Therapetuic uses of Tetracyclines: Tetracycline (Achromycin)
Avoid use in children and pregnant women.
Effective for several rare infections.
Other tetracycline interactions:
Have a signficant biliary excretion; a longer half-life and most complete oral absorption
Mechanism of Macrolides: erythromycin (Ilotycin, E-Mycin)
Inhibits protein synthesis by bidning to 50S ribosome subunit. It stimulates tRNA dissociation. It inhibits amino acid incorporation into proteins.
Resistance to Macrolides: erythromycin (Ilotycin, E-Mycin)
Decreased permeability leading to an increased efflux.
Altered ribosomal binding site.
Complete cross resistance to other in family.
Adverse effects of Macrolides: erythromycin (Ilotycin, E-Mycin)
GI distress
Liver toxicity
Drug Interaction by inactivating P450.
Therapeutic uses of Macrolides: erythromycin (Ilotycin, E-Mycin)
A penicillin alternative for respiratory tract infections.
May be an antiinflammatory.
New derivates of Macrolides: erythromycin (Ilotycin, E-Mycin)
Have effectiveness against H. pylori.
Mechanism of Aminoglycosides: Gentamicin (Garamycin)
Inhibits bacterial prtoein synthesis by decreasing fidelity of mRNA translation; requires binding of drug molecule to 30S ribosome subunit.
Has a broad specturm, and is bactericidal
Bacterial reistance mechanism to Aminoglycosides: Gentamicin (Garamycin)
Mutation of binding subunit.
Decreased membrane permeabilty.
Increased bacterial synthesis of degradative enzymes (transferase).
Cross resistance amongst family members not complete so no cross resistance.
Pharmacokinetics of Aminoglycosides: Gentamicin (Garamycin)
Poor oral absoprtion so need to be given IM.
Poor penetartion of the BBB.
Largely dependent on the renal filtration for eliminiation of free drug.
Need kidney function to prevent toxicity.
Once daily dosage regiment so keeps effect after an initial peak.
Adverse effect of Aminoglycosides: Gentamicin (Garamycin)
Ototoxicity.
Nephrotoxicity.
Neuromuscular blockade.
Therapeutic uses of Aminoglycosides: Gentamicin (Garamycin)
Reserved for severe gram negative infections when safer agents are ineffective.
Use in combination with penicillin or cephaosporins leading to a synergistic effect.
Useful in initial therapy of sepsis before causative pathogen has been identified.
Mechanism of Sulfonamides: Sulfisoxazole (Gantrisin)
Competitively inhibits p-aminobenzoic acid (PABA) incorporation into the folic acid pathway.
Interferes with the production of cofactors for DNA and RNA synthesis.
Resistance mechanism of Sulfonamides: Sulfisoxazole (Gantrisin)
Increased bacterial production of PABA.
Decreased enzyme affinity (plasmid-encoded)
Adverse effects of Sulfonamides: Sulfisoxazole (Gantrisin)
Drug precipitation in urine leading to crystalluria.
Urinary solubility varies among the drugs.
Have allergic reactions that has a cross allerginicity with thiazides, oral hypoglycemia.
Therapetuic effects of Sulfonamides: Sulfisoxazole (Gantrisin)
Treats urinary tract infections.
Have combination products
Used as a topical for burns and other local infections
Trimethoprim + sulfamethoxazole (Bactrim, Septra, TMP-SMZ) effects
Both inhibit the folic acid pathway.
Supra-additive combination.
Useful for urinary tract infections.
It inhibits 2 enzymes and will be very effective if sulfmonamide is given.
Effective alternative to beta-lactam drugs for treatment of upper respiratory.
IV form used for treating pneumonia in AIDS patients.
Pharmaokinetics of Fluoroquinolones: Ciprofloxacin (Cipro)
Absorption is inhibited by cations.
Adverse effects of Fluoroquinolones: Ciprofloxacin (Cipro)
May damage growing cartilage in children.
Want to avoid in pregnant women and in children under 18.
Usually is reversible.
Can lead to tendinitis and spontaneous rupture especially at the achilles.